UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 20-F
(Mark One)
REGISTRATION STATEMENT PURSUANT TO SECTION 12(b) OR (g) OF THE SECURITIES EXCHANGE ACT OF 1934
☐
OR
☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the fiscal year ended December 31, 2022
OR
☐
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the transition period from _________ to _________
OR
SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
Date of event requiring this shell company report
Commission File Number 001-39084
Innate Pharma SA
(Exact name of registrant as specified in its charter and translation of registrant’s name into English)
France
(Jurisdiction of incorporation or organization)
117, Avenue de Luminy
13009 Marseille France
(Address of principal executive offices)
Mondher Mahjoubi, M.D.
Chairman and Chief Executive Officer
Innate Pharma S.A.
117 Avenue de Luminy
13009 Marseille France
Tel: +33 4 30 30 30 30
(Name, Telephone, E-mail and/or Facsimile number and Address of Company Contact Person)
Securities registered or to be registered pursuant to Section 12(b) of the Act.
Title of each class
American Depositary Shares, each representing one
ordinary share, nominal value €0.05 per share
Ordinary shares, nominal value €0.05 per share
Trading Symbol
IPHA*
Name of each exchange on which registered
The Nasdaq Global Select Market
The Nasdaq Global Select Market*
*Not for trading, but only in connection with the registration of the American Depositary Shares.
Securities registered or to be registered pursuant to Section 12(g) of the Act. None
Securities for which there is a reporting obligation pursuant to Section 15(d) of the Act. None
Indicate the number of outstanding shares of each of the issuer’s classes of capital or common stock as of the close of the period
covered by the annual report.
Ordinary shares, nominal value €0.05 per share: 79,542,627 as of December 31, 2022
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. ☐ Yes ☒ No
If this report is an annual or transition report, indicate by check mark if the registrant is not required to file reports pursuant to
Section 13 or 15(d) of the Securities Exchange Act of 1934. ☐ Yes ☒ No
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities
Exchange Act of 1934 during the preceding 12 months (or for such shorter period that the registrant was required to file such
reports), and (2) has been subject to such filing requirements for the past 90 days. ☒ Yes ☐ No
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted
pursuant to Rule 405 of Regulation S-T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that
the registrant was required to submit such files). B Yes ☒ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, or an
emerging growth company. See definition of “large accelerated filer,” “accelerated filer,” and “emerging growth company” in
Rule 12b-2 of the Exchange Act.
Large accelerated filer
Non-accelerated filer
☐ Accelerated filter
☒ Emerging growth company
☐
☒
If an emerging growth company that prepares its financial statements in accordance with U.S. GAAP, indicate by check mark if
the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting
standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the
effectiveness of its internal control over financial reporting under Section 404(b) of the Sarbanes-Oxley Act (15 U.S.C.7262(b))
by the registered public accounting firm that prepared or issued its audit report. ☐ Yes ☒ No
Indicate by check mark which basis of accounting the registrant has used to prepare the financial statements included in this filing:
U.S. GAAP ☐
International Financial Reporting Standards
as issued by the International Accounting Standards Board ☒
Other ☐
If “Other” has been checked in response to the previous question, indicate by check mark which financial statement item the
registrant has elected to follow.
☐ Item 17 ☐ Item 18
If this is an annual report, indicate by check mark whether the registrant is a shell company (as defined in Rule 12b-2 of the
Exchange Act). ☐ Yes ☒ No
Indicate the number of outstanding shares of each of the issuer’s classes of capital or common stock as of the close of the period
covered by the annual report.
TABLE OF CONTENTS
INTRODUCTION ....................................................................................................................... 5
PART I ......................................................................................................................................... 9
Item 1. Identity of Directors, Senior Management and Advisers. ............................................... 9
Item 2. Offer Statistics and Expected Timetable. ........................................................................ 9
Item 3. Key Information. ............................................................................................................. 9
Selected Financial Data .................................................................................................. 9
A.
Capitalization and Indebtedness ..................................................................................... 11
B.
Reasons for the Offer and Use of Proceeds .................................................................... 11
C.
Risk Factors .................................................................................................................... 11
D.
Item 4. Information on the Company. .......................................................................................... 76
History and Development of the Company .................................................................... 76
A.
Business Overview ......................................................................................................... 77
B.
Organizational Structure. ................................................................................................ 137
C.
D.
Property, Plants and Equipment. ..................................................................................... 137
Item 4A. Unresolved Staff Comments. ........................................................................................ 137
Item 5. Operating and Financial Review and Prospects. ............................................................. 137
Operating Results ............................................................................................................ 145
A.
Liquidity and Capital Resources ..................................................................................... 163
B.
Research and Development ............................................................................................ 171
C.
Trend Information ........................................................................................................... 171
D.
E.
Critical Accounting Estimates. ....................................................................................... 171
Item 6. Directors, Senior Management and Employee. ............................................................... 171
Directors and Senior Management. ................................................................................ 171
A.
Compensation. ................................................................................................................ 177
B.
Board Practices ............................................................................................................... 191
C.
Employees ....................................................................................................................... 197
D.
E.
Share Ownership. ............................................................................................................ 197
Item 7. Major Shareholders and Related Party Transactions ....................................................... 198
Major Shareholders ......................................................................................................... 198
A.
Related Party Transactions. ............................................................................................ 200
B.
Interests of Experts and Counsel. ................................................................................... 204
C.
Item 8. Financial Information ...................................................................................................... 204
Consolidated Statements and Other Financial Information. ........................................... 204
A.
Significant Changes. ....................................................................................................... 205
B.
Item 9. The Offer and Listing. ..................................................................................................... 205
Offer and Listing Details. ............................................................................................... 205
A.
Plan of Distribution. ........................................................................................................ 205
B.
3
Markets. .......................................................................................................................... 205
C.
Selling Shareholders. ...................................................................................................... 205
D.
Dilution. .......................................................................................................................... 205
E.
Expenses of the Issue. ..................................................................................................... 205
F.
Item 10. Additional Information. ................................................................................................. 205
Share Capital. .................................................................................................................. 205
A.
Memorandum and Articles of Association. .................................................................... 205
B.
Material Contracts. .......................................................................................................... 206
C.
Exchange Controls. ......................................................................................................... 214
D.
Taxation. ......................................................................................................................... 214
E.
Dividends and Paying Agents. ........................................................................................ 224
F.
Statement by Experts. ..................................................................................................... 224
G.
H.
Documents on Display. ................................................................................................... 224
Subsidiary Information. .................................................................................................. 224
I.
Item 11. Quantitative and Qualitative Disclosures About Market Risk. ..................................... 225
Item 12. Description of Securities Other than Equity Securities. ................................................ 226
Debt Securities. ............................................................................................................... 226
A.
B. Warrants and Rights. ....................................................................................................... 226
Other Securities. .............................................................................................................. 226
C.
American Depositary Shares. ......................................................................................... 226
D.
PART II ........................................................................................................................................ 230
Item 13. Defaults, Dividend Arrearages and Delinquencies. ....................................................... 230
Item 14. Material Modifications to the Rights of Security Holders and Use of Proceeds. .......... 230
Item 15. Controls and Procedures. ............................................................................................... 231
Item 16. Reserved. ....................................................................................................................... 232
Item 16A. Audit Committees Financial Expert. .......................................................................... 232
Item 16B. Code of Business Conduct and Ethics. ....................................................................... 232
Item 16C. Principal Accountant Fees and Services. .................................................................... 232
Item 16D. Exemptions from the Listing Standards for Audit Committees. ................................ 233
Item 16E. Purchases of Equity Securities by the Issuer and Affiliated Purchasers. .................... 233
Item 16F. Change in Registrant’s Certifying Accountant. .......................................................... 233
Item 16G. Corporate Governance. ............................................................................................... 234
Item 16H. Mine Safety Disclosure. .............................................................................................. 234
PART III ...................................................................................................................................... 234
Item 17. Financial Statements. ..................................................................................................... 235
Item 18. Financial Statements. ..................................................................................................... 235
Item 19. Exhibits. ......................................................................................................................... 235
4
INTRODUCTION
Unless otherwise indicated in this annual report (this “Annual Report”), “Innate Pharma,” “Innate,” “the
company,” “the Company,” “we,” “us,” and “our” refer to Innate Pharma S.A. and its consolidated
subsidiaries.
“Innate Pharma,” the Innate Pharma logo, ANKET® and other trademarks or service marks of Innate
Pharma S.A. appearing in this Annual Report are the property of Innate Pharma S.A. or its
subsidiaries. Solely for convenience, the trademarks, service marks and trade names referred to in
this Annual Report are listed without the ® and ™ symbols, but such references should not be
construed as any indicator that their respective owners will not assert, to the fullest extent under
applicable law, their right thereto. All other trademarks, trade names and service marks appearing in
this Annual Report are the property of their respective owners. The Company does not intend to use
or display other companies’ trademarks and trade names to imply any relationship with, or
endorsement or sponsorship of Innate by, any other companies.
The audited consolidated financial statements have been prepared in accordance with International
Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board, or
IASB. The consolidated financial statements are presented in euros, and unless otherwise specified, all
monetary amounts are in euros. All references in this Annual Report to “$,” “US$,” “U.S.$,” “U.S.
dollars,” “dollars” and “USD” mean U.S. dollars and all references to “€” and “euros” mean euros, unless
otherwise noted. Throughout this Annual Report, references to ADSs mean American Depositary Shares
or ordinary shares represented by such ADSs, as the case may be.
5
SPECIAL NOTE REGARDING FORWARD-LOOKING STATEMENTS
This Annual Report contains forward-looking statements within the meaning of Section 27A of the
Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as
amended, that are based on the management’s beliefs and assumptions and on information currently
available to the management. All statements other than present and historical facts and conditions
contained in this Annual Report, including statements regarding the future results of operations and
financial position, business strategy, plans and the Company's objectives for future operations, are
forward-looking statements. When used in this Annual Report, the words “anticipate,” “believe,” “can,”
“could,” “estimate,” “expect,” “intend,” “is designed to,” “may,” “might,” “plan,” “potential,” “predict,”
“objective,” “should,” or the negative of these and similar expressions identify forward-looking
statements. Forward-looking statements include, but are not limited to, statements about:
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
•
the prospects of attaining, maintaining and expanding marketing authorization for
monalizumab, lacutamab and other product candidates;
the initiation, timing, progress and results of the Company's preclinical studies and clinical
trials and those conducted by third parties, including the Company's collaborators,
AstraZeneca and Sanofi;
the Company's ability to successfully develop and advance its pipeline of product candidates;
the timing or likelihood of regulatory filings and approvals;
the Company's ability to contract with third-party suppliers and manufacturers and their ability
to perform adequately;
future agreements with third parties in connection with the late-stage development and
commercialization of the Company's product candidates and any other approved product;
the Company's ability to develop sales and marketing capabilities and transition into a
commercial-stage company;
the pricing and reimbursement of the Company's product candidates, if approved;
the effects of increased competition as well as innovations by new and existing competitors in
the Company's industry;
the Company's ability to obtain funding for its operations;
the Company's ability to obtain, maintain, protect and enforce its intellectual property rights
and propriety technologies and to operate its business without infringing the intellectual
property rights and proprietary technology of third parties;
regulatory developments in the United States, Europe and other countries;
costs of compliance and failure to comply with new and existing governmental regulations
including, but not limited to, tax regulations;
statements regarding future revenue, hiring plans, expenses, capital expenditures, capital
requirements and stock performance;
the impact of the current state of the world financial market and economic conditions as well
as recent health and geopolitical events; and
other risks and uncertainties, including those listed in the section of this Annual Report titled
“Risk Factors”.
6
You should refer to the section of this Annual Report titled “Item 3.D – Risk Factors” for a discussion of
important factors that may cause actual results to differ materially from those expressed or implied by the
forward-looking statements. As a result of these factors, Innate cannot assure you that the forward-
looking statements in this Annual Report will prove to be accurate. Furthermore, if the forward-looking
statements prove to be inaccurate, the inaccuracy may be material. In light of the significant uncertainties
in these forward-looking statements, you should not regard these statements as a representation or
warranty by Innate or any other person that the Company will achieve its objectives and plans in any
specified time frame or at all. The Company undertakes no obligation to publicly update any forward-
looking statements, whether as a result of new information, future events or otherwise, except as required
by law. The Private Securities Litigation Reform Act of 1995 and Section 27A of the Securities Act do
not protect any forward-looking statements that Innate Pharma makes in connection with this Annual
Report.
In addition, statements that “Innate believes” and similar statements reflect its beliefs and opinions on the
relevant subject. These statements are based upon information available to Innate Pharma as of the date of
this Annual Report, and while the Company believes such information forms a reasonable basis for such
statements, such information may be limited or incomplete, and the statements should not be read to
indicate that the Company has conducted an exhaustive inquiry into, or review of, all potentially available
relevant information. These statements are inherently uncertain and investors are cautioned not to unduly
rely upon these statements.
You should read this Annual Report and the documents that the Company references in this Annual
Report and have filed as exhibits to this Annual Report completely and with the understanding that the
Company's actual future results, levels of activity, performance and events and circumstances may be
materially different from what the Company expects. The Company qualifies all of its forward-looking
statements by these cautionary statements.
Unless otherwise indicated, information contained in this Annual Report concerning the industry and the
markets in which the Company operates, including its general expectations and market position, market
opportunity and market size estimates, is based on information from independent industry analysts, third-
party sources and management estimates. Management estimates are derived from publicly available
information released by independent industry analysts and third-party sources, as well as data from
internal research, and are based on assumptions made by the Company based on such data and its
knowledge of such industry and market, which the Company believes to be reasonable. In addition, while
the Company believes the market opportunity information included in this Annual Report is generally
reliable and is based on reasonable assumptions, such data involve risks and uncertainties and are subject
to change based on various factors, including those discussed under the section of this Annual Report
titled “Item 3.D—Risk Factors.”
7
SUMMARY RISK FACTORS
Investing in the Company's shares involves numerous risks, including the risks described in "Item 3.D—
Risk Factors" of this Annual Report on Form 20-F. Below are some of the principal risks, any one of
which could materially adversely affect the Company's business, financial condition, results of operations,
and prospects:
• Biopharmaceutical development involves a high degree of uncertainty and most of the Company's
product candidates are in early stages of development.
•
•
•
•
•
•
•
•
The scientific evidence to support the feasibility of developing product candidates is both
preliminary and limited.
The Company intends to develop several of its product candidates in combination with other
therapies, which exposes it to additional risks.
The Company is heavily dependent on the success of its current clinical-stage product candidates
The Company may not be successful in its efforts to develop additional products that receive
regulatory approval and are successfully commercialized.
The Company may encounter substantial delays in its clinical trials, or may be unable to conduct
its clinical trials on the timelines the Company expects.
The Company's product candidates in development may cause undesirable side effects or have
other properties that could halt or delay their clinical development, prevent their regulatory
approval, limit their commercialization or result in other negative consequences.
The Company faces substantial competition from companies with significantly greater resources
and experience.
The regulatory processes that will govern the approval of the Company's product candidates are
complex and changes in regulatory requirements could result in delays or discontinuation of
development or unexpected costs in obtaining regulatory approval.
• Any of the Company's other product candidates, if approved and commercialized, may fail to
achieve market acceptance by physicians, patients, third-party payors or the medical community
to a degree that is necessary for commercial success.
• A fast track, breakthrough therapy or other designation by the FDA may not actually lead to a
faster development or faster regulatory review or approval.
•
•
•
•
•
The Company has no manufacturing capabilities and rely on third-party manufacturers for its
product candidates.
The Company relies on third parties to supply key materials used in its research and development,
to provide services to the Company and to assist with clinical trials.
The Company depends upon its existing collaboration partners, AstraZeneca, Sanofi and other
third parties, and may depend upon future collaboration partners to commit to the research,
development, manufacturing and marketing of its drugs.
The late-stage development and marketing of the Company's product candidates may partially
depend on its ability to establish collaborations with major biopharmaceutical companies.
The Company has incurred and may in the future incur significant operational losses related to its
research and development activities.
8
•
•
•
•
•
•
•
•
•
•
The Company may need to raise additional funding to complete the development and any
commercialization of its product candidates, which may not be available on acceptable terms, or
at all, and failure to obtain this necessary capital when needed may force the Company to delay,
limit or terminate its product development efforts or other operations.
If the Company does not achieve its product development or commercialization objectives in the
timeframes it expects, the Company may not receive product revenue or milestone or royalty
payments and it may not be able to conduct its operations as planned.
The revenues generated from the Company's collaboration and license agreements have
contributed and are expected to contribute a large portion of its revenue for the foreseeable future.
The Company benefits from tax credits in France that could be reduced or eliminated.
The global COVID-19 pandemic could adversely affect the Company's business, financial
condition and results of operations.
The Company's business could be affected by natural disaster, such as wildfire, and this could be
exacerbated by climate change.
The Company's ability to compete may be adversely affected if the Company does not adequately
obtain, maintain, protect and enforce its intellectual property or proprietary rights, or if the scope
of intellectual property protection the Company obtains is not sufficiently broad.
The Company's patents could be found invalid or unenforceable if challenged and it may not be
able to protect its intellectual property.
The dual listing of the Company's ordinary shares and the ADSs may adversely affect the
liquidity and value of the ADSs.
The Company may be affected by political, social, legal and economic instability, civil unrest,
war and other geopolitical tension, such as the ongoing military conflict between Russia and
Ukraine and economic sanctions related thereto.
• Report titled "Item 3.D—Risks Factors."
PART I
Item 1. Identity of Directors, Senior Management and Advisers.
Not applicable.
Item 2. Offer Statistics and Expected Timetable.
Not applicable.
Item 3. Key Information.
A. Selected Financial Data
Innate's consolidated audited financial statements have been prepared in accordance with IFRS, as issued
by the IASB. The Company derived the selected consolidated statement of income (loss) data for the
years ended, December 31, 2020, 2021 and 2022 and the selected consolidated statement of financial
position data as of December 31, 2020, 2021 and 2022 from the consolidated audited financial statements
included elsewhere in this Annual Report. This data should be read together with, and is qualified in its
entirety by reference to, “Item 5. Operating and Financial Review and Prospects” as well as the financial
statements and notes thereto appearing elsewhere in this Annual Report. Innate's historical results are not
necessarily indicative of the results to be expected in the future.
9
Consolidated Statement of Income (Loss) Data:
Revenue and other income
Operating expenses
Research and development expenses
General and administrative expenses
Impairment of intangible assets
Operating income (loss)
Net financial income (loss)
Income tax expense
Net income (loss) from continuing operations
Net income (loss) from discontinued operations
Net income (loss)
Net income (loss) per share attributable to equity holders
- Basic income (loss) per share
- Diluted income (loss) per share
- Basic income (loss) per share from continuing operations
- Diluted income (loss) per share from continuing operations
- Basic income (loss) per share from discontinued operations
- Diluted income (loss) per share from discontinued operations
Number of ordinary shares outstanding used for computing basic net
income (loss) per share
Number of ordinary shares outstanding used for computing diluted
net income (loss) per share
Year ended December 31,
2020 (1)
2021
2022
(in thousands of euros, except per share data and
number of ordinary shares)
€
69,773 €
24,703 €
57,674
(49,708)
(18,986)
—
1,079
(1,908)
—
(829)
(63,155)
(63,984)
(0.81)
(0.81)
(0.01)
(0.01)
(0.80)
(0.80)
(47,004)
(25,524)
—
(47,825)
2,347
—
(45,478)
(7,331)
(52,809)
(0.66)
(0.66)
(0.57)
(0.57)
(0.09)
(0.09)
(51,663)
(22,436)
(41,000)
(57,425)
(546)
—
(57,972)
(131)
(58,103)
(0.73)
(0.73)
(0.73)
(0.73)
—
—
78,934,960
79,542,627
79,639,826
78,934,960
79,542,627
79,639,826
(1) The 2020 comparatives has been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17 of our consolidated financial statements appearing elsewhere in this Annual Report.
Consolidated Statement of Financial Position Data:
Cash and cash equivalents, short-term investments and non-current
financial assets (1)
Total assets
Total financial debt and defined benefit obligations
Total shareholders’ equity
As of December 31,
2020
2021
2022
(in thousands of euros)
€ 190,571
€ 159,714
€ 136,604
307,423
23,264
267,496
47,226
€ 155,976
€ 107,440
207,863
44,801
€ 54,151
(1) Non-current financial assets account for € 38.9, 39.9 and 35.1 million for the years ended December 31, 2020, 2021 and 2022, respectively.
10
B. Capitalization and Indebtedness
Not applicable.
C. Reasons for the Offer and Use of Proceeds
Not applicable.
D. Risk Factors
The Company's business faces significant risks. You should carefully consider all of the information set
forth in this Annual Report and in the other filings with the United States Securities and Exchange
Commission, or the SEC, including the following risk factors which Innate faces and which are faced by
its industry. The Company's business, financial condition or results of operations could be materially
adversely affected by any of these risks. This report also contains forward-looking statements that involve
risks and uncertainties. Innate's results could materially differ from those anticipated in these forward-
looking statements, as a result of certain factors including the risks described below and elsewhere in this
Annual Report and its other SEC filings. See “Special Note Regarding Forward-Looking Statements”
above.
Risks Related to the Development of the Product Candidates
Biopharmaceutical development involves a high degree of uncertainty and most of the product
candidates are in early stages of development, which makes it difficult to evaluate the current business
and future prospects and may increase the risk of your investment.
Innate Pharma is a global, clinical stage oncology-focused biotech company. In December 2020, Innate
decided to return Lumoxiti commercial rights to AstraZeneca and to re-focus investments in its R&D
portfolio consisting of product candidates, some of which Innate is co-developing, in the early stages of
clinical development and preclinical programs.
A key element of Innate's strategy is to mature and expand its portfolio of proprietary and partnered
product candidates to address unmet medical needs in immuno-oncology. Although Innate's research and
development efforts to date have resulted in a pipeline of product candidates, all of its product candidates
require additional development, regulatory review and approvals, substantial investment, access to
sufficient commercial manufacturing capacity and significant marketing efforts before they can be
commercialized and before Innate can generate any revenue from product sales or royalties. If the
Company or its collaboration partners are unable to successfully develop and market these product
candidates, its business, prospects, financial condition and results of operations may be adversely
affected.
Aside from Innate's acquisition of Lumoxiti, its operations to date have been limited to developing its
product candidates and undertaking preclinical studies and clinical trials of its product candidates,
including monalizumab and IPH5201, through its partnership with AstraZeneca, IPH6101/SAR'579
through its partnership with Sanofi, lacutamab, avdoralimab and IPH5301, its most advanced product
candidates, currently in clinical stage. The success in development of its current and future product
candidates by the Company or its collaborators will depend on many factors, including:
•
•
obtaining positive results in clinical trials including by demonstrating efficacy, safety and
durability of effect of such product candidates;
completing preclinical studies and receiving regulatory approvals or clearance for conducting
clinical trials for its preclinical programs;
11
•
•
•
•
•
•
receiving and maintaining approvals for commercialization of such product candidates from
regulatory authorities;
manufacturing or overseeing the manufacturing of its product candidates in acceptable
quantities and at an acceptable cost;
negotiating favorable terms in any collaboration, licensing or other arrangements into which
the Company may enter, and performing its obligations pursuant to such arrangements;
maintaining, protecting, enforcing and expanding its portfolio of intellectual property rights,
including patents, trade secrets and know-how;
avoiding and defending against third-party interference, infringement or other intellectual
property claims; and
maintaining and growing an organization of scientists, medical professionals, marketing,
distribution and sales personnel and executives who can develop its product candidates and
commercialize any approved products.
In addition, if the Company is unable to reduce its dependence on its current clinical and preclinical
product candidates, either by in-licensing or acquiring new product candidates, developing its other
product candidates or discovering new product candidates, the Company may be similarly adversely
affected.
The scientific evidence to support the feasibility of developing product candidates is both preliminary
and limited.
Innate Pharma innovative approach to immuno-oncology aims to activate both the innate and adaptive
immune systems against abnormal or cancerous cells and restore the body’s ability to disrupt their
proliferation, potentially leading to durable responses in patients. This approach is focused on developing
checkpoint inhibitors, tumor-targeting antibodies and antibodies that affect the tumor microenvironment,
and several of the product candidates rely on novel mechanisms of action and on innovative formats for
which the Company has limited scientific evidence and preclinical and clinical data.
The Company may not ultimately be able to provide the FDA, European Medicines Agency, or EMA, or
other regulatory authorities with substantial clinical evidence to support a claim of efficacy and durability
of response to enable the applicable regulators to approve its product candidates for any indication. This
may occur because later clinical trials fail to reproduce favorable data obtained in earlier clinical trials,
because the applicable regulator disagrees with how the Company interprets the data from these clinical
trials or because the applicable regulator does not accept these therapeutic effects as valid endpoints in
pivotal clinical trials that are sufficient to grant marketing approval. Additionally, because product
candidates in later stages of clinical trials may fail to show the desired safety and efficacy traits despite
having progressed through preclinical studies and earlier clinical trials its collaborators in earlier stages of
clinical trials may eventually choose to discontinue later stage trials. For example, following initial
promising results assessing the safety and efficacy of the Company's product candidate lirilumab for the
treatment of various cancer indications, the Company's collaborator decided not to continue development
after receiving Phase 2 clinical trial data. Moreover, in 2022, AstraZeneca informed Innate Pharma of the
discontinuation of the Interlink-1 Phase 3 clinical trial assessing monalizumab in combination with
cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck, as this
combination did not meet a pre-defined threshold for efficacy.
In addition to the safety and efficacy traits of any product candidate, clinical trial failures may result from
a multitude of factors including flaws in trial design, dose selection, placebo effect and patient enrollment
criteria. A number of companies in the pharmaceutical industry have suffered significant setbacks in
12
advanced clinical trials due to lack of efficacy or adverse safety profiles, notwithstanding promising
results in earlier trials, and it is possible that the Company will as well. Based upon negative or
inconclusive results, the Company or its collaborators may decide, or regulators may require the
Company, to conduct additional clinical trials or preclinical studies. In addition, data obtained from trials
and studies are susceptible to varying interpretations, and regulators may not interpret the Company's data
as favorably as the Company does, which may delay, limit or prevent regulatory approval.
The Company will also need to demonstrate that its product candidates are safe and well tolerated. The
Company does not have significant data on possible harmful long-term effects of its product candidates
and does not expect to have this data in the near future. As a result, its ability to generate clinical safety
and efficacy data sufficient to support submission of a marketing application or commercialization of its
product candidates is uncertain and is subject to significant risk.
The Company intends to develop several of its product candidates in combination with other therapies,
which exposes the Company to additional risks.
The Company is currently developing monalizumab, lacutamab and IPH5201, and may develop other
product candidates, in combination with one or more currently approved cancer therapies. Specifically,
AstraZeneca is currently evaluating monalizumab in ongoing Phase 1, 2 and 3 trials in combination with
durvalumab, an anti-PD-L1 immune checkpoint inhibitor. Lacutamab is also currently evaluated in
combination with chemotherapy GEMOX (gemcitabine in combination with oxaliplatin) in patients with
PTCL (Peripheral T Cell Lymphoma). In addition, IPH5201 is also currently under clinical investigation,
in a Phase 2 trial in combination with durvalumab and chemotherapy. Finally, IPH5301 is currently under
clinical investigation in a Phase 1 trial in combination with a chemotherapy, paclitaxel and trastuzumab.
Patients may not be able to tolerate the Company's product candidates in combination with other
therapies, and preliminary clinical results indicate that monalizumab, for example, has no meaningful
clinical activity as a monotherapy. Even if any product candidate the Company develops were to receive
marketing approval or be commercialized for use in combination with other existing therapies, the
Company would continue to be subject to the risks that the FDA, EMA or other comparable foreign
regulatory authorities could revoke approval of the therapy used in combination with its product candidate
or that safety, efficacy, manufacturing or supply issues could arise with these existing therapies.
Combination therapies are commonly used for the treatment of cancer, and the Company would be
subject to similar risks if the Company develops any of its product candidates for use in combination with
other therapies or for indications other than cancer. This could result in its own products, if approved,
being removed from the market or being less successful commercially.
The Company may also evaluate any of its current and future product candidates in combination with one
or more other cancer therapies that have not yet been approved for marketing by the FDA, EMA or
comparable foreign regulatory authorities. The Company will not be able to market and sell
monalizumab, lacutamab, IPH5201 or IPH5301 or any other product candidate the Company develops in
combination with any such unapproved cancer therapies that do not ultimately obtain marketing approval.
If the FDA, EMA or other comparable foreign regulatory authorities do not approve, revoke their
approval of, or if safety, efficacy, manufacturing or supply issues arise with, the products or product
candidates the Company chooses to evaluate in combination with monalizumab, lacutamab, IPH5201,
IPH5301 or any other product candidate the Company develops, the Company may be unable to obtain
approval of or market monalizumab or any other such product candidate the Company develops.
13
The Company are heavily dependent on the success of its current clinical-stage product candidates and
the Company cannot be certain that the Company or its collaborators will be able to obtain regulatory
approval for, or successfully commercialize, these product candidates.
The Company's business and future success depend on receiving regulatory approval for, and the
commercial success of, its proprietary and partnered product candidates. The Company has agreements
with AstraZeneca with respect to the advanced development, clinical trial collaboration and potential
future registration and marketing of several of its product candidates, including monalizumab and
IPH5201, and with Sanofi for the research and development of IPH6101/SAR'579, IPH6401/SAR’514
and IPH62. Its near-term prospects depend heavily on AstraZeneca’s successful clinical development and
commercialization of monalizumab as well as the successful clinical development of its other product
candidates. The clinical success of these product candidates will depend on a number of factors, including
the ability and willingness of AstraZeneca and the Company's other collaborators to complete ongoing
clinical trials for monalizumab or other partnered assets, the ability to complete the clinical trials for
which the Company is responsible, and the safety, tolerability and efficacy of its product candidates.
The Company may not be successful in its efforts to develop additional products that receive regulatory
approval and are successfully commercialized.
The development of a product candidate is a long, costly and uncertain process, aimed at demonstrating
the therapeutic benefit of a product candidate that competes with existing products or those being
developed. There is no guarantee that the Company or its collaborators will be able to demonstrate a
sufficient degree of clinical efficacy or safety of one or more of its proprietary or licensed product
candidates in order to gain regulatory approval or to become commercially viable. The degree of
uncertainty associated with clinical development and the risks associated with developing new product
candidates may make it difficult to evaluate its current business and its future prospects.
IPH5201,
lacutamab, avdoralimab,
The Company intends to continue to develop its product candidates that are currently in clinical trials,
including monalizumab,
IPH6101/SAR'579.
Monalizumab is currently being investigated in multiple Phase 1, Phase 2 and Phase 3 clinical trials under
a co-development agreement with AstraZeneca. Lacutamab is currently being investigated in an open-
label, multi-cohort Phase 2 clinical trial in CTCL and in Phases 1 and 2 in PTCL. IPH5201 is currently
being investigated in an open-label Phase 2 clinical trial. IPH5301 is currently being investigated in a
Phase 1 clinical trial sponsored by the Institut Paoli-Calmettes. IPH6101/SAR'579 is currently
investigated in a Phase 1/2 clinical trial sponsored by Sanofi. The clinical investigation of avdoralimab in
bullous pemphigoid is not pursued and the will continue to evaluate its strategic options for potential next
steps.
IPH5301 and
While the Company believes that it will eventually have the in-house capabilities to complete the
development and/or support the development by a partner of monalizumab, lacutamab, avdoralimab,
IPH5201, IPH5301 and IPH6101/SAR'579, the Company has not yet completed the clinical trials for
these or other product candidates, and there can be no assurance that these or other product candidates
will gain regulatory approval or become commercially viable.
Delays in the preclinical development of a product candidate could lead to delays in initiating its clinical
development. A failure in the preclinical development of a product candidate could lead to abandoning its
development. Further delays or failures at the various clinical stages for a given indication could result in
delay or halt the development of the product candidate in such indication or in other indications.
Moreover, disappointing results during the initial Phases of development are often not a sufficient basis
for deciding whether or not to continue a project. At these early stages, sample sizes, the duration of
studies and the parameters examined may not be sufficient to enable a definitive conclusion to be drawn,
in which case further investigations are required. Conversely, promising results during the initial Phases,
14
and even after advanced clinical trials have been conducted, do not guarantee that a product candidate or
an approved drug will be successfully approved and commercialized.
The risks related to the failure of a product candidate’s development are highly related to the stage of
maturity of the product candidate. Given the relatively early stage of the product candidates in the
pipeline, there is a substantial risk that some or all of the product candidates will not obtain regulatory
approval or be commercialized, which would have an adverse impact on the Company's business,
prospects, financial condition and results of operations.
The Company may not be successful in its efforts to identify, discover or develop additional product
candidates, including those based on its innovative ANKET® technology.
The Company is seeking to develop a broad and innovative pipeline of product candidates in addition to
monalizumab, lacutamab, avdoralimab, IPH5201, IPH5301 and IPH6101/SAR'579. The Company may
not be successful in identifying additional product candidates for clinical development for a number of
reasons. For example, its research methodology may be unsuccessful in identifying potential product
candidates or the potential product candidates, the Company identifies may have harmful side effects,
lack of efficacy or other characteristics that make them unmarketable or unlikely to receive regulatory
approval.
Moreover, some of its innovative pipeline of product candidates are based on its innovative ANKET®
platform which is not yet approved. The ANKET® platform consists of two different formats, tri-specific
and tetra-specific antibodies. IPH6101/SAR'579, in partnership with Sanofi, a tri-specific antibody, which
is the most advanced product candidate, is currently being investigated in a Phase 1 clinical trial. Another
tri-specific antibody also developed in partnership with Sanofi is currently in preclinical stage (IPH6401/
SAR’514). Another multi-specific is also developed in partnership with Sanofi (IPH62). Moreover, the
Company is developing IPH6501, a tetra-specific proprietary antibody, which is currently moving
towards an Investigational New Drug application, or IND. Even if the Company aims at maintaining a
diversified pipeline, the use of an innovative technology represents additional risks in the product
candidate development.
Research programs to pursue the development of the product candidates for additional indications and to
identify new product candidates and disease targets require substantial technical, financial and human
resources. the Company's research programs may initially show promise in identifying potential
indications or product candidates, yet fail to yield results for clinical development for a number of
reasons, including:
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the research methodology used may not be successful in identifying potential indications or
product candidates;
potential product candidates and/or its ANKET® technology may, after further study, be
shown to have harmful adverse effects or other characteristics that indicate they are unlikely to
be effective drugs; or
it may take greater human and financial resources to identify additional therapeutic
opportunities for its product candidates or to develop suitable potential product candidates
through internal research programs than the Company will possess, thereby limiting its ability
to diversify and expand its product portfolio.
Accordingly, there can be no assurance that the Company will ever be able to identify additional
indications for its product candidates or to identify and develop new product candidates through internal
research programs. The Company may focus its efforts and resources on potential product candidates or
other potential programs that ultimately prove to be unsuccessful.
15
The Company may encounter substantial delays in its clinical trials, or may be unable to conduct its
clinical trials on the timelines the Company expects.
Clinical testing is expensive, time consuming, and subject to uncertainty. The Company cannot guarantee
that any clinical trials will be conducted as planned or completed on schedule, if at all. A failure of one or
more clinical trials can occur at any stage of testing, and its future clinical studies may not be successful.
Events that may prevent successful or timely completion of clinical development include:
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inability to generate sufficient preclinical, toxicology, or other in vivo or in vitro data to
support the initiation of clinical trials;
delays or failure in reaching a consensus with regulatory agencies on clinical trial design;
delays in reaching agreement on acceptable terms with prospective Contract Research
Organisations, or CROs, and investigational sites, the terms of which can be subject to
extensive negotiation and may vary significantly among different CROs and investigational
sites;
imposition of a temporary or permanent clinical hold by regulatory agencies, including as a
result of a new safety finding that presents unreasonable risk to clinical trial participants, a
negative finding from an inspection of its clinical trial operations or investigational sites,
developments in trials conducted by competitors for related technology that raise regulators’
concerns about risk to patients of the technology broadly or if a regulatory body finds that the
investigational protocol or plan is clearly deficient to meet its stated objectives. For example,
in November 2019, its TELLOMAK trial was put on full or partial holds in a number of
countries. The Company was authorized to fully resume patient enrollment and treatment after
having been able to produce a new conform batch;
delays in recruiting suitable patients to participate in its clinical trials;
difficulty collaborating with patient groups and investigators;
failure by the Company, its CROs or other third parties, including its collaborators, to adhere
to clinical trial requirements;
delays in having patients complete participation in a clinical trial or return for post-treatment
follow-up;
patients withdrawing from a clinical trial;
occurrence of adverse events associated with a product candidate that are viewed to outweigh
its potential benefits;
changes in regulatory requirements and guidance that require amending or submitting new
clinical trial protocols;
regulatory feedback requiring the Company to amend the protocols of ongoing clinical trials in
response to safety considerations, as the Company has previously been required to;
changes in the standard of care on which a clinical development plan was based, which may
require new or additional clinical trials;
the cost of clinical trials of its product candidates being greater than the Company anticipates;
clinical trials of its product candidates producing negative or inconclusive results, which may
result in the Company deciding, or regulators requiring the Company, to conduct additional
clinical trials or abandon product development programs;
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transfer of manufacturing processes to larger-scale facilities operated by either a contract
manufacturing organization, or CMO, or by , and delays or failure by its CMOs or the
Company to make any necessary changes to such manufacturing process; and
batch recalls, recalls of manufactured product candidates or delays in manufacturing, testing,
releasing, validating, or importing or exporting sufficient stable quantities of its product
candidates for use in clinical trials or the inability to do any of the foregoing.
Any inability to successfully complete preclinical and clinical development could result in additional
costs to the Compnay or impair its ability to generate revenue. In addition, if the Company makes
manufacturing or formulation changes to its product candidates, it may be required to or it may elect to
conduct additional studies to bridge its modified product candidates to earlier versions. Clinical study
delays could also shorten any periods during which its products have patent protection and may allow its
competitors to bring products to market before the Company does, which could impair its ability to
successfully commercialize its product candidates and may harm its business and results of operations.
The Company depends on enrollment of patients in its clinical trials for its product candidates.
Successful and timely completion of clinical trials will require that the Company or its subcontractors
enroll a sufficient number of suitable patients. Clinical trials may be subject to delays as a result of patient
enrollment taking longer than anticipated or patient withdrawal. Patient enrollment depends on many
factors, including the size and nature of the patient population, which is typically limited for rare or
orphan diseases making the enrollment more difficult, eligibility criteria for the trial, the proximity of
patients to clinical sites, the design of the clinical protocol, the availability of competing clinical trials, the
availability of new drugs approved for the indication the clinical trial is investigating, and clinicians’ and
patients’ perceptions as to the potential advantages of the drug being studied in relation to other available
therapies. For example, the Company is developing lacutamab for the treatment of cutaneous T-cell
lymphoma, or CTCL. CTCL is an orphan disease, which means that the potential patient population is
limited. In addition, there are several other product candidates potentially in development for the
indications for which the Company is developing product candidates, and the Company may compete for
patients with the sponsors of trials for those drugs. These factors may make it difficult for the Company to
enroll enough patients to complete its clinical trials in a timely and cost-effective manner. Delays in the
completion of any clinical trial of any of its product candidates will increase its costs, slow down its
product candidate development and approval process and delay or potentially jeopardize its ability to
commence product sales and generate revenue. In addition, some of the factors that cause, or lead to, a
delay in the commencement or completion of clinical trials may also ultimately lead to the inability to
obtain regulatory approval of its product candidates.
The Company's product candidates in development may cause undesirable side effects or have other
properties that could halt or delay their clinical development, prevent their regulatory approval, limit
their commercialization or result in other negative consequences.
Use of the Company's product candidates in development could be associated with side effects or adverse
events which can vary in severity and in frequency. Undesirable side effects or unacceptable toxicities
caused by its products or product candidates could cause the Company or regulatory authorities to
interrupt, delay, or halt clinical trials. The FDA or European regulatory authorities could delay or deny
approval of the Company's product candidates for any or all targeted indications and negative side effects
could result in a more restrictive label for any drug that is approved. Side effects such as toxicity or other
safety issues associated with the use of the Company's product candidates could also require it or its
collaborators to perform additional studies or halt development of product candidates or sale of approved
products.
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Treatment-related side effects could also affect patient recruitment or the ability of enrolled subjects to
complete the trial, or could result in potential product liability claims. In addition, these side effects may
not be appropriately or timely recognized or managed by the treating medical staff, as toxicities resulting
from immunotherapy are not normally encountered in the general patient population and by medical
personnel. Inadequate training in recognizing or managing the potential side effects of its product
candidates could result in adverse effects to patients, including death. Any of these occurrences may have
an adverse impact on the Company's business, prospects, financial condition and results of operations.
The Company faces substantial competition from companies with significantly greater resources and
experience.
The biotechnology and pharmaceutical market, and notably the immuno-oncology field, is characterized
by rapidly advancing technologies, products protected by intellectual property rights and intense
competition and is subject to significant and rapid change as researchers learn more about diseases and
develop new technologies and treatments. The Company faces potential competition from many different
sources, including major pharmaceutical companies, specialty pharmaceutical and biotechnology
companies, academic institutions and governmental agencies and public and private research institutions.
Any product candidates that the Company or its collaborators successfully develop will compete with
existing therapies and new therapies that may become available in the future. If competing products are
marketed before Innate's ones, or at lower prices, or cover a wider therapeutic spectrum, or if they prove
to be more effective or better tolerated, the Company's business, prospects, financial condition and results
of operations could be affected.
Many of the Company's competitors who are developing immuno-oncology and anti-cancer therapies
have considerably greater resources and experience in research, access to patients for clinical trials, drug
development, finance, manufacturing, marketing, technology and personnel than the Company does. In
particular, large pharmaceutical companies have substantially more experience than the Company does in
conducting clinical trials and obtaining regulatory authorizations. Mergers and acquisitions in the
pharmaceutical, biotechnology and diagnostic industries may result in even more resources being
concentrated among a smaller number of the Company's competitors. Smaller or early-stage companies
may also prove to be significant competitors, particularly through collaborative arrangements with large
and established companies. These competitors are also likely to compete with Company to recruit and
retain scientific and management personnel, acquire rights for promising product candidates and other
complementary technologies, establish clinical trial sites and patient registration for clinical trials and
acquire technologies complementary to, or necessary for, its programs, as well as to enter into
collaborations with partners who have access to innovative technologies. If the Company cannot
successfully compete with new or existing products, its marketing and sales will suffer and the Company
may never be profitable. Should any of these risks materialize, Innate's business, prospects, financial
condition and results of operations may be adversely affected.
The Company cannot guarantee that its product candidates will:
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obtain regulatory authorizations or become commercially available before those of its
competitors;
remain competitive in the face of other products developed by its competitors, which may
prove to be safer, are more effective, have fewer or less severe side effects, are more
convenient, have a broader label, have more robust intellectual property protection or are less
expensive;
remain competitive in the face of products of competitors that are more efficient in their
manufacturing or more effective in their marketing; and
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•
not become obsolete or unprofitable due to technological progress or other therapies developed
by its competitors.
In addition, while any future product candidate that is approved may compete with many existing drugs or
other therapies, to the extent it is solely used in combination with these therapies, the Company's product
candidates will not be competitive with such therapies but any sales of such products could be limited to
sales of the combination therapy. In this case, the Company would be exposed to the same competitive
risks as the product used in combination with its product, such as a product that is marketed before the
combination therapy, has lower prices, covers a wider therapeutic spectrum or proves to be more effective
or better tolerated. For additional information regarding competition to its business see “Business—
Competition.”
Risks Related to Regulatory Approval and Marketing of Innate's Product Candidates and Legal
Compliance Matters
Even if the Company complete the necessary preclinical studies and clinical trials, the marketing
approval process is expensive, time-consuming and uncertain and may prevent Innate from obtaining
approvals for the commercialization of some or all of its product candidates. If the Company is not able
to obtain, or if there are delays in obtaining, required regulatory approvals, in particular in the United
States or the European Union, the Company will not be able to commercialize its product candidates,
and its ability to generate revenue will be materially impaired.
The research and development of pharmaceutical products is governed by complex regulatory
requirements. The regulatory agencies that oversee these requirements have the authority to permit the
commencement of clinical trials or to temporarily or permanently halt a study. They are entitled to request
additional clinical data before authorizing the commencement or resumption of a study, which could
result in delays or changes to the product development plan. As the Company advances its product
candidates, the Company will be required to consult with these regulatory agencies and comply with all
applicable guidelines, rules and regulations. If the Company fails to do so, the Company may be required
to delay or discontinue development of its product candidates. Delay or failure to obtain, or unexpected
costs in obtaining, the regulatory approval necessary to bring a potential product to market could decrease
its ability to generate sufficient product revenue to maintain its business.
The clinical trials of Innate's product candidates, the manufacturing and the marketing of its product
candidates are and will be, subject to regulation by numerous government authorities in the United States,
in the European Union and in other countries where the Company intend to test and, if approved, market
any product candidate. Before obtaining regulatory approvals for the commercial sale of any product
candidate, the Company must demonstrate, with substantial evidence gathered in well-controlled clinical
trials, and, with respect to approval in the United States, to the satisfaction of the FDA, with respect to
approval in the European Union, to the satisfaction of the EMA or, with respect to approval in other
countries, similar regulatory authorities in those countries, that the product candidate is safe and effective
for use in each target indication.
When the Company acquired Lumoxiti, AstraZeneca had already obtained marketing approval from the
FDA and they also filed the Marketing Authorization in the European Union. The Company has never
submitted a product candidate for marketing approval in the United States, in the European Union or
elsewhere.
In the United States, the Company expects that the requisite regulatory submission to seek marketing
authorization for its product candidates will be a Biologic License Application, or BLA, and the
competent regulatory authority is the FDA. In the European Union, the requisite approval is a Marketing
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Authorization, or MA, which for products developed by the means of antibody-based therapeutics, gene
or cell therapy products as well as tissue engineered products, is issued through a centralized procedure
involving the EMA (see “Business—Regulation”). Satisfaction of these and other regulatory requirements
is costly, time consuming, uncertain and subject to unanticipated delays. Failure to comply with the
applicable requirements at any time during the product development process, approval process or after
approval, may subject an applicant to administrative or judicial sanctions. These sanctions could include,
for example, the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical
hold, untitled or warning letters, product recalls or withdrawals from the market, product seizures, total or
partial suspension of production or distribution injunctions, fines, refusals of government contracts,
restitution, disgorgement, or civil or criminal penalties.
Data from preclinical and clinical studies are likely to give rise to different interpretations, which could
delay regulatory authorization, restrict the scope of any such authorization or force Innate to repeat trials
in order to meet the requirements of the various regulators. Regulatory requirements and processes vary
widely among countries, and the Company may be unable to obtain authorization within each relevant
country in a timely manner. Regulatory authorities may prevent Innate from starting clinical trials or
continuing clinical development if the data were not produced according to applicable regulations or if
they consider that the balance between the expected benefits of the product and its possible risks is not
sufficient to justify the trial.
Despite the Company's efforts, its product candidates may not:
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offer improvement over existing, comparable products;
be proven safe and effective in clinical trials; or
meet applicable regulatory standards.
This process can take many years and may include post-marketing studies and surveillance, which will
require the expenditure of substantial resources beyond the existing cash on hand. Of the large number of
drugs in development globally, only a small percentage successfully complete the regulatory approval
process and not all approved drugs are successfully commercialized. Delay or failure to obtain, or
unexpected costs in obtaining, the regulatory approval necessary for the Company or its partners to bring
a potential product candidate to market could have a material adverse effect on its business, prospects,
financial condition and results of operations.
The regulatory processes that will govern the approval of Innate's product candidates are complex and
changes in regulatory requirements could result in delays or discontinuation of development or
unexpected costs in obtaining regulatory approval.
Innate's product candidates are based on new approaches and/or technologies that are constantly evolving
and have not been extensively tested on humans. The applicable regulatory requirements vary between
jurisdictions and are also complex, potentially difficult to apply and subject to significant modifications.
Modifications to regulations during the course of clinical development and regulatory review may lead to
delays or the refusal of authorization.
In Europe, the United States and other countries, regulations can potentially:
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significantly delay or increase the cost of development, testing, manufacturing and marketing
of Innate's products;
limit the indications for which the Company will be authorized to market its products; and
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impose new, more stringent, requirements, suspend marketing authorizations, or request the
suspension of clinical trials or the marketing of its products if unexpected results are obtained
during trials performed by other researchers on products similar to its products.
Marketing authorization in one jurisdiction does not ensure marketing authorization in another, but a
failure or delay in obtaining marketing authorization in one jurisdiction may have a negative effect on the
regulatory process in others. Failure to obtain marketing authorization in other countries or any delay or
setback in obtaining such approval would impair the Company's ability to develop additional markets for
its product candidates. This would reduce Innate's target market and limit the full commercial potential of
its product or product candidates. Should any of these risks materialize, this could harm its business.
Innate Pharma's failure to obtain marketing approval in jurisdictions other than the United States and
Europe would prevent Innate's product candidates from being marketed in these other jurisdictions,
and any approval the Company is granted for its product candidates in the United States and Europe
would not assure approval of product candidates in other jurisdictions.
In order to market and sell its other product candidates in jurisdictions other than the United States and
Europe, the Company must obtain separate marketing approvals and comply with numerous and varying
regulatory requirements. The approval process varies among countries and can involve additional testing.
The time required to obtain approval may differ from that required to obtain FDA approval or approvals
from regulatory authorities in the European Union. The regulatory approval process outside the United
States and Europe generally includes all of the risks associated with obtaining FDA approval or approvals
from regulatory authorities in the European Union. In addition, some countries outside the United States
and Europe require approval of the sales price of a product before it can be marketed. In many countries,
separate procedures must be followed to obtain reimbursement and a product may not be approved for
sale in the country until it is also approved for reimbursement. The Company may not obtain marketing,
pricing or reimbursement approvals outside the United States and Europe on a timely basis, if at all.
Approval by the FDA or regulatory authorities in the European Union does not ensure approval by
regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside
the United States and Europe does not ensure approval by regulatory authorities in other countries or
jurisdictions or by the FDA or regulatory authorities in the European Union. The Company may not be
able to file for marketing approvals and may not receive necessary approvals to commercialize its
products in any market. Marketing approvals in countries outside the United States and Europe do not
ensure pricing approvals in those countries or in any other countries, and marketing approvals and pricing
approvals do not ensure that reimbursement will be obtained.
Side effects that appear following the launch of a drug on the market may result in the product being
taken off the market or additional warnings being added to the label despite having obtained all
regulatory approvals.
A drug’s launch in the market may expose a large number of patients to potential risks associated with the
treatment with a new pharmaceutical product. Certain side effects, which may not have been identified
during clinical trials, can subsequently appear. For these reasons, regulatory agencies require companies
to implement post-approval monitoring. Depending on the occurrence of serious undesirable effects, the
agencies may require that the Company or a collaboration partner of its takes a drug off the market
temporarily or permanently, even if it is effective and has obtained all the necessary marketing
authorizations. Such an action would negatively impair its ability to generate revenue from such product
and could more generally negatively affect its ability to develop, obtain regulatory approval for, and
commercialize its other product candidates and its reputation generally, each of which could have a
material adverse effect on its business and results of operations. In addition, if the product candidates the
Company develops receive marketing authorization and the Company or others identified undesirable side
effects caused by any product after the approval, a number of potentially significant negative
21
consequences could result, including that regulatory authorities may require the addition of labeling
statements, such as a “boxed” warning or a contraindication, the Company may be required to create a
medication guide outlining the risks of such side effects for distribution to patients and its reputation may
suffer.
Any product candidate for which the Company obtains marketing approval will be subject to strict
enforcement of post-marketing requirements and the Company could be subject to substantial
penalties, including withdrawal of its product from the market, if the Company fails to comply with all
regulatory requirements or if the Company experiences unanticipated problems with its product and
product candidates, when and if any of them are approved.
Any product candidate for which the Company obtains marketing approval, will be subject to continual
requirements of and review by the FDA, EMA and other regulatory authorities, including requirements
relating to manufacturing processes, post-approval clinical data, labeling, advertising and promotional
activities for such product. These requirements include, but are not limited to, restrictions governing
promotion of an approved product, submissions of safety and other post-marketing information and
reports, registration and listing requirements, current good manufacturing practice, or cGMP,
requirements relating to manufacturing, quality control, quality assurance and corresponding maintenance
of records and documents, and requirements regarding the distribution of samples to physicians and
recordkeeping. In addition, even if marketing approval of a product candidate is granted, the approval
may be subject to limitations on the indicated uses for which the product may be marketed, restrictions for
specified age groups, warnings, precautions or contraindications or to the conditions of approval.
The FDA and other federal and state agencies, including the U.S. Department of Justice, or DOJ, closely
regulate compliance with all requirements governing prescription products, including requirements
pertaining to marketing and promotion of products in accordance with the provisions of the approved
labeling and manufacturing of products in accordance with cGMP requirements. The FDA and DOJ
impose stringent restrictions on manufacturers’ communications regarding off-label use and if the
Company does not market its products for their approved indications, the Company may be subject to
enforcement action for off-label marketing. Prescription products may be promoted only for the approved
indications and in accordance with the provisions of the approved label. However, companies may also
share truthful and not misleading information that is otherwise consistent with the labeling. Violations of
such requirements may lead to investigations alleging violations of the Food, Drug and Cosmetic Act and
other statutes, including the False Claims Act and other federal and state health care fraud and abuse laws
as well as state consumer protection laws. Innate's failure to comply with all regulatory requirements, and
later discovery of previously unknown adverse events or other problems with its products, manufacturers
or manufacturing processes, may yield various results, including:
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litigation involving patients taking its products;
restrictions on such products, manufacturers or manufacturing processes;
restrictions on the labeling or marketing of a product;
restrictions on product distribution or use;
requirements to conduct post-marketing studies or clinical trials;
warning letters or untitled letters;
withdrawal of the products from the market;
refusal to approve pending applications or supplements to approved applications that the
Company submits;
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recall of products;
fines, restitution or disgorgement of profits or revenues;
suspension or withdrawal of marketing approvals;
damage to relationships with any potential collaborators;
unfavorable press coverage and damage to its reputation;
refusal to permit the import or export of its products;
product seizure; or
injunctions or the imposition of civil or criminal penalties.
Non-compliance by Innate or any future collaborator with the FDA, EMA or other regulatory
requirements regarding safety monitoring or pharmacovigilance, and with requirements related to the
development of products for the pediatric population, can also result in significant financial penalties.
Similarly, failure to comply with regulatory requirements regarding the protection of personal information
can also lead to significant penalties and sanctions.
Coverage and reimbursement may be limited or unavailable in certain market segments for the
Company's product candidates, if approved, which could make it difficult for Innate Pharma to sell its
product candidates profitably.
Successful sales of its product candidates, if approved, will depend, in part, on the availability of adequate
coverage and reimbursement from government authorities and third-party payors, such as private health
insurers and health maintenance organizations. Patients who are provided medical treatment for their
conditions generally rely on third-party payors to reimburse all or part of the costs associated with their
treatment. Adequate coverage and reimbursement from governmental healthcare programs, such as
Medicare and Medicaid in the United States or the Social Security in France, and commercial payors are
critical to new product acceptance.
Government authorities and third-party payors, such as private health insurers and health maintenance
organizations, decide which drugs and treatments they will cover and the amount of reimbursement.
Coverage and reimbursement by a third-party payor may depend upon a number of factors, including the
third-party payor’s determination that use of a product is:
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a covered benefit under its health plan;
safe, effective and medically necessary;
appropriate for the specific patient;
cost-effective; and
neither experimental nor investigational.
Policies for coverage and reimbursement for products vary among third-party payors. No uniform policy
of coverage and reimbursement for products exists among third-party payors, and third-party payors are
increasingly challenging the price, examining the medical necessity, and reviewing the cost-effectiveness
of approved drugs and medical services, in addition to questioning their safety and efficacy. As a result,
obtaining coverage and reimbursement approval of a product from a government or other third-party
payor is a time-consuming and costly process that could require the Company or its partners to provide to
each payor supporting scientific, clinical and cost-effectiveness data for the use of its products on a payor-
by-payor basis, with no assurance that coverage and adequate reimbursement will be obtained. Coverage
decisions may depend upon clinical and economic standards that disfavor new drug products when more
23
established or lower cost therapeutic alternatives are already available or subsequently become available.
Even if the Company obtains coverage for a given product, the resulting reimbursement payment rates
might not be adequate for it to achieve or sustain profitability or may require co-payments that patients
find unacceptably high. Additionally, third-party payors may not cover, or provide adequate
reimbursement for, long-term follow-up evaluations required following the use of the Company's product
candidates or approved products.
Because its product candidates represent new approaches to the treatment of cancer and accordingly, may
have a higher cost than conventional therapies and may require long-term follow-up evaluations, the risk
that coverage and reimbursement rates may be inadequate for the Company to achieve profitability may
be elevated. There are currently a limited number of immunotherapy products that are designed to treat
cancer on the market and, accordingly, there is less experience or precedent for the reimbursement of such
treatments by governmental entities or third-party payors.
Government restrictions on pricing and reimbursement and other healthcare cost-containment
initiatives may negatively affect its ability to generate revenues for its product candidates for which the
Company obtains regulatory approval.
Government authorities and other third-party payors are developing increasingly sophisticated methods of
controlling healthcare costs, including by limiting coverage and the amount of reimbursement for
particular medications. Increasingly,
that pharmaceutical and
biotechnology companies provide them with predetermined discounts from list prices as a condition of
coverage, are using restrictive formularies and preferred drug lists to leverage greater discounts in
competitive classes and are challenging the prices charged for medical products.
third-party payors are requiring
In the United States, the European Union and other foreign jurisdictions, there have been a number of
legislative and regulatory changes to the healthcare system that could affect the Company's or its partners’
ability to sell its products profitably. By way of example, in the United States, the Patient Protection and
Affordable Care Act, or ACA, as amended by the Health Care and Education Reconciliation Act, which
the Company collectively refers to as the ACA, was enacted in March 2010 and is having a significant
impact on the provision of, and payment for, healthcare in the United States. The ACA was intended to
broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance
remedies against fraud and abuse, add new transparency requirements for the healthcare and health
insurance industries, impose new taxes and fees on the health industry and impose additional health
policy reforms.
Among the provisions of the ACA of importance to its product candidates are:
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an annual, nondeductible fee on any entity that manufactures or imports specified branded
prescription drugs and biologic agents, apportioned among these entities according to their
market share in certain government healthcare programs;
an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid
Drug Rebate Program to 23.1% and 13.0% of the average manufacturer price for branded and
generic drugs, respectively;
a new Medicare Part D coverage gap discount program, in which manufacturers must now
agree to offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to
eligible beneficiaries during their coverage gap period, as a condition for a manufacturer’s
outpatient drugs to be covered under Medicare Part D;
extension of a manufacturer’s Medicaid rebate liability to covered drugs dispensed to
individuals who are enrolled in Medicaid managed care organizations;
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expansion of eligibility criteria for Medicaid programs by, among other things, allowing states
to offer Medicaid coverage to additional individuals and by adding new mandatory eligibility
categories for certain individuals with income at or below 133% of the federal poverty level,
thereby potentially increasing a manufacturer’s Medicaid rebate liability;
expansion of the entities eligible for discounts under the Public Health Service pharmaceutical
pricing program; and
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and
conduct comparative clinical effectiveness research, along with funding for such research.
There have been judicial and Congressional challenges to certain aspects of the ACA, as well as efforts by
the Trump administration to repeal and replace certain aspects of the ACA, and such challenges may
occur again. Former President Trump signed two executive orders designed to delay the implementation
of certain provisions of the ACA or otherwise circumvent some of the requirements for health insurance
mandated by the ACA. Concurrently, Congress has considered legislation that would repeal or repeal and
replace all or part of the ACA. While Congress has not passed comprehensive repeal legislation, two bills
affecting the implementation of certain taxes under the ACA have been signed into law. The Tax Cuts and
Jobs Act of 2017 includes a provision that repealed, effective January 1, 2019, the tax-based shared
responsibility payment imposed by the ACA on certain individuals who fail to maintain qualifying health
coverage for all or part of a year that is commonly referred to as the “individual mandate.” In addition, the
2020 federal spending package permanently eliminated, effective January 1, 2020, the ACA-mandated
“Cadillac” tax on high-cost employer-sponsored health coverage and medical device tax and, effective
January 1, 2021, also eliminated the health insurer tax. In July and December 2018, the Centers for
Medicare & Medicaid Services, or CMS, within the U.S. Department of Health and Human Services, or
HHS, published final rules with respect to permitting further collections and payments to and from certain
ACA qualified health plans and health insurance issuers under its risk adjustment program in response to
the outcome of federal district court litigation regarding the method CMS uses to determine this risk
adjustment. On December 14, 2018, a Texas U.S. District Court Judge ruled that the ACA is
unconstitutional in its entirety because the “individual mandate” was repealed by the U.S. Congress as
part of the Tax Cuts and Jobs Act of 2017 Act. Additionally, on June 17, 2021, the U.S. Supreme Court
dismissed a challenge on procedural grounds that the ACA is unconstitutional in its entirety because the
"individual mandate" was repealed by Congress. Thus the ACA will remain in effect in its current form.
Further, prior to the U.S. Supreme Court ruling, on January 28, 2021, President Biden issued an executive
order to initiate a special enrollment period which began on February 15, 2021 and remained open
through August 15, 2021 for purposes of obtaining health insurance coverage through the ACA
marketplace. The executive order also instructs certain governmental agencies to review and reconsider
their existing policies and rules that limit access to healthcare, including among others, reexamining
Medicaid demonstration projects and waiver programs that include work requirements, and policies that
create unnecessary barriers to obtaining access to health insurance coverage through Medicaid or the
ACA. It is unclear how judicial and Congressional challenges and the healthcare reform measures of the
Biden administration will impact ACA.
In addition, other legislative changes have been proposed and adopted since the ACA was enacted. These
changes include aggregate reductions to Medicare payments to providers of 2% per fiscal year, which
went into effect in April 2013 and will remain in effect through 2030 unless additional Congressional
action is taken. However, COVID-19 relief support legislation suspended the 2% Medicare sequester
from May 1, 2020 through December 31, 2021. Both the Budget Control Act of 2011 and the American
Taxpayer Relief Act of 2012, or ATRA, further reduced Medicare payments to several providers and the
ATRA increased the statute of limitations period for the government to recover overpayments to
providers from three to five years. Additional legislative proposals to reform healthcare and government
25
insurance programs, along with the trend toward managed healthcare in the United States, could influence
the purchase of medicines and reduce demand and prices for Innate's product candidates, if approved.
This could harm Innate's or its partners’ ability to market any drugs and generate revenues. Cost
containment measures that healthcare payors and providers are instituting and the effect of further
healthcare reform could significantly reduce potential revenues from the sale of any of its product
candidates approved in the future, and could cause an increase in its compliance, manufacturing, or other
operating expenses.
In addition, in the United States, federal programs impose penalties on drug manufacturers in the form of
mandatory additional rebates and/or discounts if commercial prices increase at a rate greater than the U.S.
Bureau of Labor Statistics consumer price index, and these rebates or discounts, which can be substantial,
may affect the Company's ability to raise commercial prices.
Further, there has been increasing legislative and enforcement interest in the United States with respect to
drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries and
proposed and enacted federal and state legislation designed to, among other things, bring more
transparency to drug pricing, review the relationship between pricing and manufacturer patient programs,
reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies
for drugs. At the federal level, the Trump administration’s budget proposal for fiscal years 2020 contains
further drug price control measures that could be enacted during the budget process or in other future
legislation. The Trump administration also released a “Blueprint”, or plan, to lower drug prices and
reduce out of pocket costs of drugs that contains additional proposals to increase manufacturer
competition, increase the negotiating power of certain federal healthcare programs, incentivize
manufacturers to lower the list price of their products and reduce the out of pocket costs of drug products
paid by consumers. On July 24, 2020 and September 13, 2020, the Trump administration announced
several executive orders related to prescription drug pricing that seek to implement several of the
administration’s proposals. As a result, the FDA released a final rule on September 24, 2020, effective
November 30, 2020, providing guidance for states to build and submit importation plans for drugs from
Canada. Further, on November 20, 2020, HHS finalized a regulation removing safe harbor protection for
price reductions from pharmaceutical manufacturers to plan sponsors under Part D, either directly or
through pharmacy benefit managers, unless the price reduction is required by law. The implementation of
the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in
response to ongoing litigation. The rule also creates a new safe harbor for price reductions reflected at the
point-of-sale, as well as a safe harbor for certain fixed fee arrangements between pharmacy benefit
managers and manufacturers, the implementation of which have also been delayed until January 1, 2023.
On November 20, 2020, CMS issued an interim final rule implementing President Trump’s Most Favored
Nation executive order, which would tie Medicare Part B payments for certain physician-administered
drugs to the lowest price paid in other economically advanced countries, effective January 1, 2021. As a
result of litigation challenging the Most Favored Nation model, on August 10, 2021, CMS published a
proposed rule that seeks to rescind the Most Favored Nation Model interim final rule. In July 2021, the
Biden administration released an executive order, "Promoting Competition in American Economy," with
multiple provisions aimed at prescription drugs. In response to Biden's executive order, on September 9,
2021, HHS released a Comprehensive Plan for Addressing High Drug Prices that outlines principles for
drug pricing reform and sets out a variety of potential legislative policies that Congress could pursue to
advance these principles. In addition, Congress is considering drug pricing as part of the budget
reconciliation process. It is unclear whether the Biden administration will work to reverse these measures
or pursue similar policy initiatives. At the state level, legislatures have increasingly passed legislation and
implemented regulations designed to control pharmaceutical and biological product pricing, including
price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing
26
cost disclosure and transparency measures, and, in some cases, designed to encourage importation from
other countries and bulk purchasing.
In some countries, the proposed pricing for a biopharmaceutical product must be approved before it may
be lawfully marketed. In addition, in certain foreign markets, the pricing of biopharmaceutical product is
subject to government control and reimbursement may in some cases be unavailable. The requirements
governing drug pricing vary widely from country to country. For example, the European Union provides
options for its member states to restrict the range of medicinal products for which their national health
insurance systems provide reimbursement and to control the prices of medicinal products for human use.
An EU member state may approve a specific price for the medicinal product, it may refuse to reimburse a
product at the price set by the manufacturer or it may instead adopt a system of direct or indirect controls
on the profitability of the company placing the medicinal product on the market. There can be no
assurance that any country that has price controls or reimbursement limitations for biopharmaceutical
products will allow favorable reimbursement and pricing arrangements for any of Innate's products.
Historically, biopharmaceutical products launched in the European Union do not follow price structures
of the United States and generally tend to have significantly lower prices.
The Company believes that pricing pressures will continue and may increase, which may make it difficult
for it to sell any of its product candidates that may be approved in the future at a price acceptable to the
Company or any of its existing or future collaborators.
Any of Innate Pharma product candidates, if approved and commercialized, may fail to achieve market
acceptance by physicians, patients, third-party payors or the medical community to a degree that is
necessary for commercial success.
Even if the medical community accepts a product as safe and efficacious for its indicated use, physicians
may choose to restrict the use of the product if the Company is unable to demonstrate that, based on
experience, clinical data, side-effect profiles and other factors, its drug is preferable to any existing drugs
or treatments. The Company cannot predict the degree of market acceptance of any product candidate that
will receive marketing authorization, which will depend on a number of factors, including, but not limited
to:
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the demonstration of the clinical efficacy and safety of the drug;
the approved labeling for the drug and any required warnings;
prevalence and severity of adverse side effects;
the advantages and disadvantages of the drug compared to alternative treatments;
ease of the drug’s use;
its ability to educate the medical community about the safety and effectiveness of the drug;
the scope of any approval provided by the FDA or foreign regulatory authorities;
publicity about its product or about competitive products;
the coverage and reimbursement policies of government and commercial third-party payors
pertaining to the drug;
the market price of its drugs relative to competing treatments; and
due to the rarity of orphan diseases, it could be difficult finding patients seeking treatment.
Poor market penetration could have an adverse effect on its business, prospects, financial condition and
results of operations.
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Innate's commercial experience is currently limited to Lumoxiti. Although Lumoxiti received a Marketing
Authorization in 2018 in the US, the level of sales in 2020 was lower than expected, leading Innate to
make the decision in December 2020 to return the commercial rights of Lumoxiti to AstraZeneca. Beyond
the financial impacts, the direct consequence of this decision was the immediate reduction of commercial
operations in the Company's U.S. affiliate. A retrospective analysis identified two major causes: (i) a
more complex patient access than expected due to geographic dispersion and (ii) the global pandemic of
COVID-19. The COVID-19 pandemic significantly limited the interactions with prescribing physicians.
Moreover, the indolent and non-fatal nature of hairy cell leukemia in the short term encouraged
physicians to delay or cancel treatment for some patients during the pandemic. This retrospective analysis
of its commercial experience will help Innate Pharma capitalize on this experience for future registration
and commercialization of its drug candidates.
Even if some of its product candidates receive marketing authorization, the terms of such approval,
ongoing regulation and potential post-marketing restrictions or withdrawal from the market may limit
how the drug may be marketed and may subject Innate to penalties for failure to comply with
regulatory requirements, which could impair its ability to generate revenues.
Even if any of its product candidates receives a marketing authorization, such approval may carry
conditions that limit the market for the drug or put the drug at a competitive disadvantage relative to
alternative therapies. Regulators may limit the marketing of products to particular indications or patient
populations. Regulators may require warning labels and drugs with warnings are subject to more
restrictive marketing regulations than drugs without such warnings. These restrictions could make it more
difficult to market any drug effectively. Marketing restrictions may reduce the revenue that the Company
is able to obtain.
Any of its product candidates for which the Company obtains marketing authorization, and the
manufacturing processes, post-approval studies and measures, labeling, advertising and promotional
activities for such products, among other things, will be subject to continual requirements of and review
by the Food and Drug Administration (FDA), the European Medicines Agency, or EMA, and other
regulatory authorities. These requirements include submissions of safety and other post-marketing
information and reports, registration and listing requirements, requirements relating to manufacturing,
quality control, quality assurance and corresponding maintenance of records and documents, requirements
regarding the distribution of samples to physicians and recordkeeping. Even if marketing authorization of
a product candidate is granted, the approval may be subject to limitations on the indicated uses for which
the product may be marketed or to the conditions of approval, including the FDA requirement to
implement a risk evaluation and mitigation strategy to ensure that the benefits of a drug or biological
product outweigh its risks.
The FDA, EMA and other national authorities may also impose requirements for costly post-marketing
studies or clinical trials and surveillance to monitor the safety or efficacy of a product, such as long-term
observational studies on natural exposure. The FDA and other agencies, including the U.S. Department of
Justice, closely regulate and monitor the post-approval marketing and promotion of products to ensure
that they are manufactured, marketed and distributed only for the approved indications and in accordance
with the provisions of the approved labeling. Later discovery of previously unknown problems with
Innate's product candidates or with manufacturing processes, including adverse events of unanticipated
severity or frequency, or failure to comply with regulatory requirements, may result in revisions to the
approved labeling to add new safety information; imposition of post-market studies or clinical studies to
assess new safety risks, or the imposition of distribution or other restrictions including suspension of
production and/or distribution and withdrawal of regulatory approvals. Failure to comply with these
requirements may lead to financial penalties, compliance expenditures, total or partial suspension of
28
production and/or distribution, product seizure or detention, refusal to permit the import or export of
products, suspension of the applicable regulator’s review of a company’s submissions, enforcement
actions, product recalls, injunctions and even criminal prosecution, any of which could materially and
adversely affect the Company's business, financial condition and results of operations.
Innate's future growth depends, in part, on its ability to penetrate multiple markets, in which the
Company would be subject to additional regulatory burdens and other risks and uncertainties.
Innate's future profitability will depend, in part, on its ability to commercialize its product candidates, if
approved, in markets in Europe, the United States and other countries where the Company maintains
commercialization rights. If the Company commercializes its product candidates, if approved, in multiple
markets, the Company would be subject to additional risks and uncertainties, including:
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foreign currency exchange rate fluctuations and currency controls;
economic weakness, including inflation, or political instability in particular economies and
markets;
potentially adverse and/or unexpected tax consequences, including penalties due to the failure
of tax planning or due to the challenge by tax authorities on the basis of transfer pricing and
liabilities imposed from inconsistent enforcement;
the burden of complying with complex and changing regulatory, tax, accounting and legal
requirements, many of which vary between countries;
different medical practices and customs in multiple countries affecting acceptance of drugs in
the marketplace;
differing payor reimbursement regimes, governmental payors or patient self-pay systems and
price controls;
tariffs, trade barriers, import or export licensing requirements or other restrictive actions;
compliance with tax, employment, immigration and labor laws for employees living or
traveling abroad;
workforce uncertainty in countries where labor unrest is common;
reduced or loss of protection of intellectual property rights in some foreign countries, and
related prevalence of generic alternatives to therapeutics; and
becoming subject to the different, complex and changing laws, regulations and court systems
of multiple jurisdictions and compliance with a wide variety of foreign laws, treaties and
regulations.
Russia’s military intervention in Ukraine may affect regional stability and economic growth throughout
Europe. These and other risks associated with international operations may adversely affect Innate's
ability to attain or maintain profitable operations. Future sales of the Company's product candidates, if
they are approved, will be dependent on purchasing decisions of and reimbursement from government
health administration authorities, distributors and other organizations. As a result of adverse conditions
affecting the global economy and credit and financial markets, including disruptions due to political
instability or otherwise, these organizations may defer purchases, may be unable to satisfy their
purchasing or reimbursement obligations, or may affect milestone payments or royalties for monalizumab
or any of Innate's product candidates that are approved for commercialization in the future. Should any of
these risks materialize, this could have a material adverse effect on Innate Pharma's business, prospects,
financial condition and results of operations.
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Even if its product candidates obtain regulatory approval, they will be subject to continuous regulatory
review.
If marketing authorization is obtained for any of its product candidates, the candidate will remain subject
to continuous review and therefore authorization could be subsequently withdrawn or restricted. The
Company will be subject to ongoing obligations and oversight by regulatory authorities, including adverse
event reporting requirements, marketing restrictions and, potentially, other post-marketing obligations, all
of which may result in significant expense and limit its ability to commercialize such products.
If there are changes in the application of legislation or regulatory policies, or if problems are discovered
with a product or its manufacture of a product, or if the Company or one of its distributors, licensees or
co-marketers fails to comply with regulatory requirements, the regulators could take various actions.
These include imposing fines on us, imposing restrictions on the product or its manufacture and requiring
Innate to recall or remove the product from the market. The regulators could also suspend or withdraw its
marketing authorizations, requiring Innate to conduct additional clinical trials, change its product labeling
or submit additional applications for marketing authorization. If any of these events occurs, its ability to
sell such product may be impaired, and the Company may incur substantial additional expense to comply
with regulatory requirements, which could materially adversely affect its business, financial condition and
results of operations.
Even if one of its product candidates has orphan drug designation, the Company may not be able to
obtain any benefit from such designation. Furthermore, if a product is granted orphan drug exclusivity
in the same indication for which the Company is developing lacutamab or its other product candidates
that is granted orphan drug designation, the Company may not be able to have its product candidate
approved by the applicable regulatory authority for a significant period of time.
Regulatory authorities in some jurisdictions, including the United States and Europe, may designate drugs
for relatively small patient populations as orphan drugs. Under the Orphan Drug Act, the FDA may
designate a product candidate as an orphan drug if it is a drug intended to treat a rare disease or condition,
which is generally defined as a patient population of fewer than 200,000 individuals in the United States.
In the European Union, the European Commission may designate a product candidate as an orphan
medicinal product if it is a medicine for the diagnosis, prevention or treatment of life-threatening or very
serious conditions that affects not more than five in 10,000 persons in the European Union, or it is
unlikely that marketing of the medicine would generate sufficient returns to justify the investment needed
for its development. Generally, if a product candidate with an orphan drug designation receives the first
marketing approval for the indication for which it has such designation, the product is entitled to a period
of marketing exclusivity, which, subject to certain exceptions, precludes the FDA from approving the
marketing application of another drug for the same indication for that time period or precludes the EMA,
and other national drug regulators in the European Union, from accepting the marketing application for
another medicinal product for the same indication. The applicable period is seven years in the United
States and ten years in the European Union. The European Union period can be reduced to six years if a
product no longer meets the criteria for orphan drug designation or if the product is sufficiently profitable
so that market exclusivity is no longer justified. Orphan drug exclusivity may be lost in the United States
if the FDA determines that the request for designation was materially defective or if the manufacturer is
unable to assure sufficient quantity of the product to meet the needs of patients with the rare disease or
condition. The granting of a request for orphan drug designation does not alter the standard regulatory
requirements and process for obtaining marketing approval.
Lacutamab has been granted orphan drug designation for cutaneous T-cell lymphoma (CTCL) in Europe
and in the United States and the Company may pursue orphan drug designation for another product
candidate that the Company may develop in the future in the United States and/or Europe. However, there
is no assurance the Company will be able to receive orphan drug designation for other product candidates
30
that the Company may develop in the United States and/or Europe or for any other product candidate in
any jurisdiction. Even if the Company is successful in obtaining orphan drug designation, orphan drug
status may not ensure that the Company has market exclusivity in a particular market. Even if the
Company obtains orphan drug exclusivity for any of its product candidates, that exclusivity may not
effectively protect the product from competition because exclusivity can be suspended under certain
circumstances. In the United States, even after an orphan drug is approved, the FDA can subsequently
approve another drug for the same condition if the FDA concludes that the later drug is clinically superior
in that it is shown to be safer, more effective or makes a major contribution to patient care. In the
European Union, orphan exclusivity will not prevent a marketing authorization being granted for a similar
medicinal product in the same indication if the new product is safer, more effective or otherwise clinically
superior to the first product or if the marketing authorization holder of the first product is unable to supply
sufficient quantities of the product. In addition, if another product is granted marketing approval and
orphan drug exclusivity in the same indication for which the Company is developing a product candidate
with orphan drug designation, the Company may not be able to have its product candidate approved by
the applicable regulatory authority for a significant period of time.
A fast track, breakthrough therapy or other designation by the FDA, or equivalent in other territories,
may not actually lead to a faster development.
The Company may seek fast track, breakthrough therapy or similar designation for its product candidates.
If a product is intended for the treatment of a serious or life-threatening condition and the product
demonstrates the potential to address unmet medical need for this condition, the sponsor may apply for
FDA fast track designation. The Company has received fast track designation in the U.S. and PRIME
designation in EU for lacutamab for the treatment of adult patients with relapsed or refractory Sézary
syndrome, or SS, who have received at least two prior systemic therapies.
Additionally, the Company may in the future seek a breakthrough therapy designation or an equivalent in
other territories for some of its product candidates that reach the regulatory review process. A
breakthrough therapy is a drug candidate that is intended, alone or in combination with one or more other
drugs, to treat a serious or life-threatening disease or condition, and that, as indicated by preliminary
clinical evidence, may demonstrate substantial improvement over existing therapies on one or more
clinically significant endpoints, such as substantial treatment effects observed early in clinical
development. Drugs designated as breakthrough therapies by the FDA are eligible for accelerated
approval and increased interaction and communication with the FDA designed to expedite the
development and review process.
However, these designations do not ensure that the Company will experience a faster development
process, review or approval compared to conventional FDA procedures. In addition, the FDA may
withdraw a designation if it believes that the designation is no longer supported by data from its clinical
development program. A designation alone does not guarantee qualification for the FDA’s priority review
procedures.
Priority review designation by the FDA, or the equivalent in other territories, may not lead to a faster
regulatory review or approval process and, in any event, does not assure FDA approval of Innate's
product candidates.
If the FDA determines that a product candidate offers major advances in treatment or provides a treatment
where no adequate therapy exists, the FDA may designate the product candidate for priority review. A
priority review designation means that the goal for the FDA to review an application is six months, rather
than the standard review period of ten months. the Company may request priority review for its product
candidates. The FDA has broad discretion with respect to whether or not to grant priority review status to
a product candidate, so even if the Company believes a particular product candidate is eligible for such
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designation or status, the FDA may decide not to grant it. Moreover, a priority review designation does
not necessarily mean a faster regulatory review process or necessarily confer any advantage with respect
to approval compared to conventional FDA procedures. Receiving priority review from the FDA does not
guarantee approval within the six-month review cycle or thereafter.
The Company is subject to anti-corruption laws, as well as export control laws, customs laws, sanctions
laws and other laws governing its operations. If the Company fails to comply with these laws, the
Company could be subject to civil or criminal penalties, other remedial measures and legal expenses,
which could adversely affect its business, results of operations and financial condition.
The Company is subject to other laws and regulations governing its international operations, including
regulations administered by the governments of the United States, and authorities in the European Union,
including applicable export control regulations, economic sanctions on countries and persons, customs
requirements and currency exchange regulations, collectively referred to as the trade control laws.
The Foreign Corrupt Practices Act, or FCPA, prohibits any U.S. individual or business from paying,
offering, authorizing payment or offering of anything of value, directly or indirectly, to any foreign
official, political party or candidate for the purpose of influencing any act or decision of the foreign entity
in order to assist the individual or business in obtaining or retaining business. The FCPA also obligates
companies whose securities are listed in the United States to comply with certain accounting provisions
requiring the company to maintain books and records that accurately and fairly reflect all transactions of
the corporation, including international subsidiaries, and to devise and maintain an adequate system of
internal accounting controls for international operations.
Compliance with the FCPA is expensive and difficult, particularly in countries in which corruption is a
recognized problem. In addition, the FCPA presents particular challenges in the pharmaceutical industry,
because, in many countries, hospitals are operated by the government, and doctors and other hospital
employees are considered foreign officials. Certain payments to hospitals in connection with clinical trials
and other work have been deemed to be improper payments to government officials and have led to
FCPA enforcement actions.
French anti-corruption laws also prohibit acts of bribery and influence peddling:
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Articles 433-1 1° and 432-11 1° of the French Criminal Code (bribery of domestic public
officials);
Articles 433-1 2° and 432-11 2° of the French Criminal Code (influence peddling involving
domestic public officials);
Article 434-9 of the French Criminal Code (bribery of domestic judicial staff);
Article 434-9-1 of the French Criminal Code (influence peddling involving domestic judicial
staff);
Articles 445-1 and 445-2 of the French Criminal Code (bribery of private individuals);
Article 433-2 of the French Criminal Code (influence peddling involving private individuals);
Articles 435-1 and 435-3 of the French Criminal Code (bribery of foreign or international
public officials);
Articles 435-7 and 435-9 of the French Criminal Code (bribery of foreign or international
judicial staff);
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Articles 435-2, 435-4, 435-8 and 435-10 of the French Criminal Code (active and passive
influence peddling involving foreign or international public officials and foreign or
international judicial staff); and
French Law of December 9, 2017 on Transparency, the Fight Against Corruption and the
Modernization of the Economy (Sapin 2 Law).
There is no assurance that the Company will be effective in ensuring its compliance with all applicable
anti-corruption laws, including the FCPA, the French anti-corruption laws or other legal requirements,
including trade control laws. If the Company is not in compliance with the FCPA, the French anti-
corruption laws and other anti-corruption laws or trade control laws, the Company may be subject to
criminal and civil penalties, disgorgement and other sanctions and remedial measures, and legal expenses,
which could have an adverse impact on its business, financial condition, results of operations and
liquidity. Likewise, any investigation of any potential violations of the FCPA, the French anti-corruption
laws, other anti-corruption laws or trade control laws by U.S. or other authorities could also have an
adverse impact on its reputation, its business, results of operations and financial condition.
The Company is subject to healthcare laws and regulations which may require substantial compliance
efforts and could expose Innate to criminal sanctions, civil penalties, contractual damages,
reputational harm and diminished profits and future earnings, among other penalties.
Healthcare providers, physicians and others will play a primary role in the recommendation and
prescription of its products, if approved. The Company's arrangements with such persons and third-party
payors and its operations will expose Innate to broadly applicable fraud and abuse and other healthcare
laws and regulations that may constrain the business or financial arrangements and relationships through
which the Company researches, markets, sells and distributes its products, if the Company obtains
marketing authorization. Restrictions under applicable U.S. federal, state and foreign healthcare laws and
regulations include, but are not limited to, the following:
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the U.S. Anti-Kickback Statute, which prohibits, among other things, persons or entities from
knowingly and willfully soliciting, offering, receiving or providing remuneration, including
any kickback, bribe or rebate, directly or indirectly, in cash or in kind, to induce or reward, or
in return for, either the referral of an individual for, or the purchase or lease, order or
recommendation of, any item, good, facility or service, for which payment may be made under
federal healthcare programs such as Medicare and Medicaid;
U.S. federal civil and criminal false claims laws and civil monetary penalties laws, including
the civil False Claims Act, which impose criminal and civil penalties, including those from
civil whistle-blower or qui tam actions, against individuals or entities for, among other things,
knowingly presenting, or causing to be presented, claims for payment that are false or
fraudulent or making a false statement to avoid, decrease, or conceal an obligation to pay
money to the federal government;
the U.S. Health Insurance Portability and Accountability Act of 1996, or HIPAA, which
created additional federal criminal statutes that impose criminal and civil liability for, among
other things, executing or attempting to execute a scheme to defraud any healthcare benefit
program or knowingly and willingly falsifying, concealing or covering up a material fact or
making false statements relating to healthcare matters;
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health
Act and its implementing regulations, which impose certain requirements on covered entities
and their business associates, including mandatory contractual terms, with respect to
33
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safeguarding the privacy, security and transmission of individually identifiable health
information;
U.S. federal transparency requirements under the Physician Payments Sunshine Act, enacted
as part of the Affordable Care Act (ACA), that require applicable manufacturers of covered
drugs, devices, biologics and medical supplies for which payment is available under Medicare,
Medicaid, or the Children’s Health Insurance Program, with specific exceptions, to track and
annually report to CMS payments and other transfers of value provided to physicians and
teaching hospitals, and certain ownership and investment interests held by physicians or their
immediate family members; and
analogous state or foreign laws and regulations, such as state anti-kickback and false claims
laws, including the French “Bertrand Law”, French Ordinance n°2017-49 of January 19, 2017,
and the UK’s Bribery Act 2010, which may apply to items or services reimbursed by any
third-party payor, including commercial insurers, state marketing and/or transparency laws
applicable to manufacturers that may be broader in scope than the federal requirements, state
laws that require biopharmaceutical companies to comply with the biopharmaceutical
industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated
by the federal government, state laws that require the reporting of information relating to drug
and biologic pricing; state and local laws that require the registration of pharmaceutical sales
representatives and state laws governing the privacy and security of health information in
certain circumstances, many of which differ from each other in significant ways and may not
have the same effect as HIPAA, thus complicating compliance efforts.
Ensuring that Innate's business arrangements with third parties comply with applicable healthcare laws
and regulations will likely be costly. It is possible that governmental authorities will conclude that its
business practices do not comply with current or future statutes, regulations or case law involving
applicable fraud and abuse or other healthcare laws and regulations. If Innate Pharma's operations were
found to be in violation of any of these laws or any other governmental regulations that may apply to us,
the Company may be subject to significant civil, criminal and administrative penalties, damages, fines,
disgorgement, imprisonment, possible exclusion from government funded healthcare programs, such as
Medicare and Medicaid, additional reporting requirements and oversight if the Company becomes subject
to a corporate integrity agreement or similar agreement to resolve allegations of non-compliance with
these laws, contractual damages, reputational harm, diminished profits and future earnings, and
curtailment of its operations, any of which could substantially disrupt its operations. If the physicians or
other providers or entities with whom the Company expects to do business are found not to be in
compliance with applicable laws, they may be subject to criminal, civil or administrative sanctions,
including exclusions from government funded healthcare programs. Should any of these risks materialize,
this could have a material adverse effect on its business, prospects, financial condition and results of
operations.
European data collection is governed by restrictive regulations governing the collection, use,
processing and cross-border transfer of personal information.
The Company may collect, process, use or transfer personal information from individuals located in the
European Union in connection with its business, including in connection with conducting clinical trials in
the European Union. The collection and use of personal health data in the European Union are governed
by the provisions of the General Data Protection Regulation ((EU) 2016/679), or the GDPR. This
legislation imposes requirements relating to having legal bases for processing personal information
relating to identifiable individuals and transferring such information outside of the European Economic
Area, or EEA, including to the United States, providing details to those individuals regarding the
processing of their personal information, keeping personal information secure, having data processing
34
agreements with third parties who process personal information, responding to individuals’ requests to
exercise their rights in respect of their personal information, reporting security breaches involving
personal data to the competent national data protection authority and affected individuals, appointing data
protection officers, conducting data protection impact assessments and record-keeping. The General Data
Protection Regulation (GDPR) imposes additional responsibilities and liabilities in relation to personal
data that the Company processes and the Company may be required to put in place additional mechanisms
ensuring compliance with the new data protection rules. The GDPR applies across the European
Economic Area (EEA) and, by virtue of the GDPR as it forms part of United Kingdom law in a broadly
uniform manner through section 3 of the European Union (Withdrawal) Act 2018, or the UK GDPR, in
the United Kingdom. However, the GDPR provides that EEA member states can make their own further
laws and regulations to introduce specific requirements related to the processing of ‘special categories of
personal data’, including personal data related to health, biometric data used for unique identification
purposes and genetic information; as well as personal data related to criminal offenses or convictions – in
the United Kingdom, the United Kingdom Data Protection Act 2018 complements the UK GDPR in this
regard. This fact may lead to greater divergence on the law that applies to the processing of such data
types across the EEA and/or United Kingdom, compliance with which, as and where applicable, may
increase the Company's costs and could increase its overall compliance risk. Such country-specific
regulations could also limit its ability to collect, use and share data in the context of the Company's EEA
and/or United Kingdom establishments (regardless of where any processing in question occurs), and/or
could cause its compliance costs to increase, ultimately having an adverse impact on Innate's business,
and harming its business and financial condition. Failure to comply with the requirements of the GDPR
and related national data protection laws of the member states of the European Union may result in
substantial fines, other administrative penalties and civil claims being brought against us, which could
have a material adverse effect on Innate's business, prospects, financial condition and results of
operations. Moreover, in some European countries, including France, the hosting of personal health data
must be carried out by specifically certified hosting service providers. The absence or suspension of the
appropriate certification of such hosting service provider may adversely affect Innate Pharma's business,
or even lead to penalties related to breach of security of personal data.
Risks Related to Innate's Reliance on Third Parties
The Company have no manufacturing capabilities and rely on third-party manufacturers for its
product candidates.
Innate Pharma's product candidates that are tested during its preclinical and clinical trials are
manufactured by third parties. The Company has no production capabilities and rely on third parties to
manufacture its products.
This strategy means that the Company does not directly control certain key aspects of its product
development, such as:
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the quality of the product manufactured;
the delivery times for drugs for a given clinical trial;
the clinical and commercial quantities that can be supplied; and
compliance with applicable laws and regulations.
Its reliance on third-party manufacturers creates risks that may not exist if the Company had its own
manufacturing capabilities. These risks include:
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failure of third-party manufacturers to comply with regulatory and quality-control standards;
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production of insufficient quantities;
damage during transport and/or storage of its product candidates;
breach of agreements by third-party manufacturers; and
termination or non-renewal of the agreements for reasons beyond its control.
Should its third-party manufacturers breach their obligations or should the Company fails to renew its
contracts with them, the Company cannot guarantee that the Company will be able to find new suppliers
within a timeframe and under conditions that would not be detrimental. The Company could also be faced
with delays or interruptions in its supplies, which could result in a delay in the clinical trials and,
ultimately, a delay in the commercialization of the product candidates that the Company is developing.
For example, manufacturing issues, leading to out-of-specification product, can occur during a
manufacturing campaign at the Contract Manufacturing Organization, or CMO, in charge of the
production of its product candidates.
Reproducing a batch of product is a lengthy and costly process and sometimes can lead to drug shortage
that can in turn lead to a delay in the development of the candidate, or even an early stop of a clinical trial.
This happened in the early clinical development of lacutamab and led to the decision to limit the number
of patients in order to ensure drug supply for treated patients in the Phase 1 clinical trial.
In November 2019, Impletio Wirkstoffabfüllung GmbH (formerly known as Rentschler Fill Solutions
GmbH), the subcontractor in charge of the fill-and-finish manufacturing operations of lacutamab,
unilaterally decided to withdraw the certificates of conformance of all clinical batches produced at their
facilities, including the lacutamab batch used for the TELLOMAK Phase 2 clinical trial assessing
lacutamab in multiple indications. Impletio Wirkstoffabfüllung GmbH decided to withdraw the
certificates of conformance even though the compliance of its manufacturing site with Good
Manufacturing Practices had been confirmed by two on-site inspections performed by the Austrian Health
Agency before and after the Company began to work with them.
The transfer of the manufacturing process to another contract manufacturing organization took few
months and came with additional costs but allowed Innate to have a conform batch in the middle of 2020
and to resume the enrollment and treatment of patients in the clinical trials after getting Regulatory
Agencies approval. During this period of time, the TELLOMAK trial was on partial or full hold in the
United States, Spain, Germany and Italy.
Should any of these risks materialize, this could have a material adverse effect on Innate's business,
prospects, financial condition and results of operations.
The Company is reliant upon third parties to manufacture and supply components of certain
substances necessary to manufacture its product candidates.
The Company is reliant on several third-party CMOs for the manufacture and supply of components and
substances for all of the product candidates the Company is developing. In addition, certain component
materials are currently available from a single supplier, or a small number of suppliers. The Company
cannot be sure that these suppliers will remain in business, or that they will not be purchased by one of its
competitors or another company that is not interested in continuing to manufacture these materials for us.
The Company cannot assure that, if required, the Company will be able to identify alternate sources with
the desired scale and capability and establish relationships with such sources. A loss of any CMO or
component supplier and delay in establishing a replacement could delay Innate's clinical development and
regulatory approval process.
36
Its production costs may be higher than the Company currently estimates.
Innate's product candidates are manufactured according to manufacturing best practices applicable to
drugs for clinical trials and to specifications approved by the applicable regulatory authorities. If any of
its products were found to be non-compliant, the Company would be required to manufacture the product
again, which would entail additional costs and may prevent delivery of the product to patients on time.
Other risks inherent in the production process may have the same effect, such as:
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contamination of the controlled atmosphere area;
unusable premises and equipment;
new regulatory requirements requiring a partial and/or extended stop to the production unit to
meet the requirements;
unavailable qualified personnel;
power failure of extended duration; and
logistical error.
Should any of these risks materialize, this could have a material adverse effect its business, prospects,
financial condition and results of operations.
The Company relies on third parties to supply key materials used in its research and development, to
provide services to Innate and to assist with clinical trials.
The Company makes considerable use of third-party suppliers for the key materials used in its business.
The failure of third-party suppliers to comply with regulatory standards could result in the imposition of
sanctions on us. These sanctions could include fines, injunctions, civil penalties, refusal by regulatory
organizations to grant approval to conduct clinical trials or marketing authorization for its products,
delays, suspension or withdrawal of approvals, license revocation, seizure or recalls of its products,
operating restrictions and legal proceedings. Furthermore, the presence of non-conformities, as detected
in regulatory toxicology studies, could result in delays in the development of one or more of its product
candidates and would require further tests to be financed. Although the Company is involved in
establishing the protocols for the production of these materials, the Company does not control all the
stages of production and cannot guarantee that the third parties will fulfil their contractual and regulatory
obligations. In particular, a partner’s failure to comply with protocols or regulatory constraints, or
repeated delays by a partner, could compromise the development of its products or limit its liability. Such
events could also inflate the product development costs incurred by us.
The Company also use third parties to provide certain services such as scientific, medical or strategic
consultancy services. These service providers are generally selected for their specific expertise, as is the
case with the academic partners with whom the Company collaborates. To build and maintain such a
network under acceptable terms, the Company faces intense competition. Such external collaborators may
terminate, at any time, their involvement. The Company can exert only limited control over their
activities. the Company may not be able to obtain the intellectual property rights to the product candidates
or technologies developed under collaboration, research and license agreements under acceptable terms or
at all. Moreover, its scientific collaborators may assert intellectual property rights or other rights beyond
the terms of their engagement.
Finally, the Company uses third-party investigators to assist with conducting clinical trials. All clinical
trials are subject to strict regulations and quality standards. Should any of these risks materialize, this
could have a material adverse effect on its business, prospects, financial condition and results of
operations.
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The Company and its collaborators rely on third parties to conduct some of its preclinical studies and
clinical trials and perform other clinical development tasks. If these third parties do not successfully
carry out their contractual duties, meet expected deadlines or comply with regulatory requirements, it
may not be possible to obtain regulatory approval for, or commercialize, its product candidates and its
business could be substantially harmed.
The Company has relied upon and plan to continue to rely upon third parties to conduct clinical trials of
its product candidates or product candidates that the Company has licensed to partners. For example,
under its license and collaboration agreements with AstraZeneca, AstraZeneca is responsible for a number
of clinical trials relating to monalizumab and IPH5201, which are subject to such agreements. In addition,
the Company and its collaborators are responsible for and are supporting several clinical trials that are
sponsored by academic or research institutions, known as investigator-sponsored trials, as it is the case for
the clinical trial assessing IPH5301, which is sponsored by Institut Paoli-Calmettes. By definition, the
financing, design and conduct of an investigator-sponsored trial are the sole responsibility of the sponsor,
and the Company or its collaborators, as applicable, have limited control over these aspects of these
clinical trials, or the timing and reporting of the data from these trials. The Company and its collaborators
also depend on independent clinical investigators and CROs to conduct clinical trials. CROs may also
assist in the collection and analysis of data. There are a limited number of CROs that have the expertise to
run clinical trials of its product candidates. Identifying, qualifying and managing performance of third-
party service providers can be difficult and time consuming and can cause delays in its development
programs. These investigators and CROs are not Innate's employees and the Company is not able to
control, other than by contract, the amount of resources, including the amount of time, that they devote to
Innate's product candidates and clinical trials. If the investigators sponsoring trials of its product
candidates, independent investigators participating in clinical trials that Innate Pharma or its collaborators
are sponsoring or CROs fail to devote sufficient resources to its clinical trials and development of its
product candidates or product candidates the Company has licensed to others, or if their performance is
substandard, it may delay or compromise the prospects for approval and commercialization of any
product candidates that the Company or its collaborators develop. In addition, the use of third-party
service providers requires Innate to disclose its proprietary information to these parties, which could
increase the risk that this information will be misappropriated, and the Company may not be able to
obtain adequate remedies for such disclosure or misappropriation. Further, the FDA, EMA and other
regulatory authorities require that the Company complies with standards, commonly referred to as Good
Clinical Practice, or GCP, and other local legal requirements, including data privacy regulations, for
conducting, recording and reporting clinical trials to assure that data and reported results are credible and
accurate and that the rights, integrity and confidentiality of clinical trial subjects are protected. If clinical
investigators or CROs fail to meet their obligations to Innate or comply with GCP procedures or other
applicable legal requirements, the data generated in these trials may be deemed unreliable and the FDA,
EMA or comparable foreign regulatory authorities may require Innate to perform additional trials before
approving Innate Pharma's marketing applications. The Company cannot assure that upon inspection by a
given regulatory authority, such regulatory authority will determine that all of its clinical trials comply
with GCP regulations.
In addition, Innate's clinical trials must be conducted with product produced under current Good
Manufacturing Practice, or cGMP, regulations. The Company's failure to comply with these regulations
may require the Company to repeat clinical trials, which would delay the regulatory approval process. If
clinical investigators or CROs do not successfully carry out their contractual duties or obligations or meet
expected deadlines, if they need to be replaced or if the quality or accuracy of the data they obtain is
compromised due to the failure to adhere to Innate's protocol or regulatory requirements, or for other
reasons, its clinical trials or those of its collaborators may be extended, delayed or terminated, and the
Company or its collaborators may not be able to obtain regulatory approval for or successfully
38
commercialize its product candidates. As a result, its results of operations and the commercial prospects
for its product candidates would be harmed, its costs could increase and its ability to generate revenue
could be delayed.
Manufacturing facilities and clinical trial sites are subject to significant government regulations and
approvals and if Innate's or its partners’ third-party manufacturers fail to comply with these
regulations or maintain these approvals, its business could be materially harmed.
Innate's third-party manufacturers are subject to ongoing regulation and periodic inspection by national
authorities, including the EMA, FDA and other regulatory bodies to ensure compliance with cGMP, when
producing batches of its product candidates for clinical trials. CROs and other third-party research
organizations must also comply with Good Laboratory Practices (GLP) when carrying out regulatory
toxicology studies. Any failure to follow and document the Company's or their adherence to such GMP
and GLP regulations or other regulatory requirements may lead to significant delays in the availability of
products for commercial sale or clinical trials, may result in the termination of or a hold on a clinical trial,
or may delay or prevent filing or approval of marketing applications for its products.
Failure to comply with applicable regulations could also result in national authorities, the EMA, FDA or
other applicable regulatory authorities taking various actions, including:
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levying fines and other civil penalties;
imposing consent decrees or injunctions;
requiring Innate to suspend or put on hold one or more of its clinical trials;
suspending or withdrawing regulatory approvals;
delaying or refusing to approve pending applications or supplements to approved applications;
requiring Innate Pharma to suspend manufacturing activities or product sales, imports or
exports;
requiring Innate to communicate with physicians and other customers about concerns related
to actual or potential safety, efficacy, and other issues involving its products;
mandating product recalls or seizing products;
imposing operating restrictions; and
seeking criminal prosecutions.
Any of the foregoing actions could be detrimental to Innate's reputation, business, financial condition or
operating results. Furthermore, its key suppliers may not continue to be in compliance with all applicable
regulatory requirements, which could result in its failure to produce its products on a timely basis and in
the required quantities, if at all. In addition, before any additional products would be considered for
marketing authorization in Europe, the United States or elsewhere, its suppliers will have to pass an
inspection by the applicable regulatory agencies. The Company is dependent on its suppliers’ cooperation
and ability to pass such inspections, and the inspections and any necessary remediation may be costly.
Failure to pass such inspections by Innate Pharma or any of its suppliers would affect its ability to
commercialize its product candidates in Europe, the United States or elsewhere. Should any of these risks
materialize, this could have a material adverse effect on the Company's business, prospects, financial
condition and results of operations. For example, in November 2019, Impletio Wirkstoffabfüllung GmbH
(formerly known as Rentschler Fill Solutions GmbH), the subcontractor in charge of the fill-and-finish
manufacturing operations of lacutamab unilaterally decided to withdraw the certificates of conformance
of all clinical batches produced at their facilities, including the lacutamab batch used for the TELLOMAK
39
Phase 2 clinical trial assessing lacutamab in multiple indications, which resulted in partial or full holds in
a number of countries.
The Company depends upon its existing collaboration partners, AstraZeneca, Sanofi and other third
parties, and may depend upon future collaboration partners to commit to the research, development,
manufacturing and marketing of its drugs.
The Company has significant collaborations with AstraZeneca for the development of monalizumab,
IPH5201 and other product candidates. The Company also collaborates with Sanofi for the development
of IPH6101/SAR'579, IPH6401/SAR’514 and IPH62, and the Company may enter into additional
collaborations for other of its product candidates or technologies in development. The Company cannot
control the timing or quantity of resources that its existing or future collaborators will dedicate to
research, preclinical and clinical development, manufacturing or marketing of its products. Innate's
collaborators may not perform their obligations according to its expectations or standards of quality.
Innate Pharma's collaborators could terminate its existing agreements for a number of reasons, including
that they may have other, higher priority products in development or because its partnered programs may
no longer be a priority for them. If any of the Company's collaboration agreements were to be terminated,
the Company could encounter significant delays in developing its product candidates, lose the opportunity
to earn any revenues Innate expected to generate under such agreements, incur unforeseen costs, and
suffer damage to the reputation of its product, product candidates and as a company generally.
In order to optimize the launch and market penetration of certain of its future product candidates, the
Company may enter into distribution and marketing agreements with pharmaceutical industry leaders. For
these product candidates, the Company would not market its products alone once they have obtained
marketing authorization. The risks inherent in entry into these contracts are as follows:
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the negotiation and execution of these agreements is a long process that may not result in an
agreement being signed or that can delay the development or commercialization of the product
candidate concerned;
these agreements are subject to cancellation or non-renewal by its collaborators, or may not be
fully complied with by its collaborators;
in the case of a license granted by us, the Company loses control of the development of the
product candidate licensed; in such cases the Company would have only limited control over
the means and resources allocated by its partner for the commercialization of its product; and
collaborators may not properly obtain, maintain, enforce, or defend Innate's intellectual
property or proprietary rights or may use its proprietary information in such a way as to invite
litigation that could jeopardize or invalidate its proprietary information or expose the
Company to potential litigation.
Should any of these risks materialize, or should the Company fails to find suitable collaborators, this
could have a material adverse effect on its business, prospects, financial condition and results of
operations.
The late-stage development and marketing of its product candidates may partially depend on its ability
to establish collaborations with major biopharmaceutical companies.
In order to develop and market some of its product candidates, the Company relies on collaboration,
research and license agreements with pharmaceutical companies to assist Innate in the development of
product candidates and the financing of their development. For its most advanced clinical product
candidate, monalizumab, the Company entered into an agreement with AstraZeneca, in part because of
their late-stage development and marketing capabilities. As the Company identifies new product
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candidates, Innate Pharma will determine the appropriate strategy for development and marketing, which
may result in the need to establish collaborations with major biopharmaceutical companies. Innate may
also enter into agreements with institutions and universities to participate in its other research programs
and to share intellectual property rights.
The Company may fail to find collaboration partners and to sign new agreements for its other product
candidates and programs. The competition for partners is intense, and the negotiation process is time-
consuming and complex. Any new collaboration may be on terms that are not optimal for us, and the
Company may not be able to maintain any new collaboration if, for example, development or approval of
a product candidate is delayed, sales of an approved product candidate do not meet expectations or the
collaborator terminates the collaboration. Any such collaboration, or other strategic transaction, may
require Innate to incur non-recurring or other charges, increase Innate's near- and long-term expenditures
and pose significant integration or implementation challenges or disrupt its management or business.
These transactions would entail numerous operational and financial risks, including exposure to unknown
liabilities, disruption of Innate's business and diversion of its management’s time and attention in order to
manage a collaboration or develop acquired products, product candidates or technologies, incurrence of
substantial debt or dilutive issuances of equity securities to pay transaction consideration or costs, higher
than expected collaboration, acquisition or integration costs, write-downs of assets or goodwill or
impairment charges, increased amortization expenses, difficulty and cost in facilitating the collaboration
or combining the operations and personnel of any acquired business, impairment of relationships with key
suppliers, manufacturers or customers of any acquired business due to changes in management and
ownership and the inability to retain key employees of any acquired business. Accordingly, although there
can be no assurance that the Company will undertake or successfully complete any transactions of the
nature described above, any transactions that the Company does complete may be subject to the foregoing
or other risks and have a material and adverse effect on its business, financial condition, results of
operations and prospects. Conversely, any failure to enter any additional collaboration or other strategic
transaction
the development and potential
commercialization of its product candidates and have a negative impact on the competitiveness of any
product candidate that reaches market.
that would be beneficial
to Innate could delay
The Company does not and will not have access to all information regarding its product candidates
that are subject to collaboration and license agreements. Consequently, its ability to inform its
shareholders about the status of product candidates that are subject to these agreements, and its ability
to make business and operational decisions, may be limited.
Innate does not and will not have access to all information regarding its product candidates that are
subject to its license and collaboration agreements with AstraZeneca, Sanofi and other third parties,
including potentially material information about clinical trial design, execution and timing, safety and
efficacy, clinical trial results, regulatory affairs, manufacturing, marketing and other areas known by its
collaborators. In addition, the Company has confidentiality obligations under its collaboration and license
agreements. Therefore, its ability to keep its shareholders informed about the status of product candidates
subject to such agreements will be limited by the degree to which its collaborators keep Innate informed
and allow Innate Pharma to disclose information to the public or provide such information to the public
themselves. If its collaborators do not inform Innate about its product candidates subject to agreements
with them, the Company may make operational and investment decisions that the Company would not
have made had the Company been fully informed, which may have an adverse impact on its business,
prospects, financial condition and results of operations.
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Risks Related to Innate Pharma's Financial Position and Capital Needs
The Company has incurred and may in the future incur significant operational losses related to its
research and development activities.
The Company have incurred net losses in each year since its inception except for the years ended
December 31, 2016 and 2018. Innate's net income (loss) was €(58.1) million and €(52.8) million for the
years ended December 31, 2022 and 2021, respectively. Substantially all of its net losses resulted from
costs incurred in connection with its development programs and from selling, general and administrative
expenses associated with its ongoing operations. The Company expects to incur significant expenses and
operating losses for the foreseeable future.
The Company had one product, Lumoxiti, that has received regulatory approval for sale or has generated
revenues from commercial sales, and none of its other product candidates have received regulatory
approval. Unless this happens, the likelihood and amount of its future operational losses will depend on
several factors, including the pace and amount of its future expenditures in connection with its product
candidates and development programs and its ability to obtain funding through milestone or royalty
payments under its license and collaboration agreements, equity or debt financings, strategic
collaborations and government grants and tax credits. The Company expects that its main source of
income for the near- and medium-term will be:
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payments received under its license and collaboration agreements with third parties, including
AstraZeneca and Sanofi; and
government grants and research tax credits.
The interruption of one or more of those sources of income could have a material adverse effect on
Innate's business, prospects, financial condition and results of operations.
The Company's ability to be profitable in the future will depend on its ability to generate revenue from
sales relating to its product candidates, if approved, and its ability to obtain regulatory approval for
marketing its product candidates. If its product candidates receive regulatory approval, its future revenues
will depend upon the size of any markets in which its product candidates have received approval, and
market acceptance, reimbursement from third-party payors and market share. Any of these factors could
have a material adverse effect on Innate's business, prospects, financial condition and results of
operations.
The Company may need to raise additional funding to complete the development and any
commercialization of its product candidates, which may not be available on acceptable terms, or at all,
and failure to obtain this necessary capital when needed may force it to delay, limit or terminate its
product development efforts or other operations.
Innate Pharma is currently advancing its product candidates through preclinical and clinical development,
and anticipates relying on partners as the Company advances them. Innate currently retains the full
development and marketing rights to lacutamab, avdoralimab and IPH5301 and may retain rights to
additional proprietary product candidates in the future. The development of immunotherapy product
candidates is expensive, and Innate expects its research and development expenses to increase as the
Company advances its product candidates through clinical trials and regulatory approvals. If clinical trials
are successful and if Innate obtains regulatory approval for product candidates that the Company
develops, Innate expects to incur commercialization expenses before these product candidates are
marketed and sold.
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The Company anticipate that its expenses will increase substantially if and as we:
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continue its research, preclinical and clinical development of its product candidates if its
current collaboration partners cease their collaborations with us;
expand the scope of its current clinical trials for its product candidates;
initiate additional preclinical, clinical or other studies for its product candidates;
further develop manufacturing processes for its product candidates;
change or add additional manufacturers or suppliers;
seek regulatory and marketing authorizations for its product candidates that successfully
complete clinical studies;
establish a sales, marketing and distribution infrastructure to commercialize any product for
which the Company may obtain marketing authorization;
seek to identify and validate additional product candidates that may result in additional
preclinical, clinical or other product studies;
acquire or in-license other product candidates and technologies;
make milestone or other payments under any in-license agreements;
maintain, protect, defend and expand its intellectual property portfolio;
attract and retain new and existing skilled personnel;
create additional infrastructure to support its operations as a public company in the United
States following the completion of the October 2019 global offering; and
experience any delays or encounter issues with any of the above.
As of December 31, 2022, the Company had cash, cash equivalents, short-term investments and non-
current financial assets of €136.6 million. The Company believes its cash, cash equivalents, short-term
investments and non-current financial assets together with its cash flow from operations, will be sufficient
to fund its operations for the next two years. However, in order to complete the development process,
obtain regulatory approval and, if approved, commercialize its product candidates that the Company is
developing in-house, including lacutamab, avdoralimab and IPH5301, develop its proprietary technology
and develop a pipeline of additional product candidates, the Company will require additional funding.
Innate's existing resources may not be sufficient to cover any additional financing needs, in which case
new funding would be required. See “—the Company has incurred and may in the future incur significant
operational losses related to its research and development activities.” The conditions and arrangements for
such new financing would depend, among other factors, on economic and market conditions that are
beyond its control, including the current volatility in the capital markets.
Any additional fundraising efforts may divert Innate's management from their day-to-day activities, which
may adversely affect its ability to develop and commercialize its product candidates. In addition, the
Company cannot guarantee that future financing will be available in sufficient amounts or on terms
acceptable to us, if at all. Under French law, Innate's share capital may be increased only with
shareholders’ approval at an extraordinary general shareholders’ meeting on the basis of a report from the
Executive Board. In addition, the French Commercial Code imposes certain limitations on Innate's ability
to price certain offerings of its share capital without preferential subscription rights (droit préférentiel de
souscription), which limitation may prevent Innate from successfully completing any such offering. See
“Description of Share Capital—Key Provisions of the Company's Bylaws and French Law Affecting Its
Ordinary Shares.”
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Moreover, the terms of any financing may adversely affect the holdings or the rights of Innate's
shareholders and the issuance of additional securities, whether equity or debt, by us, or the possibility of
such issuance, may cause the market price of its ordinary shares or the ADSs to decline. The sale of
additional equity or convertible securities would dilute its shareholders. the Company may seek funds
through arrangements with collaborative partners or otherwise at an earlier stage of product development
than otherwise would be desirable and the Company may be required to relinquish rights to some of its
technologies or product candidates or otherwise agree to terms unfavorable to Innate Pharma, any of
which may have a material adverse effect on its business, prospects, financial condition and results of
operations.
If the Company needs and is unable to obtain funding on a timely basis, the Company may be required to
significantly curtail, delay or discontinue one or more of its research or development programs or the
commercialization of any product or product candidate or the Company may be unable to expand its
operations or otherwise capitalize on its business opportunities as desired, which could impair its growth
prospects. Should any of these risks materialize, this could have a material adverse effect on Innate's
business, prospects, financial condition and results of operations.
The terms of Innate's loans agreements with Société Générale, BNP Paribas and certain other loan
obligations place restrictions on its operating and financial flexibility.
In July 2017, the Company entered into a loan and security agreement with Société Générale (the “Loan
Agreement”) in order to finance the construction of its future headquarters. The Loan Agreement is
secured by collateral in the form of financial instruments valued at €15.2 million held at Société Générale.
As of December 31, 2022, Innate Pharma had drawn down €15.2 million under the Loan Agreement. The
Loan Agreement subjects Innate to a covenant to maintain a minimum balance of its total cash, cash
equivalents and current and non-current financial assets as of each fiscal year end at least equal to the
amount of outstanding principal under the Loan Agreement. Compliance with this covenant may limit its
flexibility in operating its business and its ability to take actions that might be advantageous to Innate and
its shareholders. For example, if the Company fails to meet its minimum cash covenant and Innate is
unable to raise additional funds or obtain a waiver or other amendment to the Loan Agreement, Innate
Pharma may be required to delay, limit, reduce or terminate certain of its clinical development efforts.
Additionally, Innate may be required to repay the entire amount of outstanding indebtedness under the
Loan Agreement in cash if the Company fails to stay in compliance with its covenant or suffer some other
event of default under the Loan Agreement. Under the Loan Agreement, an event of default will occur if,
among other things, Innate fails to make payments under the Loan Agreement or Innate breaches its
covenant under the Loan Agreement. The Company may not have enough available cash or be able to
raise additional funds through equity or debt financings to repay such indebtedness at the time any such
event of default occurs. In that case, Innate may be required to delay, limit, reduce or terminate its clinical
development efforts or grant rights to others to develop and market product candidates that the Company
would otherwise prefer to develop and market itself. Société Générale could also exercise its rights as
collateral agent to take possession and dispose of the collateral securing the loan for its benefit. Innate's
business, financial condition and results of operations could be substantially harmed as a result of any of
these events.
On January 5, 2022, the Company announced that it had obtained €28.7 million in non-dilutive financing
in the form of two State Guaranteed Loans from Société Générale (€20.0 million) and BNP Paribas
(€8.7 million). The Company received the funds related to these two loans on December 27 and 30, 2021
respectively. Both loans have an initial maturity of one year with an option to extend to five years. They
are 90% guaranteed by the French government as part of the package of measures put in place by the
French government to support companies during the COVID-19 pandemic. The effective interest rate
applied to these contracts is 0.5% which is the contractual rate for repayment within one year.
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On August 2022, the Company requested the extension repayment of the non-dilutive financing of €28.7
million obtained in December 2021 in the form of two State Guaranteed Loans ( “PGE”), respectively for
20.0 and 8.7 million euros for an additional period of five years starting in 2022 and including a one-year
grace period. Consequently, the Company has obtained agreements from Société Générale and BNP
Paribas. The effective interest rates applied to these contracts during the additional period are 1.56% and
0.95% for Société Générale and BNP Paribas loans, respectively, excluding insurance and guarantee fees,
with an amortization exemption for the entire year 2023. During this grace period, the Company will only
be liable for the payment of interest and the guarantee fees, with amortization of the two loans starting in
2024 over a period of four years
Innate is also subject to a €1.5 million PTZI loan (Prêt à Taux Zéro Innovation—interest-free loan for
innovation) from Banque Publique d’Investissement, or BPI France, entered into in 2013. The PTZI loan
is fully amortized as of December 31, 2021. In addition, in 2008 the Company entered into a finance lease
agreement with Sogebail, a subsidiary of Société Générale. The present value of all minimum payments
under this contract is nil as of December 31, 2021, the contract having expired. Innate's business, financial
condition and results of operations could likewise be substantially harmed if, among other things, Innate
Pharma fails to make payments under these agreements, or the Company breaches any of its covenants
under these agreements.
If Innate does not achieve its product development or commercialization objectives in the timeframes
Innate expects, the Company may not receive product revenue or milestone or royalty payments and
Innate Pharma may not be able to conduct its operations as planned.
Innate has received and expect to continue to receive payments from its collaborators when the Company
satisfies certain pre-specified milestones in its licensing or collaboration agreements. Innate Pharma
currently depends to a large degree on these milestone payments from its existing collaborators in order to
fund its operations and Innate may enter into new collaboration agreements that also provide for
milestone payments. For example, the Company has granted options to license or acquire intellectual
property rights in certain of its programs to its collaborators which, if exercised, will result in up-front
option exercise fees and, assuming Innate meets all specified development, clinical, regulatory and sales
milestones, could result in substantial milestone payments. These milestone payments are generally
dependent on the accomplishment of various scientific, clinical, regulatory, sales and other product
development objectives, and the successful or timely achievement of many of these milestones is outside
of its control, in part because some of these activities are being or will be conducted by its collaborators.
If Innate or its collaborators fail to achieve the applicable milestones, Innate Pharma may not receive such
milestone payments. A failure to receive any such milestone payment may cause Innate to:
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delay, reduce or terminate certain research and development programs;
reduce headcount;
raise funds through additional equity or convertible debt financings that could be dilutive to its
shareholders and holders of its ADSs;
obtain funds through collaboration agreements that may require Innate to assign rights to
technologies or products that Innate would have otherwise retained;
sign new collaboration or license agreements that may be less favorable than those the
Company would have obtained under different circumstances; and
consider strategic transactions or engaging in a joint venture with a third-party.
In addition, although Innate may be eligible to receive an aggregate of approximately $3.6 billion in
future contingent payments from existing collaboration agreements and any license agreements that
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become effective upon the exercise by its collaborators of options to license future product candidates,
there is no guarantee that the Company will receive any contingent payments or that its collaborators will
exercise any options to license or acquire additional intellectual property rights in any of its programs. If
its collaborators decide not to exercise such options with respect to a program, the Company will not
receive the up-front option exercise fee and will not be eligible to receive any of the related commercial,
development, royalty or other milestone payments. Even if its collaborators exercise such options with
respect to a particular program, Innate Pharma may never achieve the related milestones for any number
of reasons. The failure to receive milestone or royalty payments and the occurrence of any of the events
above may have a material adverse impact on Innate's business, prospects, financial condition and results
of operations.
The revenues generated from its collaboration and license agreements have contributed and are
expected to contribute a large portion of its revenue for the foreseeable future.
The Company has entered into collaboration and license agreements with pharmaceutical companies,
including AstraZeneca and Sanofi. The cash payments received from its partners were €56.9 million,
€15.3 million and €57.8 million for the years ended December 31, 2022, 2021 and 2020, respectively.
Innate also enhances its research efforts by establishing collaborations with academic or non-profit
research institutions and other biopharmaceutical companies. The participation in these collaborations
may generate revenue and funding in the form of operating grants or the reimbursement of research and
development expenses.
Innate Pharma may not be able to renew or maintain its license agreements or collaborative research
contracts or may be unable to sign new agreements with new collaborators on reasonable terms or at all.
The early termination of a contract, the non-renewal of a contract or its inability to find new collaborators
would adversely affect its business. Should any of these risks materialize, this could have an adverse
effect on Innate's business, prospects, financial condition and results of operations.
The Company benefits from tax credits in France that could be reduced or eliminated.
As a French biopharmaceutical company, Innate benefits from certain tax advantages, including the
Research Tax Credit (Crédit Impôt Recherche), which is a French tax credit aimed at stimulating research
and development. The Research Tax Credit is calculated based on Innate's claimed amount of eligible
research and development expenditures in France and represented €7.9 million, €10.3 million and
€13.1 million for the years ended December 31, 2022, 2021 and 2020, respectively. The Research Tax
Credit is a source of financing to Innate that could be reduced or eliminated by the French tax authorities
or by changes in French tax law or regulations.
The Research Tax Credit can be offset against French corporate income tax due by the company with
respect to the year during which the eligible research and development expenditures have been made. The
portion of tax credit in excess which is not being offset, if any, represents a receivable against the French
Treasury which can in principle be offset against the French corporate income tax due by the company
with respect to the three following years. The remaining portion of tax credit not being offset upon expiry
of such a period may then be refunded to the company.
Until the end of the year ended December 31, 2018, the Company qualified as a small- and medium-size
business and the French Treasury refunded each of its 2016, 2017 and 2018 Research Tax Credit claims
immediately (meaning that, in practice, Innate received the refund during the year following the year in
which the eligible research and development expenditures are made). Innate Pharma no longer qualifies
as a small and medium-size business since the year ended December 31, 2019, and therefore, the
Company will no longer be entitled to the immediate reimbursement of the Research Tax Credit but
instead will be reimbursed within the expiry of the period of three years mentioned above. As of
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December 31, 2021, Innate is qualified again as a small or medium size business. As a result, Innate
Pharma is eligible for reimbursement by the French treasury of the 2021 Research Tax Credit during the
fiscal year 2022.
The French tax authorities, with the assistance of the Higher Education and Research Ministry, may audit
each research and development program in respect of which a Research Tax Credit benefit has been
claimed and assess whether such program qualifies in their view for the Research Tax Credit benefit. The
French tax authorities may challenge Innate's eligibility for, or its calculation of, certain tax reductions or
deductions in respect of its research and development activities (and therefore the amount of Research
Tax Credit claimed), or the accelerated reimbursement allowed for small- and medium-size businesses
and the Company's credits may be reduced, which would have a negative impact on its revenue and future
cash flows. Furthermore, the French Parliament may decide to eliminate, or to reduce the scope or the rate
of, the Research Tax Credit benefit, either of which it could decide to do at any time. If Innate fails to
receive future Research Tax Credit amounts or if its calculations are challenged, even if Innate Pharma
complies with the current requirements in terms of documentation and eligibility of its expenditure, its
business, prospects, financial condition and results of operations could be adversely affected.
The Company may be unable to carry forward existing tax losses.
Innate has accumulated tax loss carry forwards of €466.2 million as of December 31, 2022. Applicable
French law provides that, for fiscal years ending after December 31, 2012, the use of these tax losses is
limited to €1.0 million, plus 50% of the portion of net earnings exceeding this amount. The unused
balance of the tax losses in application of such rule can be carried forward to future fiscal years, under the
same conditions and without time restriction. There can be no assurance that future changes to applicable
tax law and regulation will not eliminate or alter these or other provisions in a manner unfavorable to us,
which could have an adverse effect on Innate's business, prospects, financial condition, cash flows or
results of operations.
Innate's business may be exposed to foreign exchange risks.
The Company incurs some of its expenses, and derive certain of its revenues, in currencies other than the
euro. In particular, as Innate expands its operations and conduct additional clinical trials in the United
States, Innate will incur additional expenses in U.S. dollars. As a result, Innate is exposed to foreign
currency exchange risk as its results of operations and cash flows are subject to fluctuations in foreign
currency exchange rates.
The Company currently does not engage in hedging transactions to protect against uncertainty in future
exchange rates between particular foreign currencies and the euro. Therefore, an unfavorable change in
the value of the euro against the U.S. dollar could have a negative impact on its revenue and earnings
growth. Innate cannot predict the impact of foreign currency fluctuations, and foreign currency
fluctuations in the future may adversely affect its financial condition, results of operations and cash flows.
The ADSs being offered in the U.S. offering are quoted in U.S. dollars on Nasdaq, while Innate's ordinary
shares trade in euro on Euronext Paris. Innate's financial statements are prepared in euro. Therefore,
fluctuations in the exchange rate between the euro and the U.S. dollar will also affect, among other
matters, the value of Innate's ordinary shares and ADSs.
Under Innate's license and collaboration agreements with AstraZeneca, the payments the Company
receives are in U.S. dollars. The level of completion of the operations covered by this collaboration
agreement is based on the costs converted at the historical exchange rate. The effects of reevaluation
therefore have no impact on the technical progress used for revenue recognition. Consequently, there may
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be a difference between the level of completion that would take into account the last known rate and the
level of completion as calculated. This difference could result in a future exchange gain or loss.
Moreover, in the future, Innate could generate part of its sales in the United States and part in Europe and
could therefore be subject to an unfavorable euro/dollar exchange rate. Therefore, for example, an
increase in the value of the euro against the U.S. dollar could be expected to have a negative impact on its
revenue and earnings growth as U.S. dollar revenue and earnings, if any, would be translated into euro at
a reduced value. The Company could also sign contracts denominated in other currencies, which would
increase its exposure to currency risk. In accordance with Innate's business decisions, its exposure to this
type of risk could change depending on:
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the currencies in which Innate receives its revenues;
the currencies chosen when agreements are signed, such as licensing agreements, or co-
marketing or co- development agreements;
the location of clinical trials on product candidates; and
its policy for insurance cover.
At present, Innate has not put any specific hedging arrangements in place to address these risks. Should
any of these risks materialize, this could have a material adverse effect on its business, prospects,
financial condition and results of operations.
Changes to U.S. and non-U.S. tax laws could materially adversely affect Innate Pharma.
The Company is unable to predict what tax law may be proposed or enacted in the future or what effect
such changes would have on its business, but such changes, to the extent they are brought into tax
legislation, regulations, policies or practices, could affect its effective tax rates in the future in countries
where it has operations and have an adverse effect on its overall tax rate in the future, along with
increasing the complexity, burden and cost of tax compliance. The Company urges its shareholders and
holders of its ADSs to consult with their legal and tax advisors with respect to the potential tax
consequences of investing in or holding Innate's ordinary shares or ADSs.
Tax authorities may disagree with Innate's positions and conclusions regarding certain tax positions,
resulting in unanticipated costs, taxes or non-realization of expected benefits.
A tax authority may disagree with tax positions that the Company has taken, which could result in
increased tax liabilities. For example, the French tax authorities, the U.S. Internal Revenue Service or
another tax authority could challenge Innate's allocation of income by tax jurisdiction and the amounts
paid between its affiliated companies pursuant to its intercompany arrangements and transfer pricing
policies, including amounts paid with respect to its intellectual property development. Similarly, a tax
authority could assert that the Company is subject to tax in a jurisdiction where Innate believes it has not
established a taxable connection, often referred to as a “permanent establishment” under international tax
treaties, and such an assertion, if successful, could increase the Company's expected tax liability in one or
more jurisdictions. A tax authority may take the position that material income tax liabilities, interest and
penalties are payable by us, in which case, the Company expects that it might contest such assessment.
Contesting such an assessment may be lengthy and costly and if Innate was unsuccessful in disputing the
assessment, the result could increase its anticipated effective tax rate.
On March 16, 2022, the Company received a notification from tax authorities relating to the 2019 and
2020 financial years as well as to the research tax credit and the accuracy of its calculation for the 2018 to
2020 financial years. A provision amounting to €1,270 thousand has been booked, based on estimated
amounts and adjustments not disputed by the Company. On March 3, 2023, the Company received the
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rectification proposal, confirming the amount of the provision recognized on the amounts of the
rectifications not disputed by the Company - Refer to Note 18. "Provisions".
Risks Related to Innate Pharma's Organization and Operations
There is a material weakness in the Company's internal control over financial reporting and if Innate
Pharma is unable to maintain effective internal controls over financial reporting, the accuracy and
timeliness of its financial reporting may be adversely affected, which could hurt its business and/or
lessen investor confidence.
The Company must maintain effective internal control processes over financial reporting in order to
accurately report its results of operations and financial condition on a timely basis. A company’s internal
control over financial reporting is a process designed by, or under the supervision of, a company’s
principal executive and principal financial officers, or persons performing similar functions, and effected
by a company’s executive board, management and other personnel to provide reasonable assurance
regarding the reliability of financial reporting and the preparation of financial statements in accordance
with generally accepted accounting principles.
As a public company listed in the United States, the Sarbanes-Oxley Act requires, among other things,
that the Company assesses the effectiveness of its internal control over financial reporting as of the end of
each fiscal year, beginning with the end of the first full fiscal year following the completion of the Global
Offering, i.e., since the end of fiscal year 2020. However, Innate's independent registered public auditor
will not be required to attest to the effectiveness of its internal controls over financial reporting for as long
as the Company is an EGC, i.e. an “emerging growth company,” according to the Jumpstart Our Business
Startups Act of 2012, or JOBS Act, which may be up to five fiscal years following the date of the October
2019 public Global Offering. An independent assessment of the effectiveness of Innate's internal controls
over financial reporting could detect issues that its management’s assessment might not.
In this context, in order to comply with Section 404(a) of the Sarbanes-Oxley Act within the prescribed
timeframe, the Company initiated a project to improve the documentation and the evaluation of its
internal control processes over financial information with the support of an expert company at the end of
2019. In addition, in order to make the information system, on which the management and production of
financial information is based, more reliable, the plan aiming at transforming Innate's information system
initiated in 2019 took shape with the launch of its new Enterprise Resource Planning, or ERP, on August
1, 2020. Since then, the Company has reinforced its internal control processes, especially those related to
manual entries and management of significant and unusual transactions identified as a material weakness
at the end of the 2020 financial year.
The Company's management carried out an evaluation of the effectiveness of its internal control at the
end of the year ended December 31, 2022. See "Item 15. Controls and Procedures." Although significant
progress has been observed in terms of improving the reliability of its internal control system, the
management concluded in a material weakness. Under standards established by the Public Company
Accounting Oversight Board, a material weakness is a deficiency or combination of deficiencies in
internal control over financial reporting, such that there is a reasonable possibility that a material
misstatement in Innate Pharma's annual or interim financial statements will not be prevented or detected
and corrected on a timely basis. The control deficiencies identified are due to a lack of granularity and
precision of the design and, constitute a material weakness in the aggregate primarily relating to (i)
prevention or detection of material errors in the classification and presentation of the consolidated
financial statements, and related disclosures and (ii) recording of all third-party services in the correct
period. The deficiencies in control activities contributed to errors related to misclassification and
presentation which have been corrected throughout 2022 and during the year-end closing.
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Although the Company has identified corrective actions aiming at resolving the material weakness, the
Company cannot give assurance that the measures taken to remediate the material weakness will be
sufficient or that they will prevent future material weaknesses. If the Company does not succeed in
maintaining the appropriate level of internal control, it could result in material misstatements in its
financial statements, result in the loss of investor confidence in the reliability of its financial statements
and subject it to regulatory scrutiny and sanctions, which in turn could harm the market value of its
ordinary shares and ADSs.
Innate's internal computerized systems, or those of its third-party contractors or consultants, may fail
or suffer security breaches and be subject to malicious intent or cyber-attack, which could result in a
material disruption of its product development programs and in its operations in general.
The Company has implemented a security policy that is intended to secure its data against impermissible
access and to preserve the integrity and confidentiality of the data. Despite the implementation of such
security measures, including a cybersecurity program, Innate's internal computer systems and those of its
third-party contractors and consultants are vulnerable to damage from computer viruses, unauthorized
access, natural disasters, terrorism, war, telecommunication and electrical failures, and other sources.
Moreover, part of the Company's information system is “cloud”-based and thus is not fully under its
control.
In addition, Innate's research and development facility and headquarters in Luminy, France is located in
an area that may be more susceptible to wildfires. If Innate's facility or computer systems are damaged by
fire despite the fire prevention and data archiving measures it has put in place, it could suffer financial
losses and delays in its operations.
If such an event were to occur and cause interruptions in Innate's operations, it could result in a material
disruption of its programs and more generally of its operations. For example, the loss of clinical trial data
for Innate's product candidates could result in delays in its regulatory approval efforts and significantly
increase its costs to recover or reproduce the lost data. To the extent that any disruption or security breach
results in a loss of or damage to Innate's data or applications or other data or applications relating to its
technology or product candidates, or inappropriate disclosure of confidential or proprietary information, it
could incur liabilities, including penalties under data privacy laws such as the GDPR and other
regulations, and the further development of its product candidates could be delayed. Even if the Company
has not experienced any cyber breach to date, should any of these risks materialize, this could have a
material adverse effect on Innate's business, prospects, financial condition and results of operations.
The Company has subscribed an insurance related to "cyber" and fraud. This insurance may be
insufficient with regard to the level of financial, legal, operational and reputational impacts that could
arise from a disruption or a break of the Company information systems.
The Company may encounter difficulties in managing the Company development and support changes
in its strategy, which could disrupt its operations.
The opportunities taken, the decisions made, the successes and failures of Innate's research and
development programs and its operations in general can have significant impacts on its workforce and the
scope of its operations.
The strong growth in the Company's headcount over the last five years as well as the recent
transformations of the Company, in particular in connection with the acquisition in 2018 of Lumoxiti,
Innate's first commercial product, have been accompanied by structural changes within the organization
and its operating modes. Such rapid changes may lead to a deterioration in working conditions and the
leave of employees, which could lead to a loss of knowledge and expertise, a decrease in the performance
of Innate's operations and therefore a reduced level of achievement of its objectives.
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Moreover, in December 2020, the decision of returning Lumoxiti commercial rights to AstraZeneca was
followed by an immediate reduction of Innate's commercial operations and headcounts in the US.
Although the Company gained some experience in the late stage development and marketing and
commercialization of pharmaceutical products, such experience was short, and may not have resulted in a
sufficient gain of skills to anticipate and tackle the marketing and commercialization of Innate's other
drug candidates.
In addition, in order to support the development of the Company and changes in strategy, the Company
must continue to implement and improve its management, operational and financial systems, adapt its
facilities and recruit and train qualified personnel. Due to Innate's limited financial resources, it may not
be able to effectively manage the development of Innate's business, which could result in weaknesses in
its infrastructure, operational errors, loss of business opportunities, loss of employees and reduced
productivity of remaining employees. The Company may also experience difficulties in recruiting,
training and retaining additional qualified personnel, particularly in key positions. Added to this is the fact
that the Company is located in Marseille and is competing with other locations that potential recruits may
find more attractive.
If the Company were to acquire assets or companies, the success of such an acquisition would depend on
its capacity to carry out such acquisitions and to integrate such assets or companies into its existing
operations. The implementation of such a strategy could impose significant constraints, including:
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human resources: recruiting, integrating, training, managing, motivating and retaining a
growing number of employees;
financial and management system resources: identification and management of appropriate
financing and management of its financial reporting systems; and
infrastructure: expansion or transfer of its laboratories or the development of its information
technology system.
If the Company is unable to manage such changes or has difficulty integrating any acquisitions, it could
have a material adverse effect on its business, prospects, financial condition and results of operations.
The Company would need to hire new employees and expand its use of service providers.
As of December 31, 2022, the Company had 211 employees. As Innate's development plans and strategies
develop, Innate Pharma must need additional managerial, operational, marketing, financial and other
personnel.
The Company currently relies, and for the foreseeable future will continue to rely, in part on certain
independent organizations, partners, advisors and consultants to provide certain services. There can be no
assurance that the services of these independent organizations, partners, advisors and consultants will
continue to be available to Innate on a timely basis when needed, or that Innate can find qualified
replacements. In addition, if Innate Pharma is unable to effectively manage its outsourced activities or if
the quality or accuracy of the services provided by consultants is compromised for any reason, its clinical
trials may be extended, delayed, or terminated, and it may not be able to obtain regulatory approval of its
product candidates or otherwise advance its business. There can be no assurance that Innate will be able
to manage its existing consultants or find other competent outside contractors and consultants on
economically reasonable terms, if at all.
If the Company is not able to effectively expand its organization by hiring new employees and expanding
its groups of consultants and contractors, it may not be able to successfully implement the tasks necessary
to further develop and commercialize its product candidates and, accordingly, may not achieve its
research, development and commercialization goals.
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The Company depends on qualified management personnel and its business could be harmed if Innate
loses key personnel and cannot attract new personnel.
Innate's ability to retain key persons in its organization and to recruit qualified personnel is crucial for its
success. In particular, its success depends heavily on its ability to retain key people in its organization,
including key scientific and medical personnel.
Should the Company be unable to retain the individuals who form its team of key managers and key
scientific advisors, it could have a material adverse effect on its business and development and could
consequently affect its business, prospects, financial condition and results of operations.
Innate Pharma will need to recruit qualified scientific and medical personnel to carry out its clinical trials
and expand into new areas that require specialized skills, such as regulatory matters, marketing and
manufacturing. Innate compete with other companies, research organizations and academic institutions in
recruiting and retaining highly qualified scientific, technical and management personnel. Competition for
such personnel is very intense in the biopharmaceutical field and there can be no assurance that the
Company will be successful in attracting or retaining such personnel and the failure to do so could harm
its operations and its growth prospects. Should any of these risks materialize, this could have a material
adverse effect on Innate's business, prospects, financial condition and results of operations.
Innate's Research and Development facility and Headquarters in Luminy, France are exposed to forest
fires
The Company's Research and Development facility and Headquarters in Luminy, France are exposed to
forest fires. Luminy is an area on the outskirts of Marseille, composed in part of undeveloped hills
covered with shrubs and pine trees. It is also located next to a natural park entirely covered by the same
type of Mediterranean vegetation. Summers are hot and dry and this type of vegetation is prone to forest
fires. Indeed, in September 2016, such a forest fire came relatively close to inhabited areas, including the
Company's facilities, where employees had to remain confined for several hours.
In order to prevent the risk of fire, fire prevention measures are implemented, such as pruning shrubs in
the surrounding green areas and implementing a maintenance plan for fire-fighting equipment. In
addition, computer data backup and archiving measures are implemented, allowing the regularly backed-
up data to be stored on the premises of a specialized service provider. In addition, rare biological material
used by the Company has been identified, duplicated and stored at other sites, at the premises of
specialized service providers.
However, these measures do not guarantee that another forest fire would not damage the Company's
premises in Luminy, which would result in financial losses, development delays of various durations or
even the suspension of the Company's activities.
The Company may use hazardous chemicals and biological materials in its business and any claims
relating to improper handling, storage or disposal of these materials could be time-consuming and
costly.
Innate's research and development processes involve the controlled use of hazardous materials, including
chemicals, biological and radioactive materials. The Company cannot eliminate the risk of accidental
contamination or discharge and any resultant injury from these materials. Innate also handles genetically
recombined material, genetically modified species and pathological biological samples. Consequently, in
France and in the jurisdictions where the Company conducts clinical trials, it is subject to environment
and safety laws and regulations governing the use, storage, handling, discharge and disposal of hazardous
materials, including chemical and biological products and radioactive materials. The Company impose
preventive and protective measures for the protection of its workforce and waste control management in
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accordance with applicable laws, including part four of the French Labor Code, relating to occupational
health and safety.
In France, the Company is required to comply with a number of national, regional and local legislative or
regulatory provisions regarding radiation and hazardous materials, including specific regulations
regarding the use, handling and storage of radioactive materials and the potential exposure of employees
to hazardous materials and radiation. Innate must also comply with French regulations concerning the use
and handling of genetically modified organisms, or GMOs, in confined spaces.
If Innate fails to comply with applicable regulations, it could be subject to fines and may have to suspend
all or part of its operations. Compliance with environmental, health and safety regulations involves
additional costs, and Innate Pharma may have to incur significant costs to comply with future laws and
regulations in relevant jurisdictions. Compliance with environmental laws and regulations could require
Innate to purchase equipment, modify facilities and undertake considerable expenses. The Company
could be liable for any inadvertent contamination, injury or damage, which could negatively affect its
business, although the Company has subscribed to an insurance policy covering certain risks inherent to
its business.
Product liability and other lawsuits could divert Innate's resources, result in substantial liabilities,
reduce the commercial potential of its product candidates and damage its reputation.
Given that the Company develops therapeutic products intended to be tested on humans and used to treat
humans, the risk that Innate Pharma may be sued on product liability claims is inherent in its business.
Side effects of, or manufacturing defects in, products that the Company develops could result in the
deterioration of a patient’s condition, injury or even death. For example, its liability could be sought after
by patients participating in the clinical trials in the context of the development of the therapeutic products
tested and unexpected side effects resulting from the administration of these products. Once a product is
approved for sale and commercialized, the likelihood of product liability lawsuits increases. Criminal or
civil proceedings might be filed against Innate by patients, regulatory authorities, biopharmaceutical
companies and any other third-party using or marketing Innate's products. These actions could include
claims resulting from acts by Innate's partners, licensees and subcontractors, over which the Company has
little or no control. These lawsuits may divert Innate's management from pursuing its business strategy
and may be costly to defend. In addition, if the Company is held liable in any of these lawsuits, it may
incur substantial liabilities, may be forced to limit or forgo further commercialization of the affected
products and may suffer damage to its reputation.
Although the clinical trial process is designed to identify and assess potential side effects, it is always
possible that a drug, even after regulatory approval, may exhibit unforeseen side effects. If any of Innate's
product candidates were to cause adverse side effects during clinical trials or after approval of the product
candidate, the Company may be exposed to substantial liabilities. Physicians and patients may not comply
with any warnings that identify known potential adverse effects and patients who should not use Innate's
product candidates.
The Company has obtained liability insurance coverage for each of its clinical trials in compliance with
local legislation and rules. In the United States, Innate's aggregate insurance coverage for its ongoing
clinical trials is limited to €10.0 million per year and in the aggregate. Innate's insurance coverage may
not be sufficient to cover any expenses or losses the Company may suffer. Moreover, insurance coverage
is becoming increasingly expensive, and, in the future, Innate Pharma may not be able to maintain
insurance coverage at a reasonable cost or in sufficient amounts to protect itself against losses due to
liability. On occasion, large judgments have been awarded in class action lawsuits based on drugs that had
unanticipated side effects. The cost of any product liability litigation or other proceedings, even if
resolved in Innate's favor, could be substantial. A successful product liability claim, or series of claims,
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brought against Innate could cause Innate's share price to decline and, if judgments exceed its insurance
coverage, could decrease its cash and adversely affect its business.
To date, the Company is covered by a product liability insurance with a coverage amount of €10 million
per year and in the aggregate. If Innate is the subject of a successful product liability claim that exceeds
the limits of any insurance coverage Innate Pharma obtains, the Company would incur substantial charges
that would adversely affect its earnings and require the commitment of capital resources that might
otherwise be available for the development and commercial launch of its product programs. Should any of
these risks materialize, this could have a material adverse effect on Innate's business, prospects, financial
condition and results of operations.
Innate Pharma's employees may engage in misconduct or other improper activities, including violating
applicable regulatory standards and requirements, engaging in insider trading or violate the terms of
their confidentiality agreements, which could significantly harm Innate's business.
The Company are exposed to the risk of employee fraud or other misconduct. Misconduct by employees
could include intentional failures to comply with legal requirements or the requirements of national
authorities, the EMA, FDA and other government regulators, provide accurate information to applicable
government authorities, comply with fraud and abuse and other healthcare laws and regulations in the
United States, Europe and elsewhere, report financial information or data accurately or disclose
unauthorized activities to us. In particular, sales, marketing and business arrangements in the healthcare
industry are subject to extensive laws and regulations intended to prevent fraud, misconduct, kickbacks,
self-dealing and other abusive practices. These laws and regulations restrict or prohibit a wide range of
pricing, discounting, marketing and promotion, sales commission, customer incentive programs and other
business arrangements. Employee misconduct could also involve the improper use of, including trading
on, information obtained in the course of clinical trials, which could result in regulatory sanctions and
serious harm to Innate's reputation. Innate Pharma has a Code of Ethics that applies to all employees and
consultants, and other policies and charters, but it is not always possible to identify and deter employee
misconduct, and the precautions it takes to detect and prevent this activity may be ineffective in
controlling unknown or unmanaged risks or losses or in protecting Innate from governmental
investigations or other actions or lawsuits stemming from a failure to comply with these laws or
regulations.
In order to protect its proprietary technology and processes, the Company relies in part on confidentiality
agreements with its partners, employees, consultants, outside scientific collaborators and sponsored
researchers, and other advisors. These agreements may not effectively prevent disclosure of confidential
information and may not provide an adequate remedy in the event of unauthorized disclosure of
confidential information. Costly and time-consuming litigation could be necessary to enforce and
determine the scope of Innate's proprietary rights, and failure to obtain or maintain trade secret protection
could adversely affect its competitive business position. Should any of these risks materialize, this could
have a material adverse effect on Innate's business, prospects, financial condition and results of
operations.
The Company may acquire businesses or products in the future and Innate may not realize the benefits
of such acquisitions.
Although Innate's current strategy involves continuing to grow its business internally, the Company may
grow externally through selective acquisitions of complementary products and technologies, or of
companies with such assets. If such acquisitions were to become necessary or attractive in the future, the
Company may not be able to identify appropriate targets or make acquisitions under satisfactory
conditions, in particular, satisfactory price conditions. In addition, Innate Pharma may be unable to obtain
the financing for these acquisitions under favorable conditions, and could be led to finance these
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acquisitions using cash that could be allocated to other purposes in the context of existing operations.
Innate may encounter numerous difficulties in developing, manufacturing and marketing any new
products resulting from an acquisition that delay or prevent Innate from realizing their expected benefits
or enhancing its business. The Company cannot assure you that, following any such acquisition, the
Company will achieve the expected synergies to justify the transaction, which could have a material
adverse effect on Innate's business, financial conditions, earnings and prospects.
Climate change or legal, regulatory or market measures to address climate change may negatively
affect Innate's business and results of operations.
Climate change presents risks to Innate's operations, including the potential for additional regulatory
requirements and associated costs, and the potential for more frequent and severe weather events and
water availability challenges that may impact Innate's facilities and those of Innate's suppliers. Natural
disasters and extreme weather conditions, such as a hurricane, tornado, earthquake, wildfire or flooding,
may pose physical risks to Innate's facilities and disrupt the operation of Innate's supply chain.
Concern over climate change may also result in new or additional legal or regulatory requirements
designed to reduce greenhouse gas emissions and/or mitigate the effects of climate change on the
environment. If such laws or regulations are more stringent than current legal or regulatory obligations,
the Company may experience disruption in, or an increase in the costs associated with sourcing,
manufacturing and distribution of Innate's products, which may adversely affect Innate's business, results
of operations or financial condition.
The current state of the world financial market and current economic conditions could have a material
adverse impact on the Company's business, financial condition and results of operations.
The global economy is facing a number of actual and potential challenges, including the ongoing
COVID-19 pandemic, the military conflict between Ukraine and Russia and the banking crises or failures,
such as the recent Silicon Valley Bank failure. If the conditions in the global economy remain uncertain
or continue to be volatile, or if they deteriorate, including as a result of the ongoing COVID-19 pandemic,
the military conflict between Russia and Ukraine, banking crises or other geopolitical events, the
Company's business, financial condition and results of operation may be materially adversely affected.
In addition, increases in inflation raise the Company's costs for labor, materials and services and other
costs required to grow and operate our business, and failure to secure these on reasonable terms may
adversely impact its financial condition. Increases in inflation, along with the uncertainties surrounding
the ongoing COVID-19 pandemic, geopolitical developments, banking crises and global supply chain
disruptions, have caused, and may in the future cause instability and lack of liquidity in capital markets,
potentially making it more difficult for Innate to obtain additional funds. Such risks and disruptions may
also negatively impact Innate's supply chain, manufacturing arrangements, preclinical studies and clinical
trials, which could have a materially adverse impact on its results of operations, financial condition and
prospects. The extent and duration of the current economic conditions and resulting market disruptions
are impossible to predict, but could be substantial. Any such disruptions may also magnify the impact of
other risks described in this Annual Report on Form 20-F.
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Risks Related to Intellectual Property Rights
Its ability to compete may be adversely affected if the Company does not adequately obtain, maintain,
protect and enforce Innate's intellectual property or proprietary rights, or if the scope of intellectual
property protection the Company obtains is not sufficiently broad.
Innate's success depends, in large part, on its ability to obtain and maintain patent and other intellectual
property protection in the United States and other countries with respect to Innate's product candidates.
However, the Company may not be able to obtain, maintain or enforce Innate's patents and other
intellectual property rights which could affect its ability to compete effectively. For example, the
Company cannot guarantee:
•
•
•
•
•
•
that the Company will file all necessary or desirable patent applications or that the Company
will obtain the patents that the Company has applied for and that are under review;
that the Company will be able to develop new patentable product candidates or technologies or
obtain patents to protect such new product candidates or technologies;
that the Company or its licensing or collaboration partners were the first to make the product
candidates or technologies covered by the issued patents or pending patent applications that
the Company licenses or own;
that the Company will be able to obtain sufficient rights to all necessary or desirable patents or
other intellectual property rights, whether at all or on reasonable terms;
that the scope of any issued patents that the Company owns or licenses will be broad enough
to protect its product candidates or effectively prevent others from commercializing
competitive technologies and product candidates; and
that there is no risk of its owned and licensed patents being challenged, invalidated or
circumvented by a third-party.
The patent prosecution process is expensive, time-consuming, and complex, and Innate may not be able to
file, prosecute, maintain, enforce, or license all necessary or desirable patent applications at a reasonable
cost or in a timely manner. For example, the Company does not intend to systematically file, maintain,
prosecute and defend patents on its product candidates in all countries. Consequently, Innate may not be
able to prevent third parties from exploiting products that are the same as or similar to its products and
product candidates in countries in which it does not obtain patent protection, or from selling or importing
such products in and into the countries in which it does have patent protection. It is also possible that the
Company will fail to identify patentable aspects of its research and development output in time to obtain
patent protection. Although the Company enters into confidentiality agreements with parties who have
access to confidential or patentable aspects of its research and development output, such as its employees,
consultants, CROs, outside scientific collaborators, sponsored researchers, and other advisors, any of
these parties may breach the agreements and disclose such output before a patent application is filed,
thereby jeopardizing its ability to seek patent protection. Given the amount of time required for the
development, testing and regulatory review of new product candidates, patents protecting such candidates
might expire before or shortly after such candidates are commercialized. As a result, Innate's intellectual
property may not provide Innate with sufficient rights to exclude others from commercializing product
candidates similar or identical to its. In addition, in some circumstances, the Company may not have the
right to control the preparation, filing, prosecution, maintenance, enforcement and defense of patents and
patent applications covering technology that the Company licenses to or from third parties. For example,
pursuant to its license agreement with AstraZeneca for monalizumab, AstraZeneca retains control of such
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activities for certain patents that the Company licenses to it under the agreement and patents that arise
under the collaboration. Innate cannot be certain that these patents and patent applications will be
prepared, filed, prosecuted, maintained, enforced, and defended in a manner consistent with the best
interest of its business. If any third-party that controls Innate's patents and patent applications fails to
maintain Innate's patents or such third-party loses rights to Innate's patents or patent applications, Innate's
rights to those patents and underlying technology may be reduced or eliminated and the Company's right
to develop and commercialize its product candidates that are subject to such rights could be adversely
affected.
Moreover, some of Innate's patents and patent applications are, and may in the future be, co-owned with
third parties. If the Company is unable to obtain an exclusive license to any such third-party co-owners’
interest in such patents or patent applications, such co-owners may be able to license their rights to other
third parties, including its competitors, and its competitors could market competing products and
technology. Innate may also need the cooperation of any such co-owners of its patents in order to enforce
such patents against third parties, and such cooperation may not be provided to us.
The coverage claimed in a patent application can be significantly reduced before the patent is issued, and
its scope can be reinterpreted after issuance. The issuance of a patent is not conclusive as to its
inventorship, scope, validity or enforceability. Even if patent applications the Company licenses or owns
currently or in the future issue as patents, they may not issue in a form that will provide Innate with any
meaningful protection, prevent competitors or other third parties from circumventing its patents by
developing similar or alternative technologies or products in a non-infringing manner, or otherwise
provide Innate with any competitive advantage. Challenges from competitors or other third parties could
reduce the scope of Innate's patents or render them invalid or unenforceable, which could limit its ability
to stop others from using or commercializing similar or identical technology and product candidates, or
limit the duration of the patent protection for Lumoxiti and Innate Pharma's product candidates. The legal
proceedings that the Company may then have to enter into in order to enforce and defend its intellectual
property could be very costly and could distract its management and other personnel from their normal
responsibilities, notably in the case of lawsuits in the United States. The probability of disputes arising
over Innate's intellectual property will increase progressively as patents are granted and as the value and
appeal of the inventions protected by these patents are confirmed. The occurrence of any of these events
concerning any of Innate's patents or intellectual property rights could have a material adverse effect its
business, prospects, financial condition and results of operations. These risks are even higher for the
Company, because of its limited financial and human resources.
The patent position of biotechnology and pharmaceutical companies generally is highly uncertain,
involves complex legal and factual questions, and has been the subject of much litigation in recent years.
As a result, the issuance, scope, validity, enforceability, and commercial value of Innate's patent rights are
highly uncertain. The Company's pending and future patent applications may not result in patents being
issued which protect its technology or product candidates or which effectively prevent others from
commercializing competitive technologies and product candidates. Furthermore, its owned and in-
licensed patents may be subject to a reservation of rights by one or more third parties. For example, the
research resulting in certain of its owned and licensed patent rights and technology was funded in part by
the U.S. government. As a result, the government may have certain rights, or march-in rights, to such
patent rights and technology. When new technologies are developed with government funding, the
government generally obtains certain rights in any resulting patents, including a non-exclusive license
authorizing the government to use the invention for non-commercial purposes. These rights may permit
the government to disclose Innate's confidential information to third parties and to exercise march-in
rights to use or allow third parties to use its licensed technology. The government can exercise its march-
in rights if it determines that action is necessary because the Company fails to achieve practical
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application of the government-funded technology, because action is necessary to alleviate health or safety
needs, to meet requirements of federal regulations, or to give preference to U.S. industry. In addition,
Innate's rights in such inventions may be subject to certain requirements to manufacture products
embodying such inventions in the United States. Any exercise by the government of such rights could
harm Innate Pharma's competitive position, business, financial condition, results of operations, and
prospects.
Third parties may allege that the Company or its partners infringe, misappropriate or otherwise violate
such third parties’ intellectual property rights, which could prevent or delay its development efforts,
stop Innate from commercializing its product candidates, or increase the costs of commercializing its
product candidates.
The Company's commercial success depends on its ability and the ability of its partners to develop,
manufacture, market and sell its product candidates, and use its proprietary technologies, without
infringing, misappropriating or otherwise violating any intellectual property or proprietary rights of third
parties. The field of biopharmaceuticals involves significant patent and other intellectual property
litigation, which can be highly uncertain and involve complex legal and factual questions. The
interpretation and breadth of claims allowed in some patents covering biopharmaceutical compositions
also may be uncertain and difficult to determine.
Innate may not be aware of all third-party intellectual property rights potentially relating to its product
candidates. In general, in the United States patent applications are not published until 18 months after
filing or, in some cases, not at all. Therefore, the Company cannot be sure that it was the first to make the
inventions claimed in any owned or licensed patents or pending patent applications, or that its was the
first to file for patent protection for such inventions. If the Company was not the first to invent such
inventions or first to file any patent or patent application for such inventions, it may be unable to make
use of such inventions in connection with its products. Innate may need to obtain licenses from third
parties (which may not be available under commercially reasonable terms, or at all), delay the launch of
product candidates, or cease the production and sale of certain product candidates or develop alternative
technologies that are the subject of such patents or patent applications, any of which could have a material
adverse effect on its business, prospects, financial condition and results of operations. For example, third
parties may claim that lacutamab and other product candidates may use technology protected by their
patents. Although the Company believes that its current activities and its planned development of
lacutamab does not and will not infringe on such patents, which expire in the near term, third parties may
disagree.
Third parties may allege that Innate or its partners infringe, misappropriate or otherwise violate any such
third-party’s patents or other intellectual property rights and assert infringement claims against us,
regardless of their merit. A court of competent jurisdiction could hold that these third-party patents are
valid, enforceable and infringed, which could materially and adversely affect Innate's ability to
commercialize any product candidates it may develop and any other product candidates or technologies
covered by the asserted third-party patents. In order to successfully challenge the validity of any such
U.S. patent in federal court, Innate would need to overcome a presumption of validity. As this burden is a
high one requiring Innate to present clear and convincing evidence as to the invalidity of any such U.S.
patent claim, there is no assurance that a court of competent jurisdiction would invalidate the claims of
any such U.S. patent. If the Company is found to infringe a third-party’s intellectual property rights, and
the Company is unsuccessful in demonstrating that such rights are invalid or unenforceable, the Company
could be required to:
•
bear the potentially significant costs of proceedings brought against us;
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•
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•
pay damages, which may include treble damages and attorney’s fees if the Company is found
to have willfully infringed a third-party’s patent rights;
cease developing, manufacturing and commercializing the infringing technology or product
candidates; and
acquire a license to such third-party intellectual property rights, which may not be available on
commercially reasonable terms, or at all, and may be non-exclusive thereby giving the
Company's competitors and other third parties access to the same technologies licensed to us.
Even if resolved in Innate's favor, litigation or other intellectual property proceedings may cause Innate to
incur significant expenses and could distract its management and other personnel from their normal
responsibilities. In addition, there could be public announcements of the results of hearings, motions or
other interim proceedings or developments and if securities analysts or investors perceive these results to
be negative, it could have a material adverse effect on the price of Innate's ordinary shares or ADSs. The
Company may not have sufficient financial or other resources to adequately conduct such litigation or
proceedings. Some of Innate's competitors may be able to sustain the costs of such litigation or
proceedings more effectively than Innate can because of their greater financial resources and more mature
and developed intellectual property portfolios. Should one or more of the foregoing risks materialize, this
could have a material adverse effect on Innate's reputation, business, prospects, financial condition and
results of operations.
Its patents could be found invalid or unenforceable if challenged and the Company may not be able to
protect its intellectual property.
Innate's and its licensors’ patents and patent applications, if issued, may be challenged, invalidated or
circumvented by third parties. U.S. patents and patent applications may also be subject to interference
proceedings, re-examination proceedings, derivation proceedings, post-grant review or inter partes review
in the United States Patent and Trademark Office, or USPTO, challenging Innate's or its licensors’ patent
rights. Foreign patents may be subject also to opposition or comparable proceedings in the corresponding
foreign patent office. For example, two of its European patents with claims directed to a class of anti-
NKG2A antibodies defined by characteristics shared with monalizumab have been challenged in
oppositions at the European Patent Office, or the EPO. The Board of Appeals of the EPO issued a
decision confirming the maintenance of one of these patents, directed to such class of anti-NKG2A
antibodies, is valid and revoked the other of these patents. The Company has also been notified of a third
party opposition which challenges one of its European patents with claims directed to use of anti-NKG2A
antibodies for treating cancer in an individual having progressive disease following treatment with an
antibody that neutralizes the inhibitory activity of PD-1 and another third party opposition which
challenges one of Innate's patents directed to a class of NK cell activity-enhancing antibodies that bind
both Siglec-7 and Siglec-9. Both of the aforementioned oppositions are currently pending. The Company
has also been notified of third party oppositions which challenge two of its in-licensed European patents
directed to CD39 technology. These oppositions are currently pending, and the EPO has revoked one of
these patents directed to CD39 technology, which revocation might be appealed by Innate or its
licensor(s).
In addition, the Company may allege that third parties infringe Innate's or its licensors’ patents and the
defendant could counterclaim that such patents are invalid or unenforceable. In patent litigation in the
United States, defendant counterclaims alleging invalidity or unenforceability are commonplace. Grounds
for a validity challenge could be an alleged failure to meet any of several statutory requirements,
including lack of novelty, obviousness, or non-enablement. Grounds for an unenforceability assertion
could be an allegation that someone connected with prosecution of the patent withheld relevant
information from the USPTO, or made a misleading statement, during prosecution. The outcome
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following legal assertions of invalidity and unenforceability is unpredictable. With respect to the validity
question, for example, Innate Pharma cannot be certain that there is no invalidating prior art, of which the
Company or its licensing partners and the patent examiner were unaware during prosecution.
Any such patent litigation or proceeding could result in the loss of Innate or its licensors’ patents, denial
of Innate's or its licensors’ patent applications or loss or reduction in the scope of one or more of the
claims of such patents or patent applications. Accordingly, Innate's or its licensors’ rights under any
issued patents may not provide Innate with sufficient protection against competitive product candidates or
processes, Innate could become unable to manufacture or commercialize its product candidates without
infringing third-party patent rights, and the duration of the patent protection of its product candidates
could be limited. Furthermore, because of the substantial amount of discovery required in connection with
intellectual property litigation, there is a risk that some of Innate's confidential information could be
compromised by disclosure during this type of litigation. Even if the Company is successful, such
litigation or proceedings may be costly and may distract its management and other personnel from their
normal responsibilities. Any of the foregoing could have a material adverse effect on Innate's business,
prospects, financial condition and results of operations.
Obtaining and maintaining the Company's patent protection depends on compliance with various
procedural, document submission, fee payment and other requirements imposed by government patent
agencies, and its patent protection could be reduced or eliminated for non-compliance with these
requirements.
Periodic maintenance fees, renewal fees, annuity fees and various other government fees on patents and/
or applications will be due to be paid to the USPTO, and various government patent agencies outside of
the United States over the lifetime of Innate's owned and licensed patents and/or patent applications and
any patent rights the Company may own in the future. In certain circumstances, Innate Pharma may rely
on its licensing partners to pay these fees. The USPTO and various foreign patent agencies require
compliance with several procedural, documentary, fee payment and other similar provisions during the
patent application process. In many cases, an inadvertent lapse can be cured by payment of a late fee or
by other means in accordance with the applicable rules. There are situations, however, in which non-
compliance can result in abandonment or lapse of the patent or patent application, resulting in partial or
complete loss of patent rights in the relevant jurisdiction. In such an event, potential competitors might be
able to enter the market with similar or identical products or technology, which could have a material
adverse effect on Innate's business, prospects, financial condition and results of operations.
Developments in patent law could have a negative impact on the Company' business.
Changes in either the patent laws or interpretation of the patent laws could increase the uncertainties and
costs surrounding the prosecution of patent applications and the enforcement or defense of issued patents.
For example, from time to time, the U.S. Congress, the USPTO or similar foreign authorities may change
the standards of patentability and any such changes could have a negative impact on Innate's business.
One example is the Leahy-Smith America Invents Act, or the America Invents Act, which was signed into
law in September 2011, and includes a number of significant changes to U.S. patent law. These changes
included a transition from a “first-to-invent” system to a “first-to-file” system, changes to the way issued
patents are challenged and changes to the way patent applications are disputed during the examination
process such as allowing third-party submission of prior art to the USPTO during patent prosecution.
Changes in patent laws may also modify the jurisdictions relevant to patents. For example, in Europe, the
unitary patent (UP), or "European patent with unitary effect", established under Regulation 1257/2012 of
17 December 2012, will provide a single supra-national patent right covering up to 25 EU Member States
as from June 1st 2023 with transitional period as from January 1st 2023.
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Trademarks
In addition, changes to or different interpretations of patent laws in the United States and other countries
may permit others to use Innate's or its partners’ discoveries or to develop and commercialize Innate's
technology and product candidates without providing any compensation to Innate, or may limit the
number of patents or claims it can obtain. The patent positions of companies in the biotechnology and
pharmaceutical market are particularly uncertain. Recent U.S. Supreme Court rulings have narrowed the
scope of U.S. patent protection available in certain circumstances and weakened the rights of patent
owners in certain situations. This combination of events has created uncertainty with respect to the
validity and enforceability of patents, once obtained. Depending on future actions by the U.S. Congress,
the federal courts, and the USPTO, as well as similar bodies in other countries, the laws and regulations
governing patents could change in unpredictable ways that could have a material adverse effect on
Innate's existing patent portfolio and its ability to protect and enforce its intellectual property in the future,
which could have a material adverse effect on its business, prospects, financial condition and results of
operations.
If the Company does not obtain protection under the Hatch-Waxman Amendments and similar non-
U.S. legislation for extending the term of patents covering each of its product candidates, its business
may be materially harmed.
Depending upon the timing, duration and conditions of FDA marketing authorization of Lumoxiti and
Innate's product candidates, one or more of its U.S. patents may be eligible for limited patent term
extension under the Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch-
Waxman Amendments, and similar legislation in the European Union. The Hatch-Waxman Amendments
permit a patent term extension of up to five years for a patent covering an approved product as
compensation for effective patent term lost during product development and the FDA regulatory review
process. A patent term extension cannot extend the remaining term of a patent beyond a total of 14 years
from the date of product approval, only one patent may be extended and only those claims covering the
approved product, a method for using it or a method for manufacturing it may be extended. However, the
Company may not receive an extension if the Company fails to apply within applicable deadlines, fails to
apply prior to expiration of relevant patents, fails to exercise due diligence during the testing Phase or
regulatory review process or otherwise fails to satisfy applicable requirements. Moreover, the length of
the extension could be less than what the Company requests. If the Company is unable to obtain patent
term extension or the term of any such extension is less than its requests, the period during which the
Company can enforce its patent rights for that product will be shortened and its competitors may obtain
approval to market competing products sooner. As a result, Innate's revenue from Lumoxiti or an
applicable product could be reduced, possibly materially, which could have a material adverse effect on
its business, prospects, financial condition and results of operations.
The Company will not seek to protect its intellectual property rights in all jurisdictions throughout the
world and Innate may not be able to adequately enforce its intellectual property rights in all
jurisdictions where Innate Pharma seeks intellectual property protection.
Filing, maintaining, prosecuting and defending patents on Innate's product candidates in all countries and
jurisdictions throughout the world would be prohibitively expensive, and its intellectual property rights in
some countries outside the United States could be less extensive than those in the United States.
Consequently, the Company may not be able to prevent third parties from using its product candidates or
technologies in all countries outside the United States, or from selling or importing products made using
its product candidates or technologies in and into the United States or other jurisdictions. Competitors
may use Innate's technologies in jurisdictions where Innate Pharma does not pursue and obtain patent
protection to develop their own products and further, may export otherwise infringing products to
territories where the Company has patent protection, and enforcement is not as strong as that in the United
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States. These products may compete with Innate's products, and its patents or other intellectual property
rights may not be effective or sufficient to prevent them from competing. Even if the Company pursues
and obtains issued patents in particular jurisdictions, its patent claims or other intellectual property rights
may not be effective or sufficient to prevent third parties from so competing.
In addition, the laws of some foreign countries do not protect intellectual property rights to the same
extent as the federal and state laws in the United States. Many companies have encountered significant
problems in protecting and defending intellectual property rights in certain foreign jurisdictions. The legal
systems of some countries, particularly developing countries, do not favor the enforcement of patents and
other intellectual property protection, especially those relating to biopharmaceuticals or biotechnologies.
This could make it difficult for Innate Pharma to stop the infringement of its patents, if obtained, or the
misappropriation or other violation of its other intellectual property rights. For example, many foreign
countries have compulsory licensing laws under which a patent owner must grant licenses to third parties.
In addition, many countries limit the enforceability of patents against third parties, including government
agencies or government contractors. In these countries, patents may provide limited or no benefit. Patent
protection must ultimately be sought on a country-by-country basis, which is an expensive and time-
consuming process with uncertain outcomes. Accordingly, the Company may choose not to seek patent
protection in certain countries, and the Company will not have the benefit of patent protection in such
countries.
Proceedings to enforce Innate's patent rights in foreign jurisdictions could result in substantial costs and
divert its efforts and attention from other aspects of its business, could put its patents at risk of being
invalidated or interpreted narrowly, could put its patent applications at risk of not issuing and could
provoke third parties to assert claims against us. The Company may not prevail in any lawsuits that the
Company initiates and the damages or other remedies awarded, if any, may not be commercially
meaningful. In addition, changes in the law and legal decisions by courts in the United States and other
countries may affect Innate's ability to obtain adequate protection for its technology and the enforcement
of its intellectual property. Accordingly, Innate's efforts to enforce its intellectual property rights around
the world may be inadequate to obtain a significant commercial advantage from the intellectual property
that the Company develops or licenses. Should any of these risks materialize, this could have a material
adverse effect on Innate's business, prospects, financial condition and results of operations.
Third parties may assert ownership or commercial rights to products, product candidates or
technologies that Innate develops.
Third parties have made, and may in the future make, claims challenging the inventorship or ownership of
Innate's intellectual property, which may result in the imposition of additional obligations on us, such as
development, royalty and milestone payments. Innate has written agreements with partners or other third
parties that provide for the ownership of intellectual property arising from its collaborations and its other
work with such third parties. These agreements provide that the Company must negotiate certain
commercial rights with partners and other third parties with respect to joint inventions or inventions made
by its partners or such third parties that arise from the results of the collaboration or other work with such
third parties. In some instances, there may not be adequate written provisions to address clearly the
resolution of intellectual property rights that may arise under Innate's agreements. For example, following
an arbitration proceeding to assess claims by Orega Biotech SAS, or Orega Biotech, of joint ownership of
certain patents relating to IPH5201, the Company will share joint ownership of such patents with Orega
Biotech and have an exclusive license to such patents. If the Company cannot successfully negotiate
sufficient ownership and commercial rights to the inventions that result from its use of a third-party’s
materials where required, or if disputes otherwise arise with respect to the intellectual property developed
with the use of a third-party’s samples, the Company may be limited in its ability to capitalize on the
market potential of these inventions. In addition, the Company may face claims by third parties that its
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agreements with employees, contractors, or consultants obligating them to assign intellectual property to
itself are ineffective, or in conflict with prior or competing contractual obligations of assignment, which
could result in ownership disputes regarding intellectual property the Company has developed or will
develop and interfere with its ability to capture the commercial value of such inventions. The Company
also may be unsuccessful in executing assignment agreements with each party who, in fact, conceives or
develops intellectual property that the Company regards as its own, or such agreements might not be self-
executing or might be breached.
Litigation may be necessary to resolve an ownership dispute, and if the Company is not successful, Innate
may be precluded from using certain intellectual property, may lose its exclusive rights in such
intellectual property or may be required to acquire a license to such intellectual property, which may not
be available on commercially reasonable terms or at all. Any of the foregoing could have a material
adverse impact on Innate's business.
If the Company fails to comply with its obligations under license or technology agreements with third
parties, Innate Pharma could lose license rights that are critical to its business, and the Company may
not be successful in obtaining necessary intellectual property rights.
Innate licenses intellectual property from third parties that is critical to its business through license
agreements, including but not limited to licenses related to the manufacture, composition, use and sale of
its product candidates, and in the future Innate may enter into additional agreements that provide it with
licenses to valuable intellectual property or technology. For example, Innate depends on its license
agreement with Novo Nordisk A/S for the development and commercialization of monalizumab. Innate's
license agreements impose various obligations on us, which may include development, royalty and
milestone payments. If the Company fails to comply with any of these obligations, its licensors may have
the right to terminate the agreements. If its license agreements with AstraZeneca or Novo Nordisk A/S or
any other current or future licensors terminate, the Company would lose valuable rights and may be
required to cease its development, manufacture or commercialization of its product candidates, including
monalizumab. In addition, its business would suffer if its licensors fail to abide by the terms of the
agreements, if its licensors fail to prevent infringement by third parties, or if the licensed patents or other
rights are found to be invalid or unenforceable. Should any of these risks materialize, this could have a
material adverse effect on Innate's business, prospects, financial condition and results of operations.
In addition, disputes may arise regarding intellectual property subject to a license agreement, including:
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the scope of rights granted under the license agreement and other interpretation-related issues;
the extent to which its technology and processes infringe on intellectual property of the
counterparty that is not subject to the license agreement;
Innate's diligence obligations under the license agreement and what activities satisfy those
diligence obligations;
the inventorship or ownership of inventions and know-how resulting from the joint creation or
use of intellectual property by its counterparties and us; and
the priority of invention of patented technology.
The agreements under which the Company currently licenses intellectual property from third parties are
complex, and certain provisions in such agreements may be susceptible to multiple interpretations. The
resolution of any contract dispute that may arise could narrow what Innate believes to be the scope of its
rights to the relevant intellectual property, or modify in a manner adverse to Innate what the Company
believes to be Innate's or its counterpart’s financial or other obligations under the relevant agreement, any
of which could have material adverse effect on its business, financial condition, results of operations and
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prospects. If disputes over intellectual property that Innate Pharma has licensed prevent or impair its
ability to maintain its current license agreement on acceptable terms, the Company may be unable to
unsuccessfully develop and commercialize the affected product candidates.
Additionally, the growth of Innate's business may depend, in part, on its ability to acquire, in-license or
use proprietary rights held by third parties. the Company may be unable to acquire or in-license
intellectual property rights from third parties that Innate identifies as necessary for its product candidates
on reasonable terms or at all. The licensing or acquisition of third-party intellectual property rights is a
competitive area, and several more established companies may pursue strategies to license or acquire
third-party intellectual property rights that the Company may consider attractive. These established
companies may have a competitive advantage over Innate due to their size, capital resources, and greater
clinical development and commercialization capabilities. In addition, companies that perceive Innate to be
a competitor may be unwilling to assign or license rights to us. Innate also may be unable to license or
acquire third-party intellectual property rights on terms that would allow Innate to make an appropriate
return on its investment.
As part of its business, the Company collaborates with non-profit and academic institutions to accelerate
its preclinical research or development under agreements with these institutions. Typically, these
institutions provide Innate with an option to negotiate a license to any of the institution’s or its
employees’ rights in technology resulting from the collaboration. Regardless of such option, Innate may
be unable to negotiate a license within the specified timeframe or under terms that are acceptable to us. If
the Company is unable to do so, the institution may offer the intellectual property rights to other parties,
potentially blocking its ability to pursue its applicable development or commercialization program. If
Innate Pharma is unable to successfully obtain rights to required third-party intellectual property rights or
maintain the existing intellectual property rights Innate Pharma has, Innate may have to abandon the
development and commercialization of the relevant program and its business, financial conditions, results
of operations and prospects could be adversely affected.
Third parties may assert that Innate's employees, consultants or independent contractors have
wrongfully used or disclosed confidential information or misappropriated trade secrets of their current
or former employers.
The Company employs individuals who are currently, or were previously, employed at universities or
other biotechnology or pharmaceutical companies, including its competitors or potential competitors.
Although Innate tries to ensure that its employees, consultants and independent contractors do not use the
proprietary information or know-how of others in their work for Innate, and no such claims against it are
currently pending, Innate may be subject to claims that Innate or its employees, consultants or
independent contractors have used or disclosed intellectual property, including trade secrets or other
proprietary information, of any such individual’s current or former employer or other third parties.
Litigation may be necessary to defend against these claims. If Innate fails in defending any such claims,
in addition to paying monetary damages, Innate may lose valuable intellectual property rights or
personnel. Even if Innate is successful in defending against such claims, litigation could result in
substantial costs and be a distraction to its management and other employees. Should any of these risks
materialize, this could have a material adverse effect on Innate's business, prospects, financial condition
and results of operations.
If the Company is unable to protect the confidentiality of its trade secrets, its business and competitive
position could be materially harmed.
In addition to patent protection, because the Company operates in the highly technical field of
biopharmaceutical drug development, it relies in part on trade secret protection in order to protect its
proprietary technology and processes. However, trade secrets are difficult to protect. The Company seeks
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to protect its trade secrets, in part, by entering into confidentiality agreements with its employees,
consultants, CROs, outside scientific collaborators, sponsored researchers, and other advisors. These
agreements generally require that the other party keep confidential and not disclose to third parties all
confidential information developed by such party or made known to such party by Innate during the
course of such party’s relationship with us. However, Innate cannot guarantee that it has entered into such
agreements with each party that may have or have had access to its trade secrets and confidential
information and these agreements may be breached, and Innate may not have adequate remedies for any
breach.
In addition to contractual measures, the Company tries to protect the confidential nature of its proprietary
information using physical and technological security measures. Such measures may not, for example, in
the case of misappropriation of a trade secret by an employee or third-party with authorized access,
provide adequate protection for Innate's proprietary information. Innate's security measures may not
prevent an employee or consultant from misappropriating its trade secrets and providing them to a
competitor, and recourse it takes against such misconduct may not provide an adequate remedy to protect
its interests fully. Enforcing a claim that a party illegally disclosed or misappropriated a trade secret can
be difficult, expensive, and time-consuming, and the outcome is unpredictable. In addition, courts outside
the United States may be less willing to protect trade secrets. Moreover, trade secrets may be
independently developed by others in a manner that could prevent legal recourse by Innate. If any of
Innate's confidential or proprietary information, such as its trade secrets, were to be disclosed to or
misappropriated by a third-party, or if any such information was independently developed by a third-
party, its competitive position could be materially harmed.
Innate's trade and technical secrets include:
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certain unpatented technical expertise that the Company believes provides itself with an
advantage in conducting research and development work in its field;
certain scientific knowledge generated by the work the Company carries out;
certain information relating to the product candidates the Company is currently developing;
and
certain information relating to the agreements signed between the Company and third parties.
The unauthorized disclosure or misappropriation of certain of these secrets could allow third parties to
offer products or services to compete with its or generally have a material adverse effect on Innate's
business.
The structures put in place to protect Innate's trade and technical secrets do not constitute a guarantee that
one or more of its trade and technical secrets will not be disclosed or misappropriated. The agreements or
other arrangements to protect the Company's trade secrets may fail to provide the protection sought, or are
breached, or that its trade secrets are disclosed to, or developed independently by, its competitors. Should
any of these risks materialize, this could have a material adverse effect on Innate's business, prospects,
financial condition and results of operations.
Unauthorized use of Innate's trademarks may generate confusion and result in costs and delays to the
detriment of its marketing efforts.
Innate's trademarks are a key component of its identity and its products. Although the key components of
its trademarks have been registered, notably in France and the United States, other companies in the
pharmaceutical sector might use or attempt to use similar trademarks or components of the Company's
trademarks, and thereby create confusion in the minds of third parties. Innate Pharma's registered
trademarks may be challenged, infringed, circumvented or declared generic or determined to be infringing
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on other marks. In addition, there could be potential trademark infringement claims brought by owners of
other trademarks that incorporate variations of Innate's registered or unregistered trademarks.
In the event the Company develops trademarks for products that conflict with intellectual property rights
of third parties, Innate would then have to redesign or rename its products in order to avoid encroaching
on the intellectual property rights of third parties. This could prove to be impossible or costly in terms of
time and financial resources and could be detrimental to Innate's marketing efforts. Should any of these
risks materialize, this could have a material adverse effect on Innate's business, prospects, financial
condition and results of operations.
Intellectual property rights do not necessarily address all potential threats.
The degree of future protection afforded by the Company's intellectual property rights is uncertain
because intellectual property rights have limitations and may not adequately protect its business or permit
it to maintain its competitive advantage. For example:
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others may be able to make products that are the same as or similar to Lumoxiti and its product
candidates or utilize similar technology but that are not covered by the claims of the patents
that the Company licenses or may own in the future;
the Company, or its license partners or current or future collaborators, might not have been the
first to make the inventions covered by the issued patent or pending patent application that the
Company licenses or may own in the future;
the Company, or its license partners or current or future collaborators, might not have been the
first to file patent applications covering certain of its or their inventions;
others may independently develop similar or alternative technologies or duplicate any of the
Company's technologies without infringing its owned or licensed intellectual property rights;
it is possible that the Company's owned or licensed pending patent applications will not lead to
issued patents;
issued patents that the Company holds rights to may be held invalid or unenforceable,
including as a result of legal challenges by its competitors;
its competitors might conduct research and development activities in countries where the
Company does not have patent rights and then use the information learned from such activities
to develop competitive products for sale in its major commercial markets;
the Company may not develop additional proprietary technologies that are patentable;
the patents of others may harm the Company's business; and
the Company may choose not to file a patent in order to maintain certain trade secrets or
know-how, and a third-party may subsequently file a patent covering such intellectual
property.
Should any of these events occur, they could have a material adverse effect on Innate's business, financial
condition, results of operations, and prospects.
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Risks Related to Ownership of the Company's Ordinary Shares and the ADSs
The trading price of Innate's equity securities may be volatile, and purchasers of its ordinary shares or
ADSs could incur substantial losses.
It is likely that the price of the Company's ordinary shares and ADSs will be significantly affected by
events such as announcements regarding scientific and clinical results concerning product candidates
currently being developed by us, its collaboration partners or its main competitors, changes in market
conditions related to its sector of activity, announcements of new contracts, technological innovations and
collaborations by Innate or its main competitors, developments concerning intellectual property rights, as
well as the development, regulatory approval and commercialization of new products by Innate or its
main competitors and changes in its financial results.
Equity markets are subject to considerable price fluctuations, and often, these movements do not reflect
the operational and financial performance of the listed companies concerned. In particular, biotechnology
companies’ share prices have been highly volatile and may continue to be highly volatile in the future. As
the Company operates in a single industry, Innate is especially vulnerable to these factors to the extent
that they affect its industry. Fluctuations in the stock market as well as the macro-economic environment
could significantly affect the price of its ordinary shares. As a result of this volatility, investors may not
be able to sell their ordinary shares or ADSs at or above the price originally paid for the security. The
market price for Innate Pharma's ordinary shares and ADSs may be influenced by many factors,
including:
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actual or anticipated fluctuations in its financial condition and operating results;
actual or anticipated changes in its growth rate relative to its competitors;
competition from existing products or new products that may emerge;
announcements by Innate or its competitors of significant acquisitions, strategic partnerships,
joint ventures, collaborations or capital commitments;
adverse results of delays in Innate's or any of its competitors’ preclinical studies or clinical
trials;
adverse regulatory decisions, including failure to receive regulatory approval for any of its
product candidates;
the termination of a strategic alliance or the inability to establish additional strategic alliances;
failure to meet or exceed financial estimates and projections of the investment community or
that the Company provides to the public;
issuance of new or updated research or reports by securities analysts;
fluctuations in the valuation of companies perceived by investors to be comparable to us;
ordinary share and American Deposit Share (ADS) price and volume fluctuations attributable
to inconsistent trading volume levels of its ordinary shares and ADSs;
price and volume fluctuations in trading of its ordinary shares on Euronext Paris;
additions or departures of key management or scientific personnel;
disputes or other developments related to proprietary rights, including patents, litigation
matters and its ability to obtain patent and other intellectual property protection for its
technologies;
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changes to coverage policies or reimbursement levels by commercial third-party payors and
government payors and any announcements relating to coverage policies or reimbursement
levels;
announcement or expectation of additional debt or equity financing efforts;
sales of its ordinary shares or ADSs by Innate, its insiders or its other shareholders; and
general economic and market conditions.
These and other market and industry factors may cause the market price and demand for Innate's ordinary
shares and ADSs to fluctuate substantially, regardless of its actual operating performance, which may
limit or prevent investors from readily selling their ordinary shares or ADSs and may otherwise
negatively affect the liquidity of the trading market for the ordinary shares and ADSs.
If securities or industry analysts do not publish research or publish inaccurate or unfavorable research
about Innate's business, the price of the ordinary shares or ADSs and their trading volume could
decline.
The trading market for the ADSs and ordinary shares depends in part on the research and reports that
securities or industry analysts publish about Innate or its business. As a public company in France since
2006, the Company's equity securities are currently subject to coverage by a number of analysts. If fewer
securities or industry analysts cover its company, the trading price for the ADSs and ordinary shares
would be negatively impacted. If one or more of the analysts who covers Innate downgrades Innate's
equity securities or publishes incorrect or unfavorable research about Innate's business, the price of the
ordinary shares and ADSs would likely decline. If one or more of these analysts ceases coverage of the
Company or fails to publish reports on Innate regularly, or downgrades Innate's securities, demand for the
ordinary shares and ADSs could decrease, which could cause the price of the ordinary shares and ADSs
or their trading volume to decline.
The Company does not currently intend to pay dividends on its securities and, consequently, your
ability to achieve a return on your investment will depend on appreciation in the price of the ordinary
shares and ADSs. In addition, French law (including any temporary measures taken in response to
COVID-19 pandemic) may limit the amount of dividends the Company is able to distribute.
Innate has never declared or paid any cash dividends on its ordinary shares and do not currently intend to
do so for the foreseeable future. The Company currently intends to invest its future earnings, if any, to
fund its growth. Therefore, the holders of Innate's ordinary shares and ADSs are not likely to receive any
dividends for the foreseeable future and the success of an investment in its ordinary shares and ADSs
depends upon any future appreciation in value. Consequently, investors may need to sell all or part of
their holdings of the ordinary shares or ADSs after price appreciation, which may never occur, as the only
way to realize any future gains on their investment. There is no guarantee that the ordinary shares or
ADSs will appreciate in value or even maintain the price at which Innate's shareholders have purchased
them.
Further, under French law, the determination of whether the Company has been sufficiently profitable to
pay dividends is made on the basis of its statutory financial statements prepared and presented in
accordance with accounting standards applicable in France. Moreover, pursuant to French law, the
Company must allocate 5% of its unconsolidated net profit for each year to its legal reserve fund before
dividends, should the Company propose to declare any, may be paid for that year, until the amount in the
legal reserve is equal to 10% of the aggregate nominal value of its issued and outstanding share capital. In
addition, payment of dividends may subject Innate to additional taxes under French law. Therefore, Innate
may be more restricted in its ability to declare dividends than companies that are not incorporated in
France. See “Description of Share Capital—Key Provisions of Its Bylaws and French Law Affecting Its
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Ordinary Shares” for further details on the limitations on Innate's ability to declare and pay dividends and
the taxes that may become payable by Innate if the Company elects to pay a dividend.
In addition, exchange rate fluctuations may affect the amount of euro that the Company is able to
distribute, and the amount in U.S. dollars that its shareholders receive upon the payment of cash dividends
or other distributions the Company declares and pays in euro, if any. These factors could harm the value
of the ADSs, and, in turn, the U.S. dollar proceeds that holders receive from the sale of the ADSs.
Future sales, or the possibility of future sales, of a substantial number of Innate's ADSs or ordinary
shares could adversely affect the market price of its ADSs and ordinary shares.
Future sales of a substantial number of Innate's ADSs or ordinary shares, or the perception that such sales
will occur, could cause a decline in the market price of its ADSs and/or ordinary shares. Sales in the
United States of Innate ADSs and ordinary shares held by its directors, officers and affiliated shareholders
or ADS holders are subject to restrictions. If these shareholders or ADS holders sell substantial amounts
of ordinary shares or ADSs in the public market, or the market perceives that such sales may occur, the
market price of Innate's ADSs or ordinary shares and its ability to raise capital through an issue of equity
securities in the future could be adversely affected.
The dual listing of Innate's ordinary shares and the ADSs may adversely affect the liquidity and value
of the ADSs.
Innate's ADSs are listed on Nasdaq, and its ordinary shares are admitted to trading on Euronext Paris.
Trading of the ADSs or ordinary shares in these markets take place in different currencies (U.S. dollars on
Nasdaq and euro on Euronext Paris), and at different times (resulting from different time zones, different
trading days and different public holidays in the United States and France). The trading prices of the
Company's ordinary shares on these two markets may differ due to these and other factors. Any decrease
in the price of Innate's ordinary shares on Euronext Paris could cause a decrease in the trading price of the
ADSs on Nasdaq. Investors could seek to sell or buy Innate's ordinary shares to take advantage of any
price differences between the markets through a practice referred to as arbitrage. Any arbitrage activity
could create unexpected volatility in both its share prices on one exchange, and the ordinary shares
available for trading on the other exchange. In addition, holders of ADSs are not immediately able to
surrender their ADSs and withdraw the underlying ordinary shares for trading on the other market without
effecting necessary procedures with the depositary. This could result in time delays and additional cost for
holders of ADSs. The Company cannot predict the effect of this dual listing on the value of its ordinary
shares and the ADSs. However, the dual listing of its ordinary shares and the ADSs may reduce the
liquidity of these securities in one or both markets and may adversely affect the development of an active
trading market for the ADSs in the United States.
The rights of shareholders in companies subject to French corporate law differ in material respects
from the rights of shareholders of corporations incorporated in the United States.
The Company is a French company with limited liability. Its corporate affairs are governed by its bylaws
and by the laws governing companies incorporated in France. The rights of shareholders and the
responsibilities of members of Innate's Executive Board and of its Supervisory Board are in many ways
different from the rights and obligations of shareholders in companies governed by the laws of U.S.
jurisdictions. For example, in the performance of its duties, Innate's Executive Board is required by
French law to consider the interests of Innate, its shareholders, its employees and other stakeholders,
rather than solely Innate's shareholders and/or creditors. It is possible that some of these parties have
interests that are different from, or in addition to, your interests as a shareholder or holder of ADSs. See
“Item 16G.—Corporate Governance.”
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U.S. investors may have difficulty enforcing civil liabilities against the Company and members of the
Executive Board and the Supervisory Board.
Most of the members of Innate's Executive Board and Supervisory Board and the experts named therein
are non-residents of the United States, and all or a substantial portion of its assets and the assets of such
persons are located outside the United States. As a result, it may not be possible to serve process on such
persons or Innate in the United States or to enforce judgments obtained in U.S. courts against them or
Innate based on civil liability provisions of the securities laws of the United States. Additionally, it may
be difficult to assert U.S. securities law claims in actions originally instituted outside of the United States.
Foreign courts may refuse to hear a U.S. securities law claim because foreign courts may not be the most
appropriate forums in which to bring such a claim. Even if a foreign court agrees to hear a claim, it may
determine that the law of the jurisdiction in which the foreign court resides, and not U.S. law, is
applicable to the claim. Further, if U.S. law is found to be applicable, the content of applicable U.S. law
must be proved as a fact, which can be a time-consuming and costly process, and certain matters of
procedure would still be governed by the law of the jurisdiction in which the foreign court resides. In
particular, there is some doubt as to whether French courts would recognize and enforce certain civil
liabilities under U.S. securities laws in original actions or judgments of U.S. courts based upon these civil
liability provisions. In addition, awards of punitive damages in actions brought in the United States or
elsewhere may be unenforceable in France. An award for monetary damages under the U.S. securities
laws would be considered punitive if it does not seek to compensate the claimant for loss or damage
suffered but is intended to punish the defendant. French law provides that a shareholder, or a group of
shareholders, may initiate a legal action to seek indemnification from the directors of a corporation in the
corporation’s interest if it fails to bring such legal action itself. If so, any damages awarded by the court
are paid to the corporation and any legal fees relating to such action may be borne by the relevant
shareholder or the group of shareholders. The enforceability of any judgment in France will depend on the
particular facts of the case as well as the laws and treaties in effect at the time. The United States and
France do not currently have a treaty providing for recognition and enforcement of judgments, other than
arbitration awards, in civil and commercial matters.
Innate's bylaws and French corporate law contain provisions that may delay or discourage a takeover
attempt.
Provisions contained in the Company's bylaws and French corporate law could make it more difficult for
a third-party to acquire the Company, even if doing so might be beneficial to its shareholders. In addition,
provisions of its bylaws impose various procedural and other requirements, which could make it more
difficult for shareholders to effect certain corporate actions. These provisions include the following:
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under French law, the owner of 90% of the share capital or voting rights of a public company
listed on a regulated market in a Member State of the European Union or in a state party to the
EEA Agreement, including from the main French stock exchange, has the right to force out
minority shareholders following a tender offer made to all shareholders;
under French law, a non-resident of France, as well as any French entity controlled by non-
residents of France, may have to file a declaration for statistical purposes with the Bank of
France (Banque de France) within 20 working days following the date of certain direct foreign
investments in us, including any purchase of the Company's ADSs. In particular, such filings
are required in connection with investments exceeding €15,000,000 that lead to the acquisition
of at least 10% of the Company's share capital or voting rights or cross such 10% threshold;
under French law, certain investments in a French company relating to certain strategic
industries by individuals or entities not residents in a Member State of the EU are subject to
prior authorization of the Ministry of Economy;
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a merger (i.e., in a French law context, a share for share exchange following which the
Company would be dissolved into the acquiring entity and its shareholders would become
shareholders of the acquiring entity) of the Company into a company incorporated in the
European Union would require the approval of the Company's Executive Board, as well as a
two-thirds majority of the votes held by the shareholders present, represented by proxy or
voting by mail at the relevant meeting;
a merger of the Company into a company incorporated outside of the European Union would
require 100% of its shareholders to approve it;
under French law, a cash merger is treated as a share purchase and would require the consent
of each participating shareholder;
Innate's shareholders may in the future grant the Company's Executive Board broad
authorizations to increase Innate's share capital or to issue additional ordinary shares or other
securities (for example, warrants) to Innate's shareholders, the public or qualified investors,
including as a possible defense following the launching of a tender offer for Innate's ordinary
shares;
its shareholders have preferential subscription rights on a pro rata basis on the issuance by
Innate of any additional securities for cash or a set-off of cash debts, which rights may only be
waived by the extraordinary general meeting (by a two-thirds majority vote) of the Company's
shareholders or on an individual basis by each shareholder;
Innate's Supervisory Board appoints the members of the Executive Board and shall fill any
vacancy within two months;
Innate's Supervisory Board has the right to appoint members of the Supervisory Board to fill a
vacancy created by the resignation or death of a member of the Supervisory Board for the
remaining duration of such member’s term of office, and subject to the approval by the
shareholders of such appointment at the next shareholders’ meeting, which prevents
shareholders from having the sole right to fill vacancies on the Company's Supervisory Board;
its Executive Board can be convened by the chairman of the Executive Board or other
members of the Executive Board delegated for this purpose;
its Supervisory Board can be convened by the chairman or the vice-chairman of the
Supervisory Board. A member of the Executive Board or one-third of the members of the
Supervisory Board may send a written request to the chairman to convene the Supervisory
Board. If the chairman does not convene the Supervisory Board 15 days following the receipt
of such request, the authors of the request may themselves convene the Supervisory Board;
its Supervisory Board meetings can only be regularly held if at least half of its members attend
either physically or by way of videoconference or teleconference enabling the members’
identification and ensuring their effective participation in the Supervisory Board’s decisions;
approval of at least a majority of the votes held by shareholders present, represented by a
proxy, or voting by mail at the relevant ordinary shareholders’ general meeting is required to
remove members of the Executive Board and/or members of the Supervisory Board with or
without cause;
the crossing of certain ownership thresholds has to be disclosed and can impose certain
obligations;
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advance notice is required for nominations to the Supervisory Board or for proposing matters
to be acted upon at a shareholders’ meeting, except that a vote to remove and replace a
member of the Supervisory Board can be proposed at any shareholders’ meeting without
notice;
transfers of shares shall comply with applicable insider trading rules and regulations, and in
particular with the Market Abuse Regulation 596/2014 of April 16, 2014, as amended; and
pursuant to French law, the Company's bylaws, including the sections relating to the number
of members of the Executive and Supervisory Boards, and election and removal of members
of the Executive and Supervisory Boards from office may only be modified by a resolution
adopted by two-thirds of the votes of the Company's shareholders present, represented by a
proxy or voting by mail at the meeting.
Purchasers of ADSs in the U.S. offering are not directly holding the Company's ordinary shares.
A holder of ADSs is not treated as one of Innate Pharma's shareholders and does not have direct
shareholder rights. French law governs Innate's shareholder rights. The depositary, through the custodian
or the custodian’s nominee, is the holder of the ordinary shares underlying ADSs held by purchasers of
ADSs in the U.S. offering. Purchasers of ADSs in the U.S. offering have ADS holder rights. The deposit
agreement among us, the depositary and purchasers of ADSs in the U.S. offering, as an ADS holder, and
all other persons directly and indirectly holding ADSs, sets out ADS holder rights, as well as the rights
and obligations of Innate and the depositary.
Your right as a holder of ADSs to participate in any future preferential subscription rights offering or
to elect to receive dividends in shares may be limited, which may cause dilution to your holdings.
According to French law, if the Company issues additional securities for cash, current shareholders will
have preferential subscription rights for these securities on a pro rata basis unless they waive those rights
at an extraordinary meeting of its shareholders (by a two-thirds majority vote) or individually by each
shareholder. However, Innate's ADS holders in the United States will not be entitled to exercise or sell
such rights unless the Company registers the rights and the securities to which the rights relate under the
Securities Act or an exemption from the registration requirements is available. In addition, the deposit
agreement provides that the depositary will not make rights available to you unless the distribution to
ADS holders of both the rights and any related securities are either registered under the Securities Act or
exempted from registration under the Securities Act. Further, if the Company offers holders of its
ordinary shares the option to receive dividends in either cash or shares, under the deposit agreement the
depositary may require satisfactory assurances from Innate that extending the offer to holders of ADSs
does not require registration of any securities under the Securities Act before making the option available
to holders of ADSs. The Company is under no obligation to file a registration statement with respect to
any such rights or securities or to endeavor to cause such a registration statement to be declared effective.
Moreover, the Company may not be able to establish an exemption from registration under the Securities
Act. Accordingly, ADS holders may be unable to participate in the Company's rights offerings or to elect
to receive dividends in shares and may experience dilution in their holdings. In addition, if the depositary
is unable to sell rights that are not exercised or not distributed or if the sale is not lawful or reasonably
practicable, it will allow the rights to lapse, in which case you will receive no value for these rights.
You may not be able to exercise your right to vote the ordinary shares underlying your ADSs.
Holders of ADSs may exercise voting rights with respect to the ordinary shares represented by the ADSs
only in accordance with the provisions of the deposit agreement. The deposit agreement provides that,
upon receipt of notice of any meeting of holders of Innate's ordinary shares, the depositary will fix a
record date for the determination of ADS holders who shall be entitled to give instructions for the
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exercise of voting rights. Upon timely receipt of notice from us, if the Company so requests, the
depositary shall distribute to the holders as of the record date (i) the notice of the meeting or solicitation
of consent or proxy sent by Innate and (ii) a statement as to the manner in which instructions may be
given by the holders.
You may instruct the depositary of your ADSs to vote the ordinary shares underlying your ADSs.
Otherwise, you will not be able to exercise your right to vote, unless you withdraw the ordinary shares
underlying the ADSs you hold. However, you may not know about the meeting far enough in advance to
withdraw those ordinary shares. If the Company asks for your instructions, the depositary, upon timely
notice from us, will notify you of the upcoming vote and arrange to deliver its voting materials to you.
The Company cannot guarantee you that you will receive the voting materials in time to ensure that you
can instruct the depositary to vote your ordinary shares or to withdraw your ordinary shares so that you
can vote them yourself. If the depositary does not receive timely voting instructions from you, it may give
a proxy to a person designated by Innate to vote the ordinary shares underlying your ADSs. In addition,
the depositary and its agents are not responsible for failing to carry out voting instructions or for the
manner of carrying out voting instructions. This means that you may not be able to exercise your right to
vote, and there may be nothing you can do if the ordinary shares underlying your ADSs are not voted as
you requested.
You may be subject to limitations on the transfer of your ADSs and the withdrawal of the underlying
ordinary shares.
Your ADSs are transferable on the books of the depositary. However, the depositary may close its books
at any time or from time to time when it deems expedient in connection with the performance of its
duties. The depositary may refuse to deliver, transfer or register transfers of your ADSs generally when
the Company's books or the books of the depositary are closed, or at any time if the Company or the
depositary thinks it is advisable to do so because of any requirement of law, government or governmental
body, or under any provision of the deposit agreement, or for any other reason subject to your right to
cancel your ADSs and withdraw the underlying ordinary shares. Temporary delays in the cancellation of
your ADSs and withdrawal of the underlying ordinary shares may arise because the depositary has closed
its transfer books or the Company has closed its transfer books, the transfer of ordinary shares is blocked
to permit voting at a shareholders’ meeting or the Company is paying a dividend on its ordinary shares. In
addition, you may not be able to cancel your ADSs and withdraw the underlying ordinary shares when
you owe money for fees, taxes and similar charges and when it is necessary to prohibit withdrawals in
order to comply with any laws or governmental regulations that apply to ADSs or to the withdrawal of
ordinary shares or other deposited securities.
As a foreign private issuer, the Company is exempt from a number of rules under the U.S. securities
laws and are permitted to file less information with the SEC than a U.S. company.
Innate is a foreign private issuer, as defined in the SEC’s rules and regulations and, consequently, it is not
subject to all of the disclosure requirements applicable to public companies organized within the United
States. For example, the Company is exempt from certain rules under the Exchange Act that regulate
disclosure obligations and procedural requirements related to the solicitation of proxies, consents or
authorizations applicable to a security registered under the Exchange Act, including the U.S. proxy rules
under Section 14 of the Exchange Act. In addition, the Company's Executive Board and Supervisory
Board members are exempt from the reporting and “short-swing” profit recovery provisions of Section 16
of the Exchange Act and related rules with respect to their purchases and sales of Innate's securities.
Moreover, while the Company currently makes annual and semi-annual filings with respect to its listing
on Euronext Paris and file financial reports on an annual and semi-annual basis, it is not required to file
periodic reports and financial statements with the SEC as frequently or as promptly as U.S. public
companies and are not required to file quarterly reports on Form 10-Q or current reports on Form 8-K
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under the Exchange Act. In addition, foreign private issuers are not required to file their annual report on
Form 20-F until four months after the end of each fiscal year. Accordingly, there is and will be less
publicly available information concerning the Company than there would be if the Company was not a
foreign private issuer.
As a foreign private issuer, the Company is permitted to adopt certain home country practices in
relation to corporate governance matters that differ significantly from Nasdaq corporate governance
listing standards and these practices may afford less protection to shareholders than they would enjoy
if Innate complied fully with Nasdaq corporate governance listing standards.
As a foreign private issuer listed on Nasdaq, the Company is subject to their corporate governance listing
standards. However, Nasdaq rules permit foreign private issuers to follow the corporate governance
practices of their home country. Some corporate governance practices in France may differ significantly
from Nasdaq corporate governance listing standards. For example, neither the corporate laws of France
nor the Company's bylaws require a majority of its Supervisory Board members to be independent and
although the corporate governance code to which the Company currently refers (the AFEP/MEDEF code)
recommends that, in a widely-held company like its, a majority of the Supervisory Board members be
independent (as construed under such code), this code only applies on a “comply-or-explain” basis and
Innate may in the future either decide not to apply this recommendation or change the corporate code to
which it refers. Furthermore, Innate includes non-independent members of the Supervisory Board as
members of its compensation and nomination committee, and its independent Supervisory Board
members do not necessarily hold regularly scheduled meetings at which only independent members of the
Supervisory Board are present. Currently, the Company intends to follow home country practice to the
maximum extent possible. Therefore, Innate Pharma's shareholders may be afforded less protection than
they otherwise would have under corporate governance listing standards applicable to U.S. domestic
issuers. For an overview of Innate's corporate governance practices, see “Item 16G.—Corporate
Governance.”
The Company is an “emerging growth company” under the JOBS Act and is able to avail itself of
reduced disclosure requirements applicable to emerging growth companies, which can make its
ordinary shares ADSs less attractive to investors.
The Company is an “emerging growth company,” as defined in the JOBS Act, and it intends to take
advantage of certain exemptions from various reporting requirements that are applicable to other public
companies that are not “emerging growth companies,” including not being required to comply with the
auditor attestation requirements of Section 404(b) of the Sarbanes-Oxley Act, and exemptions from the
requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval
of any golden parachute payments not previously approved. In addition, Section 107 of the JOBS Act also
provides that an emerging growth company can take advantage of the extended transition period provided
in Section 7(a)(2)(B) of the Securities Act, for complying with new or revised accounting standards. The
Company will not take advantage of the extended transition period provided under Section 7(a)(2)(B) of
the Securities Act for complying with new or revised accounting standards.
The Company cannot predict if investors will find the ordinary shares or ADSs less attractive because the
Company may rely on these exemptions. If some investors find the ordinary shares or ADSs less
attractive as a result, there may be a less active trading market for the ordinary shares or ADSs and the
price of the ordinary shares or ADSs may be more volatile. Innate may take advantage of these
exemptions until such time that Innate is no longer an emerging growth company. The Company would
cease to be an emerging growth company upon the earliest to occur of (1) the last day of the fiscal year in
which Innate Pharma has more than $1.07 billion in annual revenue; (2) the date the Company qualify as
a “large accelerated filer” with at least $700 million of equity securities held by non-affiliates; (3) the
issuance, in any three year period, by Innate Pharma of more than $1.0 billion in non-convertible debt
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securities held by non-affiliates; and (4) the last day of the fiscal year ending after the fifth anniversary of
its initial public offering of the ADSs.
The Company may lose its foreign private issuer status in the future, which could result in significant
additional cost and expense.
While Innate currently qualifies as a foreign private issuer, the determination of foreign private issuer
status is made annually on the last business day of an issuer’s most recently completed second fiscal
quarter and, accordingly, the Company's next determination will be made on June 30, 2022. In the future,
the Company would lose its foreign private issuer status if the Company to fails to meet the requirements
necessary to maintain its foreign private issuer status as of the relevant determination date. For example,
if more than 50% of its securities are held by U.S. residents and more than 50% of the members of its
Executive Board or Supervisory Board are residents or citizens of the United States, Innate could lose its
foreign private issuer status.
The regulatory and compliance costs to Innate under U.S. securities laws as a U.S. domestic issuer may
be significantly more than costs Innate incurs as a foreign private issuer. If the Company is not a foreign
private issuer, Innate Pharma will be required to file periodic reports and registration statements on U.S.
domestic issuer forms with the SEC, which are more detailed and extensive in certain respects than the
forms available to a foreign private issuer. The Company would be required under current SEC rules to
prepare its financial statements in accordance with U.S. generally accepted accounting principles, or U.S.
GAAP, rather than IFRS, and modify certain of its policies to comply with corporate governance
practices required of U.S. domestic issuers. Such conversion of Innate's financial statements to U.S.
GAAP would involve significant time and cost. In addition, the Company may lose its ability to rely upon
exemptions from certain corporate governance requirements on U.S. stock exchanges that are available to
foreign private issuers such as the ones described above and exemptions from procedural requirements
related to the solicitation of proxies.
If the Company is a passive foreign investment company, there could be adverse U.S. federal income
tax consequences to U.S. holders.
Based on Innate's analysis of its income, assets, activities and market capitalization for its taxable year
ended December 31, 2021, the Company believes that it was not a passive foreign investment company,
or PFIC, for the taxable year ended December 31, 2021. However, there can be no assurance that Innate
will not be a PFIC in the current year or for any future taxable year. Under the Code, a non-U.S. company
will be a PFIC for any taxable year in which (1) 75% or more of its gross income consists of passive
income or (2) 50% or more of the average quarterly value of its assets consists of assets that produce, or
are held for the production of, passive income. For purposes of these tests, passive income includes
dividends, interest, gains from the sale or exchange of investment property and certain rents and royalties.
In addition, for purposes of the above calculations, a non-U.S. corporation that directly or indirectly owns
at least 25% by value of the shares of another corporation is treated as if it held its proportionate share of
the assets and received directly its proportionate share of the income of such other corporation. If Innate is
a PFIC for any taxable year during which a U.S. holder (as defined below under “Item 10E.—Taxation –
Material U.S. Federal Income Tax”) holds its ordinary shares or ADSs, the Company will continue to be
treated as a PFIC with respect to such U.S. holder in all succeeding years during which the U.S. holder
owns the ordinary shares or ADSs, regardless of whether the Company continues to meet the PFIC test
described above, unless the U.S. holder makes a specified election once Innate ceases to be a PFIC. If the
Company is a PFIC for any taxable year during which a U.S. holder holds its ordinary shares or ADSs,
the U.S. holder may be subject to adverse tax consequences regardless of whether Innate Pharma
continues to qualify as a PFIC, including ineligibility for any preferred tax rates on capital gains or on
actual or deemed dividends, interest charges on certain taxes treated as deferred, and additional reporting
requirements. For further discussion of the PFIC rules and the adverse U.S. income tax consequences in
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the event the Company is classified as a PFIC, see the section of this Annual Report titled “Item 10E.—
Taxation– Material U.S. Federal Income Tax Considerations”
If a United States person is treated as owning at least 10% of Innate's ordinary shares, such holder
may be subject to adverse U.S. federal income tax consequences.
If a U.S. holder is treated as owning, directly, indirectly or constructively, at least 10% of the value or
voting power of Innate's ordinary shares or ADSs, such U.S. holder may be treated as a “United States
shareholder” with respect to each “controlled foreign corporation” in its group, if any. Innate Pharma
group currently includes one U.S. subsidiary and, therefore, under current law its current non-U.S.
subsidiary and any future newly formed or acquired non-U.S. subsidiaries will be treated as controlled
foreign corporations, regardless of whether the Company is treated as a controlled foreign corporation. A
United States shareholder of a controlled foreign corporation may be required to annually report and
include in its U.S. taxable income its pro rata share of “Subpart F income,” “global intangible low-taxed
income” and investments in U.S. property by controlled foreign corporations, regardless of whether
Innate makes any distributions. An individual that is a United States shareholder with respect to a
controlled foreign corporation generally would not be allowed certain tax deductions or foreign tax credits
that would be allowed to a United States shareholder that is a U.S. corporation. Failure to comply with
controlled foreign corporation reporting obligations may subject a United States shareholder to significant
monetary penalties. The Company cannot provide any assurances that it will furnish to any United States
shareholder information that may be necessary to comply with the reporting and tax paying obligations
applicable under the controlled foreign corporation rules of the Code. U.S. holders should consult their
tax advisors regarding the potential application of these rules to their investment in Innate's ordinary
shares or ADSs.
Item 4. Information on the Company.
A. History and Development of the Company
Innate's legal name and commercial name is Innate Pharma S.A. The Company was incorporated under
the laws of France on September 23, 1999 as a société par actions simplifiée and converted into a société
anonyme, or S.A., on June 13, 2005. Innate's headquarters are located at 117, Avenue de Luminy, 13009
Marseille, France. In 2008, The Company incorporated its wholly-owned U.S. subsidiary, Innate Pharma
Inc. In 2019, Innate Pharma's incorporated its wholly-owned French subsidiary, Innate Pharma France
S.A.S (registered under number SIREN 844 853 119). Innate Pharma France S.A.S. was dissolved
without liquidation on November 30, 2020 under article 1844-5 section 3 of the French Civil Code.
The Company is registered at the Marseille Business and Company Registry (Registre du commerce et
des sociétés) under the number SIREN 424 365 336 RCS Marseille. Innate's telephone number at its
principal executive offices is +33 4 30 30 30 30. Innate Pharma's wholly-owned U.S. subsidiary is located
at 2273 Research Boulevard, Suite 350, Rockville, MD 20850, United States.
Innate's website address is www.innate-pharma.com. The reference to its website is an inactive textual
reference only and information contained in, or that can be accessed through, its website is not part of this
Annual Report. The U.S. Securities and Exchange Commission maintains a website (www.sec.gov) that
contains reports, proxy and information statements and other information regarding registrants, such as
Innate, that file electronically with the SEC.
Innate's capital expenditures in the years ended December 31, 2020, 2021 and 2022 primarily related to
acquisitions and additional considerations linked to purchased licenses, and acquisitions of laboratory
equipments. Clinical research and development costs are not capitalized until marketing authorizations
are obtained.
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B. Business Overview
its ANKET®
Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for
cancer patients. Its innovative approach aims to harness the innate immune system through therapeutic
antibodies and
(Antibody-based NK cell Engager Therapeutics) proprietary
platform.Innate’s portfolio includes lead proprietary program lacutamab, developed in advanced form of
cutaneous T cell lymphomas and peripheral T cell lymphomas, monalizumab developed with
AstraZeneca in non small cell lung cancer, as well as ANKET® multi-specific NK cell engagers to
address multiple tumor types. The Company has developed, internally and through its business
development strategy, a broad and diversified portfolio including five clinical product candidates and a
robust preclinical pipeline. Innate has entered into collaborations with leaders in the biopharmaceutical
industry, such as AstraZeneca and Sanofi. Innate Pharma believes its product candidates and clinical
development approach are differentiated from current immuno-oncology therapies and have the potential
to significantly improve the clinical outcome for patients with cancer.
The immune system is the body’s natural defense against invading organisms and pathogens and is
comprised of two arms: the innate immune system and the adaptive immune system. Recent
immunotherapy developments have focused on generating a tumor antigen-specific T cell response and
have led to an unprecedented change in the treatment paradigm of many solid tumor cancers. Despite
these successes, the breadth and durability of the clinical benefit achieved has been limited to a subset of
patients and tumor types because of limited effect against solid tumors and toxicity. Its innovative
approach to immuno-oncology aims to broaden and amplify anti-tumoral immune responses by
leveraging both the adaptive and the innate immune systems.
The innate immune system is comprised of a variety of cells, including Natural Killer cells (NK cells),
which are involved in anti-cancer immunosurveillance through a variety of modalities. Activation of the
innate immune system also helps trigger the adaptive immune system to elicit a response directed against
specific antigens and can provide durable immune memory. Innate's scientific expertise, strategic
collaborations and discovery engine harness the potential of the innate immune system.
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The Company is developing a pipeline of innovative immunotherapies that it believes have the potential
to provide significant clinical benefits to cancer patients. The following table summarizes Innate's current
pipeline.
In addition to these assets, the Company has an active development pipeline with programs in the
discovery and preclinical stages.
Innate Pharma's collaborations with leaders in the biopharmaceutical industry, such as AstraZeneca and
Sanofi, allow Innate to leverage the expertise and resources of large pharmaceutical companies and
research institutions with the goal of accelerating the development, registration and launch of several of
Innate Pharma's assets while providing the Company with financing to expand the development of its
proprietary product candidates. Over the last ten years the Company has received an aggregate of
approximately $645.2 million in upfront and milestone payments and equity investments from its
collaborations. Under Innate's existing collaboration and license agreements that become effective upon
the exercise by its collaborators of options to license future product candidates, the Company may be
eligible to receive an aggregate of approximately up to $3.6 billion in future contingent payments. With
respect to the programs for which Innate Pharma has an existing collaboration or similar agreement,
future contingent payments are dependent upon Innate's achievement of specified development,
regulatory and commercial related milestones. With respect to the programs for which Innate Pharma's
collaborators have been granted an option, future contingent payments are dependent upon Innate's
collaborators exercising such options, which would result in up-front option exercise fees, and upon its
achievement of specific development and sales milestones in those particular programs. The aggregate
$3.6 billion in future contingent payments assumes that its collaborators exercise all of the options the
Company has granted to them and that Innate achieves all related development, clinical, regulatory and
sales milestones.
The Company's Strategy
Innate's goal is to harness the immune system for the treatment of oncological conditions with serious
unmet medical need. By leveraging its extensive experience in immuno-oncology research and
development, the Company strives to continue to discover and develop a broad and diversified portfolio
of first and best-in class immunotherapies across various therapeutic modalities. The key elements of its
strategy include:
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• Drive near-term value with Innate's wholly owned product candidate, lacutamab
◦
Execute the clinical development of its fully owned product candidate, lacutamab, for the
treatment of patients with cutaneous T cell lymphoma (CTCL), namely Sézary syndrome
and Mycosis Fungoides, or MF, and patients with peripheral T cell lymphoma (PTCL).
• Advance its innovative R&D pipeline
◦
Expand its pipeline of proprietary product candidates that target novel pathways in
immuno-oncology using its internal development engine.
◦ Drive the development of its proprietary portfolio, including the next generation asset NK
cell engagers (NKCEs) through Innate's proprietary Antibody-based NK cell Engager
Therapeutics (ANKET®) platform and continuing to explore Antibody Drug Conjugates
(ADC) formats.
• Build a sustainable business
◦ Maximize the value of its partnered product candidates under its various collaboration,
licence and option agreements, under which the Company has the potential to be eligible
to receive up to an aggregate of approximately $3.6 billion in future contingent payments,
including up-front option exercise fees and payments upon the achievement of specified
development and sales milestones.
◦
Invest in the ongoing clinical programs of monalizumab for the treatment of Non-small-
cell lung carcinoma (NSCLC).
◦ Continue to explore opportunities to accelerate the development of Innate's proprietary
pipeline programs through additional collaborations.
◦ Combine its disciplined business development strategy with its immuno-oncology
research and development capabilities to further expand its product portfolio.
◦ Manage its resources carefully and implement the efficiency measures necessary to
optimize its resources.
Activating Innate Immunity: Harnessing the Power of Immunotherapy to Treat Cancer
The Innate Immune System: Gatekeeper of the Adaptive Immune System
The immune system is the body’s defense against invading organisms and pathogens and is comprised of
two arms: the innate immune system and adaptive immune system.
The innate immune system represents the first barrier of immune defense because it reacts almost
immediately against threats and serves as a catalyst to mobilize other components of the immune system.
The innate immune system functions to identify, attack and kill pathogens or cancer cells, produce
cytokines and activate the complement cascade and the adaptive immune system through antigen
presentation. These functions involve a variety of cells, including NK cells, dendritic cells, monocytes,
macrophages and neutrophils. These cells then launch adaptive immune responses while also mounting
their own effector responses. Throughout the body, cells of the innate immune system play a critical role
in the immunosurveillance and detection of the formation of cancer cells.
Once activated, the adaptive immune system responds with large numbers of effector cells directed
against specific antigens and can provide durable immune memory. An adaptive immune response is
highly specific to particular antigens expressed by pathogens or cancer cells, but it requires time to
develop in a process known as priming. Key components of the adaptive immune system include
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antibodies, which are produced by B cells, bind to antigens and mark them for destruction by other
immune cells, and T cells, which recognize antigens on diseased cells and then attack and eliminate them.
The adaptive immune response is targeted and potent and has the potential to provide a long-lasting
immune memory.
Key Elements to Modulating the Activity of Immune Cells to Treat Cancer
Cells implicated in innate and adaptive immunity can have different impacts on the treatment of cancer.
While cytotoxic CD8+ T cells and NK cells help eliminate tumors, subsets of T cells, such as regulatory T
cells, and subsets of myeloid cells, such as myeloid-derived suppressor cells (MDSCs), can be harmful to
the host by contributing to an immunosuppressive environment and promoting tumor growth.
Immune cell activity is controlled by many activating and inhibitory factors, including activating
receptors and inhibitory receptors, called checkpoints, which are expressed at the surface of these cells.
PD-1, LAG-3, TIGIT and NKG2A are examples of inhibitory checkpoints while OX-40, CD137, NKG2D
and NKp46 are examples of activating checkpoints. When engaged, the inhibitory checkpoints can impair
anti-tumor immunity of adaptive and innate immune cells such as CD8+ T cells or NK cells, thereby
contributing to tumor escape from immune control. Inhibitory checkpoints are potential therapeutic
targets for restoring anti-cancer immunosurveillance.
The Role of the Innate Immune System as a Modality for Cancer Therapies with Significant Potential
Cancer has historically been treated with surgery, radiation therapy, chemotherapy, targeted therapy,
hormone therapy or a combination of these treatments that are directed at the tumor itself. More recently,
advances in the understanding of the immune system’s role in cancer have led to immunotherapy
becoming an important therapeutic modality, shifting the therapeutic target from the tumor to the host and
focusing on the immune system and the tumor microenvironment (TME) in order to reactivate its
immunosurveillance against cancer.
Cancer immunotherapy began with treatments that did not specifically activate the immune system, such
as IL-2 and IFNa cytokines therapies, which had limited efficacy, significant toxicity or both. More recent
immunotherapy developments have instead focused on the generation of a tumor antigen-specific T cell
response, in particular by modulating the activity of inhibitory receptors expressed by T cells. This
modulation can limit T cells expansion, such as with anti-CTLA-4 therapy, or limit their effector
properties, such as with anti-PD-1 or anti-PD-L1 therapies. The therapeutic targeting of inhibitory
80
receptors controlling T cell function has led to an unprecedented change in the treatment paradigm of
many cancers in solid tumors, such as melanoma, non-small cell lung cancer and renal cell carcinoma,
and in hematopoietic malignancies, such as Hodgkin lymphoma. Despite these successes, the breadth and
durability of clinical benefit achieved has been limited to a subset of patients and tumor types.
The onset, maintenance and development of long-lasting, protective T cell responses are dependent on
innate immune cells; NK cells which are lymphocytes of the innate immune system participate to this
process.
Harnessing Innate Immunity in Cancer: NK Cells as a Key Player in the Anti-Tumor Immune
Response
NK cells are part of the innate immune system and represent a significant fraction of the total number of
cytotoxic cells in the body. They are active in many hematological and solid tumors and play a key role in
the initiation of the T cell response.
Checkpoints expressed on NK cells include inhibitory cell surface receptors, such as NKG2A, and
activating NK cell receptors, such as NKp46. NKp46 is the most specific NK cell marker identified to
date across organs and species. Other receptors, such as NKG2A, are more prevalent in certain subsets of
NK cells, including NK cells infiltrating the tumor, and are also present on tumor infiltrating CD8+ T
cells.
NK cells are involved in the anti-cancer immunosurveillance through a variety of direct and indirect
effects. The figure below provides an illustration of anti-cancer functions of NK cells.
1 NK cells are able to directly and
selectively kill cells undergoing stress
caused by a cancerous transformation or
pathogen infection, a process called
natural cytotoxicity.
2 NK cells can also kill target cells when
they are coated by antibodies in a
process called antibody-dependent
cellular cytotoxicity (ADCC).
3 NK cells are also potent producers of
cytokines, which are soluble molecules
that recruit and activate an adaptive
immune response by T cells through
dendritic or other antigen-presenting
cells, which in turn may enable the
generation of immune memory against
tumor cells.
By providing the initial catalyst for the multilayered immune response, the activation of the innate
immune system through the targeting of NK cells could potentially result in an optimal anti-tumoral T cell
response.
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Innate's response to cancer: harnessing the innate immunity against cancer
The Company has developed a pipeline around the three main innovative strategies in modern immuno-
oncology:
•
The first of these strategies is to directly target cancer cells through an antibody targeting a tumor
antigen and causing its destruction. Lacutamab and the ANKET® platform molecules such as
IPH6101/SAR'579 (CD123), IPH6401/SAR'514 (BCMA) and IPH62 (B7-H3) partnered with
Sanofi, and proprietary IPH6501 (CD20) use this strategy.
• Another strategy, known as immuno-oncology, consists in unleashing the immune system. Innate
Pharma has developed two approaches to immune-oncology:
◦ Checkpoint inhibitors: the development of antibodies that target immune checkpoints has
been one of the greatest advances in cancer treatment over the last ten years. Notably, the
current approved checkpoint inhibitors target the CTLA-4 and PD-1/PD-L1 pathways on
T cells. These treatments have shown an ability to activate T cells, shrink tumors and
improve patient survival in a broad range of tumors. The Company is developing broad
spectrum checkpoint inhibitors targeting inhibitory checkpoints expressed on several cell
types in order to potentially increase the breadth and quality of anti-tumor response.
Innate's most advanced checkpoint inhibitor product candidate, monalizumab, is
potentially a first-in-class, dual checkpoint inhibitor designed to activate both tumor-
infiltrating NK cells and CD8+ T cells, likely resulting in increased effector functions and
greater killing of the tumor by the immune system. The Company has partnered with
AstraZeneca to develop this product which is currently being tested in a Phase 3 clinical
trial in unresectable, Stage III non small cell lung cancer (NSCLC) and a Phase 2 clinical
trial in resectable, early-stage NSCLC.
◦
Tumor’s microenvironment (TME): the TME can inhibit both innate and adaptive
immune responses either by producing or degrading key metabolites or by recruiting
suppressive cells, or both. For example, adenosine is one of the components of the TME
that most broadly affects immune response. It is produced by the sequential degradation
of extracellular adenosine triphosphate, or ATP, by the following two enzymes: first
CD39, which degrades the ATP into adenosine monophosphate, or AMP, and then
second, CD73, which impairs the AMP into adenosine. For this reason, this pathway has
attracted significant development efforts that have been focused primarily on the
downstream part of the adenosine degradation cascade, CD73 and the adenosine
receptors. The Company is developing IPH5301, a potentially best-in-class anti-CD73
antibody, and has also focused on the upstream part of the cascade through IPH5201, an
anti-CD39 antibody, in order to block the production of immunosuppressive adenosine
and increase the pool of immuno-stimulatory extracellular ATP. The Company believes
this approach is also potentially mechanistically synergistic with many therapies such as
checkpoint inhibitor, tumor-targeting product etc., as shown by the results of the COAST
randomized Phase 2 study, where AstraZeneca's anti-CD73 oleclumab in combination
with durvalumab improved progression-free survival (PFS) and objective response rate
(ORR) compared to durvalumab alone in patients with unresectable, Stage III non-small
cell lung cancer (NSCLC). Similarly, results from NeoCoast randomized Phase 2 study
showed that one cycle of neoadjuvant oleclumab in combination with durvalumab
improved MPR (Major Pathological Response) and pCR (pathological Complete
Response) rates versus durvalumab alone, in stage I-IIIA resectable NSCLC patients.
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The Company is using its leading antibody engineering capabilities to generate classic antibody
formats as well as innovative first-in-class antibody-derived drug candidates and synthetic molecules
such as NKCEs from Innate's ANKET® platform, to harness the anti-tumor activity of NK cells.
Antigen-targeting antibody development is highly dependent upon several factors, including the pattern of
expression of the target and the intended mechanism of action. The Company is targeting tumor antigens
that are generally highly-expressed in tumor tissues but poorly-expressed in healthy tissues in order to
develop product candidates through two approaches:
•
•
Innate's most advanced proprietary program, lacutamab, is a potentially first-in-class tumor-
targeting antibody targeting KIR3DL2, seeking to induce the killing of cells expressing the tumor
antigen. The Company is developing lacutamab for the treatment of various forms of T cell
lymphoma (TCL), such as CTCL, including its aggressive subtype, Sézary syndrome, and PTCL.
The Company has also developed a proprietary technological platform, named ANKET® (for
Antibody-based NK cell Engager Therapeutics), which develops multi-specific antibody formats
that leverage an activating receptor, NKp46. Its multi-specific antibodies co-engage NKp46, with
or without CD16, a tumor antigen and depending on the need, a variant of the interleukin-2
(IL-2v) molecule. This approach has the potential to more effectively mobilize NK cells than anti-
tumor cytotoxic antibodies because, in the TME of many solid tumors, CD16, the receptor
mediating the killing of tumor cells by IgG1 antibodies, can be downregulated on NK cells
whereas NKp46 expression is frequently expressed on tumor-infiltrating NK cells.
Innate Pharma's Product Pipeline
Lacutamab (IPH4102), a Tumor Targeting Anti-KIR3DL2 Antibody
a. Mechanism & Rationale
The Company is developing its wholly owned product candidate lacutamab for the treatment of certain
subtypes of T-Cell Lymphoma (TCLs), including Cutaneous T-Cell Lymphoma (CTCL) and Peripheral
T-Cell Lymphoma (PTCL). Lacutamab is designed to bind to the KIR3DL2 receptor and to kill cancer
cells by Antibody Directed Cell Cytotoxicity (ADCC), as illustrated in the following figure.
KIR3DL2 is a receptor of the Killer Immunoglobulin like Receptor (KIR) family. In its preclinical
studies, the Company has observed that KIR3DL2 is not expressed on healthy tissues, except on a subset
of NK cells (36%) and T cells (12% of CD8+ and 4% of CD4+) (IPH internal data). In addition, KIR3DL2
is expressed in T-cell lymphoma: 65% of CTCL patients express KIR3DL2 with approximately 50% of
83
patients with MF, the most common type of CTCL expressing KIR3DL2 (Battistella, 2017). This
frequency increases for the most aggressive CTCL subtypes, including 90% of Sézary syndrome
(Roelens, 2019). Lastly, approximately 50% of patients with PTCL also express KIR3DL2 (Cheminant,
ICML Meeting, 2019).
In January 2019, the Food and Drug Administration (FDA) granted lacutamab Fast Track Designation for
the treatment of adults with relapsed/refractory (r/r) Sézary syndrome who have received at least two prior
systemic therapies. In November 2020, Innate Pharma received Priority Medicines (PRIME) designation
from the EMA for lacutamab, for the treatment of patients with relapsed or refractory Sézary syndrome
(SS) who have received at least two prior systemic therapies. Lacutamab has also been granted orphan
drug designation by the FDA and orphan designation by the EMA for the treatment of CTCL. The US
Fast-Track and EU PRIME designations support the potential for lacutamab to benefit Sézary Syndrome
patients in need of new treatment options. The ongoing Phase 2 TELLOMAK trial, initiated in May 2019,
continues to evaluate lacutamab in different subtypes of TCL. In addition, two PTCL trials were initiated
in 2021: a Phase 1b monotherapy study sponsored by Innate Pharma and a Phase 2 study evaluating the
combination of lacutamab and GemOx sponsored by the LYSA group. These PTCL studies are an
important element of the life-cycle of lacutamab.
b.
Indication
i.
Cutaneous T Cell Lymphoma
CTCL is a heterogeneous group of non-Hodgkin’s lymphomas that are characterized by the abnormal
accumulation of malignant T cells, primarily in the skin. CTCL accounts for approximately 4% of all non-
Hodgkin’s lymphomas and has a median age at diagnosis of 55 to 60 years (Dobos, 2020; Fuji, 2020).
There are approximately 2,200-4,000 new CTCL cases diagnosed per year in Europe and the United
States combined (SEER Cancer Statistics Review 1975-2017; Dobos, 2020; Zhang, 2019; Gilson, 2019).
The most common type of CTCL is mycosis fungoides, or MF, accounting for approximately half of all
CTCLs (Dobos, 2020, Bradford, 2009). Sézary syndrome, characterized by the presence of lymphoma
cells in the blood, is a CTCL subtype with a particularly poor prognosis. The following table outlines the
most common CTCL types, their frequency as a percentage of all cases of CTCL (Dobos, 2020), and the
prognosis (WHO-EORTC classification 2018 : Willemze, 2019).
CTCL Type
Mycosis fungoides
Primary cutaneous CD30+ lympho-proliferative disorders
Primary cutaneous CD4+ small/medium T-cell
lymphoproliferative disorder
Mycosis fungoides variants
Sézary syndrome
Frequency
among CTCL
(%) Worldwide
5-year disease-specific
survival (%)
62
16
2
6
3
88
95-99
100
75-100
36
Patients with advanced CTCL have a poor prognosis with few therapeutic options and no standard of
care. Treatment generally includes skin-directed therapies, such as topical corticosteroids, and systemic
treatments, such as steroid drugs and interferon, for patients with more advanced disease or for whom
skin-directed therapies failed. There are several approved agents for the treatment of CTCL:
84
• Bexarotene, approved by FDA in 1999, for use in patients with advanced stage of MF who are
refractory to at least one prior systemic therapy
• Vorinostat, approved by FDA in 2006 for the treatment of cutaneous manifestations of CTCL in
patients with progressive, persistent, or recurrent disease on or following two systemic therapies
• Denileukin diftitox (DD) approved by the FDA in 2008 for patients with resistant and recurrent
CTCL
• Romidepsin, approved by FDA in 2009 for patients with CTCL who have received at least one
prior systemic therapy
• Brentuximab vedotin (marketed as Adcetris), was approved by the FDA in 2017 for the treatment
of patients with primary cutaneous anaplastic large cell lymphoma, or pcALCL, or CD30-
expressing MF who have received prior systemic therapy. In Europe, brentuximab vedotin is
indicated for the treatment of adult patients with R/R CD30+ CTCL who require systemic therapy.
• Mogamulizumab (marketed as Poteligeo), was approved by the FDA in 2018 and the EMA for
the treatment of adult patients with R/R MF or Sézary syndrome after at least one prior systemic
therapy.
In general, treatment guidelines distinguish CTCL by clinical appearance and localization, histological
subtype, extent and type of extracutaneous disease, aggressiveness and response to previous treatment.
Most patients are not suitable for stem cell transplantation due to their age and/or comorbid conditions.
Although brentuximab vedotin and mogamulizumab represent recent progress in the treatment of CTCL,
they are still associated with the safety and efficacy limitations observed in their respective clinical trials.
Further, even with these options, the vast majority of these treated patients eventually relapse and the
overall survival rate remains poor, which translates to unmet needs that lacutamab aims to address.
ii.
Peripheral T-Cell Lymphoma
PTCL is a diverse group of aggressive non-Hodgkin’s lymphomas that develop from mature T cells and
NK cells. PTCL arises in the lymphoid tissues outside of the bone marrow, such as in the lymph nodes,
spleen, gastrointestinal tract and skin (Hsi, 2017). The various PTCL types, their frequency as a
percentage of all TCL cases (Hsi, 2017), and prognosis (Vose, 2018) are shown in the following table.
PTCL Type
PTCL not otherwise specified
Angioimmunoblastic
Anaplastic large cell lymphoma, or ALCL, ALK positive
Anaplastic large cell lymphoma, ALK negative
Frequency (%)
U.S
5-year overall survival (%)
32
16
6
11
32
32
70
49
Irrespective of the specific regimen used (single agent chemotherapy or combination chemotherapy
including Gemcitabine and Oxaliplatin, usually referred to as GemOx), patients with R/R PTCL typically
experience a poor outcome, with a median progression-free survival and overall survival of 3.1 months
and 5.5 months, respectively (Mak, 2013).
Multi-agent chemotherapy is the recommended first line treatment for the majority of patients with PTCL.
Brentuximab vedotin is approved in combination with first line chemotherapy for patients with CD30-
85
positive PTCL. For patients who are eligible, subsequent stem cell transplantation is a potentially curative
option but it is limited to a minority of patients. Despite these treatments, a high proportion of patients
need second line therapy. Belinostat (marketed as Beleodaq), pralatrexate (marketed as Folotyn) and
romidepsin (marketed as Istodax) have each been approved by the FDA in this setting, but efficacy is
generally limited. In the respective non-randomized clinical registration trials, the response rate to
belinostat, pralatrexate and romidepsin were each less than 30%, and the median duration of response was
approximately 10 months for belinostat and pralatrexate (O'Connor, 2015 ; O'Connor, 2011; Coiffier,
2012). None of these treatments have been approved by the EMA.
Despite these approvals, current treatment guidelines (NCCN 2021) recommend participation in a clinical
trial as a preferred option for patients with relapsed PTCL after first line treatment. If clinical trials are not
available, a chemotherapy combination of gemcitabine and oxaliplatin, or GemOx, is listed as one of the
preferred treatment combinations (ESMO Lymphoma Guidelines). Several studies have been published
on the role of GemOx in patients with relapsed lymphoma and it is one of the most widely used regimens
for this patient population in the United States, Europe and Asia (Mounier, 2013; Yamaguchi, 2012).
c. Clinical Trials
Below is a summary of the clinical trials of lacutamab.
Trial
Status
Sponsor
Number of
Patients in Trial
Regimen
Indication(s)
Phase 1
Completed
Innate Pharma
44
Monotherapy
Advanced CTCL (SS, MF)
Phase 2
(TELLOMAK)
Ongoing
Innate Pharma
up to 160
Monotherapy
Advanced CTCL (SS, MF)
Phase 1b
Ongoing
Innate Pharma
20 initially + 20
depending on
preliminary data
Monotherapy
Relapsed/Refractory PTCL
that express KIR3DL2
Phase 2
(KILT)
Ongoing
LYSA 56
Lacutamab + GemOx vs
GemOx
Relapsed/Refractory PTCL
that express KIR3DL2
i.
Phase 1 Clinical Trial - CTCL
In November 2015, the lacutamab Phase 1 dose-escalating and cohort expansion clinical trial was
initiated to evaluate lacutamab for the treatment of advanced CTCL. The trial was completed in April
2020, and enrolled 44 patients, including 35 patients with Sézary syndrome, eight patients with mycosis
fungoides and one patient with CD4+ TCL not otherwise specified. The primary objective of the trial was
to evaluate lacutamab safety, and to identify dose limiting toxicities (DLTs) and the maximum tolerated
dose. Data from this trial were presented at the 2018 meeting of the American Society of Hematology,
and reported in Lancet Oncology in 2019 by Bagot et al. The Company reported clinical activity in the
subgroup of 35 Sézary syndrome patients, including an observed overall response rate of 42.9%, median
duration of response of 13.8 months, median progression-free survival of 11.7 months and approximately
90% of patients experienced an improved quality of life. The overall response rate appeared to be higher
(53.6%) in the 28 patients with no histologic evidence of large cell transformation. Clinical activity was
associated with a substantial improvement in quality of life as assessed by the Skindex29 and Pruritus
Visual Analog Scale scores. In a post-hoc analysis of seven patients with Sézary syndrome who were
previously treated with mogamulizumab, three (43%) achieved a global overall response and three others
86
had stable disease as best response. The remaining patient had a progressive disease. The median duration
of response in these patients was 13.8 months and median progression-free survival was 16.8 months.
Lacutamab was generally well tolerated. The most common adverse effects, or AEs, were peripheral
edema (27%) and fatigue (20%), all of which were grade 1 or 2. Lymphopenia was the most frequent
IPH4102-related adverse event and occurred in six (14%) patients (three (7%) grade 3). One patient
developed possibly treatment-related fulminant hepatitis six weeks after lacutamab discontinuation and
subsequently died. However, the patient had evidence of human herpes virus-6B infection. Six possibly
treatment-related, grade 3 or above adverse events were observed in five patients (11%) and only four
patients (9%) stopped treatment as a result of an adverse event. One patient stopped treatment because of
grade 2 peripheral neuropathy, one patient stopped treatment because of grade 3 general malaise, one
patient because of grade 3 skin pain and one patient stopped treatment because of several adverse events,
including renal injury, respiratory failure, dysphagia and sepsis.
ii.
Phase 2 Clinical Trial (TELLOMAK) - CTCL
In May 2019, the Company initiated a global, open-label, multi-cohort Phase 2 clinical trial, known as
TELLOMAK. This clinical trial is being conducted at approximately 50 sites within the United States and
Europe (France, Italy, Spain, Germany, Belgium, Poland and Austria). The trial aims to evaluate the
efficacy and safety of lacutamab in patients with advanced T-cell Lymphoma. Approximately 160
patients will be recruited for the trial, approximately 60 patients with Sézary syndrome who have received
at least two prior treatments (Cohort 1), and approximately 100 patients with MF who have received at
least two prior systemic therapies (Cohorts 2, 3 and all-comers). Cohorts 2 and 3 recruited KIR3DL2
expressing and non-expressing patients respectively based on an IHC assay for use on frozen tissue. The
cohorts were designed using Simon 2-stage approach which pre-defined an efficacy threshold in Stage 1
before continuing to stage 2. While Cohort 2 continues to Stage 2, the pre-specified threshold for Cohort
3 was not met, and was therefore closed in March 2022.
In March 2022, the Company announced the opening of a new mycosis fungoides (MF) all-comers cohort
in the TELLOMAK study. The all-comers cohort will recruit both KIR3DL2 expressors and non-
expressors to explore the correlation between the level of KIR3DL2 expression and treatment outcomes
utilizing a formalin-fixed paraffin embedded (FFPE) assay as a companion diagnostic. The following
graphic depicts the latest trial design :
The primary endpoint of the trial is objective response rate, measured using the 2011 Olsen criteria for
CTCL. Key secondary measures include incidence of treatment-emergent AEs, the effect of skin disease
on quality of life as measured by the Skindex29 questionnaire, pruritus as measured by the Visual Analog
87
Scale, progression-free survival and overall survival. The results of the dedicated Sézary syndrome cohort
may support a future Biologics License Application (BLA) submission to the FDA.
The TELLOMAK study experienced some supply issues within 2019/2020 which lead to clinical hold,
now resolved and summarized below:
• November 2019, Impletio Wirkstoffabfüllung GmbH (formerly known as Rentschler Fill
Solutions GmbH), the subcontractor in charge of the fill-and-finish manufacturing operations of
lacutamab unilaterally decided to withdraw the certificates of conformance of all clinical batches
produced at their facilities, including lacutamab. The company also filed for bankruptcy.
• Discussions were held with US and European national regulatory authorities regarding GMP
deficiencies resulting in a suspension of enrollment of new patients into TELLOMAK from
December 2019.
•
In January 2020, the TELLOMAK trial in Sézary syndrome and MF in France and in the United
Kingdom, was reactivated following authorization by the respective national authorities. In June
2020, the FDA lifted the partial clinical hold placed on the TELLOMAK Phase 2 clinical trial,
based on a quality assessment of a new GMP-certified batch successfully manufactured for the
lacutamab clinical development program, including the TELLOMAK trial. Regulatory agencies
in Spain, Germany and Italy also lifted, in the third quarter of 2020, their partial clinical holds on
the TELLOMAK trial, enabling Innate to resume recruitment of the trial in these countries.
Importantly, there were no safety issues related to the trial medication. This is consistent with the review
conducted by the Independent Data Monitoring Committee (IDMC), which concluded there were no
safety issues related to lacutamab, and the product appeared to be well-tolerated among current patients
enrolled in the trial. Lacutamab fill and finish manufacturing operations were transferred to alternative
CMOs.
Preliminary Data from TELLOMAK has been communicated externally
•
•
In February 2021, the Company announced that lacutamab demonstrated a positive early signal in
Cohort 2 testing lacutamab in KIR3DL2 expressing MF patients in the TELLOMAK trial. This
cohort reached the pre-determined number of responses needed to advance to stage 2, allowing
the Company to recruit additional patients.
The preliminary data from cohorts 2 and 3 were presented at the ICML and EORTC congresses in
July and October 2021 respectively. Of note, the preliminary data concluded:
•
•
•
•
•
In MF patients, KIR3DL2 expression ≥ 1% appears to be more associated with advanced
stage disease and blood and lymph node involvement compared to KIR3DL2 expression
< 1%.
Lacutamab showed high level of clinical response in MF patients with KIR3DL2
expression ≥ 1% with six global responses (four confirmed and two not confirmed at time
of DCO but confirmed thereafter) in 17 patients with a median follow-up of 4.8 months.
Expansion to stage 2 is underway.
In MF patients with KIR3DL2 expression < 1%, expansion to stage 2 would be triggered
only if one additional confirmed response is observed during follow-up.
Lacutamab shows favorable safety profile in MF, with no relevant skin toxicities
observed.
Long-term follow-up is required to provide mature conclusions on duration of response
and progression free survival.
88
• MF Cohorts 2 and 3 Stage 1 data were presented at the EORTC congress in September 2022. As
of the March 4, 2022 data cutoff
◦
◦
Patients in the KIR3DL2 ≥1% subgroup (cohort 2) received a median of four prior
systemic therapies, and had a median follow-up of 12.2 months. Objective response rate
(ORR) was 28.6% (95% CI 13.8-50.0) including two complete responses and four partial
responses. Median PFS was 12.0 months (4.6-15.4) and Median Duration of Response
was 10.2 months (4.6-NA).
Patients in the KIR3DL2 <1% subgroup (cohort 3) received a median of 4.5 prior
systemic therapies and had a median follow-up of 13.8 months. ORR was 11.1%
(3.1-32.8) with a median PFS of 8.5 months (4.1-NA)
◦ Within the advanced and heavily pre-treated population enrolled in TELLOMAK,
Lacutamab continues to demonstrates clinical activity with a favorable safety profile.
◦
◦
Lacutamab showed low immunogenicity and reached target concentration in both the
KIR3DL2 expressing and non-expressing patients.
Enrollment to TELLOMAK continues* and final data in 2023 with long-term follow-up
will provide more mature conclusions, including on duration of response and progression
free survival.
•
Interim Data from SS Cohort 1 was presented at the ASH congress in December 2022. As of the
29 April 2022 Data Cut-off, Lacutamab demonstrates clinical activity with a favorable safety
profile. Specifically.
◦
◦
The study population has advanced (IVA, IVB), highly refractory disease, and was
heavily pre-treated, with a median of 6 prior lines of therapy.
Skin ORR in ITT is 35.1% (95% CI: 21.8-51.2) and within and EES is 37.1% (95% CI:
23.2-53.7).
◦ Blood ORR in ITT is 37.8% (95% CI: 24.1-53.9) with 21.6% (8/37) achieving CRs; in
EES 40.0% (95% CI: 25.6-56.4) with 22.9% (8/35) CRs.
◦ Within the subgroup of patients that achieved a global response, mDoR is 10.8 months
(95% CI: 6.2-12.3) with median time to global response of 4.4 months (range =1.0;6.5);
median time to blood and skin response was 1.0 months (range = 1.0;6.5) and 2.8 months
(range= 0.9;10.2) respectively.
◦
Enrollment to TELLOMAK continues. Final data with long-term follow-up will provide
more mature conclusions.
•
Final Data Readouts for TELLOMAK are expected in H2 2023.
iii.
Clinical Trials in PTCL
The Company has launched a multi-pronged strategy to evaluate lacutamab in KIR3DL2 expressing
PTCL.
A company-sponsored multi center Phase 1b monotherapy trial evaluating lacutamab in relapsing
KIR3LD2 expressing PTCL patients is ongoing. This trial is recruiting patients in the United States and
South Korea. Approximately 20 patients will be initially included in the study, and 20 more may be added
based on safety and preliminary level of clinical activity. The primary endpoint is safety. Preliminary
data is expected in H2 2023.
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Lacutamab is also being evaluated by LYSA, the Lymphoma Study Association, in an investigator-
sponsored randomized Phase 2 study in relapsed/refractory KIR3DL2 expressing PTCL patients, to
evaluate lacutamab in combination with GemOx versus GemOx alone. This study, named KILT (anti-
KIR in T-Cell Lymphoma), aims to recruit 56 patients in Europe. The primary endpoint is clinical
activity.
Monalizumab, a Dual Checkpoint Inhibitor Targeting T Cells and NK Cells
a. Mechanism & Rationale
Monalizumab (IPH2201) is a potentially first-in-class immune checkpoint inhibitor targeting NKG2A
receptors expressed on tumor infiltrating cytotoxic CD8+ T cells and NK cells. NKG2A is an inhibitory
receptor for HLA-E. HLA-E is frequently overexpressed in the cancer cells of many solid tumors and
hematological malignancies. By expressing HLA-E, cancer cells can protect themselves from killing by
NKG2A+ immune cells. Monalizumab may reestablish a broad anti-tumor response mediated by NK and
T cells, and may enhance the cytotoxic potential of other therapeutic antibodies (André et al, Cell 2018).
b. Rationale for combinations with monalizumab
The Company is primarily focused on investigating monalizumab in combination with durvalumab is an
antibody directed against PD-L1. PD-L1 and HLA-E are both up-regulated on many cancer cells, and
they have both been observed to suppress tumor immune response and contribute to tumor progression.
Innate Pharma's preclinical data support its hypothesis that a monalizumab and durvalumab combination
90
therapy may result in a greater anti-tumor immune response than durvalumab alone by blocking both the
PD-1/PD-L1 and the NKG2A/HLA-E inhibitory pathways.
The following illustration depicts the way in which monalizumab, in combination with durvalumab, is
designed to result in greater anti-tumor activity.
The rationale for this combination is further supported by the favorable tolerability profile of
monalizumab that the Company observed in preclinical studies and earlier clinical trials, suggesting that
monalizumab is generally not expected to negatively impact the safety profile of combination partner
drugs.
c.
Indication
Monalizumab has been evaluated in clinical trials in head and neck, lung and other cancer indications.
Innate has been responsible for the conduct of the IPH2201-203 study in head and neck squamous cell
carcinoma, while AstraZeneca is conducting all other trials (except for the External Sponsored studies).
In lung cancer, AstraZeneca is conducting a randomized Phase 3 study PACIFIC-9 of monalizumab or
oleclumab plus durvalumab in unresectable, Stage III NSCLC setting for patients who have not
progressed after concurrent chemoradiation therapy. PACIFIC-9 follows on from the signal observed in
Phase 2 study in unresectable Stage III NSCLC (COAST). Separately, in resectable early-stage NSCLC,
AstraZeneca has conducted a randomized Phase 2 trial with neoadjuvant treatment (NeoCOAST) and also
has an ongoing Phase 2 trial (NeoCOAST-2), with neoadjuvant and adjuvant treatment, that includes an
arm with durvalumab in combination with chemotherapy and monalizumab.
In head and neck cancer, monalizumab was being evaluated in combination with cetuximab in the Phase 2
IPH 2201-203 study and the Phase 3 INTERLINK-1 trial. In 2022, Innate shared that a planned futility
interim analysis of the INTERLINK-1 Phase 3 study sponsored by AstraZeneca did not meet a pre-
91
defined threshold for efficacy. Based on this result and the recommendation of an Independent Data
Monitoring Committee, AstraZeneca informed Innate that the study would be discontinued. There were
no new safety findings. AstraZeneca plans to share the data in due course. Following Interlink-1 ending,
the IPH2201-203 Phase 1b/2 clinical trial will progress to study closure.
Lung cancer is the leading cause of cancer death, accounting for about one-third of all cancer deaths. In
2020, an estimated 2.2 million people were diagnosed with lung cancer worldwide. 80-85% are classified
as NSCLC. Stage III NSCLC represents approximately one quarter of NSCLC incidence. In 2018, the
FDA approved durvalumab for patients with unresectable stage III NSCLC whose disease has not
progressed following concurrent platinum-based chemotherapy and radiation therapy. However, there is
still a need for new treatment options to further increase the potential for cure in this setting.
d. Clinical Development Plan
i.
Overview
Monalizumab is being investigated for the treatment of NSCLC. Below is a summary of ongoing clinical
trials in oncology that AstraZeneca is conducting to evaluate monalizumab
ii. Clinical Development Plan in Lung Cancer
AstraZeneca conducted COAST a randomized trial investigating durvalumab alone or in combination
with either oleclumab (anti-CD73 monoclonal antibody) or monalizumab (anti-NKG2A monoclonal
antibody) in patients with locally advanced, unresectable Stage III NSCLC who had not progressed after
chemoradiotherapy (CRT). The PACIFIC-9 Phase 3 trial for both combinations of monalizumab or
oleclumab plus durvalumab in unresectable, Stage III NSCLC setting for patients who had not progressed
after concurrent chemoradiation therapy is now ongoing.
Separately, AstraZeneca has evaluated the effectiveness and safety of neoadjuvant durvalumab alone or in
combination with monalizumab or oleclumab in subjects with resectable, early-stage (Stage I [>2cm] to
IIIA) non-small cell lung cancer (NeoCOAST) and in 2022 initiated the Phase 2 trial, NeoCOAST-2, with
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neoadjuvant and adjuvant treatment, that includes an arm with durvalumab in combination with
chemotherapy and monalizumab.
iii. Clinical Development Plan in Head and Neck Cancer
Innate and AstraZeneca have evaluated monalizumab in combination with cetuximab in R/M SCCHN IO
naïve or IO pretreated in a Phase 1b/2 study (IPH2201-203). Based on the results and the unmet need in
the IO-pretreated population, AstraZeneca and Innate elected to advance this program to a Phase 3 study
(INTERLINK-1). Dosing of the first patient in this trial triggered a $50 million milestone payment from
AstraZeneca to Innate in October 2020.
•
IPH2201-203
IPH2201-203 is an open-label, Phase 1b/2 clinical trial in combination with cetuximab and/or durvalumab
in patients with R/M SCCHN. This study is sponsored by Innate Pharma. It includes:
•
•
a Phase 1b dose-escalation portion
a Phase 2 portion comprising three expansion cohorts:
◦ Cohort 1, which enrolled 43 patients, evaluated the combination of monalizumab and
cetuximab in patients with recurrent or metastatic squamous cell carcinoma of the head
and neck (R/M SCCHN) who had been previously treated with chemotherapy alone or
chemotherapy followed by checkpoint inhibitors;
◦ Cohort 2, which enrolled 41 patients and is evaluating the combination of monalizumab
and cetuximab in patients with R/M SCCHN who have received a maximum of two prior
systemic regimens in the R/M setting and with prior exposure to a PD-(L)1 inhibitor
(who Innate refers to as IO-pretreated patients); and
◦ Cohort 3, which enrolled 40 patients, began recruiting in April 2019 and is evaluating the
combination of monalizumab, cetuximab and durvalumab in IO-naïve patients with R/M
SCCHN.
•
Following Interlink-1 ending, the IPH2201 - 203 Phase Ib/2 clinical trial will progress to study
closure.
e. Clinical Results
i.
Lung Cancer: Phase 2 COAST Study
In September 2021, AstraZeneca presented a late-breaker abstract on the randomized COAST Phase 2
trial in patients with unresectable, Stage III non-small cell lung cancer (NSCLC) at the European Society
for Medical Oncology (ESMO) Congress. The presentation highlighted progression-free survival (PFS)
and overall response rate (ORR) results for durvalumab in combination with monalizumab, Innate’s lead
partnered asset, and oleclumab, AstraZeneca’s anti-CD73 monoclonal antibody. After a median follow-up
of 11.5 months, the results of an interim analysis showed a 10-month PFS rate of 72.7% for durvalumab
plus monalizumab, versus 39.2% with durvalumab alone in unresectable, Stage III NSCLC patients
following chemoradiation therapy. The results also showed an increase in the primary endpoint of
confirmed ORR for durvalumab plus monalizumab over durvalumab alone (36% vs. 18%).
ii.
Lung Cancer: Phase 2 NeoCOAST Study
In March 2022, the Phase 2 NeoCOAST multi-drug platform study assessing the safety and efficacy of
neoadjuvant durvalumab in combination with chemotherapy and oleclumab, monalizumab or danvasirten
and adjuvant treatment in participants with resectable, early-stage non-small cell lung cancer has been
accepted for an oral presentation on 11 April 2022 at the Annual Meeting 2022 of the American
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Association for Cancer Research (AACR).” The study demonstrated that a single cycle of neoadjuvant
durvalumab combined with oleclumab, monalizumab, or danvatirsen produced numerically improved
MPR rates (19, 30 and 31.2%, respectively) compared with durvalumab alone (11.1%). No differences in
pCR rates were observed between treatment arms.
iii.
Head and Neck Cancer: IPH2201-203 Study
•
Phase 1b dose-escalation
In the Phase 1b dose-escalation portion of the clinical trial, 17 patients with R/M SCCHN were evaluated
across five dose levels of monalizumab (0.4, 1.0, 2.0, 4.0 and 10.0 mg/kg), which was administered every
two weeks, in combination with cetuximab, which was administered intravenously with an initial dose of
400 mg/m2 and subsequent doses of 250 mg/m2. The combination was well tolerated with no additional
safety concerns compared to monalizumab or cetuximab alone. The recommended Phase 2 dose of
monalizumab in combination with cetuximab was established as 10 mg/kg, administered intravenously
every two weeks.
•
Phase 2: Expansion cohort 1
The primary endpoint for the Phase 2 portion of the trial is objective response rate, which is measured as
the rate of patients who had a complete or partial response according to RECIST 1.1. Secondary
endpoints for the Phase 2 portion of the trial include duration of response, progression-free survival and
overall survival.
As of April 30, 2019, 40 patients were enrolled globally. The monalizumab and cetuximab combination
demonstrated an acceptable safety profile. The trial was declared positive, as the required predefined
number of at least eight responses was reached with an ORR of 27.5% (36% and 17% in IO naïve and IO
pretreated patients, respectively). With a median follow-up of 17 months (mo), median OS is 8.5 mo with
a trend for improved survival in IO-pretreated pts (14.1 mo in IO-pretreated patients and 7.8 in IO naïve
patients, respectively) and 12 mo OS rate of 44% (60% in IO-pretreated and 32% in IO naïve patients,
respectively). The following figures show PFS and OS in all patients and by previous IO.
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An additional cohort of 40 patients (expansion cohort 2) with R/M SCCHN who have received both
platinum-based chemotherapy and anti-PD(L)1 has been conducted to confirm the preliminary results
observed in this subgroup, a population with a continued high unmet medical need. These results were
presented at the SITC conference in 2018.
•
Phase 2: Expansion cohort 2
As of August 31, 2020, 40 patients with R/M SCCHN post platinum and anti-PD-(L)1 were included in
cohort 2 in the United States and France. Median duration of follow-up (FU) was 13.1 months (range
7.9-15.9). The tables below show the responses, the PFS and OS of patients enrolled in cohort 2.
In cohort 1 of the study, 19 patients were enrolled with the same selection criteria and similar
characteristics as cohort 2 and received platinum and post anti-PD-(L)1. An exploratory analysis
combining these patients to those enrolled in cohort 2 is provided in the figure below.
The monalizumab and cetuximab combination therapy demonstrates a good safety profile and promising
activity in R/M SCCHN post platinum and post anti-PD-(L)1 where no treatment options were currently
approved. In this population with a high medical need, the Company observed a high response rate of
20% and promising 6- and 12-month OS of 80% and 33% with monalizumab combined with
cetuximab. These results were presented at the ESMO IO conference in 2020.
Based on these results, a randomized Phase 3 trial, INTERLINK-1, had started to evaluate the
combination monalizumab + cetuximab versus cetuximab + placebo in R/M SCCHN post platinum and
post anti-PD-(L)1 patients.
•
Phase 2: Expansion cohort 3
As of August 1, 2021, 40 patients were enrolled in the cohort 3 evaluating monalizumab, cetuximab and
durvalumab in first line treatment of R/M SCCHN. Median follow-up was 16.3 months (4.4-25.7);
13 patients had a confirmed response, ORR=32.5% [95%CI: 20-48], including three complete responses.
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Median time to response was 1.8 months [1.6-3.7]. 6/13 responders were still on treatment, with median
duration of response not yet reached [7.1-NR]. Median PFS was 6.9 months [4.4-9.3], and 12 months OS
was 59% [45-77].
Evaluation of the activity according to CPS status was performed as an exploratory analysis. In the subset
analysis, the relatively low N should be noted. Further follow-up and analysis is needed.
As a conclusion, the combination of monalizumab (anti-NKG2A), cetuximab (anti-EGFR) and
durvalumab (anti-PD-L1) demonstrates promising activity in the first line R/M SCCHN setting. Safety of
this chemotherapy free regimen is acceptable with a low rate of treatment discontinuation. There are no
new safety signals identified. This data support further evaluation of this antibody triplet combination.
These results were presented at the ESMO IO conference in 2021.
iv.
Phase 1/2 Clinical Trial in Solid Tumors, including Colorectal Cancer (in combination
with durvalumab): D419NC00001
AstraZeneca has evaluated monalizumab in combination with durvalumab in a Phase 1/2 clinical trial in
383 patients with advanced solid tumor malignancies. The study consisted of 3 parts: dose escalation (Part
1), dose expansion (Part 2) and dose exploration (Part 3). In 2018, clinical data showed preliminary anti-
tumor activity in patients with recurrent/metastatic microsatellite-stable colorectal cancer (MSS-CRC), a
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population historically unresponsive to PD-1/L1 blockade. 31% disease control rate at 16 weeks (DCR: %
of responses and stable disease) suggested that patients may benefit from stabilizing effect when 88% of
patients had 2 or more prior lines of therapy for recurrent/metastatic disease. This data formed a basis for
exploring the combination with standard of care therapies (SoC) in less heavily pretreated patients.
f. Main Ongoing Clinical Trials in Lung Cancer
AstraZeneca conducted a Phase 2 randomized studies investigating Imfinzi alone or in combination with
either oleclumab (anti-CD73 monoclonal antibody) or monalizumab (anti-NKG2A monoclonal antibody)
in patients with locally advanced, unresectable Stage III NSCLC who had not progressed after CRT
(COAST).
In February 2022, AstraZeneca initiated a Phase 3 clinical trial, PACIFIC-9, evaluating durvalumab (anti-
PD-L1) in combination with monalizumab (anti-NKG2A) or AstraZeneca’s oleclumab (anti-CD73) in
patients with unresectable, Stage III NSCLC who have not progressed following definitive platinum-
based concurrent chemoradiation therapy (CRT). The study continues to enroll with 999 participants
anticipated overall.
In September 2021, AstraZeneca announced plans to start a Phase 2 trial, NeoCOAST-2, with
neoadjuvant and adjuvant treatment that includes an arm with durvalumab in combination with
chemotherapy and monalizumab, in patients with resectable, early-stage (II to IIIA) NSCLC.
NeoCOAST-2 started in April 2022 and continues to enrol patients.
g. Partnership with AstraZeneca
On April 24, 2015, the Company signed a co-development and commercialization agreement with
AstraZeneca to accelerate and broaden the development of monalizumab. AstraZeneca obtained full
oncology rights to monalizumab in October 2018. The financial terms of the agreement include potential
cash payments of up to $1.225 billion to Innate Pharma. With the addition of the $50 million payment
triggered by dosing the first patient in the Phase 3 PACIFIC-9 clinical trial, Innate Pharma has received
$450 million to date. AstraZeneca will book all sales and will pay Innate low double-digit to mid-teen
percentage royalties on net sales worldwide except in Europe where Innate Pharma will receive if it
chooses to co-promote the licensed products in certain European countries a 50% share of the profits and
losses in these territories. Should Innate Pharma elect not to co-promote, its share of profits in Europe will
be reduced by a specified amount of percentage points not to exceed the mid-single digits. Innate will co-
fund 30% of the costs of the Phase 3 development program of monalizumab with a pre-agreed limitation
on Innate’s financial commitment.
Avdoralimab (IPH5401), an Anti-C5aR Antibody
The Company has decided to discontinue the development of avdoralimab in bullous pemphigoid. The
Company will continue to evaluate out-licensing as a potential next step.
IPH5201, an Anti-CD39 Antibody Targeting the Immunosuppressive Adenosine Pathway
a. Mechanism & Rationale
IPH5201 is a blocking antibody targeting the CD39 immunosuppressive pathway.
CD39 is an extracellular membrane-bound enzyme that is expressed by endothelial cells and immune
cells, especially granulocytes, monocytes, B cells and T regulatory cells. In the tumor microenvironment,
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CD39 is highly expressed on both tumor infiltrating immune cells and stromal cells, in several cancer
types (Allard et al, 2017).
CD39 inhibits the immune system by degrading extracellular adenosine triphosphate (ATP) into
adenosine diphosphate (ADP) and adenosine monophosphate (AMP), and AMP is then further degraded
into adenosine by CD73 (Allard et al, 2016). ATP has immune-stimulatory activity through promoting the
activation of antigen-presenting cells. In contrast, adenosine has immunosuppressive effects on multiple
immune cell types (Antonioli et al, 2013; Leone and Emens, 2018).
IPH5201 inhibits CD39-mediated hydrolysis of ATP to AMP. Therefore, inhibition of CD39-mediated
hydrolysis of ATP by IPH5201 has the potential to promote accumulation of immune-stimulatory ATP
and reduce the formation of immunosuppressive adenosine, thereby leading to increased antitumor
immunity across multiple tumor types.
IPH5201 could potentially exhibit a favorable safety and efficacy profile in patients with early stage or
advanced/metastatic disease in selected solid tumors, including serving as a candidate for combination
treatments with immune therapeutic agents (ie, PD-L1 targeting durvalumab). Inhibition of the PD-L1
and PD-1 immune checkpoint pathway has elicited durable antitumor responses and long-term remissions
in a subset of patients with a broad spectrum of cancers (Zou et al, 2016). However, a considerable
proportion of patients remain unresponsive to these treatments (known as innate resistance), and one-third
of patients relapse after initial response (known as adaptive resistance), which suggests that multiple non-
redundant immunosuppressive mechanisms coexist within the tumor microenvironment (Vijayan et al,
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2017). Combined blockade of CD39 and PD-L1, with IPH5201 and durvalumab, respectively, can
hypothetically increase response rates and improve response duration when compared to durvalumab
monotherapy by altering the balance of ATP and adenosine in the tumor microenvironment. This is
supported by the results of the COAST randomized Phase 2 study, where anti-CD73 oleclumab in
combination with durvalumab improved progression-free survival (PFS) and objective response rate
(ORR) compared to durvalumab alone in patients with unresectable, Stage III non-small cell lung cancer
(NSCLC) (Herbst, JCO, 2022) , as well as in results from NeoCoast randomized Phase 2 study showing
that one cycle of neoadjuvant oleclumab in combination with durvalumab improved MPR (Major
Pathological Response) and pCR (pathological Complete Response) rates versus durvalumab alone, in
stage I-IIIA resectable NSCLC patients (Cascone, AACR 2022).
b. Indication
IPH5201 has been evaluated in a Phase 1 clinical in advanced solid tumors, in monotherapy and in
combination with durvalumab.
Innate is responsible for the conduct of a Phase 2 study (MATISSE) with neoadjuvant and adjuvant
treatment of IPH5201 in combination with durvalumab +/- chemotherapy, in resectable early-stage
NSCLC. The trial has started and is awaiting first patient.
Lung cancer is the second most common cancer in both men and women, with an estimated 234,030 new
cases of lung cancer in the United States in 2018, and remains the main cause of cancer-related deaths
worldwide. Resectable, early-stage NSCLC is considered a potentially curable disease, and the standard
of care is surgery alone or surgery with adjuvant or neoadjuvant platinum-based doublet chemotherapy
(NCCN 2022). However, patients had 5-year survival rates ranging from approximately 70% for Stage
IA1 NSCLC to 20% for Stage IIIA NSCLC (Chansky, 2017). Recently, the role of PD-1/PD-L1 inhibition
has been evaluated for the treatment of resectable, early-stage NSCLC in adjuvant and neoadjuvant
setting. Based on ImPower010 results (Felip 2021), adjuvant atezolizumab, following resection and
platinum-based chemotherapy, has been approved for patients with stage II to IIIA NSCLC by FDA in
October 2021. Based on results of CheckMate-816 trial (Girard, 2022), the FDA granted approval on 4
March 2022 to the combination of nivolumab plus platinum-doublet chemotherapy for the neoadjuvant
treatment of non–small cell lung cancer prior to surgery. The use of perioperative immune checkpoint
inhibitors in both neo-adjuvant and adjuvant setting is under evaluation in several trials.
c. Non Clinical Development
The rationale is supported by the analysis of anti-tumor immune responses in tumor-challenged CD39
deficient mice and by its non-clinical data for IPH5201 in mouse tumor models.
CD39-deficient mice are more resistant to developing lung or liver metastatic tumors after systemic
challenge with syngeneic B16F10 or MC38 tumor cells (Sun, 2010). Subcutaneous (SC) syngeneic
B16F10 tumors also grew more slowly in CD39-deficient mice, leading to improved overall survival
versus wild-type mice, and correlated with reduced angiogenesis and improved effector function of tumor
infiltrating T cells in CD39-deficient mice (Jackson, 2007; Sun, 2013). Furthermore, CD39 deficiency
enhanced the anti-tumor activity of PD-1 blocking antibodies alone and in combination with oxaliplatin
chemotherapy in tumor-bearing mice (Perrot, 2019).
The Company's non-clinical studies demonstrated that IPH5201 blocking CD39 mAb effectively targets
and inhibits CD39 (soluble and membrane form) activity, reverses adenosine-mediated T cell suppression,
and enhances ATP-dependent macrophages and DC activation (adenosine independent). IPH5201
synergized with a blocking mAb against CD73 to restore activation of T cells isolated from cancer
patients in vitro (Perrot, 2019). In syngeneic tumor-bearing human CD39 knock-in mice, the Company
observed that a mouse version of IPH5201 enhanced the antitumor effects of PD-L1 blockade.
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CD39 is expressed in both squamous and adenocarcinoma subtypes of NSCLC with expression noted
across disease stages (Anceriz, ESMO-IO 2022, Poster 190P, abstract 384). In a mouse tumor model
engrafted in huCD39KI mice, moIPH5201 was able to decrease the human CD39 enzymatic activity and
to lower the Ado level in situ. In vitro, chemotherapies induced extracellular ATP release by tumor cells
and IPH5201 was able to accumulate the released ATP, following chemotherapy treatment. Finally, as
shown in the figure below, in vivo, in a mouse tumor model engrafted in huCD39KI mice, moIPH5201
improved the anti-tumor efficacy of gemcitabine and anti-PD-L1 combination. The 3 graphs on the left
(A) show the best tumor volume change in percentage, for each treated group in comparison to the control
group. The diagram on the right outlines survival in each group.
Altogether, the expression profile of CD39 in early-stage NSCLC and preclinical combination data
support the clinical evaluation of IPH5201 in combination with Durvalumab and chemotherapies in early-
stage NSCLC patients.
d. Clinical Trials
In October 2018, Innate Pharma and AstraZeneca entered into a development collaboration and option
agreement for further co-development and co-commercialization for IPH5201. As part of this
collaboration, A Phase 1 clinical trial (NCT04261075), sponsored by AstraZeneca, with first patient
treated in March 2020, evaluating IPH5201, an anti-CD39 blocking monoclonal antibody, in adult
patients with advanced solid tumors. The purpose of the study was to evaluate IPH5201 as monotherapy
and in combination with durvalumab (anti-PD-L1) and with or without oleclumab (anti-CD73 monoclonal
antibody). This multicenter, open-label, dose-escalation Phase 1 study evaluated the safety, tolerability,
antitumor activity, pharmacokinetics (PK), pharmacodynamics (PD) and immunogenicity of IPH5201
alone, or in combination with AstraZeneca’s anti-PD-L1 therapy, durvalumab, with or without its anti-
CD73 monoclonal antibody, oleclumab. The current study status is completed and results were presented
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at the ESMO-IO congress (Imbimbo, Poster 188P, abstract 472). IPH5201 was well tolerated when used
alone or in combination with durvalumab up to a dose of 3000 mg Q3W. The safety profile was
manageable, with the most common treatment-related adverse events being infusion-related reactions and
fatigue; no new safety signals were identified beyond those observed with durvalumab monotherapy. No
maximum tolerated dose (MTD) was identified. PK of IPH5201 was non-linear at ≤300 mg and linear at
≥1000 mg. The PD profile, including inhibition of CD39 activity in the tumours of patients treated with
IPH5201, was consistent with the proposed mechanism of action for IPH5201.
As clinical activity results, 22/57 patients (38.6%) had stable disease as their best overall response; there
were no partial or complete responses. In IPH5201 monotherapy subgroup, 17/38 patients (44.7%) had
stable disease as their best overall response
IPH5201 will be evaluated further in combination with durvalumab and chemotherapy, in an upcoming
Phase 2, Multicenter, open-label, non-randomized study of neoadjuvant and Adjuvant Treatment with
IPH5201 and durvalumab in patients with resectable, early-Stage (II-IIIA) non-Small-cell lung cancer
(MATISSE). The trial has started and is awaiting first patient.
e. Partnership
In October 2018, Innate Pharma and AstraZeneca entered into a development collaboration and option
agreement for further co-development and co-commercialization for IPH5201. Following the dosing of
the first patient on March 9, 2020 in the IPH5201 Phase 1 clinical trial, AstraZeneca made a $5 million
milestone payment to Innate under the companies’ October 2018 multi-product oncology development
collaboration. Innate made a €2.7 million milestone payment to Orega Biotech SAS after the dosing of the
first patient in the Phase 1 pursuant to Innate’s exclusive licensing agreement (see section 10C).
In June 2022, the 2018 CD39 Option Agreement was amended. Innate received a $5M milestone payment
from AstraZeneca upon signature of the amendment and is responsible for conducting a new Phase 2
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multicenter, open label, non-randomized study of neoadjuvant and adjuvant treatment with IPH5201,
durvalumab, and chemotherapy in patients with resectable, early-stage Non-small Cell Lung Cancer
(NSCLC). The "MATISSE" Study has started and is awaiting first patient. AstraZeneca and Innate will
share study costs and AstraZeneca will supply clinical trial drugs. Innate made a €0.6 million milestone
payment to Orega Biotech SAS pursuant to Innate’s exclusive licensing agreement.
IPH5301, an Anti-CD73 Antibody Targeting the Immunosuppressive Adenosine Pathway
a. Mechanism & Rationale
Targeting the pathway that metabolizes adenosine triphosphate (ATP) to adenosine in the tumor
microenvironment is an emerging therapeutic strategy to promote antitumor immunity (Di Virgilio and
al., 2018, Leone and al., 2018, Vijayan, 2017). Within the tumor microenvironment, extracellular ATP is
released by dying cells and has an immune-stimulatory activity, promoting activation of antigen
presenting cells, and a subsequent immune response (de Andrade Mello et al., 2017; Ghiringhelli et al.,
2009). The extracellular enzyme CD39 hydrolyses ATP into adenosine diphosphate (ADP) and adenosine
monophosphate (AMP) in the extracellular space, and CD73 ectonucleotidase (NT5E, ecto-5’-
nucleotidase)
exerts
immunosuppressive effects on both the myeloid and lymphoid compartments (de Andrade Mello et al.,
2017). In T cells, adenosine inhibits effector T cell activation, induces T cell anergy and expands T
regulatory cells (Ehrentraut et al., 2012; Romio et al., 2011; Zarek et al., 2008). Finally, adenosine
inhibits NK cell-mediated tumor cell lysis (Beavis et al., 2013).
(Allard, 2016). Adenosine
further metabolizes AMP
adenosine
to
The benefit of targeting CD73 in oncology has been further demonstrated by results of the COAST
randomized Phase 2 study, where anti-CD73 oleclumab in combination with durvalumab improved
progression-free survival (PFS) and objective response rate (ORR) compared to durvalumab alone in
patients with unresectable, Stage III non-small cell lung cancer (NSCLC) (Herbst, JCO, 2022), as well as
in results from NeoCoast randomized Phase 2 study showing that one cycle of neoadjuvant oleclumab in
combination with durvalumab improved MPR (Major Pathological Response) and pCR (pathological
Complete Response) rates versus durvalumab alone, in stage I-IIIA resectable NSCLC patients (Cascone,
AACR 2022).
The Company is developing IPH5301 (anti-CD73) as a potential anticancer therapy for patients with
advanced or metastatic disease in selected solid tumors. IPH5301 is a monoclonal antibody that
selectively binds to and inhibits the activity of both membrane-bound and soluble human CD73 (NT5E,
ecto-5’-nucleotidase).
IPH5301 inhibits CD73-mediated hydrolysis of adenosine monophosphate (AMP) to adenosine. CD73
has been shown to be expressed by tumor cells as well as stromal cells, endothelial cells, B and T
lymphocytes within the tumor microenvironment, and to play a significant role in promoting
immunosuppression through the pathway degrading AMP into adenosine. Therefore, inhibition of
CD73-mediated hydrolysis of AMP by IPH5301 has the potential to reduce the formation of
immunosuppressive adenosine, thereby leading to increased antitumor immunity across multiple tumor
types, as shown in the figure below.
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b.
Indication
In the tumor microenvironment, CD73 is expressed by tumor cells as well as stromal cells, endothelial
cells and B and T lymphocytes (Allard et al., 2017). Inhibition of CD73 enzymatic activity by IPH5301
has the potential to reduce the formation of immunosuppressive adenosine, thereby leading to increased
antitumor immunity across multiple tumor types.
c. Preclinical Development
CD73 immunohistochemistry studies have revealed that in breast, pancreas and ovarian cancers the vast
majority of patients expressed CD73 on either tumor or stromal cells (Wang et al; Oncotarget 2017,
Innate Pharma Internal data). Additionally, high expression of CD73 in tumors has been associated with
poor prognosis in a variety of cancer types : Non-Small Cell Lung Cancer, Prostate cancer, TNBC,
Ovarian cancer, Colorectal cancer, and Gastric cancer (Inoue et al. 2017; Leclerc et al. 2016; Loi et al.
2013; Gaudreau et al. 2016; Wu et al. 2016; Lu et al. 2013).
CD73-deficient mice have been shown to have an increased resistance to the growth of tumors derived
from a variety of certain tumor cell lines, as well as to metastasis (Stagg 2011). These mice were also
resistant to the induction of fibrosarcomas by the carcinogen 3-methylcholanthrene (MCA), as well as to
the continued growth of established MCA-induced tumors (Stagg 2012). Wild type mice showed
decreased tumor growth and metastases in some models when administered with an anti-CD73 antibody
alone (Antonioli, 2016, Antoniolli 2017). The small anti-tumor effect of anti-CD73 antibodies in mouse
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models was greatly enhanced by combination with checkpoint inhibition such as PD-1 or an adenosine
receptor antagonist (Allard, 2013; Young, 2016).
The Company published preclinical data further supporting the rationale of developing IPH5301.
IPH5301 blocked the enzymatic activity of both CD73 expressed at the cell surface and the soluble form
of CD73. IPH5301 was able to efficiently restore T cell proliferation inhibited by AMP in vitro. In
addition, IPH5301 has been observed to have a differentiated and superior activity compared to
benchmark antibodies that are currently in clinical development (Perrot, 2019).
In syngeneic murine tumor-bearing human CD73 knock-in mice, IPH5301 enhanced the antitumor effects
of PD-1 blockade, as shown in figure below. The four graphs show changes in tumor volume over time
depending on the type of treatment group, which included a control group (black), an IPH5301 (mouse
version) group (pink), an anti-mouse PD-1 group (blue) and an PD-1 and IPH5301 combination group
(green).
Thus, IPH5301 could potentially exhibit a favorable efficacy profile in patients with advanced or
metastatic disease in selected solid tumors, including serving as a candidate for combination treatments
with chemotherapy or immune therapeutic agents.
As further evidence for the negative role of CD73 in anti-tumor response, Loi and al., 2013, examined
gene expression data from 6,000 breast cancer patients and found that high CD73 expression was
associated with poor prognosis in triple-negative breast cancer (TNBC), as was the association between
high CD73 gene expression and pre-surgery treatment with the standard of care chemotherapy
anthracycline. In mice inoculated with the syngeneic 4T1.2 breast tumor cell line, a combination of an
anti-CD73 antibody and doxorubicin (an anthracycline) led to a greater reduction in tumor volume and
increase in mouse survival than either treatment alone.
In HER2-positive breast tumors, high CD73 expression was shown to promote resistance to trastuzumab.
In addition, targeting CD73 was shown to enhance efficacy of treatment with anti-HER2 therapy
(Turcotte, 2017). On the other hand, several chemotherapeutic agents including taxanes, anthracyclines
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and platinum salts were shown to increase the release of ATP (Martins and Tesniere, 2009); (Martins and
Wang, 2014).
All together, these preclinical results indicate that CD73 blockade with IPH5301 has also the potential to
enhance antitumor activity observed with not only PD1 immunotherapy, but also with chemotherapy and
trastuzumab.
d. Ongoing Clinical Trial
In December 2021, Innate Pharma initiated an investigator-sponsored Phase 1 trial of IPH5301, in
collaboration with the Institut Paoli-Calmettes. CHANCES-IPC 2021-008 (NCT05143970) is a First In
Human, Phase 1, multicenter, European study evaluating an anti-CD73, IPH5301, in advanced and/or
metastatic cancer. The trial will be conducted in two parts. The Part I-Dose escalation aims to identify the
maximum tolerated dose (MTD) of IPH5301 agent in monotherapy and recommended Phase 2 dose
(RP2D) for future trials, followed by a safety expansion study part cohort. In the Part II-Expansion
cohort, a total of 12 HER2+ cancer patients, respectively six breast cancer patients and six gastric cancer
patients, are planned to be enrolled into the next expansion cohort to select a recommended dose of
IPH5301 to be administered in combination with chemotherapy and trastuzumab for evaluation in future
trials with selected advanced solid tumors. In March 2022, The Institut Paoli Calmettes announced that
the first patient had been dosed. In December 2022, a "Trial in Progress" poster was presented by the
Institut Paoli Calmettes at ESMO-IO 2022 congress (Goncalvez, ESMO-IO 2022, Poster 199, abstract
290).
ANKET® Platform
a. General Overview
Multi-specific monoclonal antibodies, or multi-specifics, are antibody-derived formats that can
simultaneously bind to two or more different types of molecules. A number of studies of bispecific
antibodies are currently underway, such as those assessing the safety and efficacy of bispecific T cell
engagers, such as BiTEs, which engage T cells via the antigen receptor on one-side of the bispecific T cell
engager, and a tumor antigen on the other side of the BiTE. These molecules have demonstrated the
ability to reduce or slow the growth of tumors in cancer patients, but also carry a significant toxicity risk.
This toxicity risk occurs by engaging all T cells, irrespective of their specificity and development status,
potentially leading to an overt production of cytokines by these T cells, referred to as a cytokine storm. In
parallel, bispecific killer cell engagers, or BiKEs, that engage CD16 receptors found on NK cells, and tri-
specific killer cell engagers, or TriKEs, that engage CD16 receptors and contain IL-15, a cytokine that
promotes NK cell activation and survival, have also been developed to target antigens expressed on solid
tumors. BiKEs and TriKEs can be effective both in vitro and in vivo in preclinical models. These multi-
specific molecules that engage NK cells could reduce the risks associated with toxicity, as NK cell counts
only represent approximately 10% of T cell counts, thereby potentially limiting the likelihood of inducing
a cytokine storm. However, it remains unclear whether these multifunctional CD16 engager antibodies
can activate NK cells in solid tumors since they often express low levels of CD16.
ANKET® (Antibody-based NK cell Engager Therapeutics) is Innate’s proprietary platform for
developing next-generation, multi-specific NK cell engagers to treat certain types of cancer.
This versatile, fit-for-purpose technology is creating an entirely new class of molecules to induce
synthetic immunity against cancer. It leverages the advantages of harnessing NK cell effector functions
against cancer cells and also provides proliferation and activation signals targeted to NK cells.
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Innate's latest innovation, the tetra-specific ANKET® molecule, is the first NK cell engager technology
to engage activating receptors (NKp46 and CD16), a tumor antigen and an interleukin-2 receptor (via
an IL-2 variant, IL-2v) via a single molecule. This innovation is built on its existing tri-specific NK
cell engager technology, which has demonstrated potent NK cell activation, cytotoxicity and efficient
control of tumor growth in preclinical models.
Because NKp46 is expressed on all NK cells and conserved on tumor infiltrating NK cells, and NK
cells are not expected to produce a cytokine storm, ANKET® molecules may overcome the
limitations of both ADCC-inducing antibodies and T cell engagers.
ANKET® Pipeline
Sanofi's partnership
IPH6101/SAR'579, a CD123-targeting NK Cell Engager
a. Mechanism
IPH6101/SAR443579 is the first NKp46/CD16-based NK cell engager (NKCE) that targets CD123 using
Innate’s proprietary multi-specific antibody format ANKET®. It has shown anti-tumor activity in pre-
clinical models, including supporting pharmacokinetic/pharmacodynamic (PK/PD) and safety data in
non-human primate studies, leading to its selection as a drug candidate for development. It is part of a
research collaboration and licensing agreement with Sanofi, under which the companies collaborate on
the development of innovative multi-specific antibody formats engaging NK cells through the activating
receptors NKp46 and CD16 to kill tumor cells. Several NK cell therapies have been shown to induce
antitumor responses, without the complications frequently associated with T-cell therapies, such as
cytokine release syndrome (CRS) or neurotoxicity.
b.
Indication and Rationale
Acute myeloid leukemia (AML) is the most common acute leukemia in adults, mostly affecting elderly
patients, with a median age at diagnosis of 65-70 years. AML is a heterogeneous cancer characterized by
the clonal expansion of myeloid precursors in the bone marrow and peripheral blood. Despite significant
progress in the care of AML patients in the last decade, there is still a clear unmet medical need in AML,
as up to 50% of patients relapse after initial chemotherapy, and the prognosis for older patients remains
poor.
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Cytotoxic antibodies targeting CD123 displayed limited antileukemic activity in several clinical trials,
even when tested in the form of Fc-engineered antibodies designed specifically to increase antibody-
dependent cell cytotoxicity (ADCC). By contrast, T-cell engager molecules and CAR-T cell therapies
have some clinical efficacy, but are also highly toxic, confirming the need for alternative targeted
approaches for the treatment of AML. NK cell-based therapies may provide new treatment perspectives
and a safer alternative for targeting tumor cells in this context.
c. Preclinical Development
In its preclinical studies, Innate and Sanofi investigated whether NKp46-based NKCE technology could
provide more effective antitumor activity than regular IgG antibodies for AML treatment by generating a
NKCE molecule targeting CD123. Innate and Sanofi evaluated the ex vivo antitumor activity of this
molecule, comparing it with a regular IgG1 antibody derived from clone 7G3 (CD123-IgG1+) with an
engineered Fc domain for enhanced ADCC.
The anti-CD123 antibody-mediated killing of primary blasts from AML patients (AML#1 to AML#4)
was evaluated ex vivo with NK cells from healthy donors as effectors. The anti-CD123 antibody (CD123-
IgG1+) mediated the killing of blasts from half the patient samples (AML#1 and AML#2 but was barely
active against blasts from the other half of the primary samples (AML#3 and AML#4). The patient
samples could therefore be separated into two distinct groups: CD123-IgG1+-responders and CD123-
IgG1+-non-responders.
Innate and Sanofi observed that trifunctional CD123-ANKET® displayed killing activity against all
primary malignant AML cells, promoting significant antitumor activity in CD123-IgG1+-non-responders
samples from AML patients against which the regular anti-CD123 cytotoxic antibody was completely
inactive.
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The minimal level of pro-inflammatory cytokine release following the treatment of human peripheral
blood mononuclear cells (PBMCs) with NKCE in vitro (data not shown) was further confirmed in vivo, in
dedicated pharmacokinetic (PK), pharmacodynamic (PD) and toxicology studies performed in non-human
primates (NHPs).
Innate and Sanofi evaluated the PK/PD of CD123-NKCE administered by a single one-hour i.v. infusion
of a high (3 mg/kg) or low (3 µg/kg) doses in male cynomolgus monkeys (2 animals each for the 3 mg/kg
and 3 µg/kg doses). Treatment with CD123-NKCE promoted a sustained and complete depletion of
CD123+ cells in the blood of all monkeys, for more than 10 days, at both the 3 mg/kg and 3 µg/kg doses,
with only very small amounts (< 50 pg/mL) of the pro-inflammatory cytokines IL-6 and IL-10 released
without any associated clinical signs.
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d. Ongoing Clinical Trial
IPH6101/SAR443579 is currently being evaluated in a Phase 1/2 clinical trial (NCT05086315) in patients
with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute lymphoblastic leukemia (B-
ALL) or high risk-myelodysplastic syndrome (HR-MDS). Innate Pharma announced that the first patient
was dosed on December 16, 2021.
The purpose of the dose escalation and dose expansion study, which is sponsored by Sanofi, is to evaluate
the safety, pharmacokinetics, pharmacodynamics and initial clinical activity of IPH6101/SAR443579,
Innate’s lead ANKET® asset, in various CD123-expressing hematological malignancies.
e. Partnership
In 2016, Sanofi and Innate entered into a research collaboration and licensing agreement for the
generation and evaluation of up to two bispecific NK cell engagers, using technology from Innate Pharma
and Sanofi’s proprietary bispecific antibody format.
Under the terms of the original license agreement, Sanofi is responsible for the development,
manufacturing and commercialization of products resulting from the research collaboration. Innate
Pharma will be eligible to up to €400m in development and commercial milestone payments as well as
royalties on net sales for 2 targets. To date, for CD123 program, €10m milestone payments to Innate have
been announced.
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IPH6401/SAR’514, a BCMA-targeting NK Cell Engager
a. General Overview
IPH6401/SAR’514 is a BCMA-targeting NK cell engager using Sanofi’s proprietary CROSSODILE®
multi-functional platform, which comprises the Cross-Over-Dual-Variable-Domain (CODV) format.
It induces a dual targeting of the NK activating receptors, NKp46 and CD16, for an optimized NK cell
activation, based on Innate’s ANKET® (Antibody-based NK cell Engager Therapeutics) proprietary
platform.
b. Partnership
In 2016, Sanofi and Innate entered into a research collaboration and licensing agreement for the
generation and evaluation of up to two bispecific NK cell engagers, using technology from Innate Pharma
and Sanofi’s proprietary bispecific antibody format.
Under the terms of the original license agreement, Sanofi is responsible for the development,
manufacturing and commercialization of products resulting from the research collaboration. Innate
Pharma will be eligible to up to €400m in development and commercial milestone payments as well as
royalties on net sales for 2 targets. To date, for BCMA program, €4m milestone payments to Innate have
been announced.
IPH62, a B7-H3-targeting NK Cell Engager
a. General Overview
IPH62 is a B7-H3-targeting NK cell engager using Innate’s proprietary multi-specific antibody format
ANKET® platform.
It induces a dual targeting of the NK activating receptors, NKp46 and CD16, for an optimized NK cell
activation, based on Innate’s ANKET® (Antibody-based NK cell Engager Therapeutics) proprietary
platform.
b. Partnership
In December 2022, Sanofi and Innate entered into a research collaboration and license agreement under
which Innate licenses to Sanofi a natural killer (NK) cell engager program targeting B7-H3 from Innate’s
ANKET® (Antibody-based NK Cell Engager Therapeutics) platform. Sanofi will also have the option to
add up to two additional ANKET® platform targets. Upon candidate selection, Sanofi will be responsible
for all development, manufacturing and commercialization.
Under the terms of the new agreement, Sanofi gains exclusive license to Innate’s B7-H3 ANKET®
platform program and options for two additional targets; Upon candidate selection, Sanofi will be
responsible for all development, manufacturing and commercialization. Innate received €25m upfront
(received in March 2023) and will be eligible to up to €1.35bn in total milestones plus royalties from
Sanofi.
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Proprietary ANKET®
IPH6501, a CD20-targeting tetra-specific NK Cell Engager
a. Mechanism
The IPH6501 program is developing a CD20-targeting tetra-specific antibody-based NK cell engager
therapeutic (ANKET®). CD20 is an antigen expressed by a number of B cell malignancies, and its
targeting by therapeutic antibodies has shown efficacy to treat the patients although a number of the
tumors develop resistance and relapse. Compared to a classical IgG1-based antibody which engages Fc
receptors and a tumor antigen, IPH6501 co-engages on one hand NKp46 and Fc receptors, as well as
CD122 subunit of the IL-2 receptor (but not CD25 subunit), and on the other hand CD20 as a targeted
antigen on malignant B cells, leading to potent NK cell activation, cytotoxicity and control of tumor
growth.
IPH6501 was designed to induce NK cell mediated-cytotoxicity and cytokine secretion by co-engaging
CD16a and NKp46. Only the binding of IPH6501 to CD20, bridging the NK cells to the target cells, was
able to trigger the cytotoxic activity of NK cells. IPH6501 is thus a promising biologic designed to
harness the anti-tumor functions of NK cells in CD20+ B cell malignancies.
Moreover, the IL-2R binding element incorporated in IPH6501 is an IL-2 variant (IL-2v) designed with
point mutations that abolish binding to the IL-2R-α chain (CD25), with the goal of limiting toxicity and
interaction with Tregs. IL-2v incorporated into IPH6501 is directed towards NK cells through the binding
with high affinity to NKp46 and CD16a, providing its ability to interact with IL-2R preferentially on NK
cells and to promote their activation and proliferation at pM doses.
b.
Indication and Rationale
IPH6501 is being developed in patients with relapsed or refractory (R/R) CD20+ B-cell non-Hodgkin's
lymphomas (NHL).
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NHL is the most prevalent hematological malignancy, accounting for 4% of all new cancer cases and 3%
of cancer-related deaths in the US (Howlader 2020a, Howlader 2020b). For 2021, estimates for the US
include 81,560 new cases and 20,720 deaths from NHL {American Cancer Society 2021a, American
Cancer Society 2021b}. In 2020, Europe had 122,979 new cases of NHL reported, and 49,684 deaths
were attributable to NHL {World Health Organization (WHO) 2020}. The emergence of relapsed
refractory (r/r) disease among B-cell malignancies with curtailed sustained responses to treatment and
unattained long-term survivals has created a significant unmet need {National Comprehensive Cancer
Network (NCCN) 2021a}.
CD20 is expressed by >90% of B-cell non-Hodgkin's lymphomas (NHL). Several generations of CD20-
targeting monoclonal antibodies including rituximab, ofatumumab, and obinutuzumab have been widely
used for B-cell malignancy therapies. Despite the recent approvals of novel CD20-targeting agents, new
alternatives and strategies are still required for patients, which are relapsing or refractory after several
lines of treatment. High circulating NK cell numbers have been associated with better clinical responses
to anti-CD20-targeting monoclonal antibodies, supporting the role of NK cells in efficacy of these
treatments.
c. Preclinical Development
IPH6501 preclinical activity was explored both in vitro and in vivo. In vitro studies established that
IPH6501´s main modes of action were NK cell proliferation and antibody-dependent cell cytotoxicity
(ADCC) against CD20-expressing cells.
Non-saturating doses of IPH6501 on NK cells and on CD20+ cells were sufficient to promote maximal
killing activity. Furthermore, IPH6501 promoted NK cell cytotoxicity against tumor cells expressing very
low levels of CD20. IPH6501 also demonstrated superiority to control tumor cell growth in vitro, as
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compared to the CD20-targeting clinical benchmark antibodies rituximab and the Fc-optimized
obinutuzumab.
IPH6501 alone without NK cells did not induce direct killing of CD20+ cells. Culturing human purified
NK cells with CD20+ B-lymphoma cell lines and IPH6501 induced the specific lysis of tumoral CD20+
cells. Alternatively, culturing human PBMCs with IPH6501 induced the specific depletion of normal
CD20+ B lymphocytes without affecting other lymphocyte population numbers, as well as cytokine
production in line with NK cell activation. Incubation of human PBMC with IPH6501 induced a
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preferential NK cell proliferation that occurred at lower doses as compare to the proliferating effect of
IPH6501 on other CD8+ or CD4+ T lymphocytes (expressing the IL-2R).
In vivo treatment with a mouse surrogate of IPH6501 induced peripheral NK cell proliferation and
activation, and demonstrated potent antitumor efficacy in a xenograft mouse model using the aggressive
human B-lymphoma CD20+ RAJI cell line engrafted subcutaneously. Surrogate moIPH6501 also showed
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a dose dependent and significant control of tumor growth in a model of CD20-expressing B16F10 cells
injected intravenously (IV) in immunocompetent mice, as shown in figure below.
In non-human primates, a well-tolerated dose of IPH6501 led to peripheral NK cell expansion and to the
depletion of CD20+ B cells in the circulation and within lymphoid tissues, with minimal systemic
cytokine release.
In conclusion, IPH6501 is a first-in-class CD20-targeting tetra-specific NK cell engager designed to
promote NK cell proliferation and specific cytotoxicity against CD20+ cells. IPH6501 is thus a promising
biologic designed to harness the anti-tumor functions of NK cells in CD20+ B cell malignancies.
d. Future Clinical Trial
IND–enabling studies are ongoing and IND filing is expected in 2023.
Additional Preclinical Programs
a. Proprietary
Fueling the R&D engine, the Company continues to develop different approaches for the treatment of
cancer utilizing its antibody engineering capabilities to deliver novel assets, with its innovative ANKET®
platform and continuing to explore Antibody Drug Conjugates (ADC) formats. The Company has a
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robust pipeline of additional preclinical product candidates. Its additional disclosed preclinical pipeline
includes IPH4501, an ADC with an undisclosed target and IPH43, an anti-MICA/B ADC.
b. Partnered
Innate announced in April 2023 that it granted Takeda exclusive worldwide rights to research and develop
ADC using a panel of selected Innate antibodies against an undisclosed target, with a primary focus in
Celiac disease.
Takeda will be responsible for the future development, manufacture and commercialization of any
potential products developed using the licensed antibodies.
Under the terms of the license agreement, Innate will receive a $5m upfront payment and is eligible to
receive up to $410m in future development, regulatory and commercial milestones if all milestones are
achieved during the term of the agreement, plus royalties on potential net sales of any commercial product
resulting from the license.
Next Steps
Competition
The biotechnology and pharmaceutical industry, and notably the cancer field, is characterized by rapidly
advancing technologies, products protected by intellectual property rights and intense competition and is
subject to significant and rapid changes as researchers learn more about diseases and develop new
technologies and treatments. While the Company believes that its technology, knowledge, experience,
collaborations and scientific resources provide Innate with competitive advantages, the Company faces
potential competition from many different sources,
including major pharmaceutical, specialty
pharmaceutical and biotechnology companies, academic institutions, governmental agencies and public
and private research institutions. Any approved product that Innate Pharma commercializes will compete
with existing therapies and new therapies that may become available in the future.
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There are a large number of companies developing or marketing treatments for cancer, including many
major pharmaceutical and biotechnology companies. Many of its competitors have significantly greater
experience, personnel and resources as it relates to research, drug development, manufacturing and
marketing. In particular, large pharmaceutical laboratories have substantially more experience than the
Company does in conducting clinical trials and obtaining regulatory authorizations. Mergers and
acquisitions in the pharmaceutical, biotechnology and diagnostic industries may result in even more
resources being concentrated among a smaller number of its competitors. Smaller or early-stage
companies may also prove to be significant competitors, particularly through collaborative arrangements
with large and established companies. These competitors are also likely to compete with Innate to recruit
and retain top qualified scientific and management personnel, acquire rights for promising product
candidates and technologies, establish clinical trial sites and patient registration for clinical trials, acquire
technologies complementary to, or necessary for, its programs and enter into collaborations with potential
partners who have access to innovative technologies.
Innate's commercial opportunity could be reduced or eliminated if its competitors develop and
commercialize products that are more effective, have a better safety profile, are more convenient, have a
broader label, have more robust intellectual property protection or are less expensive than any products
that the Company may develop. Its competitors also may obtain regulatory approval for their products
more rapidly than the Company may obtain approval for its, which could result in its competitors
establishing a strong market position before the Company is able to enter the market. In addition, its
competitors could be more efficient in manufacturing or more effective in marketing their own products
than the Company or its partners may be in the future.
With respect to its lead product candidate, lacutamab, a monoclonal antibody product candidate targeting
KIR3DL2, the Company is aware of several pharmaceutical companies marketing and developing
products for the treatment of patients with CTCL, including MF and Sézary syndrome, and PTCL. The
latest drugs approved by the FDA for CTCL: Adcetris (brentuximab vedotin), marketed by Seattle
Genetics and approved in combination with chemotherapy for treatment of patients with primary
cutaneous anaplastic large cell lymphoma (pcALCL) or CD30-expressing MF who have received prior
systemic therapy, and Poteligeo (mogamulizumab), marketed by Kyowa Kirin and approved for the
treatment of adult patients with R/R MF or Sézary syndrome after at least one prior systemic therapy.
Zolinza (vorinostat) is the only drug approved by the FDA for CTCL patients after two prior failures. In
the second line setting of PTCL, Beleodaq (belinostat), Folotyn (pralatrexate) and Istodax (romidepsin)
have all been approved by the FDA; however, none of these treatments have been approved by the EMA.
With respect to monalizumab, a novel dual-targeting checkpoint inhibitor, there are other anti-NKG2A
that have started to be assessed in clinical trials, and there are several pharmaceutical companies
marketing and developing treatments for either NSCLC. There are currently two ongoing clinical trials
assessing other anti-NKG2A molecules. A Phase 1/2 is assessing BMS-986315 (Bristol-Myers Squibb)
monotherapy or in combination with nivolumab or cetuximab in patients with solid tumors. A Phase 1
study is assessing S095029 (Servier) monotherapy or in combination with an anti-PD-1 in patients with
solid tumors with dose expansion cohorts that add an anti-HER2 or anti-EGFR to the doublet. Exelis and
Invenra are collaborating to develop a bispecific targeting PD-L1 and NKG2A which is in the preclinical
setting. Imfinzi (durvalumab), marketed by AstraZeneca, is approved for the treatment of unresectable,
Stage III NSCLC following concurrent platinum-based chemotherapy and radiation therapy.
There are also several pharmaceutical and biotechnology companies that are focused on the tumor
microenvironment, including the complement and the adenosine pathways. Many companies are active in
the adenosine pathway, targeting CD73, CD39 or the adenosine receptors. For example, AstraZeneca and
I-Mab Biopharma US Limited each have anti-CD73 product candidates in Phase 2 clinical development,
and several other biotechnology companies are active in the adenosine pathway area, including Trishula
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Therapeutics, Inc., Novartis Pharmaceuticals, Corvus Pharmaceuticals, Inc., Gilead Sciences, Inc. and
Surface Oncology, Inc.
NK cells have been increasingly researched and the Company is aware of many companies activating
and /or harnessing NK cells to target and kill cancer cells through different approaches such as cell
therapies (Fate Therapeutics, Inc. and NantKwest, Inc.) and multi-specifics (Affimed N.V. and Dragonfly
Therapeutics, Inc.).
Intellectual Property
Commercial success of the Company depends in part on obtaining and maintaining patent, trade secret
and other intellectual property and proprietary protection of its technology, current and future products
and product candidates and methods used to develop and manufacture them. The Company cannot be sure
that patents will be granted with respect to any of its pending patent applications or to any patent
applications filed by Innate in the future, nor can the Company be sure that any of its existing patents or
any patents that may be granted to Innate in the future will be sufficient to protect its technology or will
not be challenged, invalidated or circumvented. Its success also depends on its ability to operate its
business without infringing, misappropriating or otherwise violating any patents and other intellectual
property or proprietary rights of third parties.
The Company relies, in some circumstances, on trade secrets to protect its technology. However, trade
secrets can be difficult to protect. The Company seeks to protect its trade secrets, in part, by
confidentiality agreements with its employees, consultants, scientific advisors and contractors. These
agreements may not provide meaningful protection or may be breached, and the Company may not have
an adequate remedy for any such breach. The Company also seeks to preserve the integrity and
confidentiality of its data and trade secrets by maintaining physical security of its premises and physical
and electronic security of its information technology systems. Notwithstanding these measures, these
agreements and systems may be breached, and the Company may not have adequate remedies for any
such breach. In addition, its trade secrets may otherwise become known or be independently discovered
by competitors or misused by collaborators to whom the Company discloses such information. Despite
measures taken to protect its intellectual property, unauthorized parties may attempt to copy aspects of its
products or drug candidates or obtain or use information that the Company regards as proprietary. As a
result, the Company may be unable to meaningfully protect its trade secrets and proprietary information.
To the extent that its employees, consultants, contractors or partners use intellectual property owned by
others in their work for us, disputes may arise as to the rights in related or resulting know-how and
inventions. For more information regarding the risks related to intellectual property, please see “Risk
Factors—Risks Related to Intellectual Property Rights.”
Patents
The Company files patent applications to protect its product candidates, technical processes and the
processes used to prepare its product candidates, the compounds or molecules contained in these product
candidates and medical treatment methods. The Company also licenses rights to patents owned by third
parties, academic partners or other companies in its field.
Monalizumab/IPH2201
As of December 31, 2022, the principal intellectual property rights related to monalizumab are in-licensed
from Novo Nordisk A/S and include U.S. Patent Nos. 8,206,709 and 8,901,283, European patents
EP 2 038 306 B1 and EP 2 426 150 B1 and counterpart patents in certain other countries. These patents
are directed to the composition of matter of monalizumab and have a statutory expiration date in 2027,
not including patent term adjustment or any potential patent term extension.
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Lacutamab/Anti-KIR3DL2
As of December 31, 2022, the principal intellectual property rights related to lacutamab are wholly owned
by Innate and include U.S. Patent No. 10,280,222, European patent EP 3 116 908 B1 and counterpart
patent applications in certain other countries. These patents and patent applications are directed to the
composition of matter of lacutamab, and such patents have, and any patents that issue from such
applications would have, a statutory expiration date in 2035, not including patent term adjustment or any
potential patent term extension.
Avdoralimab /Anti-C5aR
As of December 31, 2022, the principal intellectual property rights related to avdoralimab are in-licensed
from Novo Nordisk A/S and include U.S. Patent Nos. 8,613,926, 8,846,045 and 10,323,097, European
patents EP 2 718 322 B1 and EP 3 424 953 B1counterpart patents and patent applications in certain other
countries. These patents and patent applications are directed to the composition of matter of avdoralimab,
and such patents have, and any patents that issue from such applications would have, a statutory
expiration date in 2032, not including patent term adjustment or any potential patent term extension.
IPH5201/Anti-CD39
As of December 31, 2022, the principal intellectual property rights related to IPH5201 are co-owned by
Innate together with Orega Biotech, and include U.S. patent No. 11,377,503, one European patent
application, and other patent applications in certain other countries. These patents and patent applications
are directed to the composition of matter of IPH5201, and such have, and any patents that issue from such
patent application would have, a statutory expiration date in 2039, not including patent term adjustment or
any potential patent term extension.
IPH5301/Anti-CD73
As of December 31, 2022, the principal intellectual property rights related to IPH5301 are solely owned
by us, and include one U.S. non-provisional patent application, one European patent application, and
other patent applications in certain other countries. If a patent directed to IPH5301 issues from such U.S.
patent application, it would have a statutory expiration date in 2040, not including patent term adjustment
or any potential patent term extension.
The term of individual patents depends upon the legal term of patents in the countries in which they are
obtained. In most countries, including the United States, the patent term is 20 years from the earliest
claimed filing date of a non-provisional patent application or its foreign equivalent in the applicable
country. In the United States, a patent’s term may, in certain cases, be lengthened by patent term
adjustment, which compensates a patentee for administrative delays by the USPTO in examining and
granting a patent, or may be shortened if a patent is terminally disclaimed over a commonly owned patent
or a patent naming a common inventor and having an earlier expiration date. In the United States, a patent
may also be eligible for limited patent term extension under the Drug Price Competition and Patent Term
Restoration Act of 1984, or Hatch-Waxman Amendments. The Hatch-Waxman Amendments permit a
patent extension term of up to five years as compensation for patent term lost during the FDA regulatory
review process. A patent term extension cannot extend the remaining term of a patent beyond a total of 14
years from the date of product approval, only one patent applicable to each regulatory review period may
be extended and only those claims covering the approved drug, a method for using it, or a method for
manufacturing it may be extended.
Trademarks
The Company owns the mark INNATE PHARMA in the United States, Australia and Europe (EU
community trademark), and INNATE in Europe (EU community trademark). The Company also owns
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registrations for the mark ANKET® respectively in the United States and Europe (EU community
trademark).
Regulation
Research and development work, preclinical tests, clinical studies, facilities, and the manufacture and sale
of its products are and will continue to be subject to the complex legislative and regulatory provisions
implemented by the various competent authorities in Europe, the United States and other countries. The
EMA, FDA and the various national regulatory authorities impose considerable constraints on the
development, manufacture and sale of products that the Company develops and clinical trials it conducts.
In case of non-compliance with these regulations, the regulatory authorities may impose fines, seize or
withdraw products from the market or even partially or totally suspend their production. They may also
revoke previously granted marketing authorizations, reject authorization applications. These regulatory
constraints are important in considering whether an active ingredient can ultimately become a drug, as
well as for recognizing the time and investments necessary for such development.
Although there are differences from one country to another, the development of therapeutic products for
human use is subject to similar procedures and must comply with the same types of regulations in all ICH
countries (countries part of the International Council for Harmonisation of Technical Requirements for
Registration of Pharmaceuticals for Human Use). In order to obtain marketing authorization for a product,
proof of its efficacy and safety should be provided by the applicant, along with detailed information on its
composition and manufacturing process. This entails significant pharmaceutical and preclinical
developments, clinical trials and laboratory tests. The development of a new drug from fundamental
research to marketing comprises five steps: (i) research, (ii) preclinical trials, (iii) clinical trials in
humans, (iv) marketing authorization and (v) marketing.
Preclinical studies
Preclinical studies include laboratory evaluation of the purity and stability of the manufactured substance
or active pharmaceutical ingredient and the formulated product, as well as in vitro and animal studies to
assess the safety and activity of the product candidate for initial testing in humans and to establish a
rationale for therapeutic use. The conduct of preclinical studies is subject to federal regulations and
requirements, including Good Laboratory Practices (GLP) regulations. The results of the preclinical tests,
together with manufacturing information, analytical data, any available clinical data or literature and plans
for clinical studies, among other things, are submitted to the applicable regulatory agency in connection
with the application to begin human testing. Some long-term preclinical testing, such as animal tests of
reproductive adverse events and carcinogenicity, and long-term toxicity studies, may continue after
submission of the application.
Regulation of clinical trials
In humans, clinical trials are usually carried out in three Phases that are generally sequential, but under
unique circumstances Phases of trials can overlap or even be skipped, following a specific review and
determination by regulatory agencies. Clinical trials are sometimes necessary after marketing
authorization to explain certain side-effects, investigate a specific pharmacological effect, obtain more
accurate or additional data. Additional trials are also commonly conducted to explore new indications.
Regulatory authorization is needed to carry out clinical trials. The regulatory authorities may block,
suspend or require significant modifications to the clinical study protocols submitted by companies
seeking to test products.
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Clinical trial authorization in the European Union
The regulation relating to clinical trials is governed by European Directive 2001/20/EC of April 4, 2001
on clinical trials, which has been transposed into national legislation by all European Union Member
States.
The 2001 Directive cited above has been revised and replaced by the Clinical Trials Regulation EU No.
536/2014 of April 16, 2014, which aims at harmonizing and streamlining the clinical trials authorization
process. The Clinical Trial Regulation EU No. 536/2014 of April 16, 2014 entered into force on June 16,
2014. However, the new regulation became applicable six months after the European Commission
published notice of the confirmation of full functionality of the EU Clinical Trials Information System.
Therefore the Clinical Trials Regulation is in application from January 31, 2022. It applies to
interventional clinical trials on medicinal products and to clinical trials authorized under the previous
Clinical Trial Directive 2001/20/EC with a three years transition period from the Clinical Trial Regulation
has come into operation. As from January 31st 2023, all new clinical trial applications are registered on
EU-CTR. Ttrials approved under EU-CTD before 30th January 2023 can continue to be regulated under
EU-CTD until 30 January 2025.
The Clinical Trial Regulation allows better consistency throughout EU Member States:
•
•
Single submission of the clinical trial application dossier through the EU Clinical Trials
Information System (Article 5) including a common part assessed jointly by all participating
EU Member States, and a national part covering the ethical and operational aspects of the trial
assessed by each EU Member State independently.
A clinical trial authorization issued in the form of a single decision.
The Clinical Trials Regulation applies in the Member States without the requirement for separate
implementing legislation by each Member State, but some of the existing laws of the Member States
applicable at a national level will continue to apply.
This new regulation will also increase transparency of authorized clinical trials in the European Union:
the EU Clinical Trials Information System will serve as the source of public information, without
prejudice of personal data protection, commercially confidential information protection, and protection of
confidential communication and trial supervision between Member States. Public information will include
clinical trial authorization information, protocol data, and a summary of the results 12 months after the
end of the trial (or six months in case of pediatric clinical trials).
Clinical trial authorization in the United States
In the United States, IND must be submitted to the FDA and accepted before clinical trials can start on
humans. An IND is an exemption from the Federal Food, Drug, and Cosmetic Act, or FDCA, that allows
an unapproved product candidate to be shipped in interstate commerce for use in an investigational
clinical trial and a request for FDA authorization to administer an investigational product to humans. This
application contains early research data as well as the pharmaceutical dossier, preclinical and clinical data
(if any) and includes the clinical protocol. If there is no objection from the FDA, the IND application
becomes valid 30 days after it is received by the FDA. This waiting period is designed to allow the FDA
to review the IND to determine whether human research subjects will be exposed to unreasonable health
risks. At any time during or subsequent to this 30-day period, the FDA may request the suspension of
clinical trials, whether such trials are planned or in progress, and request additional information. This
temporary suspension continues until the FDA receives the information it has requested.
In addition to the foregoing IND requirements, an independent institutional review board, or IRB,
representing each institution participating in the clinical trial must review and approve the plan for any
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clinical trial before it commences at that institution, and the IRB must conduct continuing review and
reapprove the study at least annually. The IRB must review and approve, among other things, the study
protocol and informed consent information to be provided to study subjects. An IRB must operate in
compliance with FDA regulations. An IRB can suspend or terminate approval of a clinical trial at its
institution, or an institution it represents, if the clinical trial is not being conducted in accordance with the
IRB’s requirements or if the product candidate has been associated with unexpected serious harm to
patients.
The FDA’s primary objectives in reviewing an IND are to assure the safety and rights of patients and to
help assure that the quality of the investigation will be adequate to permit an evaluation of the biological
product’s safety, purity and potency. The decision to terminate development of an investigational
biological product may be made by either a health authority body such as the FDA, an IRB, or by Innate
for various reasons. Additionally, some trials are overseen by an independent group of qualified experts
organized by the trial sponsor, known as a data safety monitoring board or committee. This group
provides authorization for whether or not a trial may move forward at designated check points based on
access that only the group maintains to available data from the study. Suspension or termination of
development during any Phase of clinical trials can occur if it is determined that the participants or
patients are being exposed to an unacceptable health risk. Other reasons for suspension or termination
may be made by Innate based on evolving business objectives and/or competitive climate.
Good clinical practices (GCP)
In most countries, clinical trials must comply with the current GCP (cGCP) standards as defined by the
International Council for Harmonization of Technical Requirements for Registration of Pharmaceuticals
for Human Use, or ICH. Directive 2005/28/EC dated April 8, 2005 adopted the cGCP principles in the
context of strengthening the regulatory structure specified by Directive 2001/20/EC. The competent
authority designated in each Member State to authorize clinical trials must take into consideration, among
other factors, the scientific value of the study, the safety of the drug and the possible responsibility of the
clinical site.
Conducting clinical trials
Clinical trials must be carried out in compliance with complex regulations throughout the various Phases
of the process, based on the principle of informed consent by the patient to whom the products will be
administered.
Clinical trial Phases
Clinical trials may be conducted in the United States, in Europe or in other parts of the world as long as
such trials have been approved by health authorities and ethics committees in each country where the trial
is conducted. There are three well-established and internationally-recognized clinical Phases: Phase 1, 2
and 3. This classification is used by the FDA and the EMA, as well as other regulatory agencies. Each of
these clinical Phases is described below.
•
Phase 1: The product candidate is initially introduced into healthy human subjects and tested
for safety, dosage tolerance, absorption, metabolism, distribution and excretion. In the case of
some products for severe or life-threatening diseases, such as cancer, especially when the
product may be too inherently toxic to ethically administer to healthy volunteers, the initial
human testing is often conducted with patients. Sponsors sometimes designate their Phase 1
trials as Phase 1a or Phase 1b. Phase 1b trials are typically aimed at confirming dosing,
pharmacokinetics and safety in larger number of patients. Some Phase 1b studies evaluate
biomarkers or surrogate markers that may be associated with efficacy in patients with specific
types of diseases.
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Phase 2: This Phase involves clinical trials in a limited patient population to identify possible
adverse effects and safety risks, to preliminarily evaluate the efficacy of the product for
specific targeted diseases and to determine dosage tolerance and appropriate dosage.
Phase 3: Clinical trials are undertaken to further evaluate dosage, clinical efficacy and safety
in an expanded patient population at geographically dispersed clinical study sites. These
clinical trials, generally comparative, are intended to establish the overall risk-benefit ratio of
the product candidate and provide, if appropriate, an adequate basis for product labeling.
Post-approval trials, sometimes referred to as Phase 4 studies, may be conducted after initial marketing
approval. These trials are used to gain additional experience from the treatment of patients in the intended
therapeutic indication. In certain instances, the applicable regulator may mandate the performance of
Phase 4 clinical trials as a condition of approval.
In specific situations, certain Phases of development can be merged or even skipped when clear signs of
efficacy emerge in the early Phases of development and the product candidate is designed for patients
with major unmet medical needs. However, these deviations from the standard pattern of development
must be discussed and approved by health authorities. Given the high unmet medical need for certain
cancer patients, deviations from the typical Phases of development are frequent in oncology and
particularly in the field of immunotherapy.
Disclosure of clinical trial information
Sponsors of clinical trials of FDA-regulated drugs are required to register and disclose certain clinical trial
information, which is publicly available at www.clinicaltrials.gov. Similarly, in Europe, Sponsors are
required to register and disclose certain clinical trial information on a single portal, CTIS (Clinical Trial
Information System), replacing Eudra-CT, set up by the European Medicines Agency (EMA). CTIS is as
single entry point centralizing information and databases on clinical trials in the EU. Eudra-CT will be
definitively abandoned at the end of the transition period, i.e. on January 30, 2025. Information related to
the product, patient population, Phase of investigation, study sites and investigators, and other aspects of
the clinical trial is then made public as part of the registration. Sponsors are also obligated to disclose the
results of their clinical trials after completion. Disclosure of the results of these trials can be delayed until
the new product or new indication being studied has been approved. Competitors may use this publicly
available information to gain knowledge regarding the progress of development programs.
Regulations concerning marketing authorizations
In order to be marketed, a drug product must have regulatory authorization (known as approval of a New
Drug Application, or NDA, or a Biologics License Application, or BLA, in the United States, a Marketing
Authorization Application, or MAA, in the European Union and a Great Britain Marketing Authorisation
Application). The competent authorities are the FDA in the United States, the EMA in the European
Union and the MHRA in the United Kingdom. Companies apply for an NDA/BLA or an MAA based on
quality, safety and efficacy. In the European Union, the United States and Japan, the dossier is a standard
dossier referred to as a CTD, or Common Technical Document. The file relating to the NDA/BLA/MAA
describes the manufacturing of the active substance, the manufacturing of the final product and the
clinical and non-clinical studies.
United States review and approval process for biological products
In the United States, the FDA approves complex biological products under the Public Health Service Act,
or PHSA. In order to obtain approval to market a biological product in the United States, a marketing
application must be submitted to the FDA with data establishing the safety, purity and potency of the
proposed biological product for its intended indication. The application includes all relevant data
available from pertinent preclinical and clinical trials, including negative or ambiguous results as well as
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positive findings, together with detailed information relating to the product’s chemistry, manufacturing,
controls and proposed labeling, among other things. Data can come from company-sponsored clinical
trials intended to test the safety and effectiveness of a use of a product, or from a number of alternative
sources, including studies initiated by investigators. To support marketing approval, the data submitted
must be sufficient in quality and quantity to establish the safety, purity and potency of the biological
product to the satisfaction of the FDA.
The biologics license applications (BLA) is thus a vehicle through which applicants formally propose that
the FDA approve a new biological product for marketing and sale in the United States for one or more
indications. Every new biological product candidate must be the subject of an approved BLA before it
may be commercialized in the United States. Under federal law, the submission of most BLAs is subject
to an application user fee and the sponsor of an approved BLA is also subject to annual program user fees.
These fees typically increase annually. Certain exceptions and waivers are available for some of these
fees, such as an exception from the application fee for products with orphan designation and a waiver for
certain small businesses, an exception from the establishment fee when the establishment does not engage
in manufacturing the product during a particular fiscal year, and an exception from the product fee for a
product that is the same as another product approved under an abbreviated pathway.
Following submission of a BLA, the FDA conducts a preliminary review of the application generally
within 60 calendar days of its receipt and strives to inform the sponsor by the 74th day after the FDA’s
receipt of the submission of whether the application is sufficiently complete to permit substantive review.
The FDA may request additional information rather than accept the application for filing. In this event,
the application must be resubmitted with the additional information. The resubmitted application is also
subject to review before the FDA accepts it for filing. Once the submission is accepted for filing, the FDA
begins an in-depth substantive review. The FDA has agreed to specified performance goals in the review
process of BLAs. Under that agreement, 90% of applications seeking approval of New Molecular
Entities, or NMEs, are meant to be reviewed within ten months from the date on which FDA accepts the
application for filing., and 90% of applications for NMEs that have been designated for “priority review”
are meant to be reviewed within six months of the filing date. For applications seeking approval of
products that are not NMEs, the ten-month and six-month review periods run from the date that FDA
receives the application. The review process and the Prescription Drug User Fee Act goal date may be
extended by the FDA for three additional months to consider new information or clarification provided by
the applicant to address an outstanding deficiency identified by the FDA following the original
submission.
Before approving an application, the FDA typically will inspect the facility or facilities where the product
is or will be manufactured. These pre-approval inspections may cover all facilities associated with a BLA
submission, including component manufacturing, finished product manufacturing, and control testing
laboratories. The FDA will not approve an application unless it determines that the manufacturing
processes and facilities are in compliance with cGMP requirements and adequate to assure consistent
production of the product within required specifications. Additionally, before approving a BLA, the FDA
will typically inspect one or more clinical sites to assure compliance with GCP. In addition, as a condition
of approval, the FDA may require an applicant to develop a Risk Evaluation and Mitigation Strategy, or
REMS. REMS use risk minimization strategies beyond the professional labeling to ensure that the
benefits of the product outweigh the potential risks. To determine whether a REMS is needed, the FDA
will consider the size of the population likely to use the product, seriousness of the disease, expected
benefit of the product, expected duration of treatment, seriousness of known or potential adverse events,
and whether the product is a new molecular entity.
The FDA may refer an application for a novel product to an advisory committee or explain why such
referral was not made. Typically, an advisory committee is a panel of independent experts, including
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clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to
whether the application should be approved and under what conditions. The FDA is not bound by the
recommendations of an advisory committee, but it considers such recommendations carefully when
making decisions.
On the basis of the FDA’s evaluation of the application and accompanying information, including the
results of the inspection of the manufacturing facilities, the FDA may issue an approval letter or a
complete response letter. An approval letter authorizes commercial marketing of the product with specific
prescribing information for specific indications. A complete response letter generally outlines the
deficiencies in the submission and may require substantial additional testing or information in order for
the FDA to reconsider the application. If and when those deficiencies have been addressed to the FDA’s
satisfaction in a resubmission of the BLA, the FDA will issue an approval letter. The FDA has committed
to reviewing such resubmissions in two or six months depending on the type of information included.
Even with submission of this additional information, the FDA ultimately may decide that the application
does not satisfy the regulatory criteria for approval.
If the FDA approves a product, it may limit the approved indications for use for the product, require that
contraindications, warnings or precautions be included in the product labeling, require that post-approval
studies, including Phase 4 clinical trials, be conducted to further assess the product’s safety after approval,
require testing and surveillance programs to monitor the product after commercialization, or impose other
conditions, including distribution restrictions or other risk management mechanisms, including REMS,
which can materially affect the potential market and profitability of the product. The FDA may prevent or
limit further marketing of a product based on the results of post-marketing studies or surveillance
programs.
Registration procedures in the European Union
To access the European markets through community procedures, drug products must be submitted
through the Centralized Procedure, the Mutual Recognition Procedure or the Decentralized Procedure.
The process for doing this depends, among other things, on the nature of the medicinal product.
Regulation (EC) No 726/2004 of the European Parliament and of the Council of March 31, 2004 provides
for the Centralized Procedure. The Centralized Procedure results in a single marketing authorization
(MA), granted by the European Commission that is valid across the European Economic Area or EEA
(i.e., the European Union as well as Iceland, Liechtenstein and Norway). The Centralized Procedure is
compulsory for human drugs that are: (i) derived from biotechnology processes, (ii) contain a new active
substance indicated for the treatment of certain diseases, such as cancer, HIV/AIDS, diabetes,
neurodegenerative diseases, autoimmune and other immune dysfunctions and viral diseases, (iii) officially
designated orphan medicines and (iv) advanced-therapy medicines, such as gene therapy, somatic cell
therapy or tissue-engineered medicines.
Under Article 3 of the Regulation (EC) No 726/2004, the Centralized Procedure is optional for any other
human medicinal product if: (1) the medicinal product contains a new active substance ; or (2) the
applicant shows that the medicinal product constitutes a significant therapeutic, scientific or technical
innovation or that the granting of authorization in accordance with this Regulation is in the interests of
patients health at EU level.
Under the Centralized Procedure in the European Union, the European Medicines Agency (EMA), shall
ensure that the opinion of the Committee for Medicinal Products for Human Use (CHMP), is given within
210 days (Article 6.3). This excludes so-called clock stops, during which additional written or oral
information is to be provided by the applicant in response to questions asked by the CHMP (Article 7). At
the end of the review period, the CHMP provides its opinion through a scientific assessment report to the
European Commission. The Commission may then adopt a final decision to grant an MA. Once granted,
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the MA is valid across all EEA countries for an initial period of five years. Since 2008, as a consequence
of a European directive, a marketing authorization is now renewed only once, five years after the initial
registration. The marketing authorization shall be then valid for an unlimited period, unless the
Commission decides, on justified grounds, relating to pharmacovigilance, to proceed with one additional
five-year renewal.
National MAs, issued by the competent authorities of the member states of the EEA, are also available;
however these only cover their respective territory. National MAs may be applied for through the Mutual
Recognition Procedure or Decentralized Procedure in order that multiple competent authorities in
different member states of the EEA may each issue a national MA in their territory for the same product
on the back of the same application. National MAs are only available for products not falling within the
mandatory scope of the Centralized Procedure.
It is possible for a drug to be withdrawn from the market, upon the request of the health authorities, if a
serious problem arises, in particular a safety-related problem. The marketing authorization is then
cancelled. There can be various reasons for the withdrawal of drugs from the market, with the main
reasons being public health, major undesirable side effects and non-compliance with manufacturing rules.
Non-standard regulatory procedures
Aside from the standard procedures of granting a BLA or a European MA, as described above, there are
non-standard regulatory procedures that allow a shorter time-to-market for new medicines.
The following expedited approval programs are in place in the United States:
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The Accelerated Approval is a program that is intended to make promising products for life
threatening diseases available on the market on the basis of preliminary evidence prior to
formal demonstration of patient benefit. The FDA evaluation is performed on the basis of a
surrogate marker (a measurement intended to substitute for the clinical measurement of
interest) that is considered likely to predict patient benefit. A result of substitution or marker
(“surrogate endpoint”) is a result of laboratory or physical sign that is not in itself a direct
measure of the patient’s feelings, its functions or survival, but which allows to anticipate a
therapeutic benefit. The approval that is granted may be considered as a provisional approval
with a written commitment to complete clinical studies that formally demonstrate patient
benefit. This procedure is equivalent to the “conditional approval” in the European Union.
The Priority Review is given to drugs that offer major advances in treatment, or provide a
treatment where no adequate therapy exists. A Priority Review means that the time it takes
FDA to review a new drug application is reduced to six months rather than 10 months. This
procedure is equivalent to the “accelerated assessment” in the European Union.
The Fast Track Designation refers to a process for interacting with FDA to facilitate the
development and expedite the review of new drugs that are intended to treat serious or life-
threatening conditions and that demonstrate the potential to address unmet medical needs. The
advantages of this process include scheduled meetings to seek FDA input into clinical
development plans and to collect appropriate data that will be needed to support approval. Fast
Track designation does not necessarily lead to a Priority Review or Accelerated Approval.
The Breakthrough Therapy Designation is aimed at accelerating the development and
examination of drugs which are intended to treat serious illnesses and where the preliminary
clinical evidence indicates that the drug may exhibit a substantial improvement over the
available therapies with regard to clinically significant criterion (criteria).
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A drug which is given the designation “Breakthrough Therapy” can benefit from the following:
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All of the features of the designation “Fast Track”;
Intensive support on a program for the development of effective drugs, from Phase 1 onwards;
and
Organizational commitment involving “FDA senior managers.”
An Emergency Use Authorization (EUA) is a mechanism to facilitate the availability and use of medical
countermeasures, including vaccines, during public health emergencies, such as the current COVID-19
pandemic. Under an EUA, FDA may allow the use of unapproved medical products, or unapproved uses
of approved medical products in an emergency to diagnose, treat, or prevent serious or life-threatening
diseases or conditions when certain statutory criteria have been met, including when there are no
adequate, approved, and available alternatives.
In the European Union, non-standard registration procedures under the Centralized Procedures are as
follows:
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Conditional marketing authorization: valid one year (instead of five). It is granted only if the
benefit / risk ratio is positive, if the product addresses unmet medical needs, and if the benefits
to public health outweigh the risks associated with uncertainty because of an incomplete
evaluation of the drug (for instance, because of clinical trials still ongoing at the time of the
evaluation, or when additional clinical trials are needed). It is renewed annually if an
appropriate report is submitted annually by the sponsor. Once the results of the pending
studies are provided, it can become a “regular” marketing authorization.
Approval under exceptional circumstances: a marketing authorization may be granted in
exceptional cases, reviewed each year to reassess the risk-benefit balance when the initial
dossier for assessment of the drug cannot contain all required data, for instance when the
condition to be treated is rarely encountered.
Accelerated assessment : the evaluation process is accelerated (150 days instead of 210 days)
when a drug is of major interest from the standpoint of public health or in particular from the
viewpoint of therapeutic innovation.
The PRIME (priority medicines) scheme refers to a process for enhanced interactions and
early dialogue with EMA to facilitate the development and speed up examination of drugs
which target unmet medical needs or offer a major therapeutic advantage over existing
treatments. Through PRIME, drug developers can expect to be eligible for accelerated
assessment at the time of application for a marketing authorization.
As part of the EU pharmaceuticals strategy, the EU Commission is working on a revision of
the EU’s general legislation on medicines for human use. A draft Directive proposal and a
draft Regulation proposal are to be submitted by the Commission to the Council and the
Parliament in March 2023. The EU legislative process will then take several years. The
revision will impact the global legal framework for medicinal products in the EU, including
legislation relating to Orphan and paediatric drugs and will review the incentives system (data
protection and market exclusivity) in place.
Orphan drugs
Orphan drugs are drugs used for the prevention or treatment of life-threatening or serious rare conditions.
In the United States, the 1983 Orphan Drug Act is intended to encourage the development of treatments
for orphan diseases. The FDA grants the status of orphan drug to any drug aimed at treating diseases
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affecting fewer than 200,000 people in the United States, or more in cases in which there is no reasonable
expectation that the cost of developing and making a product available in the United States for treatment
of the disease or condition will be recovered from sales of the product. The Orphan Drug Act also
provides the possibility of obtaining grants from the American government to cover clinical trials, tax
credits to cover research costs, a possible exemption from application fees when filing for registration
with the FDA and from program fees, and a seven-year exclusivity if a marketing authorization is granted.
If a product with orphan designation receives the first FDA approval for the disease or condition for
which it has such designation or for a select indication or use within the rare disease or condition for
which it was designated, the product will generally receive orphan drug exclusivity. Orphan drug
exclusivity means that the FDA may not approve another sponsor’s marketing application for the same
drug for the same indication for seven years, except in certain limited circumstances. Orphan exclusivity
does not block the approval of a different product for the same rare disease or condition, nor does it block
the approval of the same product for different indications. If a biologic designated as an orphan drug
ultimately receives marketing approval for an indication broader than what was designated in its orphan
drug application, it may not be entitled to exclusivity. Orphan exclusivity will not bar approval of another
product under certain circumstances, including if a subsequent product with the same biologic for the
same indication is shown to be clinically superior to the approved product on the basis of greater efficacy
or safety, or providing a major contribution to patient care, or if the company with orphan drug
exclusivity is not able to meet market demand.
In the European Union, equivalent legislation has been adopted to promote treatments for rare diseases
(Regulation 141/2000/EC of December 16, 1999, as amended by Regulation 847/2000/EC of April 27,
2000). A medicinal product may be designated as orphan if: (a) it is intended for the diagnosis, prevention
or treatment of a life-threatening or chronically debilitating condition affecting not more than five in
10,000 persons in the European Union when the application is made, or (b) it is intended for the
diagnosis, prevention or treatment of a life-threatening, seriously debilitating or serious and chronic
condition in the European Union and that without incentives it is unlikely that the marketing of the
medicinal product in the European Union would generate sufficient return to justify the necessary
investment.
For either of these conditions, the applicant must demonstrate that there exists no satisfactory method of
diagnosis, prevention or treatment of the condition in question that has been authorized in the EU or, if
such method exists, the medicinal product will be of significant benefit to those affected by that condition.
Medicinal products receiving orphan designation in the European Union can receive ten years of market
exclusivity, during which time no similar medicinal product can be submitted for the same therapeutic
indication. An orphan product can also obtain an additional two years of market exclusivity in the
European Union for pediatric studies (in this case for orphan drugs no extension to any supplementary
protection certificate can be granted, see further detail below). Orphan medicinal products are also
eligible for financial incentives such as reduction of fees or fee waivers and scientific assistance for study
proposals. (Articles 6 and 9 of the above-mentioned regulation). The application for orphan drug
designation must be submitted before the application for marketing authorization (Article 5). The
applicant will receive a fee reduction for the marketing authorization application if the orphan drug
designation has been granted, but not if the designation is still pending at the time the marketing
authorization is submitted. Orphan drug designation does not convey any advantage in, or shorten the
duration of, the regulatory review and approval process.
The 10-year market exclusivity may be reduced to six years if, at the end of the fifth year, it is established
that the product no longer meets the criteria for orphan designation, for example, if the product is
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sufficiently profitable not to justify maintenance of market exclusivity (Article 8). However, marketing
authorization may be granted to a similar medicinal product for the same indication at any time if:
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•
the holder of the MA for the original orphan medicinal product has given its consent to the
second applicant;
the holder of the MA for the original orphan medicinal product cannot supply sufficient
quantities of the orphan medicinal product; or
the second applicant can establish in the application that its product, although similar to the
orphan medicinal product already authorized, is safer, more effective or otherwise clinically
superior.
Registration procedures outside of the European Union and the United States
In addition to regulation in the United States and the European Union, a variety of foreign regulations
govern clinical trials, commercial sales and distribution of drugs. Pharmaceutical firms who wish to
market their medicinal drugs outside the European Union and the United States must submit marketing
authorization application to the national authorities of the concerned countries, such as the Pharmaceutical
and Medical Device Agency, or PMDA in Japan. The approval process varies from jurisdiction to
jurisdiction and the time to approval may be longer or shorter than that required by the FDA or European
Commission.
Of note, in Great Britain, as a result of the end of the Brexit transition period, a reliance on the
Commission final decision to grant an MA applies for a period of two years from January 1, 2021, when
determining an application for a Great Britain Marketing Authorization.
Post-approval regulations
Post-approval regulation in the United States
Biologics manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing
regulation by the FDA, including, among other things, requirements relating to recordkeeping, periodic
reporting, product sampling and distribution, advertising and promotion and reporting of adverse
experiences with the product. After approval, most changes to the approved product, such as adding new
indications or other labeling claims, are subject to prior FDA review and approval. There are also
continuing, annual user fee requirements for any marketed products and the establishments at which such
products are manufactured, as well as new application fees for supplemental applications with clinical
data.
In addition, manufacturers and other entities involved in the manufacture and distribution of approved
products are required to register their establishments with the FDA and state agencies, and are subject to
periodic unannounced inspections by the FDA and aforementioned state agencies for compliance with
cGMP requirements. Changes to the manufacturing process are strictly regulated and often require prior
FDA approval before being implemented. FDA regulations also require investigation and correction of
any deviations from cGMP and impose reporting and documentation requirements upon the sponsor and
any third-party manufacturers that the sponsor may decide to use.
Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory
requirements and standards is not maintained or if problems occur after the product reaches the market.
Later discovery of previously unknown problems with a product, including adverse events of
unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory
requirements, may result in revising the approved labeling to add new safety information; imposing post-
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market studies or clinical trials to assess new safety risks; or imposing distribution or other restrictions
under a REMS program. Other potential consequences include, among other things:
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•
•
•
restrictions on the marketing or manufacturing of the product, suspension of the approval, or
complete withdrawal of the product from the market or product recalls;
fines, warning letters or holds on post-approval clinical trials;
refusal of the FDA to approve pending applications or supplements to approved BLAs, or
suspension or revocation of product license approvals;
product seizure or detention, or refusal to permit the import or export of products; and
injunctions or the imposition of civil or criminal penalties.
In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug
Marketing Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security
Act, or DSCSA, which regulate the distribution and tracing of prescription drug samples at the federal
level, and set minimum standards for the regulation of distributors by the states. The PDMA, its
implementing regulations and state laws limit the distribution of prescription pharmaceutical product
samples, and the DSCSA imposes requirements to ensure accountability in distribution and to identify
and remove counterfeit and other illegitimate products from the market.
The FDA strictly regulates marketing, labeling, advertising and promotion of products that are placed on
the market. Products may be promoted only for the approved indications and in accordance with the
provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations
prohibiting the promotion of off-label uses. Prescription products may be promoted only for the approved
indications and in accordance with the provisions of the approved label. However, companies may also
share truthful and not misleading information that is otherwise consistent with the labeling. A company
that is found to have improperly promoted off-label uses may be subject to significant liability.
Patent term restoration and extension in the United States
A patent claiming a new biologic product may be eligible for a limited patent term extension under the
Hatch-Waxman Act, which permits a patent restoration of up to five years for patent term lost during
product development and the FDA regulatory review. The restoration period granted on a patent covering
a product is typically one-half the time between the effective date a clinical investigation involving
human beings is begun and the submission date of an application, plus the time between the submission
date of an application and the ultimate approval date. Patent term extension cannot be used to extend the
remaining term of a patent past a total of 14 years from the product’s approval date. Only one patent
applicable to an approved product is eligible for the extension, the application for the extension must be
submitted prior to the expiration of the patent in question, and only those claims covering the approved
drug, a method for using it, or a method for manufacturing it may be extended. A patent that covers
multiple products for which approval is sought can only be extended in connection with one of the
approvals. The USPTO reviews and approves the application for any patent term extension or restoration
in consultation with the FDA. For more information regarding the risks related to patent term restoration
and extension, please see “Risk Factors—Risks Related to Intellectual Property Rights—If the Company
does not obtain protection under the Hatch-Waxman Amendments and similar non-U.S. legislation for
extending the term of patents covering Lumoxiti and each of its product candidates, its business may be
materially harmed.”
Healthcare law and regulation in the United States
Healthcare providers and third-party payors play a primary role in the recommendation and prescription
of biologic products that are granted marketing approval. Arrangements with providers, consultants, third-
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party payors and customers are subject to broadly applicable fraud and abuse, anti-kickback, false claims
laws, transparency laws and patient data privacy laws and regulations and other healthcare laws and
regulations that may constrain business and/or financial arrangements. Restrictions under applicable
federal and state healthcare laws and regulations, include the following:
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the U.S. Anti-Kickback Statute, which prohibits, among other things, persons and entities from
knowingly and willfully soliciting, offering, paying, receiving or providing remuneration,
directly or indirectly, in cash or in kind, to induce or reward either the referral of an individual
for, or the purchase, order or recommendation of, any good or service, for which payment may
be made, in whole or in part, under a federal healthcare program such as Medicare and
Medicaid;
the U.S. civil and criminal false claims laws, including the civil False Claims Act, and civil
monetary penalties laws, which prohibit individuals or entities from, among other things,
knowingly presenting, or causing to be presented, to the federal government, claims for
payment that are false, fictitious or fraudulent or knowingly making, using or causing to made
or used a false record or statement to avoid, decrease or conceal an obligation to pay money to
the federal government;
the U.S. Health Insurance Portability and Accountability Act of 1996, or HIPAA, which
created additional federal criminal laws that prohibit, among other things, knowingly and
willfully executing, or attempting to execute, a scheme to defraud any healthcare benefit
program or making false statements relating to healthcare matters;
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health
Act, and their respective implementing regulations, including the Final Omnibus Rule
published in January 2013, which impose obligations on covered entities and their business
associates, including mandatory contractual terms, with respect to safeguarding the privacy,
security and transmission of individually identifiable health information;
the federal transparency requirements known as the federal Physician Payments Sunshine Act,
under the Patient Protection and Affordable Care Act, as amended by the Health Care
Education Reconciliation Act, or the ACA, which requires certain manufacturers of drugs,
devices, biologics and medical supplies to report annually to the Centers for Medicare &
Medicaid Services, or CMS, within the United States Department of Health and Human
Services, information related to payments and other transfers of value made by that entity to
physicians and teaching hospitals, as well as ownership and investment interests held by
physicians and their immediate family members; and
analogous state and foreign laws and regulations, such as state anti-kickback and false claims
laws, which may apply to healthcare items or services that are reimbursed by non-
governmental third-party payors, including private insurers.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s
voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal
government in addition to requiring manufacturers to report information related to payments to physicians
and other health care providers or marketing expenditures. Certain state laws require the reporting of
information relating to drug and biologic pricing; and some state and local laws require the registration of
pharmaceutical sales representatives. State and foreign laws also govern the privacy and security of health
information in some circumstances, many of which differ from each other in significant ways and often
are not preempted by HIPAA, thus complicating compliance efforts.
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Failure to comply with these laws or any other governmental regulations as applicable, could result in the
imposition of significant civil, criminal and administrative penalties, damages, fines, disgorgement,
imprisonment, possible exclusion from government funded healthcare programs, such as Medicare and
Medicaid, additional integrity reporting requirements and oversight, as well as contractual damages,
reputational harm, diminished profits and future earnings, and curtailment of operations.
Healthcare reform in the United States
A primary trend in the United States healthcare industry and elsewhere is cost containment. There have
been a number of federal and state proposals during the last few years regarding the pricing of
pharmaceutical and biopharmaceutical products, limiting coverage and reimbursement for biologics and
other medical products, government control and other changes to the healthcare system in the United
States.
For example, the United States and state governments continue to propose and pass legislation designed
to reduce the cost of healthcare. In March 2010, the United States Congress enacted the ACA, which,
among other things, includes changes to the coverage and payment for products under government health
care programs. Among the provisions of the ACA of importance to potential product candidates are:
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an annual, nondeductible fee on any entity that manufactures or imports specified branded
prescription biologic agents, apportioned among these entities according to their market share
in certain government healthcare programs, although this fee would not apply to sales of
certain products approved exclusively for orphan indications;
expansion of eligibility criteria for Medicaid programs by, among other things, allowing states
to offer Medicaid coverage to certain individuals with income at or below 133% of the federal
poverty level, thereby potentially increasing a manufacturer’s Medicaid rebate liability;
expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by
increasing the minimum rebate for both branded and generic products and revising the
definition of “average manufacturer price,” or AMP, for calculating and reporting Medicaid
rebates on outpatient prescription product prices and extending rebate liability to prescriptions
for individuals enrolled in Medicare Advantage plans;
addressed a new methodology by which rebates owed by manufacturers under the Medicaid
Drug Rebate Program are calculated for products that are inhaled, infused, instilled, implanted
or injected;
expanded the types of entities eligible for the 340B drug discount program;
established the Medicare Part D coverage gap discount program by requiring manufacturers to
now provide a 70% point-of-sale-discount off the negotiated price of applicable brand
products to eligible beneficiaries during their coverage gap period as a condition for the
manufacturers’ outpatient products to be covered under Medicare Part D;
a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and
conduct comparative clinical effectiveness research, along with funding for such research; and
established the Center for Medicare and Medicaid Innovation within CMS to test innovative
payment and service delivery models to lower Medicare and Medicaid spending, potentially
including prescription product spending.
There have been judicial and Congressional challenges to certain aspects of the ACA, as well as efforts by
the Trump administration to repeal and replace certain aspects of the ACA, and such challenges may
occur again. Former President Trump has signed two executive orders designed to delay the
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implementation of certain provisions of the ACA or otherwise circumvent some of the requirements for
health insurance mandated by the ACA. Concurrently, Congress has considered legislation that would
repeal or repeal and replace all or part of the ACA. While Congress has not passed comprehensive repeal
legislation, two bills affecting the implementation of certain taxes under the ACA have been signed into
law. The Tax Cuts and Jobs Act of 2017 includes a provision that repealed, effective January 1, 2019, the
tax-based shared responsibility payment imposed by the ACA on certain individuals who fail to maintain
qualifying health coverage for all or part of a year that is commonly referred to as the “individual
mandate.” In addition, the 2020 federal spending package permanently eliminated, effective January 1,
2020, the ACA-mandated “Cadillac” tax on high-cost employer-sponsored health coverage and medical
device tax and, effective January 1, 2021, also eliminated the health insurer tax. In July and December
2018, CMS published final rules with respect to permitting further collections and payments to and from
certain ACA qualified health plans and health insurance issuers under its risk adjustment program in
response to the outcome of federal district court litigation regarding the method CMS uses to determine
this risk adjustment. On December 14, 2018, a Texas U.S. District Court Judge ruled that the ACA is
unconstitutional in its entirety because the “individual mandate” was repealed by the U.S. Congress as
part of the Tax Cuts and Jobs Act of 2017. Additionally, on June 17, 2021, the U.S. Supreme Court
dismissed a challenge on procedural grounds that argued the ACA is unconstitutional in its entirety
because the "individual mandate" was repealed by Congress. Thus the ACA will remain in effect in its
current form. It is unclear how judicial and Congressional challenges and other efforts to repeal and
replace the ACA will impact the ACA. The Company continues to evaluate how the ACA and recent
efforts to limit the implementation of the ACA will impact its business.
Other legislative changes have been proposed and adopted in the United States since the ACA was
enacted. For example, in August 2011, the Budget Control Act of 2011, among other things, created
measures for spending reductions by Congress. A Joint Select Committee on Deficit Reduction, tasked
with recommending a targeted deficit reduction of at least $1.2 trillion for the years 2012 through 2021,
was unable to reach required goals, thereby triggering the legislation’s automatic reduction to several
government programs. This includes aggregate reductions of Medicare payments to providers of up to 2%
per fiscal year, which went into effect in April 2013 and will remain in effect through 2030 unless
additional Congressional action is taken. However, COVID-19 relief support legislation suspended the
2% Medicare sequester from May 1, 2020 through December 31, 2021. In January 2013, President
Obama signed into law the American Taxpayer Relief Act of 2012, which, among other things, further
reduced Medicare payments to several providers, including hospitals, imaging centers and cancer
treatment centers, and increased the statute of limitations period for the government to recover
overpayments to providers from three to five years.
Furthermore, there has been increasing legislative and enforcement interest in the United States with
respect to drug pricing practices. Specifically, there have been several recent U.S. Congressional inquiries
and proposed and enacted federal and state legislation designed to, among other things, bring more
transparency to drug pricing, review the relationship between pricing and manufacturer patient programs,
reduce the cost of drugs under Medicare, and reform government program reimbursement methodologies
for drugs. At the federal level, the Trump administration’s budget proposal for fiscal year 2020 contains
further drug price control measures that could be enacted during the budget process or in other future
legislation. The Trump administration also released a “Blueprint”, or plan, to lower drug prices and
reduce out of pocket costs of drugs that contains additional proposals to increase manufacturer
competition, increase the negotiating power of certain federal healthcare programs, incentivize
manufacturers to lower the list price of their products and reduce the out of pocket costs of drug products
paid by consumers. For example, in May 2019, CMS issued a final rule to allow Medicare Advantage
Plans the option of using step therapy for Part B drugs beginning January 1, 2020. This final rule codified
CMS’s policy change that was effective January 1, 2019. While some measures may require additional
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authorization to become effective, the U.S. Congress and the Biden administration have each indicated
that it will continue to seek new legislative and/or administrative measures to control drug costs. At the
state level, legislatures are increasingly passing legislation and implementing regulations designed to
control pharmaceutical and biological product pricing, including price or patient reimbursement
constraints, discounts, restrictions on certain product access and marketing cost disclosure and
transparency measures, and, in some cases, designed to encourage importation from other countries and
bulk purchasing.
Pharmacovigilance system in the European Union
An MA holder in the EU must establish and maintain a pharmacovigilance system and appoint an
individual qualified person for pharmacovigilance, or QPPV, who is responsible for oversight of the
pharmacovigilance system. Key obligations include expedited reporting of suspected serious adverse
reactions and submission of periodic safety update reports, or PSURs.
All new MA applications must include a risk management plan, or RMP, describing the risk management
system that the company will put in place and documenting measures to prevent or minimize the risks
associated with the product. The regulatory authorities may also impose specific obligations as a
condition of the MA. Such risk-minimization measures or post-authorization obligations may include
additional safety monitoring, more frequent submission of PSURs, or the conduct of additional clinical
trials or post-authorization safety studies. RMPs and PSURs are routinely available to third parties
requesting access, subject to limited redactions.
Advertising regulation in the European Union
All advertising and promotional activities for the product must be consistent with the approved summary
of product characteristics, and therefore all off-label promotion is prohibited. Direct-to-consumer
advertising of prescription medicines is also prohibited in the European Union. Although general
requirements for advertising and promotion of medicinal products are established under European Union
directives, the details are governed by regulations in each European Union Member State and can differ
from one country to another.
If the Company fails to comply with applicable foreign regulatory requirements, the Company may be
subject to fines, suspension or withdrawal of regulatory approvals, product recalls, seizure of products,
operating restrictions and criminal prosecution.
Pharmaceutical coverage, pricing and reimbursement
European Union
In the European Union, pricing and reimbursement schemes vary widely from country to country. In
some countries, products may be marketed only after a reimbursement price has been agreed. Some
countries may require the completion of additional studies that compare the cost-effectiveness of a
particular product candidate to currently available therapies or so-called health technology assessments, in
order to obtain reimbursement or pricing approval. For example, the European Union provides options for
its member states to restrict the range of products for which their national health insurance systems
provide reimbursement for and to control the prices of medicinal products for human use. European
Union member states may approve a specific price for a product or it may instead adopt a system of direct
or indirect controls on the profitability of the company placing the product on the market. Other member
states allow companies to fix their own prices for products, but monitor and control prescription volumes
and issue guidance to physicians to limit prescriptions. Recently, many countries in the European Union
have increased the amount of discounts required on pharmaceuticals and these efforts could continue as
countries attempt to manage healthcare expenditures, especially in light of the severe fiscal and debt
crises experienced by many countries in the European Union. The downward pressure on health care costs
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in general, particularly prescription products, has become intense. As a result, increasingly high barriers
are being erected to the entry of new products. Political, economic and regulatory developments may
further complicate pricing negotiations, and pricing negotiations may continue after reimbursement has
been obtained. Reference pricing used by various European Union member states, and parallel trade, i.e.,
arbitrage between low-priced and high-priced member states, can further reduce prices. There can be no
assurance that any country that has price controls or reimbursement limitations for pharmaceutical
products will allow favorable reimbursement and pricing arrangements for any products, if approved in
those countries.
United States
In the United States, patients who have treatments prescribed for their conditions and providers
performing the prescribed services generally rely on third-party payors to reimburse all or part of the
associated healthcare costs. Significant uncertainty exists as to the coverage and reimbursement status of
products approved by the FDA and other government authorities. Thus, even if a product candidate is
approved, sales of the product will depend, in part, on the extent to which third-party payors, including
government health programs in the United States such as Medicare and Medicaid, commercial health
insurers and managed care organizations, provide coverage, and establish adequate reimbursement levels
for, the product. The process for determining whether a payor will provide coverage for a product may be
separate from the process for setting the price or reimbursement rate that the payor will pay for the
product once coverage is approved. Third-party payors are increasingly challenging the prices charged,
examining the medical necessity, and reviewing the cost-effectiveness of medical products and services
and imposing controls to manage costs. Third-party payors may limit coverage to specific products on an
approved list, also known as a formulary, which may not include all of the approved products for a
particular indication.
In order to secure coverage and reimbursement for any product that might be approved for sale, a
company may need to conduct expensive pharmacoeconomic studies in order to demonstrate the medical
necessity and cost-effectiveness of the product, in addition to the costs required to obtain FDA or other
comparable marketing approvals. Nonetheless, product candidates may not be considered medically
necessary or cost effective. A decision by a third-party payor not to cover a product candidate could
reduce physician utilization once the product is approved and have a material adverse effect on sales,
results of operations and financial condition. Additionally, a payor’s decision to provide coverage for a
product does not imply that an adequate reimbursement rate will be approved. Further, one payor’s
determination to provide coverage for a product does not assure that other payors will also provide
coverage and reimbursement for the product, and the level of coverage and reimbursement can differ
significantly from payor to payor.
The containment of healthcare costs also has become a priority of federal, state and foreign governments
and the prices of products have been a focus in this effort. Governments have shown significant interest in
implementing cost-containment programs, including price controls, restrictions on reimbursement and
requirements for substitution of generic products. Adoption of price controls and cost-containment
measures, and adoption of more restrictive policies in jurisdictions with existing controls and measures,
could further limit a company’s revenue generated from the sale of any approved products. Coverage
policies and third-party reimbursement rates may change at any time. Even if favorable coverage and
reimbursement status is attained for one or more products for which a company or its collaborators
receive marketing approval, less favorable coverage policies and reimbursement rates may be
implemented in the future.
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Anti-corruption, anti-kickback and transparency regulations
Arrangements with healthcare providers, physicians, third-party payors and customers can expose
pharmaceutical manufactures to broadly applicable anti-bribery, fraud and abuse and other healthcare
laws and regulations, which may constrain the business or financial arrangements and relationships
through which such companies sell, market and distribute pharmaceutical products.
More specifically, each of the above-mentioned steps of the development of therapeutic products for
human use is heavily regulated and therefore involves significant interaction with public officials which is
likely to cause a risk of corruption or bribery. For instance, in many countries, hospitals are operated by
the government, and doctors and other hospital employees are considered foreign officials. Certain
payments to hospitals in connection with clinical trials and other work have been deemed to be improper
payments to government officials and have led to enforcement actions. That is why business activity may
be subject to anti-bribery or anti-corruption laws, regulations or rules of other countries in which the
Company operates, including without limitation the Foreign Corrupt Practices Act, the U.K. Bribery Act
or the French Sapin 2 Law.
All these statutes generally prohibit offering, promising, giving, or authorizing others to give anything of
value, either directly or indirectly, to a government or a foreign government official or employees of
public international organizations in order to influence official action, or otherwise obtain or retain
business. The implementation of these statutes may also impose internal compliance programs,
procedures and guidelines to detect and report any suspicious activities and to mitigate any risks of
noncompliance which may occur.
In addition, the Company may be subject to specific healthcare regulations, including, without limitation:
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the French “transparency” provisions, or “French Sunshine Act” (Articles L. 1453-1 and
D. 1453-1 and seq. of the French Public Health Code or PHC), which contains provisions
regarding transparency of fees received by some healthcare professionals from industries, i.e.
companies manufacturing or marketing healthcare products (medicinal products, medical
devices, etc.) in France. According to the provisions, these companies shall publicly disclose
(on a specific public website available at https://transparence.sante.gouv.fr) the advantages and
fees paid to healthcare professionals amounting to €10 or above, as well as the agreements
concluded with the latter, along with detailed information about each agreement (the precise
subject matter of the agreement, the date of signature of the agreement, its end date, the total
amount paid to the healthcare professional, etc.); and
the French “anti-gift” provisions (Articles L.1453-3 to L.1453-12 PHC), setting out a general
prohibition of payments and rewards from industries, i.e. companies manufacturing or
marketing health products to healthcare professionals (HCP), healthcare organizations (HCO),
healthcare associations and students with limited exceptions, and strictly defining the
conditions under which such payments or awards are lawful. A new regime is applicable since
October 1st, 2020 which entails strict formalities depending on the amount paid, when
authorized, to the HCP, HCO, students or associations.
Data protection rules
The Regulation 2016/679, known as the General Data Protection Regulation, or GDPR, that came into
force on May 25, 2018, as well as EU Member State implementing legislations, apply to the collection
and processing of personal data, including health-related information, by companies located in the EU, or
in certain circumstances, by companies located outside of the EU and processing personal information of
individuals located in the EU.
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These laws impose strict obligations on the ability to process personal data, including health-related
information, in particular in relation to their collection, use, disclosure and transfer.
Also, in certain countries, in particular France, the conduct of clinical trials is subject to compliance with
specific provisions of the Act No.78-17 of January 6, 1978 on Information Technology, Data Files and
Civil Liberties, as amended. These provisions require, among others, the filing of compliance
undertakings with “standard methodologies” and a specific framework applicable to the retention of
personal data when researching in the health sector (July 2020) adopted by the French Data Protection
Authority (the CNIL), or, if not compliant, obtaining a specific authorization from the CNIL.
The most common standard methodologies are the following:
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Decision No. 2018-153 of May 3, 2018 concerning the approval of a standard methodology for
the processing of personal data carried out within the context of research in the field of clinical
trials, which requires the express consent of the person involved (standard methodology
MR-001)
Decision No. 2018-154 of May 3, 2018 concerning the approval of a standard methodology for
the processing of personal data in the context of research in the field of health, which does not
require the express consent of the person involved (methodology MR-003).
Deliberation n ° 2020-077 of June 18, 2020 adopting a framework relating to the retention periods of
personal data processed for the purposes of research, study or evaluation in the field of health.
In certain specific cases, entities processing health personal data may have to comply with article L1111-8
of the French Public Health Code which imposes certain certifications for the hosting service providers.
C. Organizational Structure.
On December 31, 2022, Innate Pharma is the sole shareholder of Innate Pharma Inc.
D. Property, Plants and Equipment.
Innate Pharma's corporate offices and laboratories are located in Luminy, Marseille, France and the
Company owns the buildings and land.
Item 4A. Unresolved Staff Comments.
Not applicable.
Item 5. Operating and Financial Review and Prospects.
You should read the following discussion of the Company financial condition and results of operations in
conjunction with the “Selected Consolidated Financial Data” and its consolidated financial statements
and the related notes thereto included elsewhere in this Annual Report. In addition to historical
information, the following discussion and analysis contains forward-looking statements that reflect the
Company plans, estimates and beliefs. The Company actual results and the timing of events could differ
materially from those anticipated in the forward-looking statements. Factors that could cause or
contribute to these differences include those discussed below and elsewhere in this Annual Report,
particularly in sections titled “Item 3.D – Risk Factors” and “Special Note Regarding Forward-Looking
Statements.” The Company audited consolidated financial statements as of and for the years ended
December 31, 2020, 2021 and 2022 have been prepared in accordance with IFRS as issued by the IASB,
which may differ in material respects from generally accepted accounting principles in other
jurisdictions, including the United States.
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Overview
Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for
cancer patients. Its innovative approach aims to harness the innate immune system through therapeutic
antibodies and its ANKET® (Antibody-based NK cell Engager Therapeutics) proprietary platform.
Innate’s portfolio includes lead proprietary program lacutamab, developed in advanced form of cutaneous
T cell lymphomas and peripheral T cell lymphomas, monalizumab developed with AstraZeneca in non
small cell lung cancer, as well as ANKET® multi-specific NK cell engagers to address multiple tumor
types. The Company has entered into collaborations with leaders in the biopharmaceutical industry, such
as AstraZeneca and Sanofi, to leverage their development capabilities and expertise for some of its
candidates. The Company believe its product candidates and clinical development approach are
differentiated from current immuno-oncology therapies and have the potential to significantly improve the
clinical outcome for patients with cancer.
Since its inception, the Company has devoted substantially all of its financial resources to research and
development efforts, including conducting preclinical studies and clinical trials of its product candidates,
providing general and administrative support for its operations and protecting its intellectual property.
The Company marketed product, Lumoxiti, was approved by the U.S. Food and Drug Administration, or
FDA, under priority review in September 2018 and was commercially launched by AstraZeneca AB, or
AstraZeneca, in November 2018. The Company has not yet generated any material revenue from product
sales.
Further to the Company decision to terminate the Lumoxiti Agreement in December 2020, a Termination
and Transition Agreement was negotiated and executed, effective as of June 30, 2021 terminating the
Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply agreement, the quality
agreement and other related agreements) and transferring the U.S. marketing authorization and
distribution rights of Lumoxiti back to AstraZeneca. Under the Termination and Transition Agreement,
Innate and AstraZeneca delivered a notice to the FDA requesting that the U.S. marketing authorization be
transferred back to AstraZeneca as from October 1, 2021. AstraZeneca has reimbursed the Company for
all Lumoxiti related costs, expenses and benefited net sales. In the year ended December 31, 2020 results
announcement, the Company reported a contingent liability of up to $12.8 million in its consolidated
financial statements, which was related to the splitting of certain manufacturing costs. As part of the
Termination and Transition Agreement, Innate and AstraZeneca agreed to split these manufacturing costs,
and Innate will pay $6.2 million (€5.5 million as of December 31,2021) to AstraZeneca on April 30,
2022.
As of December 31, 2022, the Company had €136.6 million in cash, cash equivalents, short-term
investments and non-current financial assets. Since its inception, the Company has raised a total of €311.4
million through the sale of equity securities, including €33.7 million in the initial public offering of its
ordinary shares on Euronext Paris in 2006 and €66.0 million in the initial public offering of our ordinary
shares on Euronext and ADS on Nasdaq New-York in 2019. As of December 31, 2022, the Company has
also received $601.4 million (€528.0 million) in payments from its collaborators, including AstraZeneca,
since 2011, excluding payments received for purchases of its equity securities by its collaborators.
The Company has significant agreements with AstraZeneca pursuant to which has the right to earn
milestone and royalty payments. The Company has other license agreements pursuant to which has
acquired intellectual property and under which the Company will be required to make payments to the
counterparty upon the achievement of certain milestone events and commercial sales related to its product
candidates.
The Company has incurred net losses in each year since our inception except for the years ended
December 31, 2016 and 2018. The Company net income (loss) was €(64.0) million, €(52.8) million and
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€(58.1) million for the years ended December 31, 2020, 2021 and 2022, respectively. Substantially all of
its net losses has resulted from costs incurred in connection with its research and development programs
and from selling, general and administrative expenses associated with its operations. As the Company
continue advancing its product candidates through research and development programs, the Company
expect to continue to incur significant expenses and may again incur operating losses in future periods.
The Company anticipate that such expenses will increase substantially if and as the Company:
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continues the research and development of its product candidates;
initiates clinical trials for, or additional preclinical development of, its product candidates;
further develops and refines the manufacturing processes for its product candidates;
changes or adds manufacturers or suppliers of biological materials;
seeks regulatory and marketing authorizations for any of its product candidates that
successfully complete development;
seeks to identify and validate additional product candidates;
acquires or license other product candidates, technologies or biological materials;
makes milestone, royalty or other payments under any current or future license agreements;
obtains, maintains, protects and enforces its intellectual property portfolio;
secures manufacturing arrangements for commercial production;
seeks to attract and retain new and existing skilled personnel;
creates additional infrastructure to support its operations as a U.S. public company and incurs
increased legal, accounting, investor relations and other expenses; and
experiences delays or encounters issues with any of the above.
The Company anticipates that will need to raise additional funding, prior to completing clinical
development of any of its product candidates. Until such time that the Company can generate significant
revenues from sales of its product candidates, if approved, the Company expect to finance its operating
activities through a combination of milestone payments received pursuant to its strategic alliances, equity
offerings, debt financings, government or other third-party funding and collaborations, and licensing
arrangements. However, The Company may not receive milestone payments when expected, or at all, and
the Company may be unable to raise additional funds or enter into such arrangements when needed on
favorable terms, or at all, which would have a negative impact on its financial condition and could force
the Company to delay, limit, reduce or terminate its development programs or commercialization efforts
or grant to others rights to develop or market product candidates that the Company would otherwise
prefer to develop and market itself. Failure to receive additional funding could cause the Company to
cease operations, in part or in full.
Presentation of Financial Information
The Company audited consolidated financial statements included herein as of and for the years ended
December 31, 2020, 2021 and 2022 have been prepared in accordance with IFRS as issued by the IASB.
Due to the listing of its ordinary shares on Euronext Paris and in accordance with the European Union’s
regulation No. 1606/2002 of July 19, 2002, the Company also prepares and publishes its consolidated
financial statements in accordance with IFRS as adopted by the European Union, or EU.
All the standards published by the IASB that are mandatorily applicable in the years ended December
2020, 2021 and 2022 are endorsed by the EU and are mandatorily applicable in the EU. Therefore, the
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Company audited consolidated financial statements for the years ended December 31, 2020, 2021 and
2022 are compliant with both IFRS as issued by the IASB and IFRS as adopted by the EU.
The preparation of financial statements in accordance with IFRS requires the Company to make
significant judgments and estimates which are presented below. See “—Critical Accounting Policies and
Significant Judgments and Estimates.”
Principal Collaboration and Licensing Agreements of the Company
The Company results of operations are impacted by the terms and conditions of its principal collaboration
and licensing agreements. For a description of its principal collaboration and licensing agreements, see
“Item 10C.—Material Contracts.”
Principal Components of the Company Results of Operations
Revenue and other income
The Company revenue and other income mainly consists of revenues from collaboration and licensing
agreements and government financing for research expenditure in the form of the research tax credits, as
well as other grants.
Revenue from collaboration and licensing agreements
The Company currently derives substantially all its revenues from payments pursuant to its licensing and
collaboration agreements with AstraZeneca relating to monalizumab and IPH5201 and Sanofi relating to
IPH6101/SAR443579 and IPH6401/SAR'514 consisting of (i) upfront payments, (ii) milestone payments
based upon the achievement of pre-determined development, regulatory and commercial events and (iii)
research and development fees related to charges for full time equivalents, or FTEs, at contracted rates
and reimbursement of research and development expenses.
The Company has not generated any significant revenue from product sales since its inception, with the
exception in 2018, 2019, 2020 and 2021 of Lumoxiti sales, which were previously classified in its half-
year and annual reports in the net income (loss) from distribution agreements during the transition period
with AstraZeneca (ended September 30, 2020) and as revenue since the 2020 fourth quarter.
Further Innate's decision to terminate the Lumoxiti Agreement in December 2020, a Termination and
Transition Agreement was negotiated and executed, effective as of June 30, 2021 terminating the
Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply agreement, the quality
agreement and other related agreements) and transferring the U.S. marketing authorization and
distribution rights of Lumoxiti back to AstraZeneca. Under the Termination and Transition Agreement,
Innate and AstraZeneca delivered a notice to the FDA requesting that the U.S. marketing authorization be
transferred back to AstraZeneca as from October 1, 2021. AstraZeneca has reimbursed Innate for all
Lumoxiti related costs, expenses and benefited net sales.
As a consequence of the termination of the Lumoxiti Agreement, the Lumoxiti Activity (including sales)
is presented in the consolidated income statement and the notes to the consolidated financial statements as
a discontinued operation for the 2022 and 2021 financial years in accordance with IFRS5 "non-current
assets held for sale and discontinued operations". The income statement for the year ended December 31,
2020 below has been prepared as if the Lumoxiti activity (including sales) had been a discounted
operation for the 2020 financial year in accordance with the same IFRS standard.
The Company ability to generate significant product revenue and to become profitable will depend upon
its ability to successfully develop, obtain regulatory approval for and commercialize any product
candidates. Because of the numerous risks and uncertainties associated with product development and
140
regulatory approval, the Company is unable to predict the amount, timing or whether will be able to
obtain product revenue.
Government financing for research expenditures
The Company's government financing for research expenditures consists of research tax credits (crédit
d’impôt recherche) and grants.
The research tax credit is granted to companies by the French tax authorities in order to encourage them
to conduct technical and scientific research. Companies demonstrating that they have expenses that meet
the required criteria, including research expenses located in France or, since January 1, 2005, within the
EU or in another state that is a party to the agreement in the European Economic Area that has concluded
a tax treaty with France that contains an administrative assistance clause, receive a tax credit which can be
used against the payment of the corporate tax due for the fiscal year in which the expenses were incurred
and during the next three fiscal years, or, as applicable, can be reimbursed for the excess portion. The
expenditures taken into account for the calculation of the research tax credit involve only research
expenses.
The main characteristics of the research tax credit are:
•
•
•
the research tax credit results in a cash inflow to us, i.e., it is used to offset the payment of
corporate income tax the year after the date of its record as a tax credit in the income
statement, or is paid directly to us from the tax authorities for the portion that remains unused,
in principle three years after the fiscal year for which it is determined;
The Company's corporate income tax liability does not limit the amount of the research tax
credit—if the Company does not pay any corporate income tax, the Company can offset the
remaining research tax credit the year following its record in the income statement; and
the research tax credit is not included in the determination of the corporate income tax.
When the research tax credit is not deductible from taxes payable by us, it is generally reimbursed by the
French government three years after the fiscal year for which it is determined. However, since 2011,
companies that meet the definition of small and medium sized enterprises (“SMEs”) according to the
European Union criteria are eligible for early reimbursement of their research tax credit receivable. The
status of SME is lost when the criteria for eligibility are exceeded during two consecutive years. The
Company losted its SME status at the end of the 2019 fiscal year and is eligible again since the end of the
2021 financial year.
The Company has concluded that the research tax credit meets the definition of a government grant as
defined in IAS 20 Accounting for government grants and disclosure of government assistance, or IAS 20,
and that the classification as “Revenue and other income” in its consolidated statement of income (loss) is
appropriate.
Innate also from time to time receive government grants, which are recognized in its consolidated
statement of income (loss) when comply with the conditions attached to the grants and they are non-
repayable grants.
Operating expenses from continuing operations
Since inception, Innate's operating expenses has consisted primarily of research and development
expenses and general and administration expenses.
141
Following the transfer back of the U.S marketing authorization to AstraZeneca linked to the Lumoxiti
Termination and Transition Agreement (from October 1, 2021), selling expenses relating to Lumoxiti
activities are presented as discontinued operations for the year ended December 31, 2021. The 2020 and
2019 comparatives have been restated compared to previous publications, in accordance with the same
standard (see "Discontinued Operations" below).
Research and development expenses
The Company engages in substantial research and development efforts to develop innovative product
candidates. Research and development expenses consist primarily of:
•
•
•
•
personnel costs, including salaries, related benefits and share-based compensation, for Innate's
employees engaged in scientific research and development functions;
cost of third-party contractors and academic institutions involved in preclinical studies or
clinical trials that the Company may conduct, or third-party contractors involved in field trials;
purchases of biological raw materials, real estate leasing costs as well as conferences and
travel costs; and
certain other expenses, such as expenses for use of laboratories and facilities for Innate's
research and development activities as well as depreciation and amortization.
Innate's research and development efforts are focused on its existing product candidates and preclinical
programs, including the advancement of its lead product candidates, monalizumab, lacutamab. Its direct
research and development expenses consist principally of external costs associated with subcontracting of
preclinical and clinical operations to third parties, which Innate tracks on a program-by-program basis.
The Company also use its employee and infrastructure resources across multiple research and
development programs, and do not track these indirect expenses on a program-by-program basis.
Research and development costs are expensed as incurred. Costs for certain activities are recognized
based on an evaluation of the progress to completion of specific tasks using data such as information
provided to Innate Pharma by its vendors and analyzing the progress of its preclinical studies or other
services performed. Significant judgment and estimates are made in determining the accrued expense
balances at the end of any reporting period. Non-refundable advance payments for research and
development goods or services to be received in the future from third parties are deferred and capitalized.
The capitalized amounts are expensed as the related goods are delivered or the services are performed.
Research and development activities are central to Innate's business. As product candidates in later stages
of clinical development generally have higher development costs than those in earlier stages of clinical
development, primarily due to the increased size and duration of later-stage clinical trials, the Company
expect that its research and development costs will increase in the foreseeable future. Such cost increases
are expected to occur as the Company conduct existing clinical trials and initiate future clinical trials,
manufacture pre-commercial clinical trial and preclinical study materials, expand its research and
development efforts, seek regulatory approvals for its product candidates that successfully complete
clinical trials, access and develop additional technologies and hire additional personnel to support its
research and development efforts.
The Company cannot determine with certainty the duration and total costs of its future clinical trials of its
product candidates or if, when, or to what extent Innate will generate revenues from the
commercialization and sale of any of our product candidates, or those of our collaborators, that might
obtain regulatory approval. Innate may never succeed in achieving regulatory approval for any of product
142
candidates. The duration, costs and timing of clinical trials and development of its product candidates will
depend on a variety of factors, including:
•
•
•
•
•
the scope, rate of progress and expense of its ongoing clinical trials as well as any additional
preclinical studies, clinical trials conducted by its collaborators and other research and
development activities;
clinical trial and preclinical study results;
the terms and timing of regulatory approvals;
the expense of filing, maintaining, prosecuting, defending and enforcing patent claims and
other intellectual property rights; and
the ability to market, commercialize and achieve market acceptance for any products that
receive regulatory approval.
A change in the outcome of any of these variables with respect to the development of monalizumab,
lacutamab or any other product candidate or preclinical program that the Company is developing or could
develop in the future could mean a significant change in the costs and timing associated with the
development of such product candidates or preclinical programs. For example, if the FDA, the European
Medicines Agency, or EMA, or another regulatory authority were to require Innate to conduct preclinical
studies and clinical trials beyond those that currently anticipate will be required for the completion of
clinical development, or if the Company experience significant delays in enrollment in any clinical trials,
the Company could be required to spend significant additional financial resources and time on the
completion of clinical development. For a discussion of the risks associated with completing the
development projects on schedule, see “Risk Factors—Risks Related to the Development of the Product
Candidates.”
General and administrative expenses
General and administrative expenses consist primarily of personnel costs and share-based compensation
for personnel other than research and development staff. Selling, general and administrative expenses also
consist of fees for professional services, mainly related to audit, IT, accounting, recruitment and legal
services, communication and travel costs, real-estate leasing costs, office furniture and equipment costs,
allowance for amortization and depreciation, director’s attendance fees and insurance costs and overhead
costs, such as postal and telecommunications expenses.
Net financial income (loss)
The financial income (loss) primarily consists of realized and unrealized foreign exchange gains and
losses primarily related to the purchase of services as well as deposit accounts denominated in U.S.
dollars and gains and losses and interest received in relation to cash and cash equivalents that have been
deposited in cash accounts, short-term fixed deposits and short-term highly liquid investments with
original maturities of three months or less. The Company's cash and cash equivalents generate a modest
amount of interest income. Innate expect to continue this investment philosophy in the future.
Net result from discontinued operations
Further to Innate's decision to terminate the Lumoxiti Agreement in December 2020, a Termination and
Transition Agreement was negotiated and executed, effective as of June 30, 2021 terminating the
Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply agreement, the quality
agreement and other related agreements) and transferring the U.S. marketing authorization and
distribution rights of Lumoxiti back to AstraZeneca. Under the Termination and Transition Agreement,
Innate and AstraZeneca delivered a notice to the FDA requesting that the U.S. marketing authorization be
143
transferred back to AstraZeneca as from October 1, 2021. AstraZeneca has reimbursed Innate for all
Lumoxiti related costs, expenses and benefited net sales. In the year ended December 31, 2020 results
announcement, the Company reported a contingent liability of up to $12.8 million in its consolidated
financial statements, which was related to the splitting of certain manufacturing costs. As part of the
Termination and Transition Agreement, Innate and AstraZeneca agreed to split these manufacturing costs,
and Innate has paid $6.2 million (€5.5 million as of December 31, 2021) to AstraZeneca on April 30,
2022.
As a consequence of the termination of the Lumoxiti Agreement, the Lumoxiti Activity (including sales)
is presented in the consolidated income statement and the notes to the consolidated financial statements as
a discontinued operation for the 2022 and 2021 financial years in accordance with IFRS5 "non-current
assets held for sale and discontinued operations". The income statement for the year ended December 31,
2020 below has been prepared as if the Lumoxiti activity (including sales) had been a discounted
operation for the 2020 financial year in accordance with the same IFRS standard.
Consecutively, net result from discontinued operations included revenue (including sales), operating
expenses, impairment of intangible asset and also net income (loss) from distribution agreements relating
to Lumoxiti operations for the years ended December 31, 2020, 2021 and 2022.
Impairment of intangible assets
The Group assesses at the end of each reporting period whether there is an indication that intangible
assets, property and equipment may be impaired. If any indication exists, the Group estimates the
recoverable amount of the related asset.
Whether or not there is any indication of impairment, intangible assets not yet available for use are tested
for impairment annually by comparing their carrying amount with their recoverable amount.
Pursuant to IAS 36—Impairment of Assets, criteria for assessing indication of loss in value may notably
include performance levels lower than forecast, a significant change in market data or the regulatory
environment, or obsolescence or physical damage of the asset not included in the amortization/
depreciation schedule. The recognition of an impairment loss alters the amortizable/depreciable amount
and potentially, the amortization/depreciation schedule of the relevant asset.
As of December 31, 2020, impairment of intangible assets consisted to the full depreciation of Lumoxiti
rights for an amount of €43.5 million, following the Company's decision to return the U.S. and EU
commercialization rights of Lumoxiti to AstraZeneca. This full depreciation of Lumoxiti rights is
included and presented in the net result from discontinued operations relating to Lumoxiti for the year
ended December 31, 2020.
As of December 31, 2022, impairment of intanglible assets consisted to the full depreciation of
avdoralimab rights for an amount of €41.0 million, following the Company's decision to stop avdoralimab
development in bullous phemphigoid ("BP") indication in inflammation followingdecision taken by
sponsor to stop the Phase 2 clinical trial in said indication during the 2022 fourth semester.
144
A. Operating Results
Comparisons for the years ended December 31, 2021 and 2022
The following table sets forth a summary of the Company's consolidated statements of income (loss) for
the periods presented.
Revenue from collaboration and licensing agreements
Government financing for research expenditures
Other income
Revenue and other income
Research and development expenses
General and administrative expenses
Impairment of intangible assets
Operating expenses
Operating income (loss)
Financial income
Financial expenses
Net financial income (loss)
Net income (loss) before tax
Income tax expense
Net income (loss) from continuing operations
Year ended December 31,
2021
2022
(in thousands)
€ 12,112
12,591
—
24,703
(47,004)
(25,524)
—
€ 49,580
8,035
59
57,674
(51,663)
(22,436)
(41,000)
(72,528)
(115,099)
(47,825)
(57,425)
6,344
(3,997)
2,347
4,775
(5,321)
(546)
(45,478)
(57,972)
—
(45,478)
—
(57,972)
Net income (loss) from discontinued operations
(7,331)
(131)
Net income (loss)
€ (52,809)
€ (58,103)
Revenue and other income
Revenue and other income from continuing operations resulted from collaboration and licensing
agreements and government financing for research expenditure. Revenue and other income from
continuing operations increased by €33.0 million, to €57.7 million for the year ended December 31, 2022,
as compared to revenue and other income of €24.7 million for the year ended December 31, 2021.
145
Revenue from collaboration and licensing agreements
Government financing for research expenditures
Other income
Revenue and other income
Year ended December 31,
2021
2022
(in thousands)
€ 12,112
12,591
—
€ 49,580
8,035
59
€ 24,703
€ 57,674
Revenue from collaboration and licensing agreements
Revenue from collaboration and licensing agreements from continuing operations increased by €37.5
million, to €49.6 million for the year ended December 31, 2022, as compared to revenue from
collaboration and licensing agreements of €12.1 million for the year ended December 31, 2021. Revenue
from collaboration and licensing agreements mainly resulted from the agreements with AstraZeneca
signed in April 2015 and October 2018, as well as the agreement signed with Sanofi in 2016. Revenue
from collaboration and licensing agreements is set forth in the table below.
Proceeds from collaboration and licensing agreements
of which monalizumab agreement - AstraZeneca
of which IPH5201 agreement - AstraZeneca
of which preclinical molecules agreement - AstraZeneca
of which Sanofi agreement
of which other agreements
Proceeds from collaboration and licensing agreements
Invoicing of research and development costs (IPH5201)
Exchange gains (loss) on collaboration agreements
Others
Revenue from collaboration and licensing agreements
Year ended December 31,
2021
2022
(in thousands)
€ 7,497
€ 22,376
—
—
3,000
—
10,497
1,613
—
—
4,677
17,400
4,000
353
48,806
1,391
(627)
10
€ 12,112
€ 49,580
Proceeds related to monalizumab. Revenue related to monalizumab increased by €14.9 million, to
€22.4 million for the year ended December 31, 2022, as compared to €7.5 million for the year ended
December 31,2021. This €14.9 million increase mainly results from the transaction price increase related
to the additional payment of $50.0 million (€47.7 million) made by AstraZeneca in June 2022 and
triggered by the treatment of the first patient in a second Phase 3 trial “PACIFIC-9” evaluating
monalizumab in April 2022. This additional payment has been treated as an increase of the collaboration
commitment ("collaboration liabilities" in the consolidated statements of financial position) for an
amount of $36.0 million (€34.3 million) in connection to the Phase 3 study co-funding commitment made
by the Company and notified to AstraZeneca in July 2019. The remaining amount of $14.0 million (€13.4
million) has been treated as an increase of the transaction price, recognized in the income statement in
146
line with the progress of the Phase 1/2 studies. This increase in the transaction price generated a €12.6
million favorable cumulative adjustment in the revenue related to monalizumab agreements over the
period. As of December 31, 2022, the deferred revenue related to monalizumab amounted to €14.5
million (€6.6 million as “Deferred revenue—Current portion” and €7.9 million as “Deferred revenue—
Non-current portion”).
Proceeds related to IPH5201. Revenue related to IPH5201 for the year ended December 31, 2022 is €4.7
million and results from the entire recognition in revenue of the $5.0 million (€4.7 million) milestone
payment received from AstraZeneca following the signature on June 1, 2022 of an amendment to the
initial contract signed in October 2018. This amendment sets the terms of the collaboration following
AstraZeneca’s decision to advance IPH5201 to a Phase 2 study. The Company will conduct the study.
Both parties will share the external cost related to the study and incurred by the Company and
AstraZeneca will provide products necessary to conduct the clinical trial.
Proceeds related to collaboration and option agreement related to four to-be-agreed upon molecules
(preclinical molecules). During the first half of 2022, the Company received from AstraZeneca a notice
that it will not exercise its option to license the four preclinical programs covered in the "Future Programs
Option Agreement". This license option was part of the 2018 multi-term agreement between AstraZeneca
and the Company under which the Company had received an upfront payment of $20.0 million (€17.4
million). As the rights related to these four preclinical programs have been returned to the Company, the
entire upfront payment of $20.0 million (€17.4 million) has been recognized as revenue as of June 30,
2022.
Invoicing of research and development costs - IPH5201. Pursuant to the Company's agreements with
AstraZeneca, research and development costs related to IPH5201 in connection with preclinical work are
fully borne by AstraZeneca, in accordance with the initial 2018 agreement. These costs were re-invoiced
on a quarterly basis. Following the signature on June 1, 2022 of an amendment to the initial agreement
signed in October 2018 specifying the terms of the collaboration following the decision to advance
IPH5201 to a Phase 2 study, the parties are committed to sharing the external costs of the study incurred
by the Company and AstraZeneca will provide products necessary to conduct the clinical trial.
Revenue from invoicing of research and development costs for the year ended December 31, 2022 was
€1.4 million compared to €1.6 million for the year ended December 31, 2021 , or a decrease of € 0.2
million.
Proceeds related to Sanofi 2016 agreement -. Revenues under the collaboration and license agreement
signed with Sanofi in 2016 amounted to €4.0 million for the year ended December 31, 2022 as compared
to €3.0 million for the year ended December 31, 2021. During the period, the Company announced,
notably, the decision taken by Sanofi to advance IPH6401/SAR'514 towards regulatory preclinical studies
for a new investigational drug. This decision triggered a milestone payment of €3.0 million fully
recognized in revenue. This amount was received by the Company on September 9, 2022.
Government financing for research expenditures
Government funding for research expenditures decreased by €4.6 million, or 9%, to €8.0 million for the
year ended December 31, 2022, as compared to €12.6 million for the year ended December 31, 2021. This
change is mainly due to a €2.4 million decrease in the research tax credit which is mainly due to (i) a
decrease in eligible expenses in the research tax credit calculation and (ii) a provision following the tax
inspection carried out in 2022 by the French tax authorities and recognized as a deduction from the 2022
research tax credit. This provision is based on estimated amounts and adjustments not disputed by the
147
Company.The table below details government funding for research expenditures for the years ended
December 31, 2021 and 2022.
Research Tax Credit(1)
Grant and other tax credit(2)
Government financing for research expenditures
Year ended December 31,
2021
2022
€ 10,310
2,281
€ 12,591
€ 7,925
110
€ 8,035
(1) As of December 31, 2022, the amount is mainly composed of (i) the research tax credit calculated and
recognized for the 2022 financial year for an amount of €9.2 million from which is subtracted (ii) a
provision amounting to €1.3 million following the tax inspection carried out in 2022 by the French tax
authorities and relating to the 2019 and 2020 financial years as well as to the research tax credit and the
accuracy of its calculation for the 2018 to 2018 financial years 2020. This provision was recognized as a
deduction from the 2022 research tax credit, based on estimated amounts and adjustments not disputed by
the Company. On March 3, 2023, the Company received from the tax authorities the rectification
proposal, confirming the amount of the provision recognized on the amounts of the rectifications not
disputed by the Company.
(2) As a reminder , the total amount of grants recognized in the income statement as of December 31,
2021 included an amount of €2,0 million representing the first tranche received (€1,4 million) and a
remaining amount to be received (€0,6 million) related to the BPI financing contract signed in August
2020 as a part of the program set up by the French government to help develop a therapeutic solution with
a preventive or curative aim against COVID-19. As of December 31, 2021, the financing is considered by
the Company to be non-refundable, in accordance with the terms of the agreement, in light of the
technical and commercial failure of the project based on the results of the Phase 2 "Force" trial evaluating
avdoralimab in COVID-19, published in July 6, 2021. The remaining amount of €0,6 million has been
received by Company in January and May, 2022.
The research tax credit is calculated as 30% of the amount of research and development expenses, net of
grants received, eligible for the research tax credit for the fiscal year.
Operating expenses
The table below presents our operating expenses from continuing operations for the years ended
December 31, 2022 and 2021.
Research and development expenses
General and administrative expenses
Total operating expenses
Year ended December 31,
2021
2022
(in thousands)
€ (47,004)
(25,524)
€ (51,663)
(22,436)
€ (72,528)
€ (115,099)
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Research and development expenses
Our research and development expenses are broken down as set forth in the table below for the years
ended December 31, 2021 and 2022.
Lacutamab
Monalizumab
Avdoralimab
IPH5201
IPH5301
Sub-total programs in clinical development
Sub-total programs in preclinical development
Total direct research and development expenses
Personnel expenses (including share-based payments)
Depreciation and amortization
Other expenses
Personnel and other expenses
Total research and development expenses
Year ended December 31,
2021
2022
(in thousands)
€ (14,834)
€ (12,473)
(1,913)
(3,330)
(558)
—
(20,635)
(6,089)
(26,724)
(15,208)
(3,153)
(1,918)
(1,224)
(385)
(1,648)
(625)
(16,355)
(11,129)
(27,484)
(16,373)
(2,928)
(4,877)
(20,279)
€ (47,004)
(24,178)
€ (51,663)
Research and development expenses from continuing operations increased by €4.7 million, or 9.9%, to
€51.7 million for the year ended December 31, 2022, as compared to research and development of €47.0
million for the year ended December 31, 2021. This increase over the period is mainly due to an increase
in indirect research and development expenses resulting from an increase of €3.9 million in personnel and
other expenses in line with (i) an increase in scientific and non scientific fees related to research and
development operations. In addition, direct research and development expenses increased by €0.8 million
over the period due to the significant increase in expenses relating to non-clinical development programs,
partly offset by the decrease in expenses relating to clinical programs. Research and development
expenses represented a total of 69.7% and 64.8% of operating expenses for years ended December 31,
2022 and December 31, 2021, respectively.
Direct research and development expenses increased by €0.8 million, or 2.8%, to €27.5 million for the
year ended December 31, 2022, as compared to direct research and development expenses of €26.7
million for the year ended December 31, 2021. This increase is mainly due to: (i) a €5.0 million increase
in expenses related to preclinical development programs relating notably to IPH6501, partly offset by a
€4.3 million decrease in expenses related to the Company's clinical programs. This decrease in clinical
programs expenses mainly results from a €2.9 million and decrease in expenses relating to the
avdoralimab program and a €2.4 million decrease in expenses relating to the lacutamab program, partly
offset by a €1.1 million increase in expenses related to IPH5201.
Also, as of December 31, 2022, the collaboration liabilities relating to monalizumab and the agreements
signed with AstraZeneca in April 2015, October 2018 and September 2020 amounted to €63.2 million, as
compared to collaborations liabilities of €40.4 million as of December 31, 2021. This increase of €22.8m
mainly results from the additional payment of $50.0 million (€47.7 million) made by AstraZeneca in June
2022 and triggered by the treatment of the first patient in a second Phase 3 trial “PACIFIC-9” evaluating
monalizumab in April 2022. This additional payment has been treated as an increase of the collaboration
commitment ("collaboration liabilities" in the consolidated statements of financial position) for an amount
149
of $36.0 million (€34.3 million) in connection to the Phase 3 study co-funding commitment made by the
Company and notified to AstraZeneca in July 2019. This increase was partially offset by payments made
in 2022 to AstraZeneca related to the co-funding of the monalizumab program, including the Phase 3
INTERLINK-1 and PACIFIC-9 trials.
Personnel and other expenses allocated to research and development increased by €3.9 million, or 19.2%,
to €24.2 million for the year ended December 31, 2022, as compared to an amount of €20.3 million for
the year ended December 31, 2021. This increase is due to (i) a €3.0 million increase in other expenses
related to the €1.3 million increase in non-scientific fees and the €1.0 million increase in scientific fees
allocated to research and development, mainly explained by the increase in the use of external medical
and regulatory experts, as well as (ii) the €1.2 million million increase in staff costs allocated to research
and development. This increase is mainly explained by the increase of 1.7 million euros share-based
payments expenses.
As of December 31, 2022, the Company had 152 employees in research and development functions,
compared to 148 as of December 31, 2021.
General and administrative expenses
General and administrative expenses from continuing operations decreased by €3.1 million, or 12.1%, to
€22.4 million for the year ended December 31, 2022, as compared to €25.5 million for the year ended
December 31, 2021. General and administrative expenses represented a total of 30.3% and 35.2% of our
total operating expenses for the years ended December 31, 2022 and 2021, respectively.
The table below presents our general and administrative expenses by nature for the years ended December
31, 2021 and 2022:
Personnel expenses (including share based payments)
Non scientific advisory and consulting
Other expenses (1)
Total general and administrative
.
Year ended December 31,
2021
2022
(in thousands)
€ (10,883)
€ (10,229)
(5,108)
(9,533)
(4,244)
(7,963)
€ (25,524)
€ (22,436)
(1) Other expenses are related to intellectual property, maintenance costs for laboratory equipment and our headquarters, depreciation and
amortization and other general and administrative expenses.
Personnel expenses, which includes the compensation paid to our employees and consultants, decreased
by €0.7 million, or 6.0%, to €10.2 million for the year ended December 31, 2022, as compared to
personnel expenses of €10.9 million for the year ended December 31, 2021. This decrease mainly results
from a decrease in wages of €0.6 million, mainly resulting from restructuring costs and higher annual
bonuses level in 2021 as compared to 2022. This decrease is completed by the decrease in share-based
payments of €0.1 million. As of December 31, 2022, we had 59 employees in general and administrative
functions, as compared to 65 as of December 31, 2021.
Non-scientific advisory and consulting expenses mostly consist of auditing, accounting, legal and hiring
services. These expenses decreased by €0.9 million, or 16.9%, to €4.2 million for the year ended
December 31,2022, as compared to an amount of €5.1 million for the year ended December 31, 2021.
This decrease results mainly from (i) an increase of 0.9 million euros in fees for strategic consulting and
150
implementation of the "At-the-Market" capital increase program, offset by (ii) a decrease legal assistance
costs, support costs by external service providers in the context of compliance with the Sarbanes-Oxley
(SOX) Act and costs relating to the American subsidiary.
Other general and administrative expenses relate to intellectual property, the costs of maintaining
laboratory equipment and our premises, depreciation and amortization and other general, administrative
expenses. These expenses increased by €1.6 million or 16.5% to €8.0 million for the year ended
December 31,2022, as compared to an amount of €9.5 million for the year ended December 31, 2021.
This decrease related notably to the reversals of provisions for charges in connection with restructuring
costs linked to the abandonment of the Company's commercial activities, as well as reversals of tax
provisions, both with the 2021 financial year. These elements are completed by a net position of more
favorable commercial exchange gains over the 2022 financial year.
Impairment of intangible assets
For the year ended December 31, 2022, impairment of intangible assets results from full impairment of
anti-C5aR rights acquired from Novo/Nordisk A/S (avdoralimab intangible asset) for an amount of €41.0
million. During 2022 fourth quarter, the Company was informed by the sponsor of the Phase 2 clinical
trial evaluating avdoralimab in inflammation in bullous pemphigoid ("BP") indication of its decision to
stop said trial. Consequently, the Company decided in December 2022 to stop the development of
avdoralimab in bullous pemphigoid ("BP") indication in inflammation, only indication supporting the
recoverable amount of the asset as of December 31, 2021 (as well that as of June 30, 2022).
Financial income (loss), net
Net financial result decreased by €2.9 million, to a €0.5 million loss for the year ended December 31,
2022, as compared to a €2.3 million gain for the year ended December 31, 2021. This change results
mainly from the change in the fair value of certain financial instruments (net loss of €1.6 million in 2022
as compared to a €1.1 million gain in 2021) and a net foreign exchange gain of €0.8 million in 2022 as
compared to a net foreign exchange gain of €1.2 million in 2021.
The table below presents the components of our net financial result for the years ended December 31,
2021 and 2022:
151
Interests and gains on financial assets
Unrealized gains on financials assets
Foreign exchange gains
Other financial income
Financial income
Foreign exchange losses
Unrealized losses on financial assets
Interest on financial liabilities
Other financial expenses
Financial expenses
Net financial income (loss)
Year ended December 31,
2021
2022
(in thousands)
€ 327
1,177
4,839
—
6,344
(3,591)
(95)
(312)
—
(3,997)
€ 546
418
3,810
—
4,775
(2,983)
(2,050)
(288)
—
(5,321)
€ 2,347
€ (546)
For the years ended December 31, 2021 and 2022, the foreign exchange gains and losses mainly result
from the variance of the exchange rate between the Euro and the U.S. dollar on U.S. dollar-denominated
cash and cash equivalents, short-term investments and financial assets. Unrealized gains and losses on
financial assets relate to unquoted instruments.
Net result from discontinuing operations
Further to Innate's decision to terminate the Lumoxiti Agreement in December 2020, a Termination and
Transition Agreement was negotiated and executed, effective as of June 30, 2021 terminating the
Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply agreement, the quality
agreement and other related agreements) and transferring the U.S. marketing authorization and
distribution rights of Lumoxiti back to AstraZeneca. Under the Termination and Transition Agreement,
Innate and AstraZeneca delivered a notice to the FDA requesting that the U.S. marketing authorization be
transferred back to AstraZeneca as from October 1, 2021. AstraZeneca has reimbursed Innate for all
Lumoxiti related costs, expenses and benefited net sales. Subsequently, operations related to Lumoxiti are
presented as a discontinued operation as of October 1, 2021.
As a consequence of the termination of the Lumoxiti Agreement, the Lumoxiti Activity (including sales)
is presented in the consolidated income statement and the notes to the consolidated financial statements as
a discontinued operation for the 2021 financial year in accordance with IFRS5 "non-current assets held
for sale and discontinued operations".
As a consequence, net result from discontinued operations relating to Lumoxiti represents a net loss of
€7.3 million as compared to a net loss €0.1 million for the years ended December 31, 2021 and 2022,
respectively, presented as follows :
152
Revenue and other income
Revenue from collaboration and licensing agreements
Sales
Total revenue and other income
Research and development expenses (1)
Selling, general and administrative expenses (2)
Total operating expenses
Net income (loss) from distribution agreements
Impairment of intangible assets (3)
Operating income (loss)
Financial income
Financial expenses
Net financial income (loss)
Net income (loss) before tax
Income tax expense
Net income (loss) from discontinued operations
Year ended December 31,
2021
2022
(in thousands)
€ 926
874
1,800
(624)
(8,507)
(9,131)
—
—
€ 194
22
216
—
(346)
(346)
—
(7,331)
(131)
—
—
—
(7,331)
—
(7,331)
—
—
—
(131)
—
(131)
(1) Research and development expenses. Research and development expenses relating to Lumoxiti
discontinued operations amounted to €0.6 million and nil for the years ended December 31, December 31,
2021 and 2022, respectively.
(2) Selling, general and administrative expenses. Selling, general and administrative expenses relating
to Lumoxiti discontinued operations amounted to €8.5 million and €0.3 million for the years ended
December 31, 2021 and 2022, respectively. For the year ended the December 31, 2021, these expenses
mainly consisted of the amount of $6.2 million (€5.5 million) to be paid on April 30, 2022 to AstraZeneca
under the Termination and Transition Agreement.That amount was paid in 2022 by the Company in April
2022 for €5.9 million ($6.2 million).
153
Comparisons for the years ended December 31, 2020 and 2021
The following table sets forth a summary of our consolidated statements of income (loss) for the periods
presented.
Revenue from collaboration and licensing agreements
Government financing for research expenditures
Revenue and other income
Research and development expenses
General and administrative expenses
Operating expenses
Operating income (loss)
Financial income
Financial expenses
Net financial income (loss)
Net income (loss) before tax
Income tax expense
Net income (loss) from continuing operations
Year ended December 31,
2020 (1)
2021
(in thousands)
€ 56,155
13,618
69,773
(49,708)
(18,986)
(68,694)
€ 12,112
12,591
24,703
(47,004)
(25,524)
(72,528)
1,079
(47,825)
4,855
(6,763)
(1,908)
6,344
(3,997)
2,347
(829)
(45,478)
—
(829)
—
(45,478)
Net income (loss) from discontinued operations
(63,155)
(7,331)
Net income (loss)
€ (63,984)
€ (52,809)
(1) The 2020 comparative has been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17 of the company's consolidated financial statements appearing elsewhere in this Annual Report.
Revenue and other income
Revenue and other income from continuing operations resulted from collaboration and licensing
agreements and government financing for research expenditure. Revenue and other income from
continuing operations decreased by €45.1 million, or 64.6% , to €24.7 million for the year ended
December 31, 2021, as compared to revenue and other income of €69.8 million for the year ended
December 31, 2020 .
154
Revenue from collaboration and licensing agreements
Government financing for research expenditures
Revenue and other income
Year ended December 31,
2020 (1)
2021
(in thousands)
€ 56,155
13,618
€ 69,773
€ 12,112
12,591
€ 24,703
(1) The 2020 comparative has been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17 of the company's consolidated financial statements appearing elsewhere in this Annual Report.
Revenues from collaboration and licensing agreements
Revenue from collaboration and licensing agreements from continuing operations decreased by €44.0
million, or 78.4%, to €12.1 million for the year ended December 31, 2021, as compared to revenue from
collaboration and licensing agreements of €56.2 million for the year ended December 31, 2020. Revenue
from collaboration and licensing agreements mainly resulted from the agreements with AstraZeneca
signed in April 2015, October 2018 and September 2020. Revenue from collaboration and licensing
agreements is set forth in the table below.
Proceeds from collaboration and licensing agreements
of which monalizumab agreement - AstraZeneca
of which IPH5201 agreement - AstraZeneca
of which Sanofi agreement
Proceeds from collaboration and licensing agreements
Invoicing of research and development costs (IPH5201)
Exchange gains (loss) on collaboration agreements
Others
Revenue from collaboration and licensing agreements
Year ended December 31,
2020 (1)
2021
(in thousands)
€ 33,620
13,418
7,000
54,038
2,531
(602)
188
56,155
€ 7,497
—
3,000
10,497
1,613
—
—
€ 12,112
(1) The 2020 comparatives has been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17 of our consolidated financial statements appearing elsewhere in this Annual Report.
Proceeds related to monalizumab. Revenue related to monalizumab decreased by €26.1 million, or 78%,
to €7.5 million for the year ended December 31, 2021, as compared to €33.6 million for the year ended
December 31,2020. This decrease is mainly explained by the decrease in direct monalizumab research
and development costs over the period, in connection with the Phase 1 & 2 trials maturity. As of
December 31, 2021, the deferred revenue related to monalizumab amounted to €20.2 million (€12.1
million as “Deferred revenue—Current portion” and €8.0 million as “Deferred revenue—Non-current
portion”).
155
Proceeds related to IPH5201. There is no revenue related to IPH5201 for the year ended December 31,
2021 as compared to €13.4 million for the year ended December 31, 2020. As of December 31, 2020,
since the Company had fulfilled all of its commitments on preclinical work related to the start of Phase 1
of the IPH5201 program, the initial payment of $50.0 million and the milestone payment of $5.0 million
were fully recognized in revenue.
Invoicing of research and development costs - IPH5201 & avdoralimab. Pursuant to the Company's
agreements with AstraZeneca, clinical costs for the ongoing Stellar Phase 1 trial testing avdoralimab in
oncology are equally shared between Innate and AstraZeneca and research and development costs related
to IPH5201 are fully borne by AstraZeneca, These costs are re-invoiced on a quarterly basis.
Revenue from invoicing of research and development costs for the year ended December 31, 2021 was
€1.6 million compared to €2.5 million for the year ended December 31, 2020 , or a decrease of € 0.9
million. The decrease between the two periods is mainly explained by the decrease in research and
development costs incurred by the Company under these agreements.
Proceeds related to Sanofi - IPH6101. In January 2021, a GLP-tox study was initiated for the IPH6101/
SAR443579 program. Additionally, in December 16, 2021, the Company announced that the first patient
was dosed in a Phase 1 clinical trial launched by Sanofi in humans with IPH6101/SAR443579 in relapsed
or refractory AML. These trials triggered two milestone payments from Sanofi to Innate, planned in the
research collaboration between the two companies, fully recognized in revenue as of December 31, 2021.
Government financing for research expenditures
Government funding for research expenditures decreased by €1.0 million, or 24%, to €12.6 million for the
year ended December 31, 2021, as compared to €13.6 million for the year ended December 31, 2020. The
change is mainly due to a decrease in amortization expense relating to the intangible assets related to the
IPH5201 rights and monalizumab. The table below details government funding for research expenditures
for the years ended December 31, 2020 and 2021.
Research Tax Credit(1)
Grant and other tax credit(2)
Government financing for research expenditures
Year ended December 31,
2020
2021
(in thousands)
€ 13,084
€ 534
€ 13,618
€ 10,310
€ 2,281
€ 12,591
(1) As of December 31, 2021, the total amount of grants recognized in the income statement includes an
amount of €1,988 thousand representing the first tranche received (€1,360) and a remaining amount to be
received (€628) related to the BPI financing contract signed in August 2020 as a part of the program set
up by the French government to help develop a therapeutic solution with a preventive or curative aim
against COVID-19. As of December 31, 2021, the financing is considered by the Company to be non-
refundable, in accordance with the terms of the agreement, in light of the technical and commercial failure
of the project based on the results of the Phase 2 "Force" trial evaluating avdoralimab in COVID-19,
published in July 6, 2021.
The research tax credit is calculated as 30% of the amount of research and development expenses, net of
grants received, eligible for the research tax credit for the fiscal year.
156
Operating expenses
The table below presents our operating expenses from continuing operations for the years ended
December 31, 2021 and 2020.
Research and development
Selling, general and administrative
Total operating expenses
Year ended December 31,
2020 (1)
2021
(in thousands)
€ (49,708)
(18,986)
€ (68,694)
€ (47,004)
(25,524)
€ (72,528)
(1) The 2020 comparatives has been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17 of the company's consolidated financial statements appearing elsewhere in this Annual Report.
Research and development expenses
Our research and development expenses from continuing operations are broken down as set forth in the
table below for the years ended December 31, 2020 and 2021.
Lacutamab
Monalizumab
Avdoralimab
Sub-total programs in clinical development
Sub-total programs in preclinical development
Total direct research and development expenses
Personnel expenses (including share-based payments)
Depreciation and amortization
Other expenses
Personnel and other expenses
Total research and development expenses
Year ended December 31,
2020 (1)
2021
(in thousands)
€ (9,801)
€ (14,834)
(3,851)
(4,650)
(18,350)
(5,085)
(23,434)
(14,661)
(8,231)
(3,382)
(1,913)
(3,330)
(20,635)
(6,089)
(26,724)
(15,208)
(3,153)
(1,918)
(26,274)
€ (49,708)
(20,279)
€ (47,004)
(1) The 2020 comparatives has been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17 of the company's consolidated financial statements appearing elsewhere in this Annual Report.
Research and development expenses from continuing operations decreased by €2.7 million, or 5.4%, to
€47.0 million for the year ended December 31, 2021, as compared to research and development of €49.7
million for the year ended December 31, 2020. This decrease mainly results from a decrease of €5.1
million in research and development depreciation and amortization of intangible assets acquired by the
Company, partly offset by an increase of €3.3 million in direct research and development expenses
(clinical and non-clinical). Research and development expenses represented a total of 64.8% and 72.4%
of operating expenses for years ended December 31, 2021 and December 31, 2020, respectively.
Direct research and development expenses increased by €3.3 million, or 14.0%, to €26.7 million for the
year ended December 31, 2021, as compared to direct research and development expenses of € €23.4
million for the year ended December 31, 2020. This increase is mainly due to: (i) a €5.0 million increase
in expenses relating to the lacutamab program and (ii) a €1.5 million increase in expenses related to non-
157
clinical development program relating notably to IPH65. These increases are partly offset by a €1.9
million and €1.3 million decreases in expenses relating to the monalizumab and avdoralimab programs,
respectively.
Also, as of December 31, 2021, the collaboration liabilities relating to monalizumab and the agreements
signed with AstraZeneca in April 2015, October 2018 and September 2020 amounted to €40.4m, as
compared to collaborations liabilities of €46.7m as of December 31, 2020. This decrease of €6.3m mainly
results from the payments made in 2021 to AstraZeneca relating to the co-funding of the monalizumab
program, including the INTERLINK-1 Phase 3 trial.
Personnel and other expenses allocated to research and development decreased by €6.0 million, or 22.8%,
to €20.3 million for the year ended December 31, 2021, as compared to an amount of €26.3 million for
the year ended December 31, 2020. This decrease is mainly due to the decrease by €5.2 million in
amortization relating to monalizumab rights (extension of the depreciation horizon due to the extension of
the duration of certain clinical trials) and IPH5201 rights (full amortization at December 31, 2020).
As of December 31, 2021, the Company had 148 employees in research and development functions,
compared to 164 as of December 31, 2020.
Selling, general and administrative expenses
General and administrative expenses from continuing activities increased by €6.5 million, or 34.4%, to
€25.5 million for the year ended December 31, 2021, as compared to €19.0 million for the year ended
December 31, 2020. General and administrative expenses represented a total of 35.2% and 27.6% of our
total operating expenses for the years ended December 31, 2021 and 2020, respectively.
The table below presents our selling, general and administrative expenses from continuing activities by
nature for the years ended December 31, 2020 and 2021:
Personnel expenses (including share based payments)
Non scientific advisory and consulting
Other expenses (2)
Total general and administrative
Year ended December 31,
2020 (1)
2021
(in thousands)
€ (8,250)
€ (10,883)
(4,441)
(6,295)
(5,108)
(9,533)
€ (18,986)
€ (25,524)
(1) The 2020 comparatives has been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17 of the company's consolidated financial statements appearing elsewhere in this Annual Report.
(2) Other expenses are related to intellectual property, maintenance costs for laboratory equipment and our headquarters, depreciation and
amortization and other general and administrative expenses.
Personnel expenses, which includes the compensation paid to our employees and consultants, increased
by €2.6 million, or 31.9%, to €10.9 million for the year ended December 31, 2021, as compared to
personnel expenses of €8.3 million for the year ended December 31, 2020. This increase mainly results
from an increase in wages of €2.0 million, mainly resulting from restructuring costs and higher annual
bonuses level in 2021. This increase is completed by the increase in share-based payments of €0.6
million. As of December 31, 2021, we had 65 employees in general and administrative functions, as
compared to 64 as of December 31, 2020.
158
Non-scientific advisory and consulting expenses mostly consist of auditing, accounting, legal and hiring
services. These expenses increased by €0.7 million, or 15.0%, to €5.1 million for the year ended
December 31,2021, as compared to an amount of €4.4 million for the year ended December 31, 2020.
This increase results mainly from (i) an increase of auditing and accounting fees, recruitment fees and
investor relation consultancy fees partly offset by (ii) the a decrease of costs related to the launch of the
Company's new ERP in 2020 and the support by external service providers in the context of compliance
with the Sarbanes-Oxley law following the listing of the Company in the United States in October 2019.
Other general and administrative expenses relate to intellectual property, the costs of maintaining
laboratory equipment and our premises, depreciation and amortization and other general, administrative
expenses. These expenses increased by €3.2 million or 51.5% to €9.5 million for the year ended
December 31,2021, as compared to an amount of €6.3 million for the year ended December 31, 2020.
This increase related notably to insurance costs, which increased in fiscal year 2021, following the listing
of the Company in the United States in October 2019. It also includes increases related to staff training
(catch-up observed in 2021 following the impact of COVID-19 in 2020) and local taxes.
Financial income (loss), net
Net financial result increased by €4.3 million, to a €2.3 million gain for the year ended December 31,
2021, as compared to a €1.9 million loss for the year ended December 31, 2020. This change results
mainly from the change in the fair value of certain financial instruments (loss of €0.6 million in 2020 as
compared to a €1.1 million gain in 2021) and a net foreign exchange gain of €1.2 million in 2021 as
compared to a net foreign exchange loss of €1.6 million in 2020.
The table below presents the components of our net financial result for the years ended December 31,
2020 and 2021:
Interests and gains on financial assets
Unrealized gains on financials assets
Foreign exchange gains
Other financial income
Financial income
Foreign exchange losses
Unrealized losses on financial assets
Interest on financial liabilities
Other financial expenses
Financial expenses
Net financial income (loss)
Year ended December 31,
2020
2021
(in thousands)
€ 564
313
3,978
—
4,855
(5,557)
(865)
(341)
—
(6,763)
€ 327
1,177
4,839
—
6,344
(3,591)
(95)
(312)
—
(3,997)
€ (1,908)
€ 2,347
For the years ended December 31, 2020 and 2021, the foreign exchange gains and losses mainly result
from the variance of the exchange rate between the Euro and the U.S. dollar on U.S. dollar-denominated
159
cash and cash equivalents, short-term investments and financial assets. Unrealized gains and losses on
financial assets relate to unquoted instruments.
Net result from discontinuing operations
Further to Innate's decision to terminate the Lumoxiti Agreement in December 2020, a Termination and
Transition Agreement was negotiated and executed, effective as of June 30, 2021 terminating the
Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply agreement, the quality
agreement and other related agreements) and transferring the U.S. marketing authorization and
distribution rights of Lumoxiti back to AstraZeneca. Under the Termination and Transition Agreement,
Innate and AstraZeneca delivered a notice to the FDA requesting that the U.S. marketing authorization be
transferred back to AstraZeneca as from October 1, 2021. AstraZeneca has reimbursed Innate for all
Lumoxiti related costs, expenses and benefited net sales.
As a consequence of the termination of the Lumoxiti Agreement, the Lumoxiti Activity (including sales)
is presented in the consolidated income statement and the notes to the consolidated financial statements as
a discontinued operation for the 2021 financial year in accordance with IFRS5 "non-current assets held
for sale and discontinued operations". The income statement for the year ended December 31, 2020 below
has been prepared as if the Lumoxiti activity (including sales) had been a discounted operation for the
2020 financial year in accordance with the same IFRS standard.
Thus, net result from discontinued operations relating to Lumoxiti represents a net loss of €7.3 million as
compared to a net loss of €63.2 million for the years ended December 31, 2020 and 2021, respectively,
presented as follow :
160
Revenue and other income
Revenue from collaboration and licensing agreements
Sales
Total revenue and other income
Research and development expenses (1)
Selling, general and administrative expenses (2)
Total operating expenses
Net income (loss) from distribution agreements
Impairment of intangible assets (3)
Operating income (loss)
Financial income
Financial expenses
Net financial income (loss)
Net income (loss) before tax
Income tax expense
Net income (loss) from discontinued operations
Year ended December 31,
2020
2021
(in thousands)
—
678
678
(8,905)
(12,260)
(21,165)
861
(43,529)
(63,155)
—
—
—
€ 926
874
1,800
(624)
(8,507)
(9,131)
—
—
(7,331)
—
—
—
(63,155)
(7,331)
—
(63,155)
—
(7,331)
(1) Research and development expenses. Research and development expenses relating to Lumoxiti
discontinued operations amounted to €8.9 million and €0.6 million for the years ended December 31,
December 31, 2020 and 2021, respectively. For the year ended the December 31, 2020, these expenses
were mainly composed of the amortization of the rights relating to Lumoxiti intangible asset (before
impairment, see below) and the re-invoicing issued by AstraZeneca for R&D development relating to
Lumoxiti. These re-invoicing were established until September 30, 2020, end date of the transition
following contract signed in October 2018.
(2) Selling, general and administrative expenses. Selling, general and administrative expenses relating to
Lumoxiti discontinued operations amounted to €8.5 million and €12.3 million for the years ended
December 31, 2020 and 2021, respectively. For the year ended the December 31, 2020, these expenses
mainly resulted from the costs incurred for the marketing of Lumoxiti and for our U.S subsidiary,
including the related personnel costs, until the decision to return Lumoxiti rights to AstraZeneca at the
end of 2020. For 2021, these expenses mainly consist of the amount of $6.2 million (€5.5 million) to be
paid on April 30, 2022 to AstraZeneca under the Termination and Transition Agreement.
(3) Impairment of intangible asset Following the Company decision in November 2020 to return the
marketing rights of Lumoxiti in the United States and in Europe, the Lumoxiti rights were fully written
down to their net book value as of October 31, 2020, i.e. €43,529 thousand.
161
Critical Accounting Policies and Significant Judgments and Estimates
The Company's consolidated financial statements are prepared in accordance with IFRS. Some of the
accounting methods and policies used in preparing the financial statements under IFRS are based on
complex and subjective assessments by our management or on estimates based on past experience and
assumptions deemed realistic and reasonable based on the facts and circumstances. The actual value of
the Company's assets, liabilities and shareholders’ equity as well as its income and expenses could differ
from the value derived from these estimates if conditions changed and these changes had an impact on the
assumptions adopted. See Note 2 to its consolidated financial statements appearing elsewhere in this
Annual Report.
The Company believes that the most significant management judgments and assumptions in the
preparation of its consolidated financial statements are described below.
Accounting for collaboration and licensing arrangements
To date, the Company's revenue has been generated primarily from payments received in relation to
research, collaboration and licensing agreements signed with pharmaceutical companies. These contracts
generally provide for components such as upfront payments, milestone payments upon reaching certain
predetermined development objectives, research and development funding, as well as payment of
royalties on future sales of products.
Non-refundable upfront payments are deferred and recognized as revenue over the period Innate is
engaged to deliver services to the third-party. Revenue is recognized based on completion of the
underlying work.
Milestone payments represent amounts received from Innate's collaborators, the receipt of which is
dependent upon the achievement of certain scientific, regulatory, or commercial milestones. The company
recognizes milestone payments when the triggering event has occurred, there are no further contingencies
or services to be provided with respect to that event, and the counterparty has no right to refund of the
payment. The triggering event may be scientific results achieved by the Company or another party to the
arrangement, regulatory approvals, or the marketing of products developed under the arrangement. As of
December 31, 2022, given the significant progress of the work to be performed (94.5%) and the level of
budget consumption, the impact of accounting estimates is no longer a determining factor in the
calculation of revenue related to the monalizumab agreement.
Estimate of the recoverable amount of the acquired and under progress licenses
Impairment tests are performed on a yearly basis for the intangible assets which are not amortized (such
as intangible assets in progress). The Company is testing amortizable intangible assets for impairment
when there is an indicator of impairment. Impairment tests involve comparing the recoverable amount of
the licenses to their net book value. The recoverable amount of an asset is the higher of its fair value less
costs to sell and its value in use. If the carrying amount of any asset is above its recoverable amount, the
Company recognize an impairment loss to reduce the carrying amount to the recoverable amount. The
main assumptions used for the impairment test include (a) the amount of cash flows that are set on the
basis of the development and commercialization plans and budgets approved by Management, (b)
assumptions related to the achievement of the clinical trials and the launch of the commercialization, (c)
the discount rate, (d) assumptions on risk related to the development and (e) for the commercialization,
selling price and volume of sales, and are provided in Note 6 to the Company's consolidated financial
statements which are included elsewhere in this Annual Report. Any change in these assumptions could
162
lead to the recognition of an impairment charge that could have a significant impact on the Company's
consolidated financial statements. In case of failure of the clinical trials in progress, the Company may
have to fully depreciate the intangible asset. As of December 31, 2022, given the Company's decision in
December 2022 to discontinue the development of avdoralimab in the indication of bullous pemphigoid
supporting the recoverable amount of the asset as of December 31, 2021 and June 30, 2022, the rights
related to the intangible asset have been fully impaired for the net carrying amount of the intangible asset,
of €41,000 thousand , without using the historical assumptions described above (see note 6). As a result,
the Company considers that there are no longer any critical estimates in line with intangible assets in
2022. There are therefore no longer any critical assumptions that could call into question the recoverable
amount of the asset.
B. Liquidity and Capital Resources
The liquidity and capital resources discussion that follows contains certain estimates as of the date of this
Annual Report of the Company's estimated future sources and uses of liquidity (including estimated
future capital resources and capital expenditures) and future financial and operating results. These
estimates reflect numerous assumptions made by Innate with respect to industry performance, general
business, economic, regulatory, market and financial conditions and other future events, and matters
specific to its businesses, all of which are difficult or impossible to predict and many of which are beyond
its control.
Sources and uses of liquidity
As of December 31, 2022, The Company has primarily financed its operations through its receipt of
$601.4 million (€528.0 million) in payments from its collaborators, including AstraZeneca and Sanofi,
since 2011, excluding payments received for purchases of Innate's equity securities by its collaborators.
Innate Pharma has also financed its operations since its inception through several rounds of public and
private financings. Since its inception, Innate has raised a total of €311.4 million through the sale of
equity securities, including €33.7 million in the initial public offering of Innate's ordinary shares on
Euronext Paris in 2006 and €66.0 million in the initial public offering of the Company's initial public
offering of its ordinary shares on Nasdaq New-York in 2019.
In addition, Innate has received an aggregate of €90.9 million in research tax credits through December
31, 2022. As a French biopharmaceutical company, Innate Pharma has benefited from certain tax
advantages, including, for example, the research tax credit. The research tax credit can be offset against
French corporate income tax due and the portion in excess, if any, may be refunded. The research tax
credit is calculated based on innate's claimed amount of eligible research and development expenditures
in France. The research tax credit decreased by €2.4 million, or 23% , to €7.9 million for the year ended
December 31, 2022, as compared to a research tax credit of €10.3 million for the year ended December
31, 2021.
Innate Pharma lost its status as a small or medium size business at the end of the year ended December
31, 2019 and, therefore, was no longer be entitled to the immediate reimbursement of the Research Tax
Credit for the fiscal year ended 2019 and 2020 but instead will be reimbursed within the expiry of a three-
year period. For the 2021 and 2022 financial year, the Company met again the criteria of an SME
according to the criteria of the European Union. As a result, the Company was eligible for the early
repayment by the French treasury of the 2021 Research Tax Credit during the fiscal year 2022. The
Company will also be eligible to the early repayment by the French treasury of the 2022 Research Tax
Credit during the fiscal year 2023.
163
Innate Pharma is potentially eligible to earn amount of milestone payments and royalties under its
agreements with AstraZeneca in the event that the Company satisfies certain pre-specified milestones.
Innate may enter into new collaboration agreements that also provide milestone payments. These
milestone payments are dependent on the accomplishment of various development, regulatory and
commercialization objectives, and the achievement of many of these milestones is outside of Innate's
control. However, Innate's ability to earn these payments and their timing will, in part, be dependent upon
the outcome of its research activities which is uncertain at this time.
On July 3, 2017, Innate Pharma borrowed from the bank Société Générale in order to finance the
construction of its future headquarters. This loan, amounting to a maximum of €15.2 million, can be
drawn down during the period of the construction in order to pay supplier payments as they become due,
but in any event no later than August 30, 2019. Given the development of its portfolio and in particular
the refocusing of its activities on research and development, the Company has for the time being
suspended the project to build its new head office on the land acquired in Luminy. In the meantime, the
loan will be used to finance several structuring projects (improvement of the information system,
development of a commercial platform, development of additional premises rented, etc.). Repayment of
any amounts drawn down are payable over a 12-year term beginning on August 30, 2019 and ending on
August 30, 2031. As security for the loan, Innate pledged collateral in the form of financial instruments
held at Société Générale amounting to €15.2 million. The security interest on the pledged financial
instruments will be released in accordance with the following schedule: €4.2 million in July 2024,
€5.0 million in August 2027 and €6.0 million in August 2031. The Company had drawn down €15.2
million under the loan as of December 31, 2019. The loan bears a fixed interest rate of 2.01%. Under the
loan, Innate is subject to a covenant that its total cash, cash equivalents and current and non-current
financial assets as of each fiscal year end will be at least equal to the amount of outstanding principal
under the loan. The repayment period started on August 30, 2019. As of December 31, 2022, the
remaining capital of this loan amounted to €11.3 million as compared to €12.5 million as of 31 December,
2021.
On January 5, 2022, the Company announced that it had obtained non-dilutive financing of €28.7 million
in the form of two State-Guaranteed Loans (Prêts Garantis “PGE”) from Société Générale
(€20.0 million) and BNP Paribas (€8.7 million). The funds related to these two PGEs were collected by
the Company on December 27 and 30, 2021, respectively. These two loans have an initial maturity of one
year with an option to extend up to five years from August 2022. They are 90% guaranteed by the French
State as part of a system put in place to support companies in the face of the COVID-19 health crisis. In
August 2022, the Company has requested the extension of these two loans repayment for an additional
period of five years starting in 2022 and including a one-year grace period (2023). Consequently, the
Company has obtained agreements from Société Générale and BNP Paribas. The effective interest rates
applied to these contracts during the additional period are 1.56% and 0.95% for Société Générale and
BNP Paribas loans, respectively, excluding insurance and guarantee fees, with an amortization exemption
for the entire year 2023. During this grace period, the Company will only be liable for the payment of
interest and the guarantee fees, with amortization of the two loans starting in 2024 over a period of four
years. The state guarantee fees amounts to €877 thousand and €379 thousand for Société Générale and
BNP Paribas loans respectively. As of December 31, 2022, the remaining capital of these loans amounted
to €28.7 million
Innate leased its headquarters in Luminy, Marseille, France under a finance lease agreement, ended in
June 2020. In addition, the Company obtained a €1.5 million PTZI loan (Prêt à Taux Zéro Innovation—
interest-free loan for innovation) from Banque Publique d’Investissement, or BPI France, in 2013. The
loan is repayable beginning in September 2016 over five years and fully amortized as of December 31,
2022. Lastly, during the years ended December 31, 2016 and 2017, Innate also used lease-financing and
164
bank loans to finance the acquisition of laboratory equipment and to set up new laboratories. The debt
related to these loans amounts to €0.4 million at December 31, 2022.
The following table summarizes the Company's contractual obligations (principal amount only) as of
December 31, 2022:
(in thousands of euro)
BPI PTZI IPH41
BPI Refundable advance - FORCE
State guaranteed loan Société Générale
State guaranteed loan BNP Paribas
State guaranteed loans - accrued interest
Down-payment
Lease liabilities – Building "Le Virage"
Lease liabilities – Premises Innate Inc
Lease liabilities – Laboratory equipment
Lease liabilities – Vehicles
Lease liabilities - Printers
Loans – Equipment
Loan – Building
Total
≤ 1 year
2 to 5 years
included
≥ 5 years
Total
—
—
—
—
15
—
532
90
177
16
9
55
1,210
2,102
—
—
20,000
8,700
—
—
820
255
110
17
18
99
5,089
35,110
—
—
—
—
—
—
—
—
—
—
—
—
5,039
5,039
—
—
20,000
8,700
15
—
1,353
345
287
33
27
154
11,338
42,251
The table below summarizes Innate Pharma's contractual obligations (principal amount and interest) as of
December 31, 2022:
(in thousands of euro)
BPI PTZI IPH41
BPI Refundable advance - FORCE
State guaranteed loan Société Générale
State guaranteed loan BNP Paribas
State guaranteed loans - accrued interest
Down-payment
Lease liabilities – Building "Le Virage"
Lease liabilities – Premises Innate Inc
Lease liabilities – Laboratory equipment
Lease liabilities – Vehicles
Lease liabilities - Printers
Loans – Equipment
Loan – Building
Total
≤ 1 year
2 to 5 years
included
≥ 5 years
Total
—
—
20,670
8,884
—
—
838
312
110
20
18
100
5,706
36,658
—
—
—
—
—
—
—
—
—
—
—
—
5,112
5,112
—
—
20,982
8,970
15
—
1,396
408
289
39
27
157
12,245
44,528
—
—
312
86
15
—
558
96
179
19
9
57
1,427
2,758
165
Liquidity position
Cash, cash equivalents and short-term investments decreased by €18.4 million, or 15%, to €101.5 million
as of December 31, 2022, as compared to cash, cash equivalents and short-term investments of €119.8
million as of December 31, 2021. Cash and cash equivalents are mainly composed of current bank
accounts, interest-bearing accounts and fixed-term accounts. Short-term investments primarily consist of
shares of money market funds and mutual funds. Their purpose is to finance Innate's activities, including
Innate's research and development costs.
As a reminder, Innate has received a total of cash of €306.4 million from capital increases, before
deducting the costs associated with capital increases, and after excluding proceeds from share
compensation instruments, between 1999 and December 31, 2019. The table below summarizes the main
capital increases between 1999 and December 31, 2022 :
Date
April 2000
March 2001
July 2002
March 2004
July 2004
March 2006
November 2006
December 2009
November 2013
June 2014
October 2018
October 2019
Total
Gross Proceeds
€ 1.2 million
3.3 million
20.0 million
5.0 million
10.0 million
10.0 million
33.7 million
24.3 million
20.3 million
50.0 million
62.6 million
66.0 million
€ 306.4 million
166
Cash flows
Comparisons for the year ended December 31, 2021 and 2022
The following table sets forth cash flow data for the years ended December 31, 2021 and 2022:
Cash flows from / (used in) operating activities
Cash flows from / (used in) investing activities
Cash flows from / (used in) financing activities
Effect of the exchange rate changes
Net increase / (decrease) in cash and cash equivalents
Year ended December 31,
2021
2022
(in thousands)
€ (58,457)
€ (19,154)
(917)
26,818
(483)
1,877
(1,828)
(428)
€ (33,037)
€ (19,531)
Cash flows from / (used in) operating activities
The Company's net cash flow used in operating activities decreased by €39.3 million to €19.2 million for
the year ended December 31, 2022 as compared to net cash flows used in operating activities of €58.5
million for the year ended December 31, 2021. This increase mainly results from (i) the collection of
€47.7 million ($50.0 million) and €4,6 million ($5.0 million) in June 2022 and August 2022,respectively,
under the monalizumab agreement and the amendment to the IPH5201 collaboration and option
agreement, (ii) the collection of €3.0 million received from Sanofi under the 2016 agreement and
following Sanofi's decision to advance IPH6401/SAR'514 into regulatory preclinical studies for an
investigational new drug. Finally, (iii) the Company collected during 2022 the early repayment of the
research tax credit receivable relating to the 2021 financial year for an amount of €10.3 million, paid to
the Company by the French Treasury in November 2022. These collections are partially offset by the €5.9
million payment to AstraZeneca on April 20, 2022 persuant to the Lumoxiti termination and transition
agreement and cash outflows related to the Company's operating activities. As a reminder, cash flows
used in operating activities for year ended December 31, 2021, included successive receipts for a total
amount of €10.0 million from Sanofi (in January, February and December 2021) in connection with the
IPH6101/SAR443579 agreement signed in 2016, following Sanofi's decision at the end of 2020 to
advance IPH6101/SAR443579 towards regulatory preclinical studies for a new investigational drug, and
the launch of the first related Phase 1 trial in December 2021. Restated of these receipts and payments, net
cash flows used by operating activities for the year ended December, 2022 increased by €10.4 million.
This increase is mainly explained by the increase in the Company's research and development activities,
notably related to pre-clinical trials, and also by higher cash outflows related to the re-invoicing of costs
to AstraZeneca for the Phase 3 trials evaluating monalizumab, INTERLINK-1 and PACIFIC-9, in
accordance with the Company's co-financing commitments.
Net cash flow consumed by operating activities in connection with the Lumoxiti discontinued operation
amounted to €5.1 million for the year ended December 31,2022 as compared to € 3.6 million for the year
2021. This increase is mainly related to the payment to AstraZeneca of €5.9 million in April 2022 under
the termination and transition agreement for Lumoxiti.
167
Cash flows from / (used in) investing activities
The Company's net cash flows from investing activities for the year ended December 31, 2022 amounted
to €1.9 million and are mainly composed of a disposal of a non-current financial instrument which
generated a net cash collection of €2.9 million partially offset by acquisitions of property, plant and
equipment and intangible assets for €1.1 million. As a reminder, net cash flow used in investing activities
for the year ended December 31, 2021 amounted to €0.9 million and were mainly comprised of
acquisitions of tangibles assets.
Net cash flows consumed by investing activities in connection with the Lumoxiti discontinued operation
were nil for year ended December 31, 2022 and December 31 2021, respectively.
Cash flows from / (used in) financing activities
The Company's net cash flows used in financing activities for the year ended December 31, 2022
decreased by €28.6 million to €1.8 million for year ended December 31, 2022 as compared to net cash
flows from financing activities of €26.8 million for the year ended December 31, 2021. As a reminder, the
Company's obtained in 2021 a non-dilutive financing of €28.7 million in the form of two State
Guaranteed Loans from Société Générale (€20.0 million) and BNP Paribas (€8.7 million). The Company
received the funds related to these two loans on December 27 and 30, 2021, respectively.
Loan repayments amounted to €2.0 million for the year ended December 31, 2022 as compared to €2.1
million for the year ended December 31, 2021.
In addition, net cash flow from financing activities related to Lumoxiti discontinued operation are nil for
year ended December 31, 2022 and 2021, respectively.
Comparisons for the year ended December 31, 2020 and 2021
The following table sets forth cash flow data for the years ended December 31, 2020 and 2021:
Cash flows from / (used in) operating activities
Cash flows from / (used in) investing activities
Cash flows from / (used in) financing activities
Effect of the exchange rate changes
Net increase / (decrease) in cash and cash equivalents
Year ended December 31,
2020
2021
(in thousands)
€ (51,767)
€ (58,457)
(13,370)
(1,177)
219
(917)
26,818
(483)
€ (66,096)
€ (33,037)
Cash flows from / (used in) operating activities
The Company's net cash flow used in operating activities decreased by €6.7 million to €58.5 million for
the year ended December 31, 2021 as compared to net cash flows used in operating activities of €51.8
million for the year ended December 31, 2020. As a reminder, the company received, in December 2020,
a milestone payment of $50.0 million (€41.2 million) following the inclusion by AstraZeneca of the first
patient in the Phase 3 clinical trial INTERLINK-1. Without this resource, net cash used in operating
activities would have amounted to €93.0 million for year ended December 31, 2020. In addition, cash
flows used in operating activities for year ended December 31, 2021, include successive receipts for a
168
total amount of €10.0 million from Sanofi (in January, February and December 2021) in connection with
the IPH6101/SAR443579 agreement signed in 2016, following Sanofi's decision at the end of 2020 to
advance IPH6101/SAR443579 towards regulatory preclinical studies for a new investigational drug, and
the launch of the first related Phase 1 trial in December 2021. Restated of these receipts, net cash flows
used by operating activities for the year ended December, 2021 are down by €24.6 million. This decrease
is mainly due to the discontinuation of Lumoxiti-related activities in connection with the Company's
decision at the end of 2020 to return the commercial rights in the United States and Europe to
AstraZeneca, under the termination and transition agreement signed in 2021. As a result, net cash flow
consumed by operating activities in connection with the Lumoxiti discontinued operation amounted to
€3.6 million for the year ended December 31, 2021 as compared to € 22.4 million for the year 2020.
Cash flows from / (used in) investing activities
The Company's net cash flows used in investing activities for the year ended December 31, 2021 were
€0.9 million as compared to a net cash flow used in investing activities for the year ended December 31,
2020 of €13.4 million which mainly resulted from (i) a €13.4 million ($15.0 million) additional
consideration paid, in January 2020, to AstraZeneca regarding Lumoxiti following the submission of the
Biologics License Application to the European Medicine Agency (EMA) in November 2019 (ii) a
€2.7 million additional consideration paid to Orega Biotech in April 2020 regarding IPH5201 following
the dosing of a first patient in a Phase 1 clinical trial, in March 2020 and (iii) the acquisition of financial
assets for a net amount of €3.0 million. Such items were partially offset by the reimbursement by
AstraZeneca in relation to the 2019 cost sharing mechanism for the commercialization of Lumoxiti
(€7.0 million). As a result, net cash flows consumed by investing activities in connection with the
Lumoxiti discontinued operation were nil for year ended December 31, 2021 as compared to €6.6 million
for year ended December 31 2020.
Cash flows from / (used in) financing activities
Innate's net cash flows from financing activities for the year ended December 31, 2021 increased by
€28.0 million to €26.8 million for year ended December 31, 2021 as compared to net cash flows used in
financing activities of €1.2 million for the year ended December 31, 2020. This increase results from the
Company's obtainment of €28.7 million in non-dilutive financing in the form of two State Guaranteed
Loans from Société Générale (€20.0 million) and BNP Paribas (€8.7 million). The Company received the
funds related to these two loans on December 27 and 30, 2021 respectively.
Loan repayments amounted to €2.1 million for the year ended December 31, 2021 compared to €2.2
million for the year ended December 31, 2020.
In addition, net cash flow from financing activities related to Lumoxiti discontinued operation are nil for
year ended December 31, 2021 and 2020, respectively.
Funding requirements
Innate Pharma believes that its existing cash, cash equivalents, short-term investments and non-current
financial assets, will enable Innate to fund its operations for the next twelve months. Innate has based this
estimate on assumptions that may prove to be wrong, and the Company could use its capital resources
sooner than it currently expects.
Until Innate can generate a sufficient amount of revenue from sale of approved products, if ever, it
expects to finance its operating activities through its existing liquidity and expected milestone payments
from collaborators.
169
Innate's present and future funding requirements will depend on many factors, including, among other
things:
•
•
•
•
•
•
•
the size, progress, timing and completion of its clinical trials and preclinical studies for any
current or future product candidates, including its lead product candidates, monalizumab and
lacutamab;
the number of potential new product candidates Innate identifies and decides to develop;
costs associated with its payment obligations to third parties in connection with its
development and potential commercialization of certain of its product candidates;
costs associated with expanding its organization;
the costs involved in filing patent applications and maintaining and enforcing patents or
defending against claims of infringement raised by third parties;
the time and costs involved in obtaining regulatory approval for its product candidates and any
delays the Company may encounter as a result of evolving regulatory requirements or adverse
results with respect to any of these product candidates;
the amount of revenues, if any, Innate Pharma may derive either directly, or in the form of
milestone or royalty payments from any future potential partnership agreements, from
monalizumab, IPH5201, IPH6101/SAR443579, IPH6401/SAR'514, B7H3 or relating to its
other product candidates.
For more information as to the risks associated with Innate's future funding needs, see “Risk Factors—
The Company may need to raise additional funding to complete the development and any
commercialization of its product candidates, which may not be available on acceptable terms, or at all,
and failure to obtain this necessary capital when needed may force the Company to delay, limit or
terminate its product development efforts or other operations.”
Capital expenditures
Innate Pharma's operations mainly require investment in intangible assets. Innate acquired the rights of
avdoralimab from Novo Nordisk A/S in 2017. The Company paid an upfront of €40.0 million, of which
€37.2 million was contributed in new ordinary shares and €2.8 million in cash. As part of this agreement,
an additional amount of € 1.0 million was paid in October 2020 to Novo Nordisk A / S following the
launch of the first avdoralimab Phase 2 trial.
In January 2019, Innate Pharma paid to AstraZeneca an initial payment for the license related to Lumoxiti
($50.0 million, or €43.8 million, using the foreign exchange rate of 1.1422 at the date of payment), and in
February 2019, Innate paid to Novo Nordisk A/S additional consideration relating to monalizumab
($15.0 million, or €13.1 million using the exchange of 1.1394 at the date of payment). In June 2019,
Innate paid €7.0 million to Orega Biotech in relation to the anti-CD39 program as consideration following
the collaboration and option agreement signed on October 22, 2018 with AstraZeneca regarding IPH5201.
Innate's operations generally require little investment in tangible assets because the Company outsources
most of the manufacturing and research activities to third parties. Innate Pharma leases some of its
computer equipment under operating lease agreements. Innate accounts for its payments for these items as
operating expenses in the consolidated statement of income.
The Company's capital expenditures in the years ended December 31, 2020, 2021 and 2022 primarily
related to laboratory equipment. Clinical research and development costs are not capitalized until
marketing authorizations are obtained.
170
Innate Pharma's corporate office in Luminy, Marseille, France is leased under a finance lease agreement
signed in 2008 with Sogebail, a subsidiary of Société Générale, for an aggregate of €6.6 million. The
lease-financing agreement has a 12-year term. Innate have a purchase option for all of the buildings and
land for the lump sum of €1 at the end of the term of the contract on June 9, 2020, which it has exercised.
The Company now owns its corporate office in Luminy, Marseille.
Since July 2017, Innate also rents office space in Marseille, France under a commercial lease.
On January 10, 2020, the Company signed an amendment to the lease for the “Le Virage” building in
order to expand its premises. This amendment also extended the duration of the contractual commitment
until 2025.
On March 13, 2023, the Company signed an amendment to the lease for "Le Virage Building" in order to
reduce the rental area of its premises located in the "Le Virage" building. This amendment has the effect
of reducing the amount of the commitment relating to rents by €692 thousand. The Company remains
committed under this contract until June 30, 2025.
C. Research and Development
For a discussion of our research and development activities, see “Item 4.B—Business Overview” and
“Item 5.A—Operating Results.”
D.
Trend Information
Other than as disclosed elsewhere in this annual report, we are not aware of any trends, uncertainties,
demands, commitments or events for the period from January 1, 2022 to December 31, 2022 that are
reasonably likely to have a material effect on our operating revenues, profitability, liquidity or capital
resources, or that would cause the disclosed financial information to be not necessarily indicative of
future operating results or financial conditions.
E. Critical Accounting Estimates.
Not Applicable.
Item 6. Directors, Senior Management and Employee.
A. Directors and Senior Management.
Directors and Officers
•
The following table sets forth information concerning the members of its Executive Board and
Supervisory Board and its other executive officers as of December 31, 2022.
171
Name
Age
Position
Executive Board Members
Mondher Mahjoubi, M.D.
Yannis Morel, Ph.D.
Supervisory Board Members
64
49
Chairman of the Executive Board, Chief Executive Officer, Member of
the Executive Committee
Member of the Executive Board, EVP, Product Portfolio Strategy &
Business Development, Member of the Executive Committee
Hervé Brailly, Ph.D.
61 Chairman of the Supervisory Board
Irina Staatz-Granzer, Ph.D.
62 Member and Vice Chairman of the Supervisory Board
Jean-Yves Blay, Ph.D.
60 Member of the Supervisory Board
Gilles Brisson
70 Member of the Supervisory Board
Véronique Chabernaud, M.D.
61 Member of the Supervisory Board
Olivier Martinez
52 Member of the Supervisory Board
Sally Bennett, MBChB
51 Member of the Supervisory Board
Pascale Boissel
56 Member of the Supervisory Board
Other Executive Officers
Joyson Karakunnel M.D. M.S.C
52 Member of the Executive Committee, EVP, Chief Medical Officer
Odile Belzunce
42 Member of the Executive Committee, VP Compliance, IT and Portfolio
Management
Eric Vivier, D.V.M., Ph.D.
58 Permanent Guest to the Executive Committee, SVP, Chief Scientific
Officer
Odile Laurent
60 Member of the Executive Committee, VP Human Resources
Frédéric Lombard
48 Member of the Executive Committee, Chief Financial Officer
Claire de Saint Blanquat
50 Member of the Executive Committee, VP Legal and Corporate Affairs
Henry Wheeler
Member of the Executive Committee, VP Investor Relations and
Communications
39
172
Executive Board
Mondher Mahjoubi, M.D., Chief Executive Officer and Chairman of its Executive Board, was appointed
Chief Executive Officer and Chairman of its Executive Board on December 30, 2016. Prior to joining
Innate Pharma, Dr. Mahjoubi led AstraZeneca’s oncology therapy area franchise, playing an instrumental
role in the development and execution of its oncology product strategy from 2013-2016. Prior to that role,
he served as the Senior Vice President of Global Product Strategy in Oncology at Genentech from
2010-2013. He also previously held various positions as Vice President of Marketing and Medical Affairs
at Roche, Sanofi-Aventis and Rhone Poulenc Rorer. Dr. Mahjoubi is trained as a medical oncologist,
holds a M.D. from the University of Tunis (Tunisia) and university degrees in Medical Oncology from the
University of Paris Sud (France) and in Clinical Research and Methodology from the University of
Lariboisiere-Saint Louis (France). He was resident doctor at the Faculty of Medicine in Tunis and at the
Gustave-Roussy Institute in Villejuif. He is a member of the American Society of Clinical Oncology and
European Society of Medical Oncology. He is also currently a consultant at Boston Pharmaceuticals and
an independent board member and Chairman of the Board of Directors at PDC*line Pharma, a clinical
stage biotech company developing a novel class of anticancer vaccines.
Yannis Morel, Ph.D., member of the Executive Board and EVP, Product Portfolio Strategy and Business
Development, joined Innate in December 2001. Between 2001 and 2007, he was in R&D positions,
initially as a scientist in the immunology team, before becoming team manager, and finally becoming
responsible for research programs. From 2007, he was in charge of business development for the
company. Mr. Morel holds a PhD in oncology from Aix-Marseille University (France) and is an alumnus
of Ecole Normale Supérieure de Cachan (France), with a BS in physical and molecular chemistry.
Supervisory Board
Hervé Brailly, Ph.D., Chairman of the Supervisory Board, is a biotech entrepreneur. He founded Innate
Pharma in 1999 and led the Company from 1999 to 2016 as Chief Executive Officer and Chairman of the
Executive Board before being appointed Chairman of the Supervisory Board in 2017. Mr. Brailly is also
the acting CEO and co-founder of Kalsiom (immunology, Brest), and co-founded MI-MAbs SAS
(immuno-technology, Marseille) in 2020 and Systol Dynamics (cardiology, Marseille). He is Chairman of
the Board of Directors of NH Theraguix (oncology, Grenoble) and member of the Board of Directors of
Deinove (microbiology, Montpellier). Mr. Brailly graduated from the Ecole des Mines de Paris (1983,
France) and he holds a PhD in immunology with a specialty in immune-pharmacology. During his career,
he has been involved in the governance of several public and academic bodies in the field of higher
education, research and technology transfer. He is currently Chairman of the School of Engineering of
Aix-Marseille University (AMU, France). He is also a member of the Board of Directors of Deinove SA.
Irina Staatz-Granzer, Ph.D., Vice Chairman and member of the Supervisory Board, has served on the
Supervisory Board of the Company since 2009. Dr. Staatz-Granzer has held business development
positions at Hermal (subsidiary of Merck KGaA), Boots Healthcare International, Knoll (BASF Pharma,
later Abbott) and as CEO of Scil Technology Gmbh, CEO of U3 Pharma AG and CEO of Blink
Biomedical SAS. Ms. Staatz-Granzer also serves as Chairman of PLCD (German Pharma Licensing
Club). She founded and is currently CEO of Staatz Business Development & Strategy. She is also
member of the Supervisory Board of Aelis Farma SAS. Dr. Staaz-Granzer received a degree in pharmacy
from Philipps-Universität Marburg (Germany) and a Ph.D. from the University of Tübingen (Germany).
Jean-Yves Blay, Ph.D., member of the Supervisory Board, has held the post of General Director of the
Centre Léon Bérard in Lyon, France, since 2014 and renewed in 2019. He became President of Unicancer
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in 2019. He is President of the French Sarcoma Group and Director of the European Reference Network
for Rare Adult Cancers (EURACAN). Between 2009 and 2012 he held the position of President of the
European Organisation for Research and Treatment of Cancer (EORTC). Prof. Blay currently holds
various other university and hospital positions. He is a member of the European Union Committee of
Experts of Rare Disease, the European Commission’s Scientific Panel for Health (SPH) and served as a
Faculty Coordinator for Sarcoma for the European Society of Medical Oncology (ESMO) between 2012
and 2016. Trained as a medical oncologist with a PhD from the University Claude Bernard in Lyon
(France), his research activities have been focused on the role of immune effector cells and cytokines in
cancer. Prof. Blay is a member of various scientific societies and academic expert groups, has been
awarded several honors and is the author of more than 200 publications over the last three years.
Gilles Brisson, member of the Supervisory Board, has served on the Supervisory Board of the Co since
2007 and was the Chairman until December 30, 2016. Mr. Brisson has worked in management positions
at Rhône-Poulenc and then at Aventis Pharma (Sanofi), where he served as Chairman of the Executive
Board, Chairman of the Supervisory Board and Europe Manager. Mr Brisson was member of the
Supervisory Board of Mutabilis Holding and the Carso Group and Chairman of the Board of Directors of
MaunaKea Technologies. He received a degree from Hautes Etudes Commerciales de Paris (France).
Véronique Chabernaud, M.D., member of the Supervisory Board, is an oncologist, a graduate of ESSEC
Business School (France) and has worked for 20 years in the pharmaceutical industry. In particular, she
was the Director of the French Oncological Operational Unit at Sanofi Aventis, a Vice President of
Marketing and Sales at Aventis Intercontinental and Europe, and Director of Oncology Global Medical
Affairs at Rhône Poulenc Rorer. She also works as a consultant for companies in the field of innovative
technologies with a high impact on public health, on a national and international level. Such companies
include Genomic Health, BioSystems International, MaunaKea Technologies, Ariana Pharma, Qynapse,
Omicure. In 2007, Dr. Chabernaud founded Créer la Vitalité, which helps companies and organizations in
the development of health innovations and prevention. Véronique Chabernaud graduated in 2017 from the
Institut Français des Administrateurs and Sciences Po Paris with a Certificate in Corporate Directorship
and has been involved in this program since 2017. Dr. Chabernaud also founded the association “Enfance
et Vitalité” which offers health workshops to children. She is also co-author of the book "Capital Humain
versus Humain Capital." From July 2019 to July 2021, Véronique Chabernaud has been member of the
Board of Directors and Chairman of the Compensation and nomination committee of Groupe Bastide le
confort médical (BLC).
Pascale Boissel, member of the Supervisory Board, is, with more than 30 years of financial experience,
an expert in finance, audit, transactions, internal control, growth management and restructuring
operations. Her experience has been represented in a variety of industries, including: food and beverage
(Danone), building materials (Lafarge Holcim), education and, for more than 10 years now, healthcare
and biotechnology. Before, she was Chief Financial Officer of ENYO Pharma. Pascale was the Deputy-
Chief Executive Officer and Administrative and Financial Director of the BIOASTER Institute (IRT) in
the field of infectious diseases and microbiology. In 2009, Madame Boissel joined Ipsogen a listed
company developing and marketing molecular diagnostic products as Chief Financial Officer. Pascale
Boissel began her career in audit and corporate finance at PricewaterhouseCoopers Paris.
Olivier Martinez, permanent representative of Bpifrance Participations, member of the Supervisory
Board, is Senior Investment Director of the Investments Biotech Department of the Direction of
Innovation of Bpifrance. Prior to that, Mr. Martinez was Investment Director at CDC Entreprises
(2010-2013) and Partner at Bioam Gestion
the board of
EmergenceTherapeutics AG. Mr. Martinez is an alumnus of the Ecole Normale Supérieure and holds a
(2000-2010). He also sits on
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PhD in cell biology from the University of Paris XI and an MBA from the Collège des Ingénieurs
(France).
Sally Bennett, MBChB., member of the Supervisory Board, has been selected for her significant
experience and expertise in financial analysis and capital markets, in the healthcare and biotechnology
sectors. Dr Sally Bennett has a career spanning medicine, equity & capital markets and investment
management. She spent 15 years in senior roles as both a public and private investor at HealthCor, a US
based global healthcare and life science investment manager and most recently co-led the firms move into
private investing. She is now acting as a Senior Advisor to Catalio Capital in conjunction with its
acquisition of HealthCor Management. Prior to HealthCor, she spent ten years as a senior analyst at ING
Financial Markets and then at Piper Jaffray. Dr Bennett serves as an Independent Non-Executive Director
at BerGenBio, a publicly traded European biopharmaceutical company, where she Chairs the Audit
Committee and is also an Advisory Board member of the P4 Precision Medicine Accelerator Programme
in the UK. She also serves on the Board of a private UK Company, Mosaic Therapeutics where she
represents the Sanger Institute. She was also a member of the Board of Governors of UCLH, an NHS
Foundation Trust hospital, where she served on the Research and Innovation Committee. She is a member
of the Institute of Directors (IoD) and has been awarded the CertIoD qualification. Dr Bennett received a
BSc in Anatomical Sciences and a Medical Degree, awarded with Honours, both from the University of
Manchester. She is a British citizen.
Other Executive Officers
Joyson Karakunnel, Member of the Executive Committee, EVP and Chief Medical officer, joined Innate
Pharma as Executive Vice President and Chief Medical Officer in July 2020. He is exercising these
functions as a consultant since June 2021. He is an experienced medical oncologist and hematologist with
more than 15 years of drug development expertise both in academia and the biopharmaceutical industry.
Most recently, Dr. Karakunnel served as Senior Vice President and Chief Medical Officer at Tizona
Therapeutics, where he led the development of the company’s biotherapeutics pipeline. Prior to Tizona,
he held positions with Arcus Biosciences and AstraZeneca/MedImmune. At Arcus, he established the
clinical, regulatory and safety departments, and while at AstraZeneca/MedImmune, he served as the
early-stage lung cancer lead and contributed to the regulatory filings of IMFINZI® (durvalumab). Prior to
joining the biopharmaceutical industry, he was a clinical trial investigator at the National Cancer Institute
(NCI) and team leader for the hematologic group at Walter Reed National Military Medical Center. In
addition, he was an Associate Professor at the Uniformed Services University of the Health Sciences and
a medical reviewer at the U.S. Food and Drug Administration. Dr. Karakunnel completed his oncology
and hematology fellowships at the NCI, his medical training at Annamalai University in India and holds a
Masters in Pharmacology from the University of Maryland.
Odile Belzunce, Member of the Executive Committee, Vice President, Compliance and Operations, was
appointed as a member of the Executive Committee of the Company on January 31, 2019. Odile Belzunce
joined Innate Pharma in February 2005. She was Quality Manager during 10 years before becoming Head
of Compliance. During her career at Innate, Odile Belzunce contributed to the structuration of the
processes as the Company was growing, developing its portfolio and its activities. Odile Belzunce
currently holds the position of VP, Compliance and Operations.
Nicolas Beltraminelli, PhD, Member of the Executive Committee, Vice President, Chief Development
Officer, joined Innate Pharma as Vice President and Chief Development Officer in January 2022. Dr.
Beltraminelli brings more than 20 years of biotech experience to the role, and specifically in the
development of biologic products from early discovery to GMP manufacture. Most recently, Dr.
Beltraminelli served as Chief Technical Officer at Lysogene, where he led the CMC activities for two
late-stage assets. Prior to Lysogene, he held senior level positions at HiFiBiO Therapeutics and BliNK
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Biomedical SAS. At HiFiBiO, Dr. Beltraminelli led the R&D activities of the company’s French site, as
well as its global CMC efforts, bringing three projects to the clinic. Dr. Beltraminelli holds a PhD in
Molecular Biology from the University of Lausanne, Switzerland.
Eric Vivier, D.V.M., Ph.D., Permanent guest to the Executive Committee, Senior Vice President, Chief
Scientific Officer, joined Innate in that role in 2018. Eric Vivier is a Doctor of Veterinary Medicine
(DVM) from the Ecole Nationale Vétérinaire de Maisons-Alfort and holds a PhD in Immunology from
the Paris University (Paris XI). After completing his post-doctoral fellowship at Harvard Medical School
(Dana Faber Cancer Institute), Pr. Vivier joined the Center of Immunology at Marseille-Luminy (CIML)
in 1993, becoming its director in 2008 until 2017. A pioneer in the field of innate immunity, he is one of
the four immunologists whose research led to the creation of Innate Pharma. He has twice been laureate
of the prestigious European Research Council (ERC) advanced grants. During his career, Pr. Vivier has
been a visiting professor at The Scripps Research Institute, The Rockefeller University, and The Walter
and Elisa Hall Institute. He is a member of the French National Academy of Medicine, of the Institut
Universitaire de France and of the Royal Academy of Medicine of Belgium. He is on the board of
numerous committees and has been awarded several prices and honors, including the European
Federation of Immunological Society award and the Grand Prix Charles Oberling in Oncology. He is also
Chevalier de la Légion d’Honneur and Officier de l'Ordre National du Mérite.
Odile Laurent, Member of the Executive Committee, Vice President, Human Resources Director, joined
Innate in that role in September 2017. Odile Laurent has been appointed Vice President, Human
Resources Director in January 2020. Before joining Innate Pharma, Ms. Laurent was Group Human
Resources Director at Marie Brizard Wine&Spirits Group from 2015 to 2017. Previously, Ms. Laurent
was Director of Human Resources for the ‘Power Transformers’ business unit at Areva T&D, and was
subsequently appointed Head of Global Sales at Alstom Grid. Ms. Laurent has spent most of her career at
Sanofi-Aventis where from 2005 she was successively in charge of the Multi-site and European Human
Resources Department of the ‘Matures Products and OTC’ business unit, and later of the Supply-Chain
business unit worldwide. Ms. Laurent holds a PhD in Physical Sciences from the Institut National
Polytechnique of Toulouse and a Master of Business Administration in Human Resources from the
Institut d’Administration des Entreprises of Toulouse (France).
Frederic Lombard, Member of the Executive Committee, Chief Financial Officer, joined Innate Pharma
in April 2021. Mr. Lombard joined Innate with more than 20 years of financial experience in the
pharmaceutical industry, holding senior finance roles at Ipsen, AstraZeneca and Novartis. Throughout his
career, Mr. Lombard has developed international financial teams with the aim of strengthening team
members’ skill sets and positioning the function as a collaborative business partner. He also specializes in
project management, successfully conducting significant transformation projects in multi-cultural
environments. Prior to his financial career in the healthcare sector, Mr. Lombard worked in the
information technology industry, where he became familiar with the information systems standards in
fast-changing environments. He holds a BA in Economics & Finance from Lyon 2 University and a MBA
from EM Lyon Business School.
Claire de Saint-Blanquat, Member of the Executive Committee, Vice President, Legal and Corporate
Affairs and Secretary of the Supervisory Board, joined Innate Pharma in October 2020 and was appointed
to the executive committee in January 2023. Claire de Saint-Blanquat has nearly 20 years of experience in
diverse legal positions in the pharmaceutical industry. Admitted to the Paris Bar in 1998, she started her
career at Clifford Chance and then held senior positions, notably at Teva, Servier and Biogaran, where
she was Legal and Compliance Director since 2016. Claire de Saint-Blanquat holds a master's degree in
private law from the University of Paris II - Panthéon Assas (1995), a DEA in civil and commercial
obligations law from the University of Paris V - Malakoff (1996) and a DESS in biotechnology law from
the University of Versailles- Saint Quentin (2003).
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Henry Wheeler, MSc, Member of the Executive Board, Investor Relations and Communications, joined
Innate Pharma as Vice President, Investor Relations in June 2021 and was appointed to the executive
committee in January 2023. Henry Wheeler has over 15 years’ experience across the pharmaceutical and
financial industries. Henry Wheeler joined from AstraZeneca, where he led investor relations for the
company’s oncology portfolio, having previously served within AstraZeneca’s Oncology Business Unit.
Prior to this, Henry Wheeler worked in various healthcare financial roles including at Third Bridge and
Morgan Stanley in London. Henry Wheeler graduated with a MSc in Drug Discovery Skills and a BSc
with honours in Pharmacology, both from King‘s College, London.
Family Relationships
There are no family relationships among any of the members of the Executive Board, Supervisory Board,
and other executive officers of the Company referred to above.
Arrangements with existing Major Shareholders and Customers
There are no arrangements with major shareholders, customers, suppliers or others, pursuant to which any
person referred to above was selected as members of the Executive Board, Supervisory Board, or other
executive offers of the Company.
B. Compensation.
Compensation of Members of the Executive and Supervisory Boards
Following the entry into force of the Sapin 2 Law (French law no. 2016-1691 of December 9, 2016), the
Ordonnance no. 2019-1234 dated November 27, 2019 and the Decree no. 2019-1235 dated November 27,
2019, the payment of any variable or exceptional compensation attributed for a financial year to the
Chairman of the Supervisory Board, the Chairman of the Executive Board and members of the Executive
Board, is subject to approval at the next ordinary general meeting (ex-post vote). The payments of the
below variable compensations, for the year ended December 31, 2022, will be submitted for approval to
the ordinary and extraordinary shareholder meeting to be held on May 12, 2023. In addition to the ex-post
vote described above, French law also requires that the compensation policy for the members of the
Executive and Supervisory Board for the year ending December 31, 2023 is subject to the approval at the
ordinary general meeting relating to the year ending December 31, 2022.
Compensation of Members of the Supervisory Board
Attendance Fees
The Company pays attendance fees to the members of the Supervisory Board, except for the permanent
representative of Bpifrance Participations and the Chairman of the Supervisory Board. At its general
meeting of shareholders held on May 20, 2022, shareholders set the total attendance fees to be distributed
among the members of the Supervisory Board at €300,000. The attendance fees consist of a fixed portion
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and a variable portion based on attendance at meetings of the Supervisory Board and its committees. The
following table shows the framework for its attendance fees for the year ended December 31, 2022:
Fixed Portion (annual fee)
Supervisory Board Member
€15,000
Member Role
Attendance Fee
Committee Chairman
(Audit Committee and
Compensation and
Nomination Committee)
€25,000
Variable Portion (attendance fee at each meeting of the
Supervisory Board Member
€2,000
Supervisory Board)
Variable Portion (attendance fee at each meeting of the Audit
Committee and the Compensation and Nomination Committee)
Committee Member
€2,000
Variable Portion (attendance fee at each meeting of an additional
Supervisory Board Member €1,000
Supervisory Board and at each meeting of the Transaction
Committee)
Transaction Committee
Member
€1,000
The following table sets forth information regarding the attendance fees earned by members of the
Supervisory Board during the year ended December 31, 2022:
Member
Gilles Brisson
Irina Staatz-Granzer
Patrick Langlois
Véronique Chabernaud
Jean-Yves Blay
Pascale Boissel
Attendance Fees
€30,000
€41,000
€22,417
€51,000
€20,000
€53,667
€26,000
Sally Bennett
The Supervisory Board of January 25, 2023 decided to put to the vote of its shareholders at the general
meeting of shareholders to be held on May 12, 2023, a total attendance fees envelop to be distributed
among the members of the Supervisory Board amounting to €300,000 for the year ending December 31,
2023 . The following table shows the framework for Innate's attendance fees for the year ended December
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31,
Fixed Portion (annual fee)
Member Role
Supervisory Board Member
Committee Chairman (Audit and
Compensation and Nomination)
2022:
Attendance Fee
€15,000
€25,000
Variable Portion (attendance fee at each meeting of
the Supervisory Board)
Supervisory Board Member
€2,000
Committee member (Audit and
Compensation and Nomination
Variable Portion (attendance fee at each additional
meeting of the Supervisory Board, at the Transaction
and CSR Committees meetings)
Supervisory Board member
€1,000
Committee member
Chairman Compensation
Hervé Brailly, the Chairman of the Supervisory Board, receives specific compensation pursuant to article
L.225-84 of the French Commercial Code for his duties as Chairman of the Supervisory Board. For the
year ended December 31, 2022, Innate paid Mr. Brailly €100,000 in specific compensation for his
performance of these duties.
Compensation of Members of the Executive Board
Framework for Executive Board Compensation
During the year ended December 31, 2022, the Executive Board consisted of Mondher Mahjoubi and
Yannis Morel. Dr. Mahjoubi served as Chairman of the Executive Board.
The compensation of members of the Executive Board is decided by the Supervisory Board upon
recommendation by the compensation and nomination committee. The compensation of Dr. Mahjoubi,
the Chairman of the Executive Board, is paid under his social mandate, whereas the compensation of Dr.
Morel is paid under his employment contract.
The compensation of members of the Executive Board includes the following components:
•
•
Fixed Compensation. The members of the Executive Board receive fixed compensation pursuant to
their employment agreement or, in the case of the Chairman, his social mandate.
Annual Variable Compensation. The members of the Executive Board are eligible to receive annual
variable compensation upon the recommendation of the compensation and nomination committee
based on the achievement of pre-specified objectives. For the year ended December 31, 2022, such
objectives were based on the achievement of the Company's main strategic pillars and operational
targets defined according to Innate Pharma's activities in order to (i) take into account the
outperformance inherent to a fast-growing biotech company and (ii) motivate the executives to
exceed their objectives.
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The strategic pillars are the following: (i) maximizing the value of Lacutamab, (ii) advancing the
R&D portfolio and (iii) sustaining the Company's business, (iv) financing the Company and (v) the
compliance.
Each pillar were subdivided into:
(i) a baseline target, the achievement of which weighs 20% for each pillar; and
(ii) an outperformance target, the achievement of which weighs 20% for each pillar.
If 100% of the basic target objectives are achieved, 100% of the corresponding bonus is paid. If
100% of the targets are not achieved, the percentage of the bonus paid is proportional to the
percentage of achievement of the targets. In case of outperformance for the year 2022, it may be
decided to increase the amount of the bonus beyond 100% up to a limit of 150% on other
predefined criteria. For the year ended December 31, 2022, the members of the Executive Board
were able to opt to receive a portion equivalent to 50% of their annual variable compensation in the
form of free shares, increased by a 50% premium.
•
•
Performance Free Shares. The members of the Executive Board are able to receive, upon
authorization of the Supervisory Board and upon recommendation of the compensation and
nomination committee, equity compensation in the form of performance free shares.
Other Benefits. The members of the Executive Board receive other benefits consisting of a
supplementary pension plan, in-kind benefits and, for the Chairman of the Executive Board,
unemployment insurance.
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2022 Compensation of Mondher Mahjoubi
The following table sets forth the compensation earned by Dr. Mahjoubi during the year ended December
31, 2022:
Type of Compensation
Fixed Compensation
Annual Variable
Compensation—Cash
Amount of
Compensation
€470,000
€141,000
Annual Variable
Compensation—Free Shares
€178,723
Performance Free Shares 2022
€278,000
Benefits in Kind
€23,719
Total Compensation
€1,091,442
Description
Gross fixed compensation pursuant to Dr.
Mahjoubi’s social mandate.
This amount represents 50% of Dr. Mahjoubi’s
annual variable compensation, based on his
achievement of 100%% of the annual objectives.
Dr. Mahjoubi elected to receive the other 50% of
his variable compensation in the form of free
shares.
Dr. Mahjoubi opted for the payment of 50% of
his annual variable compensation in free shares,
increased by a 50% premium. The Executive
Board of October 3, 2022 attributed 54,323 free
shares (AGA Bonus 2022) to Dr. Mahjoubi. The
number of free shares was calculated on the basis
of the weighted-average price per ordinary share
for the 20 first trading days of 2022, amounting
to €3,89 per share. On the basis of the
achievement of 100.00% of its objectives, he
benefits from 54,323 AGA Bonus. These 54,323
free shares are valued at €178,722.67 on the basis
of the stock price on December 31, 2022, or
€3.29per ordinary share.
This amount was calculated in accordance with
the IFRS 2 valuation of the grant to Dr. Mahjoubi
of 200,000 performance free shares 2022.
Primarily represents amounts paid for use of a
company car and additional retirement benefits
(known as “article 83”), among other benefits.
2022 Compensation of Yannis Morel
The following table sets forth the compensation earned by Dr. Morel during the year ended December 31,
2022:
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Type of Compensation
Fixed Compensation
Annual Variable
Compensation—Cash
Amount of
Compensation
€252,000
€50,400
Annual Variable
Compensation—Free Shares
€63,882
Performance Free Shares 2022
€139,000
Benefits in Kind
€6,501
Total Compensation
€511,783
Description
Gross fixed compensation pursuant to Dr.
Morel’s employment contract.
This amount represents 50% of Dr. Morel’s
annual variable compensation, based on his
achievement of 100.00% of the annual
objectives . Dr. Morel elected to receive the other
50% of his variable compensation in the form of
free shares.
Dr. Morel opted for the payment of 50% of his
annual variable compensation in free shares,
increased by a 50% premium. The Executive
Board of October 3, 2022 attributed 19,417 free
shares (AGA Bonus 2022) to Dr. Morel. The
number of free shares was calculated on the basis
of the weighted-average price per ordinary share
for the first 20 trading days of 2022, amounting
to €3,89 per share. On the basis of the
achievement of 100.00% of its objectives, Dr.
Morel benefits from 19,417. These 19,417 free
shares are valued at €63,881.93 on the basis of
the stock price on December 31, 2022, or €3.29
per ordinary share.
This amount was calculated in accordance with
the IFRS 2 valuation of the grant to Dr. Morel of
100,000 performance free shares 2022.
Primarily represents amounts paid for use of a
company car and additional retirement benefits
(known as “article 83”), among other benefits.
2023 Executive Board Compensation
At the general meeting of shareholders of the Company to be held on May 12, 2023 the compensation of
the members of the Executive Board set forth in the following table for the year ended December 31,
2023 will be put to the vote of its shareholders:
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Type of Compensation
Fixed Compensation
Maximum Annual Variable Compensation if 100% of the
Mondher
Mahjoubi
€470,000
Yannis Morel
€252,000
objectives are reached
€282,000
€100,800
Maximum Annual Variable Compensation if case of over-
performance (150%)
€423,000
€151,200
The variable compensation for the year ended December 31, 2023 is based on the achievement of
Company's main strategic pillars and operational targets defined according to Innate Pharma's activities in
order to (i) take into account the outperformance inherent to a fast-growing biotech company and (ii)
motivate the managers to exceed their objectives.
There are three main strategic pillars: (i) maximizing the value of Lacutamab, (ii) advancing the R&D
portfolio and (iii) sustaining the Company's business, complemented by two other pillars: (iv) finance and
(v) CSR (corporate and social responsibility), which are essential to the achievement of the three strategic
axes mentioned above.
Each pillar has been subdivided into:
(i) a baseline target; and
(ii) an outperformance target.
The weights of each pillar are:
Baseline target
Outperformance target
Lacutamab
R&D pipeline
Business Development
Finance
CSR
25%
25%
20%
20%
10%
25%
25%
20%
20%
10%
The annual objectives thus defined make it possible to reward the Company's expected performance but
also to assess outperformance.
If 100% of the basic target objectives are achieved, 100% of the corresponding bonus is paid. If 100% of
the targets are not achieved, the percentage of the bonus paid is proportional to the percentage of
achievement of the targets. In case of outperformance for the year 2022, it may be decided to increase the
amount of the bonus beyond 100% up to a limit of 150% on other predefined criteria.
The outperformance targets may only be reached if 100% of the baseline targets are reached.
At the general meeting of shareholders of the Company to be held on or about May 12, 2023, the
allocation of free performance shares subject to capitalisation evolution and internal conditions will be put
to the vote of its shareholders.
Limitations on Liability and Indemnification Matters
Under French law, provisions of bylaws that limit the liability of the members of Executive and
Supervisory Boards are prohibited. However, French law allows sociétés anonymes to contract for and
maintain liability insurance against civil liabilities incurred by members of Executive and Supervisory
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Boards involved in a third-party action, provided that they acted in good faith and within their capacities
as members of such board of the company. Criminal liability cannot be indemnified under French law,
whether directly by the company or through liability insurance.
The Company has a liability insurance for its Executive and Supervisory Board members, and insurance
coverage for liability under the Securities Act. The Company also entered into agreements with its
Executive and Supervisory Board members to provide contractual indemnification. With certain
exceptions and subject to limitations on indemnification under French law, these agreements provide for
indemnification for damages and expenses including, among other things, attorneys’ fees, judgments,
fines and settlement amounts incurred by any of these individuals in any action or proceeding arising out
of his or her actions in that capacity. The Company believes that this insurance and these agreements are
necessary to attract qualified Executive and Supervisory Board members.
These agreements may discourage shareholders from bringing a lawsuit against the Executive and
Supervisory Board members for breach of their fiduciary duty. These provisions also may have the effect
of reducing the likelihood of derivative litigation against the Executive and Supervisory Board members,
even though such an action, if successful, might otherwise benefit the Company and its shareholders.
Furthermore, a shareholder’s investment may be adversely affected to the extent the Company pays the
costs of settlement and damage awards against its Executive and Supervisory Board members pursuant to
these insurance agreements.
Equity Incentives
The Company believes that the ability to grant equity incentives is a valuable and necessary compensation
tool that allows the Company to attract and retain the best personnel for positions of substantial
responsibility, provides additional incentives to employees and promotes the success of its business. Due
to French corporate law and tax considerations, the Company has historically granted several different
equity incentive instruments to its Executive Board and Supervisory Board members, employees and
consultants, including (i) BSAs, which have historically only been granted to independent members of the
Supervisory Board and consultants, (ii) BSAARs and (iii) free shares.
The Executive Board’s authority to grant these warrants and free shares and the aggregate amount
authorized to be granted must be approved by two-thirds of the shareholders present at the relevant
extraordinary shareholders’ meeting. Once approved by the shareholders, the Executive Board can
continue to grant such awards for a specified period upon prior authorization of the Supervisory Board.
The Company has various compensation plans for its Executive Board members, Supervisory Board
members, employees and consultants that have been approved by the shareholders. The last allocation in
2015 of BSAARs no longer continue to vest following termination of the employment, office or service
of the holder within the first two years and all vested warrants must be exercised within post-termination
exercise periods set forth in the grant documents. In the event of certain changes in its share capital
structure, such as a consolidation or share split or dividend, French law and applicable grant
documentation provides for appropriate adjustments of the numbers of ordinary shares issuable and/or the
exercise price of the outstanding warrants.
As of December 31, 2022, the Company had the following equity awards, warrants and free shares
outstanding:
•
250,820 ordinary shares issuable upon the exercise of share warrants (BSA) outstanding as of
December 31, 2022 at a weighted average exercise price of €8.15 per ordinary share;
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•
•
•
•
•
•
1,105,072 ordinary shares issuable upon the exercise of redeemable share warrants (BSAAR)
outstanding as of December 31, 2022 at a weighted average exercise price of €6.92 per ordinary
share;
128,061 ordinary shares issuable upon the vesting of free shares (AGA) outstanding as of
December 31, 2022;
757,840 ordinary shares issuable upon conversion of 6,268 free preferred shares (AGAP 2016) as of
December 31, 2022, assuming all performance and presence conditions are met;
1,130,344 ordinary shares issuable upon definitive acquisition of 1,130,344 Free Performance
shares 2020 as of December 31, 2022, assuming all performance and presence conditions are met;
1,491,000 ordinary shares issuable upon definitive acquisition of 1,491,000 Free Performance
shares 2021 as of December 31, 2022 assuming all performance and presence conditions are met;
1,921,500 ordinary shares issuable upon definitive acquisition of 1,921,500 Free Performance
shares 2022 as of December 31, 2022 assuming all performance and presence conditions are met.
Equity Warrants and Redeemable Share Subscription Warrants
Share Warrants (BSA)
Share warrants, or BSA, are granted at a de minimis price and entitle the holder of one BSA to exercise
the warrant for one underlying share, at an exercise price per share determined by Executive Board of the
Company at the time of grant by reference to the then prevailing share price. The Company has granted
BSA to Supervisory Board members and certain consultants of the Company. The Company's share
warrants plans include provisions that allow for the adjustment of the one-for-one exercise ratio to
compensate for certain modifications of its share capital, such as rights issues, stock splits, mergers and
other events affecting all existing shareholders. None of those events have occurred yet. The Company's
BSA have an exercise period of 10 years – BSA not exercised after that time lapse and are automatically
cancelled. The Company's share warrants cannot be sold.
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The following table shows the BSA outstanding as of December 31, 2022:
Plan title
General assembly
meeting date
BSA 2013
June 28,
2013
BSA 2014
March 27,
2014
Date of grant
July 17, 2013
July 16, 2014
BSA 2015-1
April 27,
2015
April 27,
2015
BSA 2015-2
April 27,
2015
July 1, 2015
BSA 2017
June 2, 2016
September
20, 2017
Total number of
BSA authorized
Total number of
BSA granted
Start date of the
exercise period
End date of the
exercise period
Exercise price per
BSA/share
Number of BSA
exercised as of
December 31,
2022
BSA cancelled or
lapsed as of June
30, 2022
BSA remaining as of
December 31, 2022
300,000
150,000
150,000
150,000
150,000
237,500
150,000
70,000
14,200
37,000
July 17, 2013
July 16, 2014
July 17, 2023
July 16, 2024
April 27,
2015
April 26,
2025
July 1, 2015
June 30,
2025
September
20, 2017
September
20, 2027
€2.36
€8.65
€9.59
€14.05
€11
191,140
75,000
—
—
—
—
—
—
—
—
46,360
75,000
70,000
14,200
37,000
Redeemable Share Warrants (BSAAR)
Redeemable share warrants, or BSAAR, are identical to the share warrants of BSA (including the one-for-
one exercise ratio, its potential adjustment for certain modifications of the share capital and the exercise
period of 10 years), except for the following features:
•
•
the BSAAR are initially purchased by the beneficiary at their fair value, as determined by an expert,
and
the BSAAR plans include a “forcing” clause making it possible to encourage holders to exercise
their BSAAR when the market price exceeds the exercise price and reaches a threshold defined in
the BSAAR plan. The Company can then, subject to a time period for notifying the holders that will
permit them to exercise their BSAAR, decide to purchase the unexercised BSAAR at a unit price
equal to the BSAAR acquisition price initially paid by its holder.
Innate's redeemable share warrants cannot be sold. The BSAAR have been granted to certain of the
executive officers and employees.
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The following table shows the BSAAR outstanding as of December 31, 2022:
Plan title
General assembly meeting date
BSAAR 2012
BSAAR 2015
June 28, 2012 April 27, 2015
Date of grant
May 27, 2013
July 1, 2015
Total number of BSAAR granted
146,050
1,050,382
Start date of the exercise period
May 27, 2013
July 1, 2015
End date of the exercise period
May 27, 2023
June 30, 2025
BSAAR initial purchase price
Exercise price per BSAAR/share
€0.11
€2.04
Number of BSAAR exercised as of December 31, 2022
86,700
BSAAR cancelled or lapsed as of Decmber 31,2022
—
€1.15
€7.20
1,940
2,720
BSAAR remaining as of December 31, 2022
59,350
1,045,722
Free Shares (AGA)
Free shares, or AGA, are employee equity incentive instruments pursuant to which the beneficiaries are
granted, for free, the possibility to receive ordinary shares under certain conditions. Upon grant by the
Executive Board of the Company, the AGA are subject to an acquisition, or vesting, period of at least one
year. At the end of this period, the free shares vest and the beneficiary becomes a full shareholder.
However, if the vesting period is less than a certain period set by law of currently two years (but three
years under previous law), it must be followed by a lock-up period, so that the sum of the two periods is
equal to a minimum total period also set by law of currently two years (but three years under previous
law). Vesting can be conditional or not. The vesting of all or the Company's AGA is subject to a presence
condition at the end of the vesting period. Some of the Company's AGA are also subject to performance
conditions. Over the years, the Company has established several AGA plans, for its employees or for
management only, sometimes as a “welcome package” (with no performance conditions). The Company's
free share plans include provisions that allow for the adjustment of the number of ordinary shares to
which a beneficiary is entitled at the end of the vesting period to compensate for certain modifications of
its share capital, such as rights issues, stock splits, mergers and other events affecting all existing
shareholders, during the vesting period. Certain of the Company's plans also provide for an accelerated
vesting in case of a tender offer on the Company during the vesting period.
One particular AGA plan, the “AGA Bonus,” entitled the Company management to opt for the payment
of up to 50% of their annual variable compensation in free shares. Those who take this option benefit
from a matching compensation equal to 50% for 2022 of the corresponding portion of the annual variable
compensation, also payable in free shares. The AGA Bonus are subject to the same performance
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conditions, after a one-year vesting period, as the annual variable compensation. The number of AGA
Bonus is determined by dividing the euro amount of the annual variable compensation for which the
election is made and of the matching contribution, by an average of the trading price of its shares. Once
vested, the AGA Bonus are subject to the minimum one-year lock-up period. The Supervisory Board has
decided not to renew the AGA Bonus for 2023.
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The following table shows the AGAs outstanding as of December 31, 2022:
AGA Perf
Employee
s 2020
May 19,
2020
AGA Perf
Managem
ent 2020
May 19,
2020
AGA Perf
Employee
s 2021
May 28,
2021
AGA Perf
Managem
ent 2021
May 28,
2021
AGA Perf
Employee
s 2022 (2)
AGA Perf
Managem
ent 2022
(2)
AGA
Bonus
Managem
ent 2022
(1)
May 20,
2022
May 20,
2022
May 20,
2022
August 5,
2020
August 5,
2020
October
1st, 2021
October
1st, 2021 December
3 years
3 years
3 years
3 years
12, 2022
1 year
December
12, 2022
3 years
October
3, 2022
3 years
None
None
None
None
None
None
None
Yes
Yes
Yes
Yes
Yes
Yes
Yes
766,650
710,000
1,066,600
610,000
—
—
—
—
1371500
—
550,000
128,061
—
—
286,306
60,000
17,500
30,000
480,344
650,000
1,049,100
580,000
0
1371500
550,000
128,061
Plan title
General
assembly
meeting
date
Date of
grant
Vesting
Period
Lock-up
period
Performanc
e
Conditio
ns
Number of
AGA
granted
Number of
AGA
vested as
of
Decembe
r 31,
2022
Number of
AGA
lapsed as
of
Decembe
r 31,
2022 (2)
Number of
AGA
remainin
g to be
vested as
of
(1) The annual variable compensation performance conditions are determined on or about the beginning of the fiscal year and executives
make their election at about that time. However, because the Company needs the shareholders’ vote on the total number of free shares
available for granting AGA Bonus (like all other free shares), the Company waits until its annual shareholders meeting (generally during
the second half of the second quarter of the year) to grant the AGA Bonus – hence a granting, vesting and lock-up calendar different from
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that of the payment of the annual variable compensation, which takes place towards the end of the fiscal year or at the beginning of the
next fiscal year.
(2) Usually after the end of the vesting period, the Executive Board will convene and acknowledge the number of free shares that have vested
and the number of those that have not because the presence condition and, as applicable, the performance conditions, have not been met.
For the purpose of computing the amount of share-based compensation in its consolidated financial statements, AGA that have lapsed
because the presence condition has not been met, are excluded from the computation, even though the Executive Board has not met yet
and formally acknowledged this fact. As a result, certain of the numbers above are different from those in its consolidated financial
statements.
The following authorization will be submitted for approval to the general meeting of the shareholders to
be held on May 12, 2023: (i) up to 1,050,000free shares with performance conditions to the benefit of
executive officers, employed members of the Executive Committee, employed senior executives and/or
corporate officers, (iii) up to 1,500,000 free shares with performance conditions to the benefit of
employees, (iv) up to 600,000 free shares to the benefit of employees, without performance conditions,
(v) up to 350,000 free shares to the benefit of employees and Executive Committee and Executive Board
(excluding the Chairman) members as part of the employee saving plan and (vi) up to 100,000 warrants to
the benefit of independent Supervisory Board members to be issued at the fair market value.
Free Preferred Shares (AGAP)
Free preferred shares, or AGAP, are another employee equity incentive instrument similar to the free
shares or AGA, except that, after a one-year vesting period, the beneficiaries receive a preferred shares
(shares B) which will become convertible into ordinary shares following a lock-up period of two
additional years, if the performance conditions (and a presence condition) are met at the end of this lock-
up period. Each free preferred share is convertible into a number of ordinary shares of the Company –
which number depends upon the degree of fulfilment of the performance conditions. The free preferred
shares remain convertible into ordinary shares for a period of six years and six months. Free preferred
shares not converted at the end of this conversion period can be repurchased by Innate and cancelled. The
Company's AGAP cannot be sold.
The Company has established several AGAP plans in 2016 and 2017 for all of its employees or for
management only.
Since the end of the lock-up period, holders of the 2016 AGAP that have not yet converted them into
ordinary shares, are entitled to vote at the shareholders’ meetings, to dividends and to preferential
subscription rights, on the basis of the number of ordinary shares to which they are entitled if they convert
their AGAP.
On October 21, 2019, the performance criteria of the 2016-1 AGAP were assessed and the conversion
ratio was determined as follows: one 2016-1 AGAP gives the right to 130 ordinary shares.
On December 30, 2019, the performance criteria of the 2016-2 AGAP were assessed and the conversion
ratio was determined as follows: one 2016-2 AGAP gives the right to 111 ordinary shares.
The 2017 AGAP are not convertible since the performance criteria were not met.
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The following table shows the AGAPs outstanding as of December 31, 2022:
Plan title
General assembly meeting date
Date of grant
Number of AGAP granted
Maximum number of ordinary shares
into which each AGAP can be
converted
AGAP
Management
2016-1
June 2, 2016
AGAP
Management
2016-2
June 2, 2016
AGAP
Employees
2016-1
June 2, 2016
October 21,
2016
2,000
130
December
30, 2016
3,000
111
October 21,
2016
2,486
130
Number of AGAP lapsed during the
450
—
vesting period
Number of AGAP vested
Number of AGAP lapsed during the
lock up period
Number of outstanding AGAP
1,550
100
1,200
3,000
—
3,000
105
2,381
146
2,068
C. Board Practices
Supervisory Board
The Supervisory Board is made up of a minimum of three members and a maximum of eighteen. The
members of the Supervisory Board are appointed for a renewable term of two years at the general meeting
of shareholders. The general meeting of shareholders may revoke the appointments of the members of the
Supervisory Board at any time during the meeting by a simple majority vote. The appointees are selected
by the shareholders and may be individuals or companies. Each member must own at least one of
ordinary shares for the entire term of the appointment.
The age limit for being a member of the Supervisory Board and the limitations on holding such an
appointment concurrently with an appointment in another company are subject to the applicable legal and
regulatory provisions.
Role of the Supervisory Board in Risk Oversight
The Supervisory Board is primarily responsible for the oversight of the risk management activities and
has delegated to the audit committee the responsibility to assist the Supervisory Board in this task. While
the Supervisory Board oversees risk management, management, through the Executive Board is
responsible for day-to-day risk management processes. The Supervisory Board expects the management
to consider risk and risk management in each business decision, to proactively develop and monitor risk
management strategies and processes for day-to-day activities and to effectively implement risk
management strategies adopted by the Supervisory Board. The Company believes this division of
responsibilities is the most effective approach for addressing the risks the Company faces.
Board Diversity Matrix
Board Diversity Matrix (As of December 31, 2022)
France
Country of Principal Executive Offices:
Foreign Private Issuer
Yes
Disclosure Prohibited under Home Country Law Yes
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Total Number of Directors
8
Female
Male
Non-Binary Did Not Disclose
Gender
Part I : Gender Identity
Directors
Part II : Demographic Background
Underrepresented Individual in Home Country
Jurisdiction
LGBTQ+
Did Not Disclose Demographic Background
Supervisory Board Committees
-
-
-
-
-
-
-
The Supervisory Board has established an audit committee, a compensation and nomination committee, a
Corporate and Social Responsibility Committee and a transactions committee, which operate pursuant to
rules of procedure adopted by the Supervisory Board.
Subject to available exemptions, the composition and functioning of all of the committees will comply
with all applicable requirements of the French Commercial Code, the Exchange Act, the Nasdaq listing
rules and SEC rules and regulations.
In accordance with French law, committees of the Supervisory Board only have an advisory role and can
only make recommendations to the Supervisory Board. As a result, decisions are made by the Supervisory
Board taking into account non-binding recommendations of the relevant Supervisory Board committee.
Audit Committee
Innate's audit committee assists the Supervisory Board in its oversight of the corporate accounting and
financial reporting and oversees the selection of the auditors, their remuneration and independence and
keeps the Supervisory Board informed on control systems, key processes and procedures, security and
risks. From May 2022, the members of the audit committee as of the date of this Annual Report are
Pascale Boissel, Irina Staatz-Granzer and Sally Bennett. Pascale Boissel is the Chairman of the audit
committee.
The Company's Supervisory Board has determined that Dr. Bennett, Dr. Staatz-Granzer and Ms. Pascale
Boissel are independent within the meaning of the applicable listing rules and the independence
requirements contemplated by Rule 10A-3 under the Exchange Act. The Supervisory Board has further
determined that Ms. Boisse is an “audit committee financial expert” as defined by the Nasdaq listing rules
and that each of the members qualifies as financially sophisticated under the Nasdaq listing rules.
The principal responsibility of the audit committee is to monitor the existence and efficacy of the
financial audit and risk control procedures on an ongoing basis.
Innate's Supervisory Board has specifically assigned the following duties to the audit committee:
•
•
•
•
legal control of the half-year and annual accounts;
evaluating internal control practices, risk analysis;
supervising the creation of the financial statements published by us;
assessing accounting methods; and
192
•
selecting statutory auditors, negotiating their fees, reviewing of their conclusions and reviewing
their independence.
The audit committee reviews and approves the report from the Chairman of the Supervisory Board on
internal control.
Compensation and Nomination Committee
Innate's compensation and nomination committee assists the Supervisory Board in reviewing and making
recommendations to the Supervisory Board with respect to the appointment and the compensation of the
members of the Executive Board, Supervisory Board and Executive Committee and other key employees.
In accordance with operating rules adopted by the Supervisory Board, the nomination and compensation
committee is composed of at least two members appointed by the Supervisory Board. Following the
Supervisory Board on May 20, 2022, the members of the committee are Pascale Boissel, Hervé Brailly,
Véronique Chabernaud and Dr. Jean-Yves Blay. Currently, all of them are independent members of the
compensation and nomination committee. Dr. Chabernaud is the Chairman of the committee.
The Company's Supervisory Board has specifically assigned the following duties to the compensation and
nomination committee:
•
•
•
reviewing the remuneration policy, in particular the description of the collective objectives
(applicable company-wide) and individual objectives (for members of the Executive Board and
the Executive Committee);
reviewing the compensation of the members of the Executive Board and the Executive
Committee, the policy concerning the distribution of equity such as warrants, stock options,
grants and capital increases reserved for members of the savings plan, examining the amount of
attendance fees among the Supervisory Board and the committees members;
assisting the Supervisory Board in the selection of the members of the Executive Board and
committees; and
• making recommendations with respect to the independence of the members of the Supervisory
Board and committees and preventing conflicts of interest within the Supervisory Board.
Transactions Committee
Innate's transactions committee assists the Supervisory Board in examining the business and corporate
development opportunities available to us, which may include the acquisition of rights to products or the
acquisition of other companies as well as out-licensing opportunities. The members of this committee are
Irina Staatz-Granzer, Hervé Brailly, Bpifrance Participations and Gilles Brisson. Currently, Dr. Staatz-
Granzer is an independent member and Chairman of the transactions committee.
Innate Pharma's Supervisory Board has specifically assigned the following duties to the transactions
committee:
•
•
to analyze the fundamentals of the products and/or companies targeted by us, the feasibility of
targeted acquisitions; and
to participate in the selection of investment bankers and/or consultants.
193
CSR Committee
The Supervisory Board of 14 September 2022, on the recommendation of the Remuneration and
Nomination Committee of 12 September 2022, decided to set up a CSR Committee. The first meeting of
the Committee will be held in the second half of 2023.
The members of the CSR Committee at the date of this report are Sally Bennett, Véronique Chabernaud,
Hervé Brailly et Olivier Martinez.
The main duties of the CSR Committee are to:
• make recommendations on the CSR policy and its implementation by the Company;
•
•
•
examine the content of the non-financial information;
review the Company's CSR publications; and
determine the CSR criteria for the annual and multi-annual variable remuneration of the members
of the Management Board and the Executive Committee.
The CSR policy and its implementation are being developed by the Company at the date of this report and
will be presented to the CSR Committee for review in the second half of 2023.
Other Committees
The Strategic Advisory Board
The Company also has a Strategic Advisory Board composed of six external consultants, consisting of
three individuals from the medical community and three individuals from the scientific community. The
Strategic Advisory Board is not a committee of the Supervisory Board within the meaning of Article
R.225-29 of the French Commercial Code; its members are chosen by the Executive Board. This kind of
advisory committee is common in French companies in the biotechnology sector.
The Strategic Advisory Board’s role is to assist Innate in the strategic choices in scientific and technical
fields. Its main missions are to evaluate the relevance of the choices in terms of product development and
to propose, if necessary, changes to strategic or technical approaches; to advise management and guide
the scientific direction in identifying strategies and selecting product candidates, based, in particular, on
the scientific results obtained by us, including new targets and new compounds and to promote and advise
Innate in the alliance strategies, such as external growth supporting synergies, including acquisition of
new competences, purchase of operating rights, product candidates and innovative technologies. The
Strategic Advisory Board is comprised of Sebastian Amigorena, Aurélien Marabelle, Ruslan Medzhitov,
Miriam Merad, Tanguy Seiwert and Mario Sznol. Dr. Merad is the Chairman of the Strategic Advisory
Board.
Sebastian Amigorena, Ph.D., is “Directeur de Recherche de Classe Exceptionnelle” at the Centre National
de la Recherche Scientifique. He also leads the newly created Cancer Immunotherapy Center at Institut
Curie in Paris (France). Dr. Amigorena has made significant contributions to immunology and cell
biology at every stage of his career. His findings have helped advance the understanding of antigen
presentation and T cell priming by dendritic cells, with applications in the fields of cancer immunotherapy
and vaccination. Dr. Amigorena has received numerous national and international prizes and awards,
including the prestigious senior European Research Council award in 2008 and in 2014.
Aurélien Marabelle MD,PhD is a medical oncologist and immunologist. His clinical practice is dedicated
to early Phase clinical trials of cancer immunotherapies at the Gustave Roussy Cancer Center where he
194
also leads a translational research laboratory dedicated to cancer immunology & immunotherapies
(INSERM U1015 & CIC1428). He is a full professor of Clinical Immunology at the University of Paris
Saclay. Pr Marabelle is an active member of ESMO, ASCO, AACR, SITC, EATI and is the current
president and co-founder of the French Society for Cancer Immunotherapies (FITC). He has published
more than 200 peer reviewed publications and has a H-index of 52.
Ruslan Medzhitov, Ph.D., is a Sterling Professor at Yale University School of Medicine in New Haven,
Connecticut and an Investigator of the Howard Hughes Medical Institute. His research interests include
biology of inflammation, biological bases of diseases and evolutionary design of biological systems. Dr.
Medzhitov is a member of the National Academy of Sciences, National Academy of Medicine and
European Molecular Biology Organization. He is a fellow of the American Academy of Microbiology
and a foreign member of the Russian Academy of Sciences.
Miriam Merad, M.D., Ph.D., is the Director of the Precision Immunology Institute at Mount Sinai School
of Medicine in New York and the Director of the Mount Sinai Human Immune Monitoring Center
(HIMC). Dr. Merad is an internationally acclaimed physician-scientist and a leader in the fields of
dendritic cell and macrophage biology with a focus on their contribution to human diseases. Dr. Merad
identified the tissue resident macrophage lineage and revealed its distinct role in organ physiology and
pathophysiology. She established the contribution of this macrophage lineage to cancer progression and
inflammatory diseases and is now working on the development of novel macrophage-targeted therapies
for these conditions. In addition to her work on macrophages, Dr. Merad is known for her work on
dendritic cells, a group of cells that control adaptive immunity. She identified a new subset of dendritic
cells, which is now considered a key target of antiviral and antitumor immunity. Dr. Merad leads the
Precision Immunology Institute at the Icahn School of Medicine (PrIISM) to bring immunology
discoveries to the clinic. PrIISM integrates immunological research programs with synergistic expertise in
biology, medicine, technology, physics, mathematics and computational biology to enhance the
Company's understanding of human immunology. She also founded the Human Immune Monitoring
Center at Mount Sinai, one of the world’s most sophisticated research centers, which uses cutting-edge
single-cell technology to understand the contribution of immune cells to major human diseases or
treatment responses. Dr. Merad has authored more than 200 primary papers and reviews in high profile
journals. Her work has been cited several thousand times. She is an elected member of the American
Society of Clinical Investigation and the recipient of the William B. Coley Award for Distinguished
Research in Basic and Tumor Immunology. She is the President-elect of the International Union of
Immunological Societies (IUIS). In 2020, she was elected to the National Academy of Sciences in
recognition of her contributions to the field of immunology.
Tanguy Seiwert, M.D., is Assistant Professor of Medicine, Section of Hematology and Oncology in the
Department of Medicine at the University of Chicago. Dr. Seiwert’s research focuses on the biology of
head and neck cancer and lung cancer. In the laboratory, he studies targeted therapies that disrupt specific
pathways vital to cancer growth and metastasis. More specifically, he focuses on which novel drugs
appear most promising, which individual tumors are more likely to respond to these treatments and how
to successfully combine therapies. Dr. Seiwert uses this preclinical knowledge to develop new treatments
for use in clinical trials, and to ultimately improve patient care.
Mario Sznol, M.D., is Professor of Internal Medicine, Leader of the Melanoma-Renal Cancer Disease-
Associated Translational Research Team, and Co-Leader of the Cancer Immunology Program. Dr. Sznol
graduated from Rice University and Baylor College of Medicine (BCM) in Houston, Texas. He trained in
internal medicine at BCM and completed a medical oncology fellowship in the Department of Neoplastic
Diseases, Mount Sinai Hospital, New York. He spent the next twelve years in the Biologics Evaluation
Section (BES), Investigational Drug Branch (IDB), Cancer Therapy Evaluation Program of the National
Cancer Institute, and was Head of the BES from 1994-1999. He attended on the inpatient units of the
195
Biological Response Modifiers Program, NCI, from 1988-1996 and the Immunotherapy Service of the
Surgery Branch, NCI, from 1997-1999. From 1999-2004, he served as Vice President of Clinical
Development and Executive Officer of Vion Pharmaceuticals in New Haven, Connecticut. Dr. Sznol is
past President of the Society for Immunotherapy of Cancer (SITC). Dr. Sznol’s areas of interest include
early drug development, immunotherapy, and treatments for advanced melanoma and renal cancer.
Executive Committee
The Company also has an Executive Committee composed of members with significant experience in
strategy, financial management, medical research, research and development project management, the
negotiation of industrial and commercial agreements in the field of innovative companies, including
biotechnology companies, compliance and regulations and in business development. The Executive
Committee meets at least once a month and deals with all subject regarding the activities and the
management of the company.
The current members of the Executive Committee are Mondher Mahjoubi, Yannis Morel, Joyson
Karakunnel, Odile Belzunce, Odile Laurent, Frédéric Lombard, Nicola Beltraminelli, Claire de Saint
Blanquat and Henry Wheeler. Eric Vivier, the Senior Vice President, Chief Scientific Officer, is a
permanent guest to the meetings of the Executive Committee.
Corporate Governance Practices
As a French société anonyme, the Company is subject to various corporate governance requirements
under French law. The Company is a “foreign private issuer” under the U.S. federal securities laws and
the Nasdaq listing rules. The foreign private issuer exemption permits Innate to follow home country
corporate governance practices instead of certain Nasdaq listing requirements. A foreign private issuer
that elects to follow a home country practice instead of Nasdaq listing requirements must submit to
Nasdaq a written statement from an independent counsel in such issuer’s home country certifying that the
issuer’s practices are not prohibited by the home country’s laws.
The Company applies the Middlenext code, which recommends that at least two members of the
Supervisory Board be independent (as such term is defined under the code). Neither the corporate laws of
France nor the bylaws requires that (i) the compensation committee include only independent members of
the Supervisory Board, (ii) each committee of the Supervisory Board have a formal written charter or (iii)
the independent members of the Supervisory Board hold regularly scheduled meetings at which only
independent members of the Supervisory Board are present. The Company intends to follow French
corporate governance practices in lieu of Nasdaq listing requirements for each of the foregoing.
These exemptions do not modify the independence requirements for the audit committee, and the
Company with the requirements of the Sarbanes-Oxley Act and the Nasdaq listing rules, which require
that the audit committee be composed of at least three independent members. Rule 10A-3 under the
Exchange Act provides that the audit committee must have direct responsibility for the nomination,
compensation and choice of the auditors, as well as control over the performance of their duties,
management of complaints made, and selection of consultants. Under Rule 10A-3, if the laws of a foreign
private issuer’s home country require that any such matter be approved by the board of directors or the
shareholders of the Company, the audit committee’s responsibilities or powers with respect to such matter
may instead be advisory. Under French law, the audit committee may only have an advisory role and
appointment of the statutory auditors, in particular, must be decided by the shareholders at the annual
meeting.
In addition, Nasdaq rules require that a listed company specify that the quorum for any meeting of the
holders of share capital be at least 33 1/3% of the outstanding shares of the company’s ordinary voting
196
shares. The Company intends to follow its French home country practice, rather than complying with this
Nasdaq rule. Consistent with French Law, its bylaws provide that when first convened, general meetings
of shareholders may validly convene only if the shareholders present or represented hold at least (1) 20%
of the voting shares in the case of an ordinary general meeting or of an extraordinary general meeting
where shareholders are voting on a capital increase by capitalization of reserves, profits or share
premium, or (2) 25% of the voting shares in the case of any other extraordinary general meeting. If such
quorum required by French law is not met, the meeting is adjourned. There is no quorum requirement
under French law when an ordinary general meeting or an extraordinary general meeting is reconvened
where shareholders are voting on a capital increase by capitalization of reserves, profits or share
premium, but the reconvened meeting may consider only questions that were on the agenda of the
adjourned meeting. When any other extraordinary general meeting is reconvened, the required quorum
under French law is 20% of the shares entitled to vote. If a quorum is not met at a reconvened meeting
requiring a quorum, then the meeting may be adjourned for a maximum of two months.
Code of Ethics
The Company has adopted a Code of Ethics applicable to all of its employees and members of its
Executive Board and Supervisory Board. The Code of Ethics is available on its website. The Company
expects that any amendments to the Code of Ethics, or any waivers of its requirements, will be disclosed
on its website.
Executive Compensation Arrangements
Except the arrangements described in “Item 7.B—Related Party Transactions—Arrangements with the
Members of the Executive and Supervisory Boards,” there are no arrangements or understanding between
Innate and any of the other members of the Executive and Supervisory Boards providing for benefits upon
termination of their employment, other than as required by applicable law.
D. Employees
As of December 31, 2022, the Company had 211 full-time employees. None of its employees are
represented by collective bargaining agreements. The Company believe that it maintains good relations
with its employees. The following tables show the number of employees as of December 31, 2022 broken
out by department :
Full-time equivalent employees of Innate Pharma SA and Innate Pharma Inc.
Research and development
General and administrative
Executive committee
Total
E. Share Ownership.
As of December 31,
2022
51
6
153
210
For information regarding the share ownership of the directors and executive officers, see “Item 6.B—
Compensation” and “Item 7.A—Major Shareholders.”
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Item 7. Major Shareholders and Related Party Transactions
A. Major Shareholders
The following table and accompanying footnotes sets forth, as of December 31, 2022, information
regarding beneficial ownership of the ordinary shares by:
•
•
•
each person, or group of affiliated persons, known by Innate to beneficially own more than 5% of
the ordinary shares;
each of the Executive Board and Supervisory Board members individually; and
all of the Executive Board and Supervisory Board members as a group.
Assuming that all of the ordinary shares represented by ADSs are held by residents of the United States,
as of December 31, 2022, the Company estimates that approximately 5,8 million shares, or 7.24%% of
the ordinary shares were held of record by residents of the United States.
Beneficial ownership is determined according to the rules of the SEC and generally means that a person
has beneficial ownership of a security if he, she or it possesses sole or shared voting or investment power
of that security, including free shares that vest within 60 days of December 31, 2022 and options and
warrants that are currently exercisable or exercisable within 60 days of December 31, 2022. Ordinary
shares subject to free shares, options and warrants currently exercisable or exercisable within 60 days of
December 31, 2022 are deemed to be outstanding for computing the percentage ownership of the person
holding these free shares, options or warrants and the percentage ownership of any group of which the
holder is a member, but are not deemed outstanding for computing the percentage of any other person.
Except as indicated by the footnotes below, the Company believes, based on the information furnished to
us, that the persons named in the table below have sole voting and investment power with respect to all
ordinary shares shown that they beneficially own, subject to community property laws where applicable.
The information does not necessarily indicate beneficial ownership for any other purpose, including for
purposes of Sections 13(d) and 13(g) of the Securities Act.
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Unless otherwise indicated, the address of each beneficial owner listed in the table below is c/o Innate
Pharma S.A., 117, Avenue de Luminy – BP 30191, 13009 Marseille, France.
Number of Ordinary Shares
Beneficially Owned
Percentage of Ordinary
Shares Beneficially Owned
5% Shareholders:
Novo Nordisk A/S(1)
MedImmune Limited(2)
Bpifrance Participations(3)
Executive Board and
Supervisory Board
members and other
executive officers:
Mondher Mahjoubi, M.D.(4)
Yannis Morel, Ph.D.(5)
Hervé Brailly, Ph.D.(6)
Irina Staatz-Granzer(7)
Jean-Yves Blay(8)
Gilles Brisson(9)
Véronique Chabernaud(10)
Olivier Martinez(11)
Pascale Boissel(12)
Sally Bennett(13)
Joyson Karakunnel
Odile Belzunce(14)
Eric Vivier, D.V.M.(15)
Odile Laurent (16)
Frédéric Lombard (17)
Nicola Beltraminelli(18)
Henry Wheeler(19)
Claire de St Blanquat20)
All members of our
Executive Board and
Supervisory Board and
other executive officers as
a group(19)
12.24%
9.33%
7.97%
0.64%
0.30%
1.11%
0.06%
—%
0.12%
0.03%
—%
—%
—%
0.07%
0.23%
0.03%
—%
9,817,546
7,485,500
6,389,406
514,540
242,775
889,784
45,100
50
98,059
24,210
—
1,000
2,500
—
55,356
184,666
21,086
960
960
960
25,774,458
32.13%
(1) Consists of 9,817,546 ordinary shares. The principal business address for Novo Nordisk A/S is Novo Allé, 2880 Bagsvaerd, Danemark.
(2) Consists of 7,485,500 ordinary shares. The principal business address for MedImmune Limited is Milstein Building, Granta Park,
Cambridge, CB21 6GH, United Kingdom.
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(3) Consists of 6,389,406 ordinary shares. The principal business address for Bpifrance Participations is 27-31, avenue du Général Leclerc,
94 710 Maisons Alfort Cedex.
(4) Consists of 514,540 ordinary shares.
(5) Consists of 154,775 ordinary shares and 88,000.00 reedemable warrants (BSAAR 2015).
(6) Consists of 739,784 ordinary shares and 150,000.00 reedemable warrants (BSAAR 2015).
(7) Consists of 25,100 ordinary shares, 10,000.00 warrants (BSA 2015-1) and 10,000.00 warrants (BSA 2017)
(8) Consists of 50 ordinary shares.
(9) Consists of 73,059 ordinary shares, 15,000.00 warrants (BSA 2015-1) and 10,000.00 warrants (BSA 2017).
(10) Consists of 10 ordinary shares, 14,200.00 warrants (BSA 2015-2) and 10,000.00 warrants (BSA 2017).
(11) As representative of Bpifrance Participations, the legal entity that holds this Supervisory Board seat.
(12) Consists of 1,000 ordinary shares.
(13) Consists of 2,500ordinary shares.
(14) Consists of 40,356 ordinary shares and 15000 reedemable warrants (BSAAR 2012 and 2015).
(15) Consists of 184,666 ordinary shares.
(16) Consists of 21,086 ordinary shares.
(17) Consists of 960 ordinary shares.
(18) NA
(19) Consists of 960 ordinary shares.
(20) Consists of 960 ordinary shares.
None of the principal shareholders has voting rights different than the other shareholders.
B. Related Party Transactions.
Since January 1, 2022, the Company has engaged in the following transactions with members of its
Executive and Supervisory Boards and holders of more than 5% of its outstanding voting securities, and
their respective affiliates, which Innate refers to as its related parties.
Transactions With The Principal Shareholders
AstraZeneca
Lumoxiti Termination and Transition Agreement
Further to the decision to terminate the Lumoxiti Agreement and termination notice sent in December
2020, a Termination and Transition Agreement was discussed and executed, effective as of June 30, 2021
terminating the Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply
agreement, the quality agreement and other related agreements) and transferring of the U.S. marketing
authorization and distribution rights of Lumoxiti back to AstraZeneca. Under the Termination and
Transition Agreement, Innate and AstraZeneca delivered a notice to the FDA requesting that the U.S.
marketing authorization (BLA) be transferred back to AstraZeneca as from October 1, 2021. The BLA
was effectively transferred to AstraZeneca on February 8th 2022. AstraZeneca has reimbursed Innate for
all Lumoxiti related costs, expenses and benefited net sales. In the full year results 2020 announcement,
Innate reported a contingent liability of up to $12.8 million in its consolidated financial statements, which
was related to the splitting of certain manufacturing costs. As part of the Termination and Transition
Agreement, the Parties agreed to split these manufacturing costs, and Innate paid $6.2 million to
AstraZeneca on April 30, 2022.
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Agreement with Bpifrance Financement
In the context of the COVID-19 pandemic, the French government has launched a call for collaborative
research and development projects aiming at developing therapeutic solutions to prevent or cure
COVID-19. Projects selected by the French government are eligible to receive funding from the French
government under the Programme d'Investissements d'Avenir (PIA) managed by Bpifrance Financement
(BPI). Such funding takes the form of grants and repayable advances and provides for profit sharing.
Innate Pharma was selected by BPI to finance its current projects relating to COVID-19. In connection
with such selection, the Company executed two agreements with BPI, the Master Agreement and the
Beneficiary Agreement.
The Master Agreement and the Beneficiary Agreement set forth (i) the terms and conditions for the
payment of the aid granted by Bpifrance Financement to Innate Pharma and its partners involved in the
"FORCE" project (Assistance Publique – Hôpitaux de Marseille and Centre Léon Bérard) as well as (ii)
the terms and conditions for the financial returns due by the beneficiaries of the aid to Bpifrance
Financement. The "FORCE" project includes the translational research study EXPLORE COVID-19 with
AP-HM and the two Phase 2 clinical trials, FORCE with AP-HM and ImmunONCOVID-20 with the
Centre Léon Bérard.
The funding amounts to a total of €6,800,000, divided as follows: 20% in the form of a grant with no
repayment condition and 80% in the form of an advance repayable only in the event of technical and
commercial success. The first installment of €1,700,000 was paid on signature of the agreements, and the
three remaining installments will be paid depending on the achievement of certain clinical milestones,
notably those related to the Phase 2 FORCE trial.
The agreement is concluded for a period up to the full repayment of any sums due to Bpifrance
Financement.
Under a letter dated May 11, 2022, Bpifrance Financement confirmed to the Company that following the
termination of the FORCE trial in 2022: (i) Bpifrance Financement shall pay the remaining amount for
the project amounting to €646,756 and (ii) shall waive the debt for an amount of €1,988,000.
Arrangements with the Members of the Executive and Supervisory Boards
Director and Executive Officer Compensation
See “Item 6B—Compensation—Limitations on Liability and Indemnification Matters” for information
regarding compensation of the members of the Supervisory and Executive Boards.
Amendment to the biomedical research agreement with the Léon Bérard Centre
Innate Pharma and the Centre Léon Bérard entered into a Biomedical Research Agreement on January 11,
2016 (the "Agreement") for the performance of the biomedical research IPH2201-203 entitled "Phase Ib/
II trial evaluating IPH2201 in combination with cetuximab in patients with relapsed or metastatic HPV-
positive (+) and HPV-negative (-) head and neck squamous cell carcinoma".
At the date of signature, the Agreement was not a regulated agreement, as Mr. Jean-Yves Blay, General
Manager of the Léon Bérard Centre, was not a member of the Supervisory Board.
In accordance with the authorisation of the Supervisory Board on 17 December 2021, an amendment No.
1 was signed on 9 March 2022 in order to take into account the changes in the implementation of the
Study and the budgetary adjustments, applied accordingly.
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Such Amendment no. 1 ratifies the modification of the duration of the Study and consequently modifies
the specific operating costs charged by the Léon Bérard Centre to meet the changes requested and the
provisional budget of the Study.
Agreement with Jean-Yves Blay as member of the Supervisory Board
On December 17, 2021, the Supervisory Board authorized the conclusion of an agreement between Innate
Pharma and Jean-Yves Blay in his capacity as member of the Supervisory Board in order to define the
terms and conditions under which Jean-Yves Blay participates in the Supervisory Board.
This contract took effect on May 13, 2022 for the duration of Jean-Yves Blay's term of office, i.e. until
May 12, 2023.
The contract provides that Jean-Yves Blay may receive a maximum remuneration of €43,000 per year.
For the financial year 2022, Jean-Yves Blay received €20,000 under this contract, corresponding to the
amount of his fixed and variable remuneration as a member of the Supervisory Board.
Motivation: To regulate Jean-Yves Blay's mandate as a member of the Supervisory Board, given his
status as a civil servant subject to the provisions applicable to health professionals.
Indemnification Agreement with Mr. Hervé Brailly, Mrs. Irina Staatz-Granzer, Mr. Jean Yves Blay,
Mr. Gilles Brisson, Mrs. Véronique Chabernaud, Mrs. Pascale Boissel, Ms. Sally Bennett and Mr.
Olivier Martinez as members of the Supervisory Board and Mr. Mondher Mahjoubi and Mr. Yannis
Morel as members of the Management Board
In the context of the Nasdaq IPO and regarding the need to put in place insurances for the liability of
officers of listed companies in the US, the Supervisory board decided :
(i)
The entering into of a policy insurance covering the risks in relation with the Nasdaq IPO (IPO
insurance) and the insurance policy extension for companies listed on the Nasdaq (D&O insurance
policy) ; and
The entering into of indemnification agreement between the Company on the one hand and the
(ii)
Supervisory and Executive board member on the other hand.
Such indemnification agreements provides that the Company would cover Supervisory Board members
and Executive Board members in situations in which the IPO and D&O insurance policies would not
cover them, but always within the limits of what is legally possible in terms of indemnification of
directors and officers.
Framework agreement and order for services and equipment transfer agreement with Mi-mAbs
On January 29, 2021, the Company's Supervisory Board approved the conclusion of a framework
agreement and an order for services with Mi-mAbs, a company of which Mr. Hervé Brailly, Chairman of
the Supervisory Board, was a member of the Strategic Committee at the time of its creation.
The purpose of the framework agreement is to specify the main conditions under which Mi-mAbs will
provide services to Innate. The first service order specifies the services to be provided to Innate.
The maximum amount of the sums paid by Innate Pharma to Mi-mAbs under the framework service
agreement is €600,000. The amount of the first service order is €352,000.
This agreement was entered into on February 2, 2021, with retroactive effect to January 1, 2021, for a
term of one year, until December 31, 2021.
202
On August 6, 2021, an agreement was signed with Mi-mAbs for the transfer of equipment from Innate
Pharma to Mi-mAbs at their residual values, i.e. for a total amount of €1,281 excluding VAT. This
agreement was ratified by the Supervisory Board on December 17, 2021.
On December 17, 2021, two amendments to the framework agreement were signed with Mi-mAbs, the
first one modifying the work plan, which generated a credit of €3,578.40 to the benefit of Innate Pharma,
the second one renewing the framework agreement for one year.
These two amendments were ratified by the Supervisory Board on January 26, 2022, although they are no
longer regulated agreements, as Mr. Hervé Brailly is no longer a member of the Strategic Committee of
Mi-Mabs since November 2021, but is a 15% shareholder.
Amendment to the biomedical research agreement with the Léon Bérard Center
Innate Pharma and the Léon Bérard Center entered into a Biomedical Research Agreement on January 11,
2016 (the "Agreement") for the performance of the IPH2201-203 biomedical research entitled "Phase
1b/2 trial evaluating IPH2201 in combination with cetuximab in patients with relapsed or metastatic
HPV-positive (+) and HPV-negative (-) squamous cell carcinoma of the head and neck".
At the date of signature, the Agreement was not a regulated agreement, as Mr. Jean-Yves Blay, General
Manager of the Léon Bérard Center, was not a member of the Supervisory Board.
In accordance with the authorization of the Supervisory Board of December 17, 2021, an amendment n°1
was signed on March 9, 2022 in order to take into account the changes in the conduct the Study and
certain adjustments to the budget.
Transaction with Related Companies
From time to time, in the ordinary course of its business, the Company may contract for services from
companies or institutions in which certain members of its Executive Board or Supervisory Board may
serve as a director or advisor. The cost and provision of these services are negotiated on an arms-length
basis and none of these arrangements are material.
Related Person Transaction Policy
The Company complies with French law regarding approval of transactions with related parties. On
September 12, 2019, the Supervisory Board adopted a related person transaction policy that sets forth its
procedures for the identification, review, consideration and approval or ratification of related person
transactions. The policy became effective immediately upon the execution of the underwriting agreement
for the October 2019 global offering. For purposes of its policy only, a related person transaction is a
transaction, arrangement or similar contractual relationship, or any series of similar transactions,
arrangements or relationships, in which the Company and any related person are, were or will be
participants and the amount involved in the transaction exceeds $120,000, with the exception of usual
transactions concluded under normal conditions. A related person is any member of the Executive Board
or Supervisory Board or beneficial owner of more than 5% of any class of its voting securities, including
any of their immediate family members and any entity owned or controlled by such persons.
Under the policy, if a transaction has been identified as a related person transaction, including any
transaction that was not a related person transaction when originally consummated or any transaction that
was not initially identified as a related person transaction prior to consummation, the management must
present information regarding the related person transaction to the Supervisory Board for review,
consideration and approval or ratification. The presentation must include a description of, among other
things, the material facts, the interests, direct and indirect, of the related persons, the benefits to Innate of
the transaction and whether the transaction is on terms that are comparable to the terms available to or
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from, as the case may be, an unrelated third-party or to or from employees generally. Under the policy,
the Company will collect information that the Company deems reasonably necessary from each member
of its Executive Board and Supervisory Board and, to the extent feasible, significant shareholder to enable
Innate to identify any existing or potential related-person transactions and to effectuate the terms of the
policy.
In addition, under its Code of Business Conduct and Ethics, which Innate Pharma adopted on September
12, 2019, its employees and Executive and Supervisory Board members have an affirmative responsibility
to disclose any transaction or relationship that reasonably could be expected to give rise to a conflict of
interest.
In considering related person transactions, the Supervisory Board, will take into account the relevant
available facts and circumstances including, but not limited to:
•
•
•
•
the risks, costs and benefits to us;
the impact on the independence of a member of the Executive Board or Supervisory Board in the
event that the related person is a member of the Executive Board or Supervisory Board, immediate
family member of a member of the Executive Board or Supervisory Board or an entity with which a
member of Executive Board or Supervisory Board is affiliated;
the availability of other sources for comparable services or products; and
the terms available to or from, as the case may be, unrelated third parties or to or from employees
generally.
The policy requires that, in determining whether to approve, ratify or reject a related person transaction,
the Supervisory Board must consider, in light of known circumstances, whether the transaction is in, or is
not inconsistent with, the Company's best interests and those of its shareholders, as the Supervisory Board
determines in the good faith exercise of its discretion.
All of the transactions described above were entered into prior to the adoption of the written policy, but
the Supervisory Board evaluated and approved all transactions that were considered to be related party
transactions under French law at the time at which they were consummated.
C. Interests of Experts and Counsel.
Not applicable.
Item 8. Financial Information
A. Consolidated Statements and Other Financial Information.
Consolidated Financial Statements
Our consolidated financial statements are included as part of this Annual Report, starting at page F-1.
Legal Proceedings
From time to time, the Company may be involved in various claims and legal proceedings relating to
claims arising out of our operations. The Company is not currently a party to any legal proceedings that,
in the opinion of our management, are likely to have a material adverse effect on our business. Regardless
of outcome, litigation can have an adverse impact on the Company because of defense and settlement
costs, diversion of management resources and other factors.
204
Dividend Policy
The Company has never declared or paid any dividends on our ordinary shares. The Company do not
anticipate paying cash dividends on our equity securities in the foreseeable future and intend to retain all
available funds and any future earnings for use in the operation and expansion of our business, given our
state of development.
Subject to the requirements of French law and our bylaws, dividends may only be distributed from our
distributable profits, plus any amounts held in our available reserves which are reserves other than legal
and statutory and revaluation surplus. Dividend distributions, if any in the future, will be made in euro
and converted into U.S. dollars with respect to the ADSs, as provided in the deposit agreement. See the
information set forth in our prospectus dated October 16, 2019, filed with the SEC pursuant to Rule
424(b), under the heading “Description of Share Capital” for more information.
B. Significant Changes.
Not applicable.
Item 9. The Offer and Listing.
A. Offer and Listing Details.
The Company's ADSs have been listed on the Nasdaq Global Select Market under the symbol “IPHA”
since October 21, 2019. The Company's ordinary shares have been trading on Euronext Paris under the
symbol “IPH” since November 3, 2006. Prior to that date, there was no public trading market for the
Company's ADSs or its ordinary shares.
B. Plan of Distribution.
Not applicable.
C. Markets.
The Company's ADSs have been listed on Nasdaq under the symbol “IPHA” since October 21, 2019. The
Company's ordinary shares have been trading on Euronext Paris under the symbol “IPH” since
November 3, 2006.
D. Selling Shareholders.
Not applicable.
E. Dilution.
Not applicable.
F. Expenses of the Issue.
Not applicable.
Item 10. Additional Information.
A. Share Capital.
Not applicable.
B. Memorandum and Articles of Association.
The information set forth in the Company prospectus dated October 16, 2019, filed with the SEC pursuant
to Rule 424(b), under the heading “Description of Share Capital—Key Provisions of Innate's Bylaws and
205
French Law Affecting Innate's Ordinary Shares,” “Description of Share Capital—Differences in
Corporate Law,” and “Limitations Affecting Shareholders of a French Company” is incorporated herein
by reference.
C. Material Contracts.
Strategic Collaborations and License Agreements
AstraZeneca
2015 Agreements
In April 2015, the Company entered into two agreements with MedImmune, a wholly owned subsidiary
of AstraZeneca, which Innate refers to as AstraZeneca. The first agreement was a co-development and
license agreement relating to certain combination products containing monalizumab ( the "Original Co-
Development Agreement"), and the second agreement was a development and option agreement for
products containing monalizumab, including products using monalizumab as a monotherapy (the "2015
Option Agreement"). The Company received an initial payment of $250 million under these agreements
on June 30, 2015, of which $100 million was paid to Innate as an initial payment for the Original Co-
Development Agreement and $150 million was paid to Innate as consideration for the 2015 Option
Agreement described below. In October 2018, AstraZeneca exercised its option under the 2015 Option
Agreement, which resulted in the automatic termination of both the Original Co-Development Agreement
and the 2015 Option Agreement, and a new co-development and license agreement relating to all products
containing monalizumab (the "2015 Co-Development Agreement"), automatically came into effect. In
connection with AstraZeneca’s exercise of its option under the 2015 Option Agreement, an upfront
payment of $100 million was due under the 2015 Co-Development Agreement, which it paid in January
2019.
2015 Co-Development Agreement (monalizumab)
Under the 2015 Co-Development Agreement, the Company granted to AstraZeneca a worldwide,
exclusive license, subject to certain exclusions, to certain of its patents and know-how to develop,
manufacture and commercialize licensed products, including monalizumab, in the field of diagnosis,
prevention and treatment of oncology diseases and conditions. The Company further granted to
AstraZeneca a worldwide, non-exclusive license to certain of its other patents to develop, manufacture
and commercialize licensed products, including monalizumab, in the field of diagnosis, prevention and
treatment of oncology diseases and conditions. The Company retains the rights under the licensed patents
and know-how to, among other things, co-promote licensed products in certain European countries,
pursuant to its option to co-promote, and exploit the licensed patents and know-how to research, develop
and commercialize the licensed products outside of the field of diagnosis, prevention and treatment of
oncology diseases and conditions.
Under the 2015 Co-Development Agreement, the Company is required to collaborate with AstraZeneca to
develop and commercialize licensed products. AstraZeneca will be the lead party in developing the
licensed products and licensed product in certain major markets. Each party will have to use
commercially reasonable efforts to complete certain development activities in accordance with a specified
development plan.
The Company is required for a defined period of time to co-fund 30% of the Phase 3 clinical trials of
licensed products, subject to an aggregate cap, in order to receive 50% of the profits in Europe.
206
On July 31, 2019, the Company notified AstraZeneca of its decision to co-fund future monalizumab
Phase 3 clinical development program. In October 2020, AstraZeneca enrolled the first patient in the first
Phase 3 trial which triggered a $50 million milestone payment from AstraZeneca to Innate.
In August 2022, the Company announced that the planned futility interim analysis of the INTERLINK-1
Phase 3 study sponsored by AstraZeneca did not meet a pre-defined threshold for efficacy. Based on this
result and the recommendation of an Independent Data Monitoring Committee, AstraZeneca has informed
Company that the study will be discontinued.
In September 2021, AstraZeneca, based on data from the randomized Phase 2 trial in patients with
unresectable, Stage III non-small cell lung cancer (NSCLC) presented at the European Society for
Medical Oncology (ESMO) Congress, announced plans to initiate a Phase 3 trial for both combinations of
monalizumab or oleclumab plus durvalumab in the unresectable, Stage III NSCLC setting for patients
who had not progressed after concurrent chemoradiation therapy.
In April 2022, the Company announced that AstraZeneca enrolled the first patient in a second Phase 3
trial, PACIFIC-9, evaluating durvalumab in a combination with monalizumab or oleclumab in patients
with unresectable, Stage III NSCLC, which trigerred a $50 million milestone payment from AstraZeneca
Innate.
Separately, AstraZeneca also announced that it is starting a Phase 2 clinical trial, NeoCOAST-2, that
includes a treatment arm with durvalumab in combination with chemotherapy and monalizumab in
resectable, early-stage NSCLC.
AstraZeneca will be responsible for the promotion of licensed products worldwide, subject to Innate's
option to co-promote the licensed products in certain European countries. Should the Company elect not
to co-promote, its share of profits in Europe will be reduced by a specified amount of percentage points
not to exceed the mid-single digits.
The development by AstraZeneca of a licensed product under the 2015 Co-Development Agreement is
subject to certain reciprocal non-compete obligations.
AstraZeneca is obligated to pay Innate up to $775 million in the aggregate upon the achievement of
certain development and regulatory milestones ($350 million), including commercialization milestones
($425 million). As described above, the arrangement also provides for a 50% profit share and, subject to
certain deferrals of reimbursement, loss share of licensed products in Europe if the Company does not opt
out of its co-funding and co-promoting obligations. In addition, the Company will be eligible to receive
tiered royalties ranging from a low double-digit to mid-teen percentage on net sales of licensed products
outside of Europe. The royalties payable to Innate under the 2015 Co-Development Agreement may be
reduced under certain circumstances, including loss of exclusivity or lack of patent protection.
Innate's right to receive royalties under the 2015 Co-Development Agreement expires, on a licensed
product-by-licensed product and country-by-country basis, on the latest of: (i) the tenth anniversary of the
first commercial sale of such licensed product in such country, or in the case of European countries, in
any European country, (ii) the expiration of regulatory exclusivity for such licensed product in such
country and (iii) the expiration of the last-to-expire valid licensed patent claim subject to the agreement
that covers such licensed product in such country.
Unless earlier terminated, the term of the 2015 Co-Development Agreement will expire on the date on
which all of AstraZeneca’s payment obligations have expired. The Company may terminate the 2015 Co-
Development Agreement if AstraZeneca challenges any patent licensed to it under the agreement.
AstraZeneca may terminate the 2015 Co-Development Agreement in its entirety for convenience at any
time effective upon 120 days’ prior written notice to us. Either party may terminate the 2015 Co-
207
Development Agreement in the event of an uncured material breach by the other party or for certain
bankruptcy or insolvency events involving the other party.
If the 2015 Co-Development Agreement is terminated by AstraZeneca for convenience or by Innate for
AstraZeneca’s material breach, insolvency or a patent challenge by AstraZeneca, all licenses and rights
granted under the agreement terminate, however, upon any such termination, AstraZeneca would grant
Innate an exclusive, worldwide, royalty-bearing right and license, with the right to grant sublicenses,
under technology developed by AstraZeneca and incorporated into or necessary for the exploitation of
licensed products, except for certain manufacturing technology that would require a separate agreement.
If the 2015 Co-Development Agreement is terminated by AstraZeneca for Innate's material breach or
insolvency, AstraZeneca has the right to continue the agreement by providing written notice to us. If
AstraZeneca provides Innate with such written notice, among other things, its rights under the co-promote
option will terminate and the Company must cease any development, manufacture or commercialization
activities under the agreement.
2018 CD39 Option Agreement
In October 2018, the Company entered into a collaboration and option agreement relating to IPH5201.
The Company received an initial payment of $50 million under this agreement, $26 million of which was
received in October 2018 and $24 million of which was received in January 2019. Pursuant to the 2018
CD39 Option Agreement, the Company granted to AstraZeneca an exclusive option to obtain an
exclusive license to certain of its patents and know-how to develop and commercialize licensed products,
including IPH5201 in the field of the diagnosis, prevention and treatment of all diseases and conditions in
humans or animals, subject to certain limitations.
Under the 2018 CD39 Option Agreement, the Company must collaborate with AstraZeneca to develop
CD39 option products. Prior to the expiration of the option period, the Company and AstraZeneca are
subject to certain non-compete obligations.
AstraZeneca is responsible for funding the research and development costs of CD39 option products
contemplated in the joint development plan. Additionally, the Company may conduct certain exploratory
clinical studies at its own cost, subject to reimbursement by AstraZeneca with a premium under certain
circumstances related to subsequent development by AstraZeneca.
Following the dosing of the first patient on March 9, 2020 in the IPH5201 Phase 1 clinical trial,
AstraZeneca made a $5 million milestone payment to Innate.
In June 2022, the 2018 CD39 Option Agreement was amended. Innate received a $5M milestone payment
from AstraZeneca upon signature of the amendment and is responsible for conducting a new Phase 2
multicenter, open label, non-randomized study of neoadjuvant and adjuvant treatment with IPH5201,
durvalumab, and chemotherapy in patients with resectable, early-stage Non-small Cell Lung Cancer
(NSCLC). The "MATISSE" Study has started and is awaiting first patient. AstraZeneca and Innate will
share study costs and AstraZeneca will supply clinical trial drugs. Innate made a €0.6 million milestone
payment to Orega Biotech SAS pursuant to Innate’s exclusive licensing agreement (see below).
Unless earlier terminated, the term of the 2018 CD39 Option Agreement will expire on the earlier of
exercise of the option or expiration of the option period in the event that AstraZeneca does not exercise
the option. The Company may terminate the 2018 CD39 Option Agreement if AstraZeneca challenges
any option patent. AstraZeneca may terminate the 2018 CD39 Option Agreement in its entirety for
convenience at any time effective upon three months’ prior written notice to us. Either party may
terminate the 2018 CD39 Option Agreement in the event of an uncured material breach by the other party
or for certain bankruptcy or insolvency events involving the other party.
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CD39 Co-Development and License Agreement Upon Option Exercise by AstraZeneca
Upon exercise of the option under the 2018 CD39 Option Agreement, the Company would enter into a
co-development and license agreement with AstraZeneca, or the CD39 Potential License Agreement.
Under the CD39 Potential License Agreement, the Company would grant to AstraZeneca a worldwide,
exclusive license, subject to certain exclusions, to certain of its patents and know-how regarding, among
other things, its IPH5201 candidate, to develop, manufacture and commercialize licensed products in the
field of diagnosis, prevention and treatment of diseases and conditions in humans and in animals, subject
to certain limitations. The Company would retain certain rights under the licensed patents and know-how
to, among other things, co-promote licensed products in certain European countries, pursuant to its option
to co-promote.
The CD39 Potential License Agreement provides for a payment of $25 million upon exercise.
Additionally, AstraZeneca would be obligated to pay Innate up to $795 million in the aggregate upon the
achievement of certain development and regulatory milestones ($295 million) and commercialization
milestones ($500 million). The arrangement also provides for a 50% profit share in Europe if the
Company opts into certain co-promoting and late stage co-funding obligations. In addition, the Company
would be eligible to receive tiered royalties ranging from a high-single digit to mid-teen percentage on net
sales of IPH5201, or from a mid-single digit to low-double digit percentage on net sales of other types of
licensed products, outside of Europe. The royalties payable to Innate under the CD39 Potential License
Agreement may be reduced under certain circumstances, including loss of exclusivity or lack of patent
protection.
Under the CD39 Potential License Agreement, unless the Company has elected not to co-fund, the
Company would be required to collaborate with AstraZeneca to develop and commercialize licensed
products. AstraZeneca would be the lead party in developing and commercializing the licensed products
and each party must use commercially reasonable efforts to develop, obtain regulatory approval and
commercialize at least one licensed product in certain major markets. Each party would have to use
commercially reasonable efforts to complete its development activities in accordance with a specified
development plan.
The Company would have the option to co-fund 30% of the Phase 3 clinical trials of licensed products in
order to share in 50% of the profits and losses of licensed products in Europe. If the Company does not
exercise this co-funding option, among other things, its right to share in 50% of the profits and losses in
Europe and right to co-promote in certain European countries will terminate and will be replaced by rights
to receive royalties on net sales at the rates applicable to outside of Europe. Additionally, certain
milestone payments that may be payable to Innate would be reduced. AstraZeneca would be responsible
for the promotion of licensed products worldwide, subject to its option to co-promote the licensed
products in certain European countries if the Company elects to co-fund. Additionally, the Company
would have a right of first negotiation in the event that AstraZeneca wishes to grant a third-party the right
to commercialize licensed products in Europe or the United States.
The development by AstraZeneca of a licensed product under the Potential License Agreement is subject
to certain reciprocal non-compete obligations.
Innate's right to receive royalties under the CD39 Potential License Agreement expires, on a licensed
product-by-licensed product and country-by-country basis, on the latest of: (i) the tenth anniversary of the
first commercial sale of such licensed product in such country, or, in the case of European countries, in
any European country, (ii) the expiration of regulatory exclusivity for such licensed product in such
country and (iii) the expiration of the last-to-expire valid licensed patent claim subject to the agreement
that covers such licensed product in such country.
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Unless earlier terminated, the term of the CD39 Potential License Agreement would expire on the date on
which all of AstraZeneca’s payment obligations have expired. The Company may terminate the CD39
Potential License Agreement if AstraZeneca challenges any patent licensed to it under the agreement.
AstraZeneca may terminate the CD39 Potential License Agreement in its entirety for convenience at any
time effective upon 120 days’ prior written notice to us. Either party may terminate the CD39 Potential
License Agreement in the event of an uncured material breach by the other party or for certain bankruptcy
or insolvency events involving the other party.
2018 Future Programs Option Agreement
In October 2018, the Company entered into another option agreement with AstraZeneca, relating to four
pre-clinical programs. The Company received an initial payment of $20 million at signing. Pursuant to the
2018 Future Programs Option Agreement, the Company granted to AstraZeneca four exclusive options
that are exercisable until IND approval to obtain a worldwide, royalty-bearing, exclusive license to certain
of its patents and know-how relating to certain specified pipeline candidates to develop and
commercialize optioned products in all fields of use. The relevant programs are IPH43, IPH25, the anti-
Siglec-9 antibody program and a multi-specific NKp46 NKCE program. Upon exercise of an option, the
Company would be entitled to an option exercise payment of $35 million, as well as development and
regulatory milestone payments ($360 million) and commercialization milestone payments ($500 million)
and tiered, mid-single digit to mid-teen percentage royalties on net sales of the applicable product. The
royalties payable to Innate may be reduced under certain circumstances, including loss of exclusivity, lack
of patent protection or the specific nature of the compound included within the applicable product.
Additionally, the Company would have rights to co-fund certain development costs in order to obtain
profit and loss sharing in Europe. So long as the Company elects to co-fund such development costs, the
Company also will have a right to co-promote optioned products in Europe.
In 2022, the Company has received from AstraZeneca a notice that it will not exercise its option to license
the four pre-clinical programs covered in the Future Programs Option Agreement which is therefore
terminated.
Lumoxiti Licence Agreement
In October 2018, the Company entered into a third agreement with AstraZeneca relating to the licence of
Lumoxiti (the "Lumoxiti Agreement").
The Company made an initial payment to AstraZeneca of $50 million under this agreement in January
2019 as well as $15 million when filing of the BLA in Europe. Pursuant to the Lumoxiti Agreement, the
Company obtained an exclusive license under certain patents and knowhow of AstraZeneca to develop,
manufacture and commercialize Lumoxiti for all uses in humans and animals in the United States, the
European Union and Switzerland. In December 2020, the Company exercised its right of termination by
sending a termination notice of the Lumoxiti Agreement to AstraZeneca.
Lumoxiti Termination and Transition Agreement
Further to the decision to terminate the Lumoxiti Agreement and termination notice sent in December
2020, a Termination and Transition Agreement was executed, effective as of June 30, 2021 organizing
transition of the licensed rights and BLA back to AstraZeneca and share of different costs including
manufacturing. As provided by the Termination and Transition Agreement, Innate paid $6.2 million to
AstraZeneca on April 29, 2022. Transition of all Lumoxiti rights back to AstraZeneca has been completed
in July 2022.
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Additional agreements related to Monalizumab
Novo Nordisk A/S
On February 5, 2014, the Company in-licensed the full development and commercialization rights to
monalizumab r from Novo Nordisk A/S. In consideration for these rights, the Company paid Novo
Nordisk A/S €2 million in cash and 600,000 of its ordinary shares at a price of €8.33 per share. Novo
Nordisk A/S is eligible to receive a total of €20 million in potential regulatory milestones and tiered mid-
to-high single-digit percentage royalties on future net sales.
The agreement with Novo Nordisk A/S included a right to additional consideration in the event of an out-
licensing agreement. Consequently, following the agreement signed with AstraZeneca in April 2015, the
Company paid Novo Nordisk A/S an additional consideration amount of €6.5 million.
In October 2018 AstraZeneca exercised its option under the 2015 Option Agreement to acquire an
exclusive license to monalizumab. Pursuant to this option exercise, AstraZeneca paid $100 million to
Innate and, as a result, Novo Nordisk A/S became entitled to a second and final payment amounting to
$15.0 million (€13.1 million). If the AstraZeneca agreement is terminated for any reason, the Company
will pay to Novo Nordisk A/S a portion of any amounts that have been budgeted but have not been spent
or will not be spent under the initial research and development budget. In light of current development
plans and research and development costs incurred to date, the Company does not currently expect any
amounts to be paid pursuant to this provision.
License Agreement with Novo Nordisk for avdoralimab
In July of 2017 the Company entered into an exclusive license agreement with Novo Nordisk A/S relating
to avdoralimab, or the 2017 Novo Agreement, pursuant to which the Company obtained a worldwide,
exclusive license under certain patents and know-how of Novo Nordisk A/S to develop, manufacture and
commercialize pharmaceutical products that contain or comprise an Anti-C5aR antibody. The Company
made an initial payment to Novo Nordisk A/S of €40.0 million under the 2017 Novo Agreement which
was offset against Novo Nordisk A/S’s subscription in new shares. The Company is obligated to pay
Novo Nordisk A/S in the aggregate up to €370.0 million upon achievement of certain development,
regulatory and sales milestones and tiered royalties ranging from a low double-digit to low teen
percentage on net sales. The Company's royalty payment obligations are subject to certain reductions and
expire on a product-by-product and country-by-country basis upon the later of the date the exploitation of
a licensed product is no longer covered by a claim of a licensed patent in such country, loss of data or
regulatory exclusivity in such country, and the twelfth anniversary of the first commercial sale of such
product in such country. In connection with the 2017 Novo Agreement, the Company obtained an
exclusive sublicense from Novo Nordisk A/S under certain third-party intellectual property rights. In
consideration for such sublicense, the Company may be obligated to pay a mid-single digit royalty on its
net sales of a licensed product, however, the Company will be entitled to offset such payments against
royalties payable to Novo Nordisk A/S.
Under the 2017 Novo Agreement, the Company is obligated to use commercially reasonable efforts to
develop and seek regulatory approval for a licensed product.
The 2017 Novo Agreement shall expire upon expiration of the last royalty payment obligation under the
agreement. Either party may terminate the 2017 Novo Agreement upon any uncured material breach of
the agreement by the other party or upon a bankruptcy or insolvency of the other party. Additionally,
Novo Nordisk A/S may terminate the agreement in the event the Company challenges any patent licensed
under the agreement. The Company may terminate the 2017 Novo Agreement upon prior notice to Novo
Nordisk A/S.
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In 2020, the Company made a payment to Novo Nordisk A/S of €1 million under the 2017 Novo
Agreement, covered by BPI funding, in respect of the start of a Phase 2 clinical trial of avdoralimab in
COVID-19 patients with severe pneumonia. In July 2021, based on the Phase 2 clinical trial of
avdoralimab in COVID-19 patients with severe pneumonia results which did not meet its primary
endpoints in all three cohorts of the trial, the Company has stopped stop exploring avdoralimab in
COVID-19.
Following a strategic review in 2021, the Company was solely pursuing avdoralimab in bullous
pemphigoid ("BP"), an inflammatory disease, through an investigator-sponsored study and stopped
further development in all other indications.
In last quarter of 2022, the Company was informed by the Sponsor, the Centre Hospitalier Universitaire
de Nice, that the ongoing Phase 2 study for the treatment of BP, will be discontinued. Consequently, the
Company decided to stop further development in BP indication and will continue to review its strategy on
avdoralimab.
Collaboration and licensing agreement with Sanofi (2016)
The Company entered into a research collaboration and licensing agreement with Sanofi in January 2016
to apply its proprietary technology to the development of bispecific antibody formats engaging NK cells
to kill tumor cells through the activating receptor NKp46. The Company granted to Sanofi under certain
of its intellectual property a non-exclusive, worldwide, royalty-free research license, as well as an
exclusive, worldwide license to research, develop and commercialize products directed against two
specified targets, for all therapeutic, prophylactic and diagnostic indications and uses.
The Company will work together with Sanofi on the generation and evaluation of up to two bispecific NK
cell engagers, using its technology and Sanofi’s tumor targets. Under the terms of the license agreement,
Sanofi will be responsible for the development, manufacturing and commercialization of products
resulting from the research collaboration. The Company will be eligible for up to €400.0 million in
payments, primarily upon the achievement of development and commercial milestones, as well as
royalties ranging from a mid to high single-digit percentage on net sales.
On January 5, 2021, the Company announced that Sanofi has made the decision to progress IPH6101/
SAR443579 into investigational new drug (IND) enabling studies. IPH6101/SAR443579 is a NKp46-
based NK cell engager (NKCE) using Innate’s proprietary multi-specific antibody format. The decision
triggered a €7M milestone payment from Sanofi to Innate. Sanofi will be responsible for all future
development, manufacturing and commercialization of IPH6101/SAR443579. Additionally, in January
2021, a GLP-toxicology study was initiated for the IPH6101/SAR443579 program. In December 2021,
the Company announced that the first patient was dosed in a Phase 1/2 clinical trial, evaluating IPH6101/
SAR443579, in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute
lymphoblastic leukemia (B-ALL) or high risk-myelodysplastic syndrome (HR-MDS). The start of the
trial has triggered a milestone payment, part of the €400.0 million mentioned above. The Company
received €3.0m from Sanofi following the initiation of a GLP-tox Study and the launching of the first
Phase 1 clinical trial in humans in relapsed of refractory AML with IPH6101/SAR443579, respectively in
January and December 2021.
In July 2022, the Company announced that Sanofi has made the decision to progress IPH6401/SAR’514
into investigational new drug (IND) enabling studies, triggering a €3 million milestone payment.
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Research Collaboration and Licence agreement with Sanofi (2022)
In December 2022, the Company entered into a research collaboration and licensing agreement with
Genzyme Corporation, a wholly owned subsidiary of Sanofi ("Sanofi") under which the Company grants
Sanofi an exclusive license to Innate’s B7H3 ANKET® program and options for two additional targets.
Upon candidate selection, Sanofi will be responsible for all development, manufacturing and
commercialization.
Under the terms of the Research Collaboration and Licence agreement, Innate has received in March
2023 €25 million as upfront payment and will receive, during the term of the Research and Collaboration
Agreement, up to €1.35 billion total in preclinical, clinical, regulatory and commercial milestones plus
royalties on potential net sales.
Orega License Agreement
Pursuant to its licensing agreement with Orega Biotech, Innate acquired an exclusive license to Orega
Biotech’s intellectual property rights relating to its anti-CD39 checkpoint inhibitor program. As of
December 31, 2018, the Company had paid a total amount of €1.8 million to Orega Biotech for the
acquisition of these intellectual property rights, and in June 2019, the Company paid Orega Biotech
€7.0 million in relation to the anti-CD39 program as consideration relating to the collaboration and option
agreement signed on October 22, 2018 with AstraZeneca for IPH5201. Following the dosing of the first
patient on March 9, 2020 in the IPH5201 Phase 1 clinical trial, AstraZeneca made a $5 million milestone
pursuant to Innate's collaboration agreement with AstraZeneca and Innate made a €2.7 million milestone
payment to Orega Biotech SAS pursuant to its licensing agreement with Orega Biotech SAS. In June
2022, Innate received a $5 million milestone payment from AstraZeneca upon signature of an amendment
to the 2018 CD39 Option Agreement (see above) and made a €0.6 million milestone payment to Orega
Biotech SAS pursuant to its licensing agreement with Orega Biotech SAS.
Unless earlier terminated, the Company may also pay Orega Biotech up to an additional €48.8 million in
the aggregate upon the achievement of development and regulatory milestones. Finally, the Company will
be required to pay a low-teen percentage of sub-licensing revenues received by the Company pursuant to
its agreement with AstraZeneca regarding IPH5201.
The summaries provided above do not purport to be complete and are qualified in their entirety by
reference to the complete agreements, which are attached as exhibits to this Annual Report on Form 20-F.
For additional information on its material contracts, please see “Item 4. Information on the Company,”
“Item 6. Directors, Senior Management and Employees,” and “Item 7.B. Related Party Transactions” of
this Annual Report on 20-F.
Bank Loans
In July 17th 2017, the Company entered into one loan agreement with Société Générale, pursuant to
which the Company obtained a financing in an amount equal to €15.2 million with a term of 12 years.
On December 22nd and December 17th, 2021 the Company entered into two loan agreements with
Société Générale and BNP Paribas, respectively, pursuant to which the Company obtained non-dilutive
financing in an aggregate amount equal to €28.7 million.
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The two loans have an initial term of one year with an extension up to 5 years at Innate's option. They are
90% guaranteed by the French state ("PGE") as part of the package of measures put in place by the
French government to support companies during the COVID-19 pandemic.
D.
Exchange Controls.
Under current French foreign exchange control regulations there are no limitations on the amount of cash
payments that the Company may remit to residents of foreign countries. Laws and regulations concerning
foreign exchange controls do, however, require that all payments or transfers of funds made by a French
resident to a non-resident such as dividend payments be handled by an accredited intermediary. All
registered banks and substantially all credit institutions in France are accredited intermediaries.
E.
Taxation.
Material U.S. Federal Income Tax Considerations
The following describes material U.S. federal income tax considerations relating to the acquisition,
ownership and disposition of the ordinary shares or ADSs by a U.S. holder (as defined below) who hold
the ordinary shares or ADSs as capital assets. This summary does not address all U.S. federal income tax
matters that may be relevant to a particular U.S. holder. This summary does not address tax
considerations applicable to a holder of the ordinary shares or ADSs that may be subject to special tax
rules including, without limitation, the following:
•
•
•
•
•
•
•
•
•
•
•
banks, financial institutions or insurance companies;
brokers, dealers or traders in securities, currencies, commodities, or notional principal contracts;
tax-exempt entities or organizations, including an “individual retirement account” or “Roth IRA” as
defined in Section 408 or 408A of the Code (as defined below), respectively;
real estate investment trusts, regulated investment companies or grantor trusts;
persons that hold the ordinary shares or ADSs as part of a “hedging,” “integrated,” “wash sale” or
“conversion” transaction or as a position in a “straddle” for U.S. federal income tax purposes;
partnerships, or other entities or arrangements classified as partnerships, for U.S. federal income tax
purposes;
certain former citizens or long-term residents of the United States;
persons that received the ordinary shares or ADSs as compensation for the performance of services;
persons acquiring the ordinary shares or ADSs in connection with a trade or business conducted
outside of the United States, including a permanent establishment or a fixed base in France;
holders that own directly, indirectly, or through attribution 10% or more of the voting power or
value of the ordinary shares or ADSs; and
holders that have a “functional currency” other than the U.S. dollar.
Holders of the ordinary shares or ADSs who fall within one of the categories above are advised to consult
their tax advisor regarding the specific tax consequences which may apply to their particular situation.
For the purposes of this description, a “U.S. holder” is a beneficial owner of the ordinary shares or ADSs
that is (or is treated as), for U.S. federal income tax purposes:
•
an individual who is a citizen or resident of the United States;
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a corporation created or organized in or under the laws of the United States, any state therein or the
District of Columbia;
an estate, the income of which is subject to U.S. federal income taxation regardless of its source; or
a trust, if a court within the United States is able to exercise primary supervision over its
administration and one or more U.S. persons have the authority to control all of the substantial
decisions of such trust, or if such trust has a valid election in effect under applicable U.S. Treasury
Regulations to be treated as a U.S. person.
If an entity or arrangement treated as a partnership for U.S. federal income tax purposes holds the
ordinary shares or ADSs, the tax consequences relating to an investment in the ordinary shares or ADSs
will depend in part upon the status of the partner and the activities of the partnership. Such a partner or
partnership should consult its tax advisor regarding the specific tax considerations of acquiring, owning
and disposing of the ordinary shares or ADSs in its particular circumstances.
Persons considering an investment in the ordinary shares or ADSs should consult their own tax
advisors as to the particular tax consequences applicable to them relating to the acquisition,
ownership and disposition of the ordinary shares or ADSs, including the applicability of U.S.
federal, state and local tax laws, French tax laws and other non-U.S. tax laws.
This description does not address the U.S. federal estate, gift, or alternative minimum tax considerations,
the Medicare tax on net investment income or any U.S. state, local, or non-U.S. tax considerations of the
acquisition, ownership and disposition of the ordinary shares or ADSs.
This description is based on the U.S. Internal Revenue Code of 1986, as amended, or the Code, existing,
proposed and temporary U.S. Treasury Regulations promulgated thereunder and administrative and
judicial interpretations thereof, in each case as of the date hereof. All the foregoing is subject to change,
which change could apply retroactively, and to differing interpretations, all of which could affect the tax
considerations described below. There can be no assurances that the U.S. Internal Revenue Service, or the
IRS, will not take a position concerning the tax consequences of the acquisition, ownership and
disposition of the ordinary shares or ADSs or that such a position would not be sustained by a court. The
Company has not obtained, nor does the Company intend to obtain, a ruling with respect to the U.S.
federal income tax considerations of the purchase, ownership or disposition of its ordinary shares or
ADSs. Accordingly, holders should consult their own tax advisors concerning the U.S. federal, state, local
and non-U.S. tax consequences of acquiring, owning and disposing of the ordinary shares or ADSs in
their particular circumstances.
As indicated below, this summary is subject to the discussion below of the U.S. federal income tax rules
applicable to a “passive foreign investment company,” or a PFIC.
In general, and taking into account the earlier assumptions, for U.S. federal income tax purposes, a U.S.
holder holding ADSs will be treated as the owner of the ordinary shares represented by the ADSs.
Exchanges of ordinary shares for ADSs, and ADSs for ordinary shares, generally will not be subject to
U.S. federal income tax.
Distributions. Subject to the discussion under “—Passive Foreign Investment Company Considerations,”
below, the gross amount of any distribution (including any amounts withheld in respect of foreign tax)
actually or constructively received by a U.S. holder with respect to the ordinary shares or ADSs will
generally be taxable to the U.S. holder as a dividend to the extent of the U.S. holder’s pro rata share of the
current or accumulated earnings and profits as determined under U.S. federal income tax principles.
Distributions in excess of earnings and profits will generally be non-taxable to the U.S. holder to the
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extent of, and will be applied against and reduce, the U.S. holder’s adjusted tax basis in the ordinary
shares or ADSs. Distributions in excess of earnings and profits and such adjusted tax basis will generally
be taxable to the U.S. holder as either long-term or short-term capital gain depending upon whether the
U.S. holder has held the ordinary shares or ADSs for more than one year as of the time such distribution
is received. However, since the Company does not calculate its earnings and profits under U.S. federal
income tax principles, it is expected that any distribution will be reported as a dividend, even if that
distribution would otherwise be treated as a non-taxable return of capital or as capital gain under the rules
described above. Non-corporate U.S. holders may qualify for the preferential rates of taxation with
respect to dividends on the ordinary shares or ADSs applicable to long-term capital gains (i.e., gains from
the sale of capital assets held for more than one year), or qualified dividend income if the Company is a
“qualified foreign corporation” and certain other requirements are met. A non-U.S. corporation (other
than a corporation that is a PFIC for the taxable year in which the dividend is paid or the preceding
taxable year) generally will be considered to be a qualified foreign corporation (a) if it is eligible for the
benefits of a comprehensive tax treaty with the United States which the Secretary of Treasury of the
United States determines is satisfactory for purposes of this provision and which includes an exchange of
information provision, or (b) with respect to any dividend it pays on ADSs which are readily tradable on
an established securities market in the United States. The ADSs are listed on the Nasdaq Global Select
Market, which is an established securities market in the United States, and the Company believes the
ADSs are readily tradable on the Nasdaq Global Select Market. There can be no assurance that the ADSs
will continue to be considered readily tradable on an established securities market in the United States in
later years. The Company, which is incorporated under the laws of France, believes that it qualifies as a
resident of France for purposes of, and is eligible for the benefits of, the Convention between the
Government of the United States of America and the Government of the French Republic for the
Avoidance of Double Taxation and the Prevention of Fiscal Evasion with Respect to Taxes on Income
and Capital, signed on August 31, 1994, as amended and currently in force, or the U.S.-France Tax
Treaty, although there can be no assurance in this regard. Further, the IRS has determined that the U.S.-
France Tax Treaty is satisfactory for purposes of the qualified dividend rules and that it includes an
exchange-of-information program. Therefore, subject to the discussion under “—Passive Foreign
Investment Company Considerations,” below, such dividends will generally be “qualified dividend
income” in the hands of individual U.S. holders, provided that a holding period requirement (more than
60 days of ownership, without protection from the risk of loss, during the 121-day period beginning 60
days before the ex-dividend date) and certain other requirements are met. The dividends will not be
eligible for the dividends-received deduction generally allowed to corporate U.S. holders.
A U.S. holder generally may claim the amount of any French withholding tax on a distribution as either a
deduction from gross income or a credit against its U.S. federal income tax liability. The foreign tax credit
is subject to numerous complex limitations that must be determined and applied on an individual basis.
Dividends generally will constitute "passive category income" for purposes of the foreign tax credit. Each
U.S. holder should consult its own tax advisors regarding the foreign tax credit implications of French
withholding tax.
In general, the amount of a distribution paid to a U.S. holder in a foreign currency will be the U.S. dollar
value of the foreign currency calculated by reference to the spot exchange rate on the day the depositary
receives the distribution, in the case of the ADSs, or on the day the distribution is received by the U.S.
holder, in the case of ordinary shares, regardless of whether the foreign currency is converted into U.S.
dollars at that time. Any foreign currency gain or loss a U.S. holder realizes on a subsequent conversion
of foreign currency into U.S. dollars will be U.S. source ordinary income or loss. If dividends received in
a foreign currency are converted into U.S. dollars on the day they are received, a U.S. holder should not
be required to recognize foreign currency gain or loss in respect of the dividend.
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Sale, Exchange or Other Taxable Disposition. A U.S. holder will generally recognize gain or loss for
U.S. federal income tax purposes upon the sale, exchange or other taxable disposition of the ordinary
shares or ADSs in an amount equal to the difference between the amount realized from such sale or
exchange and the U.S. holder’s adjusted tax basis in those ordinary shares or ADSs, each as determined in
U.S. dollars. U.S. holders should consult their own tax advisors about how to account for proceeds
received on the sale, exchange or other taxable disposition of ordinary shares or ADSs that are not paid in
U.S. dollars. Subject to the discussion under “—Passive Foreign Investment Company Considerations”
below, this gain or loss will generally be a capital gain or loss. The adjusted tax basis in the ordinary
shares or ADSs generally will be equal to the U.S dollar cost of such ordinary shares or ADSs. Capital
gain from the sale, exchange or other taxable disposition of the ordinary shares or ADSs by a non-
corporate U.S. holder is generally eligible for a preferential rate of taxation applicable to capital gains, if
the non-corporate U.S. holder’s holding period determined at the time of such sale, exchange or other
taxable disposition for such ordinary shares or ADSs exceeds one year (i.e., such gain is long-term
taxable gain). The deductibility of capital losses for U.S. federal income tax purposes is subject to
limitations. Any such gain or loss that a U.S. holder recognizes generally will be treated as U.S. source
gain or loss for foreign tax credit limitation purposes.
Passive Foreign Investment Company Considerations. If the Company is a PFIC in any taxable year, a
U.S. holder will be subject to special rules generally intended to reduce or eliminate any benefits from the
deferral of U.S. federal income tax that a U.S. holder could derive from investing in a non-U.S. company
that does not distribute all of its earnings on a current basis.
The Company will be a PFIC for U.S. federal income tax purposes in any taxable year in which, after
applying certain look-through rules with respect to the income and assets of its subsidiaries, either: (1) at
least 75% of the gross income is “passive income” or (2) at least 50% of the average quarterly value of
the total gross assets (which would generally be measured by fair market value of its assets, and for which
purpose the total value of its assets may be determined in part by the market value of the ADSs and its
ordinary shares, which are subject to change) is attributable to assets that produce “passive income” or are
held for the production of “passive income.”
Passive income for this purpose generally includes dividends, interest, royalties, rents, gains from
commodities and securities transactions, the excess of gains over losses from the disposition of assets
which produce passive income, and includes amounts derived by reason of the temporary investment of
funds raised in offerings of the ordinary shares or ADSs. If a non-U.S. corporation owns directly or
indirectly at least 25% by value of the stock of another corporation, the non-U.S. corporation is treated for
purposes of the PFIC tests as owning its proportionate share of the assets of the other corporation and as
receiving directly its proportionate share of the other corporation’s income. The determination of whether
the Company is a PFIC is a fact-intensive determination made on an annual basis and the applicable law
is subject to varying interpretation. If the Company is a PFIC in any taxable year during which a U.S.
holder owns its ordinary shares or ADSs, such U.S. holder will be subject to special tax rules discussed
below and could suffer adverse tax consequences.
The market value of the assets may be determined in large part by reference to the market price of the
ADSs and its ordinary shares. Therefore, fluctuations in the market price of the ordinary shares or ADSs
may result in the Company being a PFIC for any taxable year. Whether the Company is a PFIC for any
taxable year will depend on income, assets, activities and market capitalization in each year, and because
this is a factual determination made annually after the end of each taxable year, there can be no assurance
that the Company will not be a PFIC in any taxable year. the Company does not believe it was
characterized as a PFIC in its taxable year ended December 31, 2022. However, there can be no assurance
217
that the Company will not be a PFIC in the current year or for any future taxable year. Its U.S. counsel
expresses no opinion regarding its conclusions or its expectations regarding its PFIC status.
If the Company is a PFIC in any year with respect to which a U.S. holder owns its ordinary shares or
ADSs, the Company will continue to be treated as a PFIC with respect to such U.S. holder in all
succeeding years during which the U.S. holder owns the ordinary shares or ADSs, regardless of whether
the Company continue to meet the tests described above unless the Company ceases to be a PFIC and the
U.S. holder has made a “deemed sale” election under the PFIC rules or is eligible to make and makes a
mark-to-market election (as described below), with respect to all taxable years during such U.S. holder’s
holding period in which the Company is a PFIC. If the “deemed sale” election is made, a U.S. holder will
be deemed to have sold the ordinary shares or ADSs the U.S. holder holds at their fair market value as of
the date of such deemed sale and any gain from such deemed sale would be subject to the rules described
below. After the deemed sale election, so long as the Company does not become a PFIC in a subsequent
taxable year, the U.S. holder’s ordinary shares or ADSs with respect to which such election was made
will not be treated as shares in a PFIC and the U.S. holder will not be subject to the rules described below
with respect to any “excess distribution” the U.S. holder receives from the Company or any gain from an
actual sale or other disposition of the ordinary shares or ADSs. U.S. holders should consult their tax
advisors as to the possibility and consequences of making a deemed sale election if such election becomes
available.
If the Company is a PFIC, and you are a U.S. holder that does not make one of the elections described
above (and below in further detail), a special tax regime will apply to both (a) any “excess distribution”
by the Company to you (generally, your ratable portion of distributions in any year which are greater than
125% of the average annual distribution received by you in the shorter of the three preceding years or
your holding period for its ordinary shares or ADSs) and (b) any gain realized on the sale or other
disposition of its ordinary shares or ADSs. Under this regime, any excess distribution and realized gain
will be treated as ordinary income and will be subject to tax as if (a) the excess distribution or gain had
been realized ratably over your holding period for the ordinary shares or ADSs, (b) the amount deemed
realized in each year had been subject to tax in each year of that holding period at the highest marginal
rate for such year (other than income allocated to the current period or any taxable period before the
Company became a PFIC, which would be subject to tax at the U.S. holder’s regular ordinary income rate
for the current year and would not be subject to the interest charge discussed below), and (c) the interest
charge generally applicable to underpayments of tax had been imposed on the taxes deemed to have been
payable in those years. In addition, dividend distributions made to you will not qualify for the lower rates
of taxation applicable to qualified dividends discussed above under “Distributions.”
Certain elections may alleviate some of the adverse consequences of PFIC status and would result in an
alternative treatment of the ordinary shares or ADSs. If a U.S. holder makes a mark-to-market election,
the U.S. holder generally will recognize as ordinary income any excess of the fair market value of the
ordinary shares or ADSs at the end of each taxable year over their adjusted tax basis, and will recognize
an ordinary loss in respect of any excess of the adjusted tax basis of the ordinary shares or ADSs over
their fair market value at the end of the taxable year (but only to the extent of the net amount of income
previously included as a result of the mark-to-market election). If a U.S. holder makes the election, the
U.S. holder’s tax basis in the ordinary shares or ADSs will be adjusted to reflect these income or loss
amounts. Any gain recognized on the sale or other disposition of the ordinary shares or ADSs in a year in
which the Company is a PFIC will be treated as ordinary income and any loss will be treated as an
ordinary loss (but only to the extent of the net amount of income previously included as a result of the
mark-to-market election). The mark-to-market election is available only if the Company is a PFIC and its
ordinary shares or ADSs are “regularly traded” on a “qualified exchange.” Its ordinary shares or ADSs
will be treated as “regularly traded” in any calendar year in which more than a de minimis quantity of its
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ordinary shares or ADSs are traded on a qualified exchange on at least 15 days during each calendar
quarter (subject to the rule that trades that have as one of their principal purposes the meeting of the
trading requirement are disregarded). The Nasdaq Global Select Market is a qualified exchange for this
purpose and, consequently, if the ADSs are regularly traded, the mark-to-market election will be available
to a U.S. holder. It should be noted that only the ADSs and not its ordinary shares are listed on the Nasdaq
Global Select Market. Consequently, its ordinary shares may not be marketable if Euronext Paris (where
its ordinary shares are listed) does not meet the applicable requirements. U.S. holders should consult their
tax advisors regarding the availability of the mark-to-market election for ordinary shares that are not
represented by ADSs.
However, a mark-to-market election generally cannot be made for equity interests in any lower-tier PFICs
that the Company owns, unless shares of such lower-tier PFIC are themselves “marketable.” As a result,
even if a U.S. holder validly makes a mark-to-market election with respect to its ordinary shares or ADSs,
the U.S. holder may continue to be subject to the PFIC rules (described above) with respect to its indirect
interest in any of its investments that are treated as an equity interest in a PFIC for U.S. federal income
tax purposes. U.S. holders should consult their tax advisors as to the availability and desirability of a
mark-to-market election, as well as the impact of such election on interests in any lower-tier PFICs.
The Company does not currently intend to provide the information necessary for U.S. holders to make a
“qualified electing fund election” if the Company is treated as a PFIC for any taxable year. U.S. holders
should consult their tax advisors to determine whether this election would be available and if so, what the
consequences of the alternative treatments would be in their particular circumstances.
If the Company is a PFIC, the general tax treatment for U.S. holders described in this section would apply
to indirect distributions and gains deemed to be realized by U.S. holders in respect of any of its
subsidiaries that also may be PFICs. U.S. holders should consult their tax advisors regarding the
application of the PFIC rules to the Company's subsidiaries.
If a U.S. holder owns its ordinary shares or ADSs during any taxable year in which the Company is a
PFIC, the U.S. holder generally will be required to file an IRS Form 8621 (Information Return by a
Shareholder of a Passive Foreign Investment Company or Qualified Electing Fund) with respect to the
Company, generally with the U.S. holder’s federal income tax return for that year. If the Company is a
PFIC for a given taxable year, then you should consult your tax advisor concerning your annual filing
requirements.
The U.S. federal income tax rules relating to PFICs are complex. Prospective U.S. investors are
urged to consult their own tax advisors with respect to the acquisition, ownership and disposition of
the ordinary shares or ADSs, the consequences to them of an investment in a PFIC, any elections
available with respect to the ordinary shares or ADSs and the IRS information reporting
obligations with respect to the acquisition, ownership and disposition of the ordinary shares or
ADSs.
Backup Withholding and Information Reporting. U.S. holders generally will be subject to information
reporting requirements with respect to dividends on the ordinary shares or ADSs and on the proceeds
from the sale, exchange or disposition of the ordinary shares or ADSs that are paid within the United
States or through U.S.-related financial intermediaries, unless the U.S. holder is an “exempt recipient.” In
addition, U.S. holders may be subject to backup withholding on such payments, unless the U.S. holder
provides a taxpayer identification number and a duly executed IRS Form W-9 or otherwise establishes an
exemption. Backup withholding is not an additional tax, and the amount of any backup withholding will
be allowed as a credit against a U.S. holder’s U.S. federal income tax liability and may entitle such holder
to a refund, provided that the required information is timely furnished to the IRS.
219
Foreign Asset Reporting. Certain individual U.S. holders are required to report information relating to an
interest in the ordinary shares or ADSs, subject to certain exceptions (including an exception for shares
held in accounts maintained by U.S. financial institutions) by filing IRS Form 8938 (Statement of
Specified Foreign Financial Assets) with their federal income tax return. U.S. holders are urged to consult
their tax advisors regarding their information reporting obligations, if any, with respect to their ownership
and disposition of the ordinary shares or ADSs.
THE DISCUSSION ABOVE IS A SUMMARY OF THE U.S. FEDERAL INCOME TAX
CONSEQUENCES OF AN INVESTMENT IN THE ORDINARY SHARES OR ADSs AND IS
BASED UPON LAWS AND RELEVANT INTERPRETATIONS THEREOF IN EFFECT AS OF
THE DATE OF THIS ANNUAL REPORT, ALL OF WHICH ARE SUBJECT TO CHANGE,
POSSIBLY WITH RETROACTIVE EFFECT. EACH PROSPECTIVE INVESTOR IS URGED
TO CONSULT ITS OWN TAX ADVISOR ABOUT THE TAX CONSEQUENCES TO IT OF AN
INVESTMENT IN THE ORDINARY SHARES OR ADSs IN LIGHT OF THE INVESTOR’S
OWN CIRCUMSTANCES.
Material French Tax Considerations
The following describes the material French income tax consequences to U.S. holders of purchasing,
owning and disposing of the ADSs.
This discussion does not purport to be a complete analysis or listing of all potential tax effects of the
acquisition, ownership or disposition of the ADSs to any particular investor, and does not discuss tax
considerations that arise from rules of general application or that are generally assumed to be known by
investors. All of the following is subject to change. Such changes could apply retroactively and could
affect the consequences described below.
In 2011, France introduced a comprehensive set of tax rules applicable to French assets that are held by or
in foreign trusts. These rules provide inter alia for the inclusion of trust assets in the settlor’s net assets for
the purpose of applying the former French wealth tax (replaced by the French real estate wealth tax as
from January 1, 2018), for the application of French gift and death duties to French assets held in trust, for
a specific tax on capital on the French assets of foreign trusts not already subject to the former French
wealth tax (replaced by the French real estate wealth tax as from January 1, 2018) and for a number of
French tax reporting and disclosure obligations. The following discussion does not address the French tax
consequences applicable to securities (including ADSs) held in trusts. If ADSs are held in trust, the
grantor, trustee and beneficiary are advised to consult their own tax advisor regarding the specific tax
consequences of acquiring, owning and disposing of such securities.
The description of the French income tax and real estate wealth tax consequences set forth below is based
on the double tax treaty entered into between the Government of the United States of America and the
Government of the French Republic for the Avoidance of Double Taxation and the Prevention of Fiscal
Evasion with Respect to Taxes on Income and Capital of August 31, 1994 (the “Treaty”), which came
into force on December 30, 1995 (as amended by any subsequent protocols, including the protocol of
January 13, 2009), and the tax guidelines issued by the French tax authorities in force as of the date of this
Annual Report, or the Treaty.
This discussion applies only to investors that are entitled to Treaty benefits under the “Limitation on
Benefits” provisions contained in the Treaty.
If a partnership holds ADSs, the tax treatment of the partnership and a partner in such partnership
generally will depend on the status of the partner and the activities of the partnership. Such partner or
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partnership is urged to consult its own tax advisor regarding the specific tax consequences of acquiring,
owning and disposing of ADSs.
This discussion applies only to investors that hold ADSs as capital assets that are entitled to Treaty
benefits under the “Limitation on Benefits” provision contained in the Treaty, and whose ownership of
the ADSs is not effectively connected to a permanent establishment or a fixed base in France. Certain
U.S. holders may be subject to special rules not discussed below, and are advised to consult their usual
tax advisor regarding the specific tax consequences which may apply to their particular situation.
U.S. holders are advised to consult their own tax advisor regarding the tax consequences of the purchase,
ownership and disposition of ADSs in light of their particular circumstances, especially with regard to the
“Limitations on Benefits” provision contained in the Treaty.
Tax on Sale or other Disposals
As a matter of principles, under French tax law, subject to limited exemptions, a U.S. holder should not
be subject to any French tax on any capital gain from the sale, exchange, repurchase or redemption by
Innate of ordinary shares or ADSs, provided such U.S. holder is not a French tax resident for French tax
purposes and has not held more than 25% of the dividend rights, known as “droits aux benefices sociaux,”
at any time during the preceding five years, either directly or indirectly, and, as relates to individuals,
alone or with relatives (as an exception, a U.S. holder resident, established or incorporated in certain non-
cooperative States or territories as defined in Article 238-0 A of the French tax code (Code général des
impôts, the “FTC”) should be subject to a 75% withholding tax in France on any such capital gain,
regardless of the fraction of the dividend rights it holds unless it provides evidence that the operations to
which these profits correspond have a primary purpose and effect other than enabling their location in
such non-cooperative States or territories).
Under application of the Treaty, a U.S. holder who is a U.S. resident for purposes of the Treaty and
entitled to Treaty benefits will not be subject to French tax on such capital gain unless the ordinary shares
or the ADSs form part of the business property of a permanent establishment or fixed base that the U.S.
holder has in France. U.S. holders who own ordinary shares or ADSs through U.S. partnerships that are
not resident for Treaty purposes are advised to consult their own tax advisor regarding their French tax
treatment and their eligibility for Treaty benefits in light of their own particular circumstances. A U.S.
holder that is not a U.S. resident for Treaty purposes or is not entitled to Treaty benefits (and in both cases
is not resident, established or incorporated in certain non-cooperative States or territories as defined in
Article 238-0 A of the FTC) and has held more than 25% of the dividend rights, known as “droits aux
bénéfices sociaux” at any time during the preceding five years, either directly or indirectly, and, as relates
to individuals, alone or with relatives will be subject to a levy in France (i) at the rate of 12.8% for
individuals, and (ii) a rate corresponding to the standard corporate income tax rate set forth in Article 219-
I of the FTC for legal persons. Special rules apply to U.S. holders who are residents of more than one
country.
Financial Transactions Tax and Registration Duties
Pursuant to Article 235 ter ZD of the FTC, purchases of shares or ADSs of a French company listed on a
regulated market of the European Union or on a foreign regulated market formally acknowledged by the
AMF are subject to a 0.3% French tax on financial transactions provided that the issuer’s market
capitalization exceeds 1 billion euros as of December 1 of the year preceding the taxation year. A list of
companies whose market capitalization exceeds 1 billion euros as of December 1 of the year preceding
the taxation year, within the meaning of Article 235 ter ZD of the FTC, is published annually by the
French tax authorities in their official guidelines. As at 1 December 2021, the market capitalization did
not exceed 1 billion euros, pursuant to BOI-ANNX-000467-29/12/2021.
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Moreover, Nasdaq Global Select Market, on which ADSs are listed, is not currently acknowledged by the
AMF but this may change in the future.
As a consequence, neither the ADSs nor the ordinary shares are currently within the scope of the French
tax on financial transactions.
Purchases of the ADSs may be subject to such tax in the future provided that the market capitalization
exceeds 1 billion euros in the year preceding the taxation year and that the Nasdaq Global Select Market
is acknowledged by the French AMF.
In the case where Article 235 ter ZD of the FTC is not applicable, transfers of shares issued by a French
company which are listed on a regulated or organized market within the meaning of the French monetary
code (Code monétaire et financier) are subject to uncapped registration duties at the rate of 0.1% if the
transfer is evidenced by a written statement (“acte”) executed either in France or outside France. As
ordinary shares of the company are listed on Euronext Paris, which is an organized market within the
meaning of the French monetary code, their transfer should be subject to uncapped registration duties at
the rate of 0.1% subject to the existence of a written statement (“acte”), and provided that Article 235 ter
ZD of the FTC is not applicable. There is however no case law or official guidelines published by the
French tax authorities on this point with respect to transfers of ADSs.
Taxation of Dividends
Dividends paid by a French corporation to non-residents of France are generally subject to French
withholding tax at a rate of (i) 25% for fiscal years beginning on or after January 1st, 2022, for payment
benefiting legal persons which are not French tax residents, and (ii) 12.8% for payment benefiting
individuals who are not French tax residents. Dividends paid by a French corporation in certain non-
cooperative States or territories, as defined in Article 238-0 A of the FTC, will generally be subject to
French withholding tax at a rate of 75%. However, eligible U.S. holders entitled to Treaty benefits under
the “Limitation on Benefits” provision contained in the Treaty who are U.S. residents, as defined pursuant
to the provisions of the Treaty, will not be subject to this 25% or 75% withholding tax rate, but may be
subject to the withholding tax at a reduced rate (as described below).
Under the Treaty, the rate of French withholding tax on dividends paid to an eligible U.S. holder who is a
U.S. resident as defined pursuant to the provisions of the Treaty and whose ownership of the ordinary
shares or ADSs is not effectively connected with a permanent establishment or fixed base that such U.S.
holder has in France, is generally reduced to 15%, or to 5% if such U.S. holder is a corporation and owns
directly or indirectly at least 10% of the share capital of the issuer; such U.S. holder may claim a refund
from the French tax authorities of the amount withheld in excess of the Treaty rates of 15% or 5%, if any.
For U.S. holders that are not individuals but are U.S. residents, as defined pursuant to the provisions of
the Treaty, the requirements for eligibility for Treaty benefits, including the reduced 5% or 15%
withholding tax rates contained in the “Limitation on Benefits” provision of the Treaty, are complex, and
certain technical changes were made to these requirements by the protocol of January 13, 2009. U.S.
holders are advised to consult their own tax advisor regarding their eligibility for Treaty benefits in light
of their own particular circumstances.
Dividends paid to an eligible U.S. holder may immediately be subject to the reduced rates of 5% or 15%
provided that:
•
such holder establishes before the date of payment that it is a U.S. resident under the Treaty by
completing and providing the depositary with a treaty form (Form 5000) in accordance with French
guidelines (BOI-INT-DG-20-20-20-20-12/09/2012 dated September 12, 2012); or
222
•
the depositary or other financial institution managing the securities account in the U.S. of such
holder provides the French paying agent with a document listing certain information about the U.S.
holder and its ordinary shares or ADSs and a certificate whereby the financial institution managing
the U.S. holder’s securities account in the United States takes full responsibility for the accuracy of
the information provided in the document.
Otherwise, dividends paid to a U.S. holder, if such U.S. holder is a legal person, will be subject to French
withholding tax at the rate of 25%, or 75% if paid in certain non-cooperative States or territories (as
defined in Article 238-0 A of the FTC), and then reduced at a later date to 5% or 15%, provided that such
holder duly completes and provides the French tax authorities with the treaty forms Form 5000 and Form
5001 before December 31 of the second calendar year following the year during which the dividend is
paid. Certain qualifying pension funds and certain other tax-exempt entities are subject to the same
general filing requirements as other U.S. holders except that they may have to supply additional
documentation evidencing their entitlement to these benefits.
Form 5000 and Form 5001, together with instructions, will be provided by the depositary to all U.S.
holders registered with the depositary. The depositary will arrange for the filing with the French tax
authorities of all such forms properly completed and executed by U.S. holders of ordinary shares or ADSs
and returned to the depositary in sufficient time so that they may be filed with the French tax authorities
before the distribution in order to immediately obtain a reduced withholding tax rate. Otherwise, the
depositary must withhold tax at the full rate of 25% or 75% as applicable. In that case, the U.S. holders
may claim a refund from the French tax authorities of the excess withholding tax.
In any case, individual taxpayers who are not fiscally domiciled in France should not have to comply with
these procedures if the French withholding tax applying to them is lower than 15%.
Estate and Gift Taxes
In general, a transfer of securities by gift or by reason of death of a U.S. holder that would otherwise be
subject to French gift or inheritance tax, respectively, will not be subject to such French tax by reason of
the double tax treaty entered into between the Government of the United States of America and the
Government of the French Republic for the Avoidance of Double Taxation and the Prevention of Fiscal
Evasion with Respect to Taxes on Estates, Inheritances and Gifts, dated November 24, 1978, unless (i) the
donor or the transferor is domiciled in France at the time of making the gift or at the time of his or her
death, or (ii) the ADSs were used in, or held for use in, the conduct of a business through a permanent
establishment or a fixed base in France.
Wealth Tax
As from January 1, 2018, the French wealth tax (impôt de solidarité sur la fortune) is repealed and
replaced by the French real estate wealth tax (impôt sur la fortune immobilière). The scope of such new
tax is narrowed to French real estate assets (and certain assets deemed to be real estate assets) or rights,
held directly or indirectly through one or more legal entities and whose net taxable assets amount at least
to €1,300,000.
Broadly, subject to provisions of double tax treaties and to certain exceptions, individuals who are not
residents of France for tax purposes within the meaning of Article 4 B of the FTC, are subject to real
estate wealth tax (impôt sur la fortune immobilière) in France in respect of the portion of the value of
their shares of the company representing real estate assets (Article 965, 2° of the FTC). Some exceptions
are provided by the FTC. For instance, any participations representing less than 10% of the share capital
of an operational company and shares representing real estate for the professional use of the company
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considered shall not fall within the scope of the French real estate wealth tax (impôt sur la fortune
immobilière).
Under the Treaty (the provisions of which should be applicable to this new real estate wealth tax (impôt
sur la fortune immobilière) in France), the French real estate wealth tax (impôt sur la fortune
immobilière) will however generally not apply to securities held by an eligible U.S. holder who is a U.S.
resident, as defined pursuant to the provisions of the Treaty, provided that such U.S. holder (i) does not
own directly or indirectly more than 25% of the issuer’s financial rights and (ii) that the ADSs do not
form part of the business property of a permanent establishment or fixed base in France.
U.S. holders are advised to consult their own tax advisor regarding the specific tax consequences which
may apply to their particular situation with respect to such French real estate wealth tax (impôt sur la
fortune immobilière).
F. Dividends and Paying Agents.
Not applicable.
G. Statement by Experts.
Not applicable.
H. Documents on Display.
The Company is subject to the information reporting requirements of the Exchange Act applicable to
foreign private issuers and under those requirements will file reports with the SEC. Those reports may be
inspected without charge at the locations described below. As a foreign private issuer, the Company is
exempt from the rules under the Exchange Act related to the furnishing and content of proxy statements,
and its officers, directors and principal shareholders are exempt from the reporting and short-swing profit
recovery provisions contained in Section 16 of the Exchange Act. In addition, the Company is not
required under the Exchange Act to file periodic reports and financial statements with the SEC as
frequently or as promptly as United States companies whose securities are registered under the Exchange
Act. Nevertheless, the Company will file with the SEC an Annual Report on Form 20-F containing
financial statements that have been examined and reported on, with an opinion expressed by an
independent registered public accounting firm.
The Company maintains a corporate website at www.innate-pharma.com. The Company intends to post
its Annual Report on Form 20-F on its website promptly following it being filed with the SEC.
Information contained on, or that can be accessed through, its website does not constitute a part of this
Annual Report. The Company has included its website address in this Annual Report solely as an inactive
textual reference.
The Securities and Exchange Commission maintains a website (www.sec.gov) that contains reports, proxy
and information statements and other information regarding registrants, such as us, that file electronically
with the SEC.
With respect to references made in this Annual Report to any contract or other document of the Company,
such references are not necessarily complete and you should refer to the exhibits attached or incorporated
by reference to this Annual Report for copies of the actual contract or document.
I. Subsidiary Information.
Not required.
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Item 11. Quantitative and Qualitative Disclosures About Market Risk.
The Company's activities are exposed to liquidity risk, foreign currency exchange risk, interest rate risk
and credit risk.
Liquidity risk
The Company does not believe that it is exposed to short-term liquidity risk, considering its cash and cash
equivalents and short-term investments of €101.5 million as of December 31, 2022, which consist
primarily of cash and money market funds and term deposits that are convertible into cash immediately
without penalty.
Foreign currency exchange rate risk
The Company is exposed to foreign exchange risk inherent in certain subcontracting activities related to
its operations in the United States, which are invoiced in U.S. dollars. The Company does not currently
have material recurring revenues in euro, dollars or in any other currency. As the Company further
increases its business, particularly in the United States, the Company expects to face greater exposure to
exchange rate risk.
Innate's revenue denominated in U.S. dollars has represented approximately 88%, 78% and 92% of
revenue in the years ended December 31, 2020, 2021 and 2022, respectively. Payments in U.S. dollars
represented approximately 48%, 50%, and 50% of the payments in the years ended December 31, 2020,
2021 and 2022, respectively. In order to cover this foreign currency exchange rate risk, the Company kept
in U.S. dollars a part of the consideration received from AstraZeneca in June 2015, January 2019 and
September 2020. The Company kept the entire U.S dollars portion of the proceeds received from its
October 2019 global offering in U.S dollars. The Company does not use hedging instruments in its current
operations. Refer to Item 3.D. Risk Factors - Innate's business may be exposed to foreign exchange risks.
Interest rate risk
The Company has limited exposure to interest rate risk. Its exposure primarily relates to money market
funds and time deposit accounts. Changes in interest rates have a direct impact on the rate of return on
these investments and the cash flows generated. The Company does not have any credit facilities bearing
variable interest rates. The repayment of the advances from BPI France, the borrowings subscribed in
2017 and the two State Guaranteed Loans obtained in 2021 and extended in 2022, are not subject to
interest rate risk. The effect of an increase or decrease in interest rates would have an immaterial effect on
profit or loss.
Credit risk
The credit risk related to the cash equivalents, short-term investments and non-current financial assets is
not significant in light of the quality of the issuers. The Company deemed that no instrument of its
portfolio is exposed to credit risk.
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Item 12. Description of Securities Other than Equity Securities.
A. Debt Securities.
Not applicable.
B. Warrants and Rights.
Not applicable.
C. Other Securities.
Not applicable.
D. American Depositary Shares.
Citibank, N.A. acts as the depositary bank for the ADSs. Citibank’s depositary offices are located at 388
Greenwich Street, New York, New York 10013. ADSs represent ownership interests in securities that are
on deposit with the depositary bank. ADSs may be represented by certificates that are commonly known
as American Depositary Receipts, or ADRs. The depositary bank typically appoints a custodian to
safekeep the securities on deposit. In this case, the custodian is Citibank Europe plc, 1 North Wall Quay,
Dublin 1, Ireland.
The Company has appointed Citibank, N.A. as depositary bank pursuant to a deposit agreement. A copy
of the deposit agreement has been filed with the SEC under cover of a Registration Statement on Form
F-6 (Registration No. 333-234063). You may obtain a copy of the deposit agreement from the SEC’s
website at www.sec.gov.
Each ADS represents the right to receive, and to exercise the beneficial ownership interests in, one
ordinary share that is on deposit with the depositary bank and/or custodian. An ADS also represents the
right to receive, and to exercise the beneficial interests in, any other property received by the depositary
bank or the custodian on behalf of the owner of the ADS but that has not been distributed to the owners of
ADSs because of legal restrictions or practical considerations. The Company and the depositary bank may
agree to change the ADS-to-Share ratio by amending the deposit agreement. This amendment may give
rise to, or change, the depositary fees payable by ADS owners. The custodian, the depositary bank and
their respective nominees will hold all deposited property for the benefit of the holders and beneficial
owners of ADSs. The deposited property does not constitute the proprietary assets of the depositary bank,
the custodian or their nominees. Beneficial ownership in the deposited property will under the terms of
the deposit agreement be vested in the beneficial owners of the ADSs. The depositary bank, the custodian
and their respective nominees are the record holders of the deposited property represented by the ADSs
for the benefit of the holders and beneficial owners of the corresponding ADSs. A beneficial owner of
ADSs may or may not be the holder of ADSs. Beneficial owners of ADSs are able to receive, and to
exercise beneficial ownership interests in, the deposited property only through the registered holders of
the ADSs, the registered holders of the ADSs (on behalf of the applicable ADS owners) only through the
depositary bank, and the depositary bank (on behalf of the owners of the corresponding ADSs) directly, or
indirectly, through the custodian or their respective nominees, in each case upon the terms of the deposit
agreement.
If you are or become an owner of ADSs, you are or will become a party to the deposit agreement and
therefore are or will be bound to its terms and to the terms of any ADR that represents your ADSs. The
deposit agreement and the ADR specify the rights and obligations as well as your rights and obligations
as owner of ADSs and those of the depositary bank. As an ADS holder you appoint the depositary bank to
act on your behalf in certain circumstances. The deposit agreement and the ADRs are governed by New
226
York law. However, the obligations to the holders of ordinary shares will continue to be governed by the
laws of France, which may be different from the laws in the United States.
In addition, applicable laws and regulations may require you to satisfy reporting requirements and obtain
regulatory approvals in certain circumstances. You are solely responsible for complying with such
reporting requirements and obtaining such approvals. Neither the depositary bank, the custodian, Innate or
any of their or the respective agents or affiliates shall be required to take any actions whatsoever on your
227
behalf to satisfy such reporting requirements or obtain such regulatory approvals under applicable laws
and regulations.
Fees and Expenses
Pursuant to the terms of the amended and restated deposit agreement, the holders of the ADSs are
required to pay the following fees to the depositary bank:
Service
Issuance of ADSs (e.g., an issuance of ADS upon a
deposit of ordinary shares, upon a change in the ADSs-
to-ordinary shares ratio, or for any other reason),
excluding ADS issuances as a result of distributions of
ordinary shares)
Fees
Up to U.S. 5¢ per ADS issued
Cancellation of ADSs (e.g., a cancellation of ADSs for
delivery of deposited property, upon a change in the
ADSs-to ordinary shares ratio, or for any other reason)
Up to U.S. 5¢ per ADS cancelled
Distribution of cash dividends or other cash
distributions (e.g., upon a sale of rights and other
entitlements)
Up to U.S. 5¢ per ADS held
Distribution of ADSs pursuant to (i) stock dividends or
other free stock distributions, or (ii) exercise of rights to
purchase additional ADSs
Up to U.S. 5¢ per ADS held
Distribution of securities other than ADSs or rights to
purchase additional ADSs (e.g., upon a spin-off)
Up to U.S. 5¢ per ADS held
ADS Services
Registration of ADS transfers (e.g., upon a
registration of the transfer of registered ownership
of ADSs, upon a transfer of ADSs into DTC and
vice versa, or for any other reason)
Conversion of ADSs of one series for ADSs of
another series (e.g., upon conversion of Partial
Entitlement ADSs for Full Entitlement ADSs, or
upon conversion of Restricted ADSs (each as
defined in the Deposit Agreement) into freely
transferable ADSs, and vice versa).
Up to U.S. 5¢ per ADS held on the applicable record
date(s) established by the depositary bank
Up to U.S. 5¢ per ADS (or fraction thereof) transferred
Up to U.S. 5¢ per ADS (or fraction thereof) converted
ADS holders are responsible to pay certain charges such as:
•
taxes (including applicable interest and penalties) and other governmental charges;
228
•
•
•
•
•
the registration fees as may from time to time be in effect for the registration of ordinary shares on
the share register and applicable to transfers of ordinary shares to or from the name of the
custodian, the depositary bank or any nominees upon the making of deposits and withdrawals,
respectively;
certain cable, telex and facsimile transmission and delivery expenses;
the fees, expenses, spreads, taxes and other charges of the depositary bank and/or service providers
(which may be a division, branch or affiliate of the depositary bank) in the conversion of foreign
currency;
the reasonable and customary out-of-pocket expenses incurred by the depositary bank in connection
with compliance with exchange control regulations and other regulatory requirements applicable to
ordinary shares, ADSs and ADRs; and
the fees, charges, costs and expenses incurred by the depositary bank, the custodian, or any
nominee in connection with the ADR program.
ADS fees and charges for (i) the issuance of ADSs, and (ii) the cancellation of ADSs are charged to the
person for whom the ADSs are issued (in the case of ADS issuances) and to the person for whom ADSs
are cancelled (in the case of ADS cancellations). In the case of ADSs issued by the depositary bank into
DTC, the ADS issuance and cancellation fees and charges may be deducted from distributions made
through DTC, and may be charged to the DTC participant(s) receiving the ADSs being issued or the DTC
participant(s) holding the ADSs being cancelled, as the case may be, on behalf of the beneficial owner(s)
and will be charged by the DTC participant(s) to the account of the applicable beneficial owner(s) in
accordance with the procedures and practices of the DTC participants as in effect at the time. ADS fees
and charges in respect of distributions and the ADS service fee are charged to the holders as of the
applicable ADS record date. In the case of distributions of cash, the amount of the applicable ADS fees
and charges is deducted from the funds being distributed. In the case of (i) distributions other than cash
and (ii) the ADS service fee, holders as of the ADS record date will be invoiced for the amount of the
ADS fees and charges and such ADS fees and charges may be deducted from distributions made to
holders of ADSs. For ADSs held through DTC, the ADS fees and charges for distributions other than
cash and the ADS service fee may be deducted from distributions made through DTC, and may be
charged to the DTC participants in accordance with the procedures and practices prescribed by DTC and
the DTC participants in turn charge the amount of such ADS fees and charges to the beneficial owners for
whom they hold ADSs. In the case of (i) registration of ADS transfers, the ADS transfer fee will be
payable by the ADS Holder whose ADSs are being transferred or by the person to whom the ADSs are
transferred, and (ii) conversion of ADSs of one series for ADSs of another series, the ADS conversion fee
will be payable by the Holder whose ADSs are converted or by the person to whom the converted ADSs
are delivered.
In the event of refusal to pay the depositary bank fees, the depositary bank may, under the terms of the
deposit agreement, refuse the requested service until payment is received or may set off the amount of the
depositary bank fees from any distribution to be made to the ADS holder. Note that the fees and charges
you may be required to pay may vary over time and may be changed by Innate and by the depositary
bank. You will receive prior notice of such changes. The depositary bank may reimburse Innate for
certain expenses incurred by Innate Pharma in respect of the ADR program, by making available a
portion of the ADS fees charged in respect of the ADR program or otherwise, upon such terms and
conditions as the Company and the depositary bank agree from time to time.
229
Payment of Taxes
ADS holders are responsible for the taxes and other governmental charges payable on the ADSs and the
securities represented by the ADSs. We, the depositary bank and the custodian may deduct from any
distribution the taxes and governmental charges payable by holders and may sell any and all property on
deposit to pay the taxes and governmental charges payable by holders. You are be liable for any
deficiency if the sale proceeds do not cover the taxes that are due.
The depositary bank may refuse to issue ADSs, to deliver, transfer, split and combine ADRs or to release
securities on deposit until all taxes and charges are paid by the applicable holder. The depositary bank and
the custodian may take reasonable administrative actions to obtain tax refunds and reduced tax
withholding for any distributions on your behalf. However, you may be required to provide to the
depositary bank and to the custodian proof of taxpayer status and residence and such other information as
the depositary bank and the custodian may require to fulfill legal obligations. You are required to
indemnify us, the depositary bank and the custodian for any claims with respect to taxes based on any tax
benefit obtained for you.
Depositary Payments for 2022
Not applicable.
PART II
Item 13. Defaults, Dividend Arrearages and Delinquencies.
Not applicable.
Item 14. Material Modifications to the Rights of Security Holders and Use of Proceeds.
October 2019 Global Offering
In October 2019, the Company completed a global offering of an aggregate of 14,375,000 ordinary
shares, including the full exercise of the underwriters’ option to purchase 1,875,000 additional ordinary
shares. The October 2019 global offering consisted of a U.S. initial public offering of 8,047,227 ordinary
shares in the form of American Depositary Shares, each representing one ordinary share, at an offering
price of $5.50 per ADS and a concurrent private placement in Europe and other countries outside of the
United States and Canada of 4,452,773 ordinary shares at an offering price of €4.97 per ordinary share for
aggregate gross proceeds to Innate of approximately $79.1 million (€71.4 million). The net proceeds to
us, after deducting underwriting discounts and commissions and offering expenses, were approximately
€66.0 million. The offering commenced on October 17, 2019 and did not terminate before all of the
securities registered in the registration statement were sold. The effective date of the registration
statement, File No. 333-233865, for the October 2019 global offering was October 16, 2019.
Citigroup Global Markets Inc., SVB Leerink LLC and Evercore Group L.L.C. acted as representatives of
the underwriters in the U.S. offering. Citigroup Global Markets Limited acted as a representative in the
European private placement.
The net proceeds from the October 2019 global offering have been used, and are expected to continue to
be used, as described in the final prospectus for the October 2019 global offering filed with the U.S.
Securities and Exchange Commission on October 16, 2019.
None of the net proceeds of the October 2019 global offering were paid directly or indirectly to any
director, officer, general partner of Innate Pharma or to their associates, persons owning ten percent or
more of any class of the equity securities, or to any of the affiliates.
230
Item 15. Controls and Procedures.
Disclosure Controls and Procedures
Management, with the participation of our Chief Executive Officer (principal executive officer) and the
Chief Financial Officer (principal financial officer), after evaluating the effectiveness of the disclosure
controls and procedures (as defined in Exchange Act Rules 13a-15(e) and 15d-15(e)), as of December 31,
2022, have concluded that, the disclosure controls and procedures were not effective as of December 31,
2022 as a result of the material weakness described below.
Management’s Annual Report on Internal Control over Financial Reporting
The management is responsible for establishing and maintaining adequate internal controls over financial
reporting, as such terms is defined in Exchange Act Rule 13a-15(f) and 15d-15(f) for the assessment of
the effectiveness of our internal control over financial reporting. Because of its inherent limitations,
internal control over financial reporting may not prevent or detect misstatements. Also, projections of any
evaluation of effectiveness to future periods are subject to the risk that controls may become inadequate
because of changes in conditions, or that the degree of compliance with the policies or procedures may
deteriorate.
Under the supervision and with the participation of our Chief Executive Officer (principal executive
officer) and the Chief Financial Officer (principal financial officer), the management conducted an
evaluation of internal control over financial reporting based upon the criteria established in internal
Control — Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the
Treadway Commission (COSO).
Based on evaluation under these criteria, management determined, based upon the existence of the
material weakness described below, that the Company did not maintain effective internal control over
financial reporting as of December 31, 2022.
The control deficiencies identified are due to a lack of granularity and precision of the design and,
constitute a material weakness in the aggregate primarily relating to:
•
•
prevention or detection of material errors in the classification and presentation of the consolidated
financial statements, and related disclosures
recording of all third-party services in the correct period.
The deficiencies in control activities contributed to errors related to misclassification and presentation
which have been identified and have been corrected throughout 2022 and during the year-end closing.
Management’s Plan for Remediation of Current Material Weakness
The company will enhance the design of its controls activities to apply a lower level of granularity to
avoid any material errors in the presentation of the consolidated financial statements, related disclosures,
and in relation to cutoff, in particular:
•
•
Implementing an automated control in its ERP requesting an approval of any receipt with
different allocation from the Purchase Order to avoid any misclassification between General &
Administration and Research & Development.
Simplifying and strengthening the validation of the data collection from the Company’s alliance
partners to ensure a proper classification of future debt evolution between current and non-current
in the balance sheet.
231
•
Improving existing controls to include a review of open Purchase Orders without any receipts to
make sure that all third party services are recorded in the correct period.
Notwithstanding such material weakness, management has concluded that the financial statements
included elsewhere in this Annual Report present fairly, in all material respects, the financial position,
results of operations and cash flows for the periods presented in conformity with IFRS.
The Company cannot give assurance that the measures taken to remediate the material weakness will be
sufficient or that they will prevent future material weaknesses. As management continues to evaluate and
work to improve the Company’s internal control over financial reporting, the Company may determine it
necessary to take additional measures or modify the remediation plan described above. The material
weaknesses cannot be considered remediated until the applicable controls operate for a sufficient period
of time and management has concluded, through testing, that these controls are operating effectively.
Attestation Report of the Registered Public Accounting Firm
This Annual Report does not include an attestation report of our registered public accounting firm due to
a transition period established by rules of the Securities and Exchange Commission for emerging growth
companies.
Changes in Internal Control over Financial Reporting
Except for the identification of the material weakness above, there were no changes in the Company’s
internal control over financial reporting during the year ended December 31, 2022 that have materially
affected, or are reasonably likely to materially affect, our internal control over financial reporting.
Item 16. Reserved.
Not applicable.
Item 16A. Audit Committees Financial Expert.
Innate's Supervisory board has determined that Pascale Boissel is an audit committee financial expert as
defined by SEC rules and regulations and each of the members of the board of directors has the requisite
financial sophistication under the applicable rules and regulations of the Nasdaq Stock Market. Pascale
Boissel, Dr. Staatz-Granzer and Dr. Sally Bennett are independent as such term is defined in Rule 10A-3
under the Exchange Act and under the listing standards of the Nasdaq Stock Market.
Item 16B. Code of Business Conduct and Ethics.
The Company has adopted a Code of Business Conduct and Ethics, or the Code of Ethics, that is
applicable to all of its employees, executive officers and directors. A copy of the Code of Ethics is
available on its website at www. investors.innate-pharma.com. The audit committee of its Supervisory
board is responsible for overseeing the Code of Ethics and must approve any waivers of the Code of
Ethics for employees, executive officers and directors. The Company expects that any amendments to the
Code of Ethics, or any waivers of its requirements, will be disclosed on its website.
Item 16C. Principal Accountant Fees and Services.
Deloitte & Associés, has served as the independent registered public accounting firm for 2021 and 2022.
The accountants billed the following fees to Innate for professional services in each of those fiscal years,
all of which were approved by the audit committee:
232
(in thousands of euro)
Audit fees
Non-audit fees
Total
Year ended December 31,
2021
2022
Deloitte & Associés Deloitte & Associés
855
248
1,103
702
78
780
“Audit fees” are the aggregate fees billed for the audit of the annual financial statements. This category
also includes services that Deloittes & Associés provides, such as consents and assistance with and review
of documents filed with the SEC.
“Non-audit fees” are the aggregate fees billed for services related to the production of certification in the
context of the declaration of expenses for the obtention of grants and the preparation of special reports
relating to certain operations on the Company’s capital. There were no tax fees included in "non-audit
fees" as of December 2020 and 2021, respectively.
Audit and Non-Audit Services Pre-Approval Policy
The audit committee has responsibility for appointing, setting compensation of and overseeing the work
of the independent registered public accounting firm. In recognition of this responsibility, the audit
committee has adopted a policy governing the pre-approval of all audit and permitted non-audit services
performed by the independent registered public accounting firm to ensure that the provision of such
services does not impair the independent registered public accounting firm’s independence from Innate
and the management. Unless a type of service to be provided by the independent registered public
accounting firm has received general pre-approval from the audit committee, it requires specific pre-
approval by the audit committee. The payment for any proposed services in excess of pre-approved cost
levels requires specific pre-approval by the audit committee.
Pursuant to its pre-approval policy, the audit committee may delegate its authority to pre-approve services
to the chairperson of the audit committee. The decisions of the chairperson to grant pre-approvals must be
presented to the full audit committee at its next scheduled meeting. The audit committee may not delegate
its responsibilities to pre-approve services to the management.
The audit committee has considered the non-audit services provided by Deloitte & Associés as described
above and believes that they are compatible with maintaining Deloitte & Associés’s independence as the
independent registered public accounting firm.
Item 16D. Exemptions from the Listing Standards for Audit Committees.
Not applicable.
Item 16E. Purchases of Equity Securities by the Issuer and Affiliated Purchasers.
Not applicable.
Item 16F. Change in Registrant’s Certifying Accountant.
Not applicable.
233
Item 16G. Corporate Governance.
As a French société anonyme, the Company is subject to various corporate governance requirements
under French law. The Company is a “foreign private issuer” under the U.S. federal securities laws and
the Nasdaq listing rules. The foreign private issuer exemption will permit Innate to follow home country
corporate governance practices instead of certain Nasdaq listing requirements. A foreign private issuer
that elects to follow a home country practice instead of Nasdaq listing requirements must submit to
Nasdaq a written statement from an independent counsel in such issuer’s home country certifying that the
issuer’s practices are not prohibited by the home country’s laws.
The Company applies the Middlenext code, which recommends that at least two members of the
Supervisory Board be independent (as such term is defined under the code). Neither the corporate laws of
France nor the bylaws requires that (i) each committee of the Supervisory Board have a formal written
charter or (iii) the independent members of the Supervisory Board hold regularly scheduled meetings at
which only independent members of the Supervisory Board are present. The Company intends to follow
French corporate governance practices in lieu of Nasdaq listing requirements for each of the foregoing.
These exemptions do not modify the independence requirements for the audit committee, since September
2020, the Company complies with the requirements of the Sarbanes-Oxley Act and the Nasdaq listing
rules, which require that its audit committee be composed of at least three independent members. Rule
10A-3 under the Exchange Act provides that the audit committee must have direct responsibility for the
nomination, compensation and choice of the auditors, as well as control over the performance of their
duties, management of complaints made, and selection of consultants. Under Rule 10A-3, if the laws of a
foreign private issuer’s home country require that any such matter be approved by the board of directors
or the shareholders of the Company, the audit committee’s responsibilities or powers with respect to such
matter may instead be advisory. Under French law, the audit committee may only have an advisory role
and appointment of the statutory auditors, in particular, must be decided by the shareholders at the annual
meeting.
In addition, Nasdaq rules require that a listed company specify that the quorum for any meeting of the
holders of share capital be at least 33 1/3% of the outstanding shares of the company’s ordinary voting
shares. The Company intends to follow its French home country practice, rather than complying with this
Nasdaq rule. Consistent with French Law, its bylaws provide that when first convened, general meetings
of shareholders may validly convene only if the shareholders present or represented hold at least (1) 20%
of the voting shares in the case of an ordinary general meeting or of an extraordinary general meeting
where shareholders are voting on a capital increase by capitalization of reserves, profits or share
premium, or (2) 25% of the voting shares in the case of any other extraordinary general meeting. If such
quorum required by French law is not met, the meeting is adjourned. There is no quorum requirement
under French law when an ordinary general meeting or an extraordinary general meeting is reconvened
where shareholders are voting on a capital increase by capitalization of reserves, profits or share
premium, but the reconvened meeting may consider only questions that were on the agenda of the
adjourned meeting. When any other extraordinary general meeting is reconvened, the required quorum
under French law is 20% of the shares entitled to vote. If a quorum is not met at a reconvened meeting
requiring a quorum, then the meeting may be adjourned for a maximum of two months.
Item 16H. Mine Safety Disclosure.
Not applicable.
PART III
234
Item 17. Financial Statements.
See the financial statements beginning on page F-l of this Annual Report.
Item 18. Financial Statements.
Not applicable.
Item 19. Exhibits.
The exhibits listed below are filed as exhibits to this Annual Report.
The following exhibits are filed as part of this Annual Report:
Exhibit
Number
1.1*
2.1
2.2
4.1†
4.2†
4.3†
4.4†
4.5†
4.6†
4.7†
4.8†
8.1
Description of Exhibit
Schedule/
Form
File Number Exhibit
File Date
By-laws (status) of the registrant (English
translation)
Form of Deposit Agreement
Form of American Depositary Receipt (included in
Exhibit 2.1)
Co-Development and License Agreement between
Innate Pharma S.A. and MedImmune Limited,
dated April 24, 2015, as amended to date.
Termination and Transition Agreement, between
Innate Pharma SA. and MedImmune Limited, dated
30 June 2021, as amended to date
Amendment and Restatement Agreement of the
Collaboration and Option Agreement Relating to
CD39, between Innate Pharma S.A. and
MedImmune Limited, dated April 16, 2019.
Joint Research, Development, Option and License
Agreement between Innate Pharma S.A. and Novo
Nordisk A/S, dated March 28, 2006, as amended to
date.
Finance Lease Agreement between Innate Pharma
S.A. and Sogebail S.A., dated June 9, 2008
(English translation).
Amendment to Finance Lease Agreement between
Innate Pharma S.A. and Sogebail S.A., dated
September 29, 2016 (English translation).
Loan Agreement with Société Générale, dated
December 22nd, 2021 (English translation)
Loan Agreement with BNP Paribas, dated
December 17th 2021 (English translation)
List of subsidiaries of the registrant
F-1 333-233865
4.1
10/04/19
F-1 333-233865
4.2
10/04/19
F-1 333-233865
10.1
09/20/19
20-F
001-39084
4.2
04/04/22
F-1 333-233865
10.3
09/20/19
F-1 333-233865
10.4
09/20/19
F-1 333-233865
10.5
09/20/19
F-1 333-233865
10.6
09/20/19
20-F
001-39084
4.7
04/04/22
20-F
001-39084
4.8
04/04/22
F-1 333-233865
21.1
09/20/19
12.1*
Certificate of Principal Executive Officer pursuant
to Securities Exchange Act Rules 13a-14(a) and
15d-14(a) as adopted pursuant to Section 302 of the
Sarbanes-Oxley Act of 2002
235
Exhibit
Number
12.2*
13.1**
15.1
Description of Exhibit
Schedule/
Form
File Number Exhibit
File Date
Certification by the Principal Financial Officer
pursuant to Securities Exchange Act Rules
13a-14(a) and 15d-14(a) as adopted pursuant to
Section 302 of the Sarbanes-Oxley Act of 2002
Certification by the Principal Executive Officer and
the Principal Financial Officer pursuant to 18
U.S.C. Section 1350, as adopted pursuant to
Section 906 of the Sarbanes-Oxley Act of 2002
Consent of Deloitte & Associés
101.INS* XBRL Instance Document
101.SCH* XBRL Taxonomy Extension Schema Document
101.CAL* XBRL Taxonomy Extension Calculation Linkbase
Document
101.DEF* XBRL Taxonomy Extension Definition Linkbase
Document
101.LAB* XBRL Taxonomy Extension Label Linkbase
Document
101.PRE* XBRL Taxonomy Extension Presentation Linkbase
Document
*
Filed herewith.
** Furnished herewith.
† Certain portions of this exhibit have been omitted because they are not material and would likely cause competitive harm to the registrant
if disclosed
236
The registrant hereby certifies that it meets all of the requirements for filing on Form 20-F and that it has
duly caused and authorized the undersigned to sign this annual report on its behalf.
SIGNATURES
Innate Pharma S.A.
By: /s/ Mondher Mahjoubi, M.D.
Name: Mondher Mahjoubi, M.D.
Title: Chief Executive Officer
Date: April 5, 2023
237
INDEX TO CONSOLIDATED FINANCIAL STATEMENTS
Consolidated Financial Statements as of and for the Years Ended December 31, 2020, 2021 and 2022
Report of Independent Registered Public Accounting Firm (PCAOB: 1756)
Consolidated Statements of Financial Position as of December 31, 2020, 2021 and 2022
Consolidated Statements of Income (Loss) for the Years Ended December 31, 2020, 2021 and 2022
Consolidated Statements of Comprehensive Income (Loss) for the Years Ended December 31, 2020, 2021 and
2022
Consolidated Statements of Cash Flows for the Years Ended December 31, 2020, 2021 and 2022
Consolidated Statements of Changes in Shareholders’ Equity for the Years Ended December 31, 2020, 2021 and
2022
Notes to the Consolidated Financial Statements
F-1
REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
To the shareholders and the Board of Directors of Innate Pharma
Opinion on the Financial Statements
We have audited the accompanying consolidated statements of financial position of Innate Pharma S.A.
and subsidiaries (the "Company") as of December 31, 2022, 2021 and 2020, the related consolidated
statements of income (loss), comprehensive income (loss), cash flows and changes in shareholders'
equity, for each of the three years in the period ended December 31, 2022, and the related notes
(collectively referred to as the "financial statements"). In our opinion, the financial statements present
fairly, in all material respects, the financial position of the Company as of December 31, 2022, 2021 and
2020, and the results of its operations and its cash flows for each of the three years in the period ended
December 31, 2022, in conformity with International Financial Reporting Standards as issued by the
International Accounting Standards Board (IASB).
Basis for Opinion
These financial statements are the responsibility of the Company's management. Our responsibility is to
express an opinion on the Company's financial statements based on our audits. We are a public
accounting firm registered with the Public Company Accounting Oversight Board (United States)
(PCAOB) and are required to be independent with respect to the Company in accordance with the U.S.
federal securities laws and the applicable rules and regulations of the Securities and Exchange
Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that
we plan and perform the audit to obtain reasonable assurance about whether the financial statements are
free of material misstatement, whether due to error or fraud. The Company is not required to have, nor
were we engaged to perform, an audit of its internal control over financial reporting. As part of our audits,
we are required to obtain an understanding of internal control over financial reporting but not for the
purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial
reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the financial
statements, whether due to error or fraud, and performing procedures that respond to those risks. Such
procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the
financial statements. Our audits also included evaluating the accounting principles used and significant
estimates made by management, as well as evaluating the overall presentation of the financial statements.
We believe that our audits provide a reasonable basis for our opinion.
/s/ Deloitte & Associés
Paris La Défense, France
April 5, 2023
We have served as the Company's auditor since 2014.
F-2
CONSOLIDATED STATEMENTS OF FINANCIAL POSITION
(amounts in thousands of euro)
Year Ended December 31,
Note
2020
2021
2022
ASSETS
Non-current assets
Intangible assets
Property and equipment
Non-current financial assets
Other non-current assets
Trade receivables and others - non-current
Deferred tax assets
Total non-current assets
Current assets
Cash and cash equivalents
Short-term investments
Trade receivables and others - current
Total current assets
TOTAL ASSETS
LIABILITIES AND SHAREHOLDERS' EQUITY
Shareholders' equity
Share capital
Share premium
Retained earnings
Other reserves
Net income (loss)
Total shareholders’ equity
Non-current liabilities
Collaboration liabilities – non-current portion
Financial liabilities – non-current portion
Defined benefit obligations
Deferred revenue – non-current portion
Provisions – non-current portion
Deferred tax liabilities
Total non-current liabilities
Current liabilities
Trade payables and others
Collaboration liabilities – current portion
Financial liabilities – current portion
Deferred revenue – current portion
Provisions – current portion
Total current liabilities
6
7
4
5
17
4
4
5
11
11
13
9
10
13
18
17
8
13
9
13
18
46,289
11,694
38,934
147
29,821
7,087
133,972
136,792
14,845
21,814
173,451
307,423
44,192
10,174
39,878
148
29,821
5,028
129,241
103,756
16,080
18,420
138,256
267,496
1,556
8,542
35,119
149
14,099
8,568
68,033
84,225
17,260
38,346
139,831
207,863
3,950
372,131
(156,476)
355
(63,984)
155,976
3,978
375,220
(219,404)
456
(52,809)
107,440
4,011
379,637
(272,213)
819
(58,103)
54,151
44,854
16,945
4,177
32,674
221
7,087
105,959
29,539
1,832
2,142
11,299
676
45,488
32,997
13,503
2,975
25,413
253
5,028
80,169
28,573
7,418
30,748
12,500
647
79,886
52,988
40,149
2,550
7,921
198
8,568
112,374
20,911
10,223
2,102
6,560
1,542
41,338
TOTAL LIABILITIES AND SHAREHOLDERS'
EQUITY
307,423
267,496
207,863
F-3
CONSOLIDATED STATEMENTS OF INCOME (LOSS)
(amounts in thousands of euro, except share and per share data)
Year ended December 31,
Note
2020(1)
2021
2022
Revenue and other income
Revenue from collaboration and licensing agreements
Government financing for research expenditures
Other income
Total revenue and other income
Operating expenses
Research and development expenses
General and administrative expenses
Impairment of intangible assets
Total operating expenses
Net income (loss) from distribution agreements
Operating income (loss)
Financial income
Financial expenses
Net financial income (loss)
Net income (loss) before tax
Income tax expense
Net income (loss) from continuing operations
Net income (loss) from discontinued operations
Net income (loss)
Basic income (loss) per share (€/share)
Diluted income (loss) per share (€/share)
- Basic income (loss) per share from continuing operations
- Diluted income (loss) per share from continuing operations
- Basic income (loss) per share from discontinued operations
- Diluted income (loss) per share from discontinued
operations
13
13
14
14
6
15
15
16
17
20
20
20
20
20
20
56,155
12,112
49,580
13,618
12,591
8,035
—
—
59
69,773
24,703
57,674
(49,708)
(47,004)
(51,663)
(18,986)
(25,524)
(22,436)
—
—
(41,000)
(68,694)
(72,528)
(115,099)
—
—
—
1,079
(47,825)
(57,425)
4,855
6,344
4,775
(6,763)
(3,997)
(5,321)
(1,908)
2,347
(546)
(829)
(45,478)
(57,972)
—
—
—
(829)
(45,478)
(57,972)
(63,155)
(7,331)
(131)
(63,984)
(52,809)
(58,103)
(0.81)
(0.81)
(0.66)
(0.66)
(0.73)
(0.73)
(0.01)
(0.57)
(0.73)
(0.01)
(0.57)
(0.73)
(0.80)
(0.09)
(0.80)
(0.09)
—
—
(1) The 2020 comparatives has been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17 of our consolidated financial statements appearing elsewhere in this Annual Report.
F-4
CONSOLIDATED STATEMENTS OF COMPREHENSIVE INCOME (LOSS)
(amounts in thousands of euro)
(In thousands of euro)
Year Ended December 31,
Net income (loss) for the period
Elements which will be reclassified in the consolidated
statement of income (loss):
Change in fair value of short-term investments and non-
current financial assets
Foreign currency translation gain (loss)
Items which will not be reclassified in the consolidated
statement of income (loss):
Actuarial gains and (losses) related to defined benefit
obligations
Other comprehensive income (loss)
Total comprehensive income (loss)
Note
2020
2021
2022
(63,984)
(52,809)
(58,103)
4
10
—
222
—
(483)
—
(428)
(200)
22
(63,962)
584
101
(52,708)
790
362
(57,741)
F-5
CONSOLIDATED STATEMENT OF CASH FLOWS
(amounts in thousands of euro)
Net income (loss)
Reconciliation of the net income (loss) and the cash
generated from (used for) the operating activities
Depreciation and amortization, net
Employee benefits costs
Provisions for charges
Share-based compensation expense
Change in fair value of financial assets
Foreign exchange (gains) losses on financial assets
Change in accrued interests on financial assets
Gains (losses) on assets and other financial assets
Interest paid
Other profit or loss items with no cash effect
Operating cash flow before change in working capital
Change in working capital
Net cash generated from / (used in) operating activities
Acquisition of intangible assets
Acquisition of property and equipment, net
Purchase of non-current financial instruments
Disposal of property and equipment
Disposal of other assets
Acquisition of other assets
Disposal of non-current financial instruments
Interest received on financial assets
Net cash generated from / (used in) investing activities
Proceeds from
instruments
Proceeds from borrowings
Repayment of borrowings
Net interest paid
Net cash generated from / (used in) financing activities
Effect of the exchange rate changes
Net increase / (decrease) in cash and cash equivalents
Cash and cash equivalents at the beginning of the year
Cash and cash equivalents at the end of the year
/ subscription of equity
the exercise
Year Ended December 31,
Note
2020
2021
2022
(63,984)
(52,809)
(58,103)
6, 7
10
14
4
4
4
16
6.8
7.8
4
4
4
9
9
4
4
56,797
216
604
2,475
577
1,256
372
(962)
341
(254)
(2,562)
(49,206)
(51,767)
(10,375)
(907)
(3,000)
9
—
(59)
—
962
(13,370)
48
1,360
(2,245)
(341)
(1,177)
219
(66,096)
202,887
136,792
4,596
437
4
2,617
(987)
(1,136)
(55)
(367)
312
(1,185)
(48,573)
(9,884)
(58,457)
(401)
(929)
—
7
40
(1)
—
367
(917)
499
28,700
(2,069)
(312)
26,818
(483)
(33,037)
136,792
103,756
45,405
365
839
4,249
1,372
(912)
118
—
—
15
(6,652)
(12,502)
(19,154)
(587)
(535)
—
—
—
(1)
3,000
—
1,877
198
—
(2,026)
—
(1,828)
(428)
(19,531)
103,756
84,225
F-6
Change in working capital
Note
December 31,
2021
December 31,
2022
Variance
Trade receivables and others (excluding rebates related to
capital expenditures)
Trade payables and others (excluding payables related to
capital expenditures)
Collaboration liabilities - current and non-current portion
Deferred revenue - current and non-current portion
Change in working capital
5
8
13
13
48,241
52,445
(4,204)
(28,573)
(20,911)
(7,662)
(40,415)
(37,913)
(58,660)
(63,211)
(14,481)
(46,158)
22,796
(23,432)
(12,502)
Change in working capital
Note
December 31,
2020
December 31,
2021
Variance
Trade receivables and others (excluding rebates related to
capital expenditures)
Trade payables and others (excluding payables related to
capital expenditures)
Collaboration liabilities - current and non-current portion
Deferred revenue - current and non-current portion
Change in working capital
5
8
13
13
51,635
48,241
3,394
(29,519)
(28,573)
(946)
(46,686)
(43,973)
(68,543)
(40,415)
(37,913)
(58,660)
(6,271)
(6,060)
(9,884)
F-7
CONSOLIDATED STATEMENT OF CHANGES IN SHAREHOLDERS’ EQUITY
(amounts in thousands of euro, except share data)
December 31, 2019
Net loss
Actuarial gains on defined benefit
obligations
Foreign currency translation gain
Total comprehensive income (loss)
Allocation of prior period loss
Exercise and subscription of equity
instruments
Increase capital, net
Share-based payment
December 31, 2020
Net loss
Actuarial losses on defined benefit
obligations
Foreign currency translation loss
Total comprehensive income (loss)
Impact of applying IFRIC agenda
decision on IAS 19 (1)
Allocation of prior period loss
Exercise and subscription of equity
instruments
Increase capital, net
Share-based payment
December 31, 2021
Net loss
Actuarial gains on defined benefit
obligations
Foreign currency translation gain
Total comprehensive income (loss)
Allocation of prior period loss
Exercise and subscription of equity
instruments
Increase capital, net
Share-based payment
December 31, 2022
Note
Number
of shares
78,825,621
Share
capital
3,941
Share
premiu
m
369,617
Retained
earnings
(134,912)
Other
reserves
(472)
Net
income
(loss)
(20,759)
Total
Equity
217,416
—
—
—
—
—
175,331
—
—
—
—
—
—
—
9
—
—
—
—
—
—
—
38
—
2,476
—
—
(805)
(805)
(20,759)
—
—
79,000,952
3,950
372,131
(156,476)
—
—
—
—
—
—
555,770
—
—
10
—
—
—
—
—
—
28
—
—
—
—
—
—
—
—
471
—
2,617
—
—
—
1,054
(63,984)
—
—
79,556,722
3,978
375,220
(219,404)
—
—
—
—
—
11
11
11.14
669,442
—
—
—
—
—
—
—
34
—
—
—
—
—
—
—
168
—
4,249
—
—
—
—
(52,809)
—
—
—
(63,984)
(63,984)
(200)
1,027
—
—
(200)
222
827
—
—
—
355
—
(63,984)
(63,962)
20,759
—
—
—
47
—
2,476
(63,984)
155,976
(52,809)
(52,809)
584
(483)
101
—
—
584
(483)
(52,809)
(52,708)
—
—
—
—
—
63,984
—
—
1,054
—
499
—
2,617
456
—
(52,809)
107,440
(58,103)
(58,103)
790
(428)
362
—
—
—
—
—
—
790
(428)
(58,103)
(57,741)
52,809
—
—
—
202
—
4,249
54,151
80,226,164
4,011
379,637
(272,213)
819
(58,103)
(1) This restatement represents the impact of the change in accounting method following the IFRIC (International Financial Reporting
Interpretations Committee) opinion validated by the IAS Board in June 2021, according to which the method for measuring the obligations
of certain retirement benefit plans must be modified. The details of this change in method are presented in note 10.
F-8
Note 1: The company
NOTES TO FINANCIAL STATEMENTS
Innate Pharma S.A. is a global, clinical-stage biotechnology company developing immunotherapies for
cancer patients. Its innovative approach aims to harness the innate immune system through therapeutic
antibodies and its ANKET® (Antibody-based NK cell Engager Therapeutics) proprietary platform.
Innate’s portfolio includes lead proprietary program lacutamab, developed in advanced form of cutaneous
T cell lymphomas and peripheral T cell lymphomas, monalizumab developed with AstraZeneca in non
small cell lung cancer, as well as ANKET® multi-specific NK cell engagers to address multiple tumor
types. The Company has developed, internally and through its business development strategy, a broad and
diversified portfolio including five clinical product candidates and a robust preclinical pipeline. Innate has
entered into collaborations with leaders in the biopharmaceutical industry, such as AstraZeneca and
Sanofi. Innate Pharma believes its product candidates and clinical development approach are
differentiated from current immuno-oncology therapies and have the potential to significantly improve the
clinical outcome for patients with cancer.
From its inception, the Company has incurred losses due to its research and development (“R&D”)
activity. The financial year ended December 31, 2022 generated a €58,103 thousand net loss. As of
December 31, 2022, the shareholders’ equity amounted to €54,151 thousand. Subject to potential new
milestone payments related to its collaboration agreements, the Company anticipates incurring additional
losses until such time, if ever, that it can generate significant revenue from its product candidates in
development.
The Company’s future operations are highly dependent on a combination of factors, including: (i) the
success of its R&D; (ii) regulatory approval and market acceptance of the Company’s future product
candidates; (iii) the timely and successful completion of additional financing; and (iv) the development of
competitive therapies by other biotechnology and pharmaceutical companies. As a result, the Company is
and should continue, in the short to mid-term, to be financed through partnership agreements for the
development and commercialization of its drug candidates and through the issuance of new equity
instruments.
The Company’s activity is not subject to seasonal fluctuations.
As of December 31, 2022, the Company had one wholly owned subsidiary: Innate Pharma, Inc.,
incorporated under the laws of Delaware in 2009.
This subsidiary is fully consolidated.
1.1.
Significant contracts
The following paragraphs describe the key provisions of significant contracts.
a)
Agreements related to monalizumab with Novo Nordisk A/S and with AstraZeneca
2014 Novo Nordisk A/S monalizumab agreement
On February 5, 2014, the Company acquired from Novo Nordisk A/S full development and
commercialization rights to monalizumab. Novo Nordisk A/S received €2.0 million in cash and 600,000
ordinary shares at a price of €8.33 per share (€5.0 million). Novo Nordisk A/S is eligible to receive up to
€20.0 million in potential regulatory milestones and single-digit tiered royalties on sales of monalizumab
products. The agreement with Novo Nordisk A/S included a right to additional consideration in the event
of an out-licensing agreement. Consequently, following the agreement signed with AstraZeneca in April
F-9
2015 (as described below), the Company paid to Novo Nordisk A/S additional consideration of
€6.5 million (paid in April 2016). Following the exercise of the option by AstraZeneca in October 2018
(as described below), Novo Nordisk A/S became entitled to a second and final additional payment
amounting to $15.0 million (€13.1 million) which was recognized as a liability as of December 31, 2018
and was paid in February 2019. There are no other potential additional milestones payments due to Novo
Nordisk A/S. These amounts were added to the net book value of the intangible asset and are amortized
according to the same amortization plan as the initial €7.0 million recognized in 2014. The net book value
of the license amounted to €1.6 million as of December 31, 2022.
Refer to Notes 2.h, 2.i and 6 for accounting description.
2015 AstraZeneca monalizumab agreements
Under co-development and option agreements signed with AstraZeneca in 2015, the Company granted to
AstraZeneca an exclusive license, subject to certain exclusions, to certain of its patents and know-how to
develop, manufacture and commercialize licensed products, including monalizumab, in the field of
diagnosis, prevention and treatment of oncology diseases and conditions. The Company further granted to
AstraZeneca a worldwide, non-exclusive license to certain of its other patents to develop, manufacture
and commercialize licensed products, including monalizumab, in the field of diagnosis, prevention and
treatment of oncology diseases and conditions.
The Company received an initial payment of $250 million under these agreements in June 2015, of which
$100 million was paid to the Company as an initial payment for the co-development agreement and
$150 million was paid to the Company as consideration for the option agreement. On October 22, 2018,
AstraZeneca exercised this option, triggering the payment of $100.0 million, which was received by the
Company in January 2019.
Following the option exercise, AstraZeneca became the lead party in developing the licensed products
and must use commercially reasonable efforts to develop, obtain regulatory approval for and
commercialize each licensed product in certain major markets.
In July 31, 2019, the Company notified AstraZeneca of its decision to co-fund a future monalizumab
Phase 3 clinical development program.
In September 2020, the Company signed an amendment to the collaboration and license agreement
concluded with AstraZeneca in 2015. Following the analysis of a longer patient follow-up as well as the
maturation of the survival data of the Cohort 2, and after discussion with AstraZeneca, the Company
agreed to amend the original agreement. This amendment changed the financial terms relating to the
milestone payment expected following the treatment of the first patient with AstraZeneca in the first
Phase 3 trial evaluating monalizumab. The original agreement signed in 2015 provided for a milestone
payment of $100 million. Following the inclusion by AstraZeneca of the first patient in the first Phase 3
trial evaluating monalizumab (INTERLINK-1) in October 2020, and in accordance with the amendment
signed in September 2020, the Company received a payment of $50 million . An additional payment of
$50 million was subject to an interim analysis. On August 1, 2022, the Company announced that the
combination of monalizumab and cetuximab did not reach the pre-specified efficacy threshold in the
protocol-planned interim futility analysis of the Phase 3 INTERLINK-1 clinical study conducted by
AstraZeneca. AstraZaneca has thus informed the Company that the study will be discontinued.
Consequently, the Company is not eligible for the additional payment of $50.0 million as provided for in
the amendment signed in September 2020.
F-10
On June 2022, the Company received an additionnal payment of $50.0 million from AstraZeneca
following the inclusion of the first patient in the second trial evaluating monalizumab, on April 2022
("PACIFIC-9").
In addition to the initial payment, the option exercise payment and the payment received for the inclusion
of the first patient in the first Phase 3 trial, AstraZeneca is obligated to pay the Company up to
$775 million in the aggregate upon the achievement of certain development and regulatory milestones
($350 million) and commercialization milestones ($425 million). The Company is eligible to receive
tiered royalties ranging from a low double-digit to mid-teen percentage on net sales of licensed products
outside of Europe. The Company is required for a defined period of time to co-fund 30% of the Phase 3
clinical trials of licensed products, subject to an aggregate cap, in order to receive 50% of the profits in
Europe.
Refer to Notes 2.a, 2.p and 13.a for accounting description.
b)
Agreement related to Lumoxiti with AstraZeneca
In October 2018, the Company obtained an exclusive license from AstraZeneca under certain patents and
know-how to develop, manufacture and commercialize Lumoxiti for all uses in humans and animals in
the United States, the European Union and Switzerland. Under this Agreement, AstraZeneca was
obligated to provide support for the continued development and commercialization of Lumoxiti in the
European Union and Switzerland prior to regulatory submission and approval as well as support for the
continued commercialization of Lumoxiti in the United States for a specified period running until
September 30, 2020. Following this transition period, the company took charge of all marketing of
Lumoxiti in the United States.
Under the agreement signed in 2018, the Company was obligated to pay a $50.0 million initial payment
(€43.8 million), which it paid in January 2019, and a $15.0 million regulatory milestone (€13.4 million),
which was paid in January 2020. The Company has reimbursed reimburse AstraZeneca for the
development, production and commercialization costs it incurs during the transition period, ended in
September 30, 2020.
Further to the decision to terminate the Lumoxiti Agreement and termination notice sent in December
2020, a Termination and Transition Agreement was discussed and executed, effective as of June 30, 2021
terminating the Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply
agreement, the quality agreement and other related agreements) and transferring of the U.S. marketing
authorization and distribution rights of Lumoxiti back to AstraZeneca. The FDA has effectively
transferred the BLA to AstraZeneca on February 8, 2022. AstraZeneca has reimbursed Innate Pharma for
all Lumoxiti related costs, expenses and benefited net sales. In the year ended December 31, 2020 results
announcement, the Company reported a contingent liability of up to $12.8 million in its consolidated
financial statements, which was related to the splitting of certain manufacturing costs. As part of the
Termination and Transition Agreement, Innate and AstraZeneca agreed to split these manufacturing costs,
and Innate has paid $6.2 million to AstraZeneca (€5.9 million) on April 2022.
Following the termination and transition agreement signed in 2021, Lumoxiti activities are presented as
discontinued operations as of December 31, 2021 and 2022, respectively.
Refer to Notes 2.v and 17 for accounting description.
c)
Agreement related to IPH5201 with AstraZeneca
In October 2018, the Company signed a collaboration and option agreement with AstraZeneca for co-
development and co-commercialization of IPH5201. Under the agreement, AstraZeneca paid the
Company a $50.0 million upfront payment ($26.0 million paid in October 2018 and $24.0 million paid in
F-11
January 2019), and a milestone payment of $5.0 million paid in June 2020 following the assay of the first
patient in the first Phase 1 trial evaluating IPH5201, in March 2020. AstraZeneca is obligated to pay the
Company up to an aggregate of $5.0 million upon the achievement of certain development milestones.
On June 1, 2022, the Company signed an amendment to the collaboration and license option agreement
IPH5201 concluded with AstraZeneca in October 2018. Subsequently, the Company announced on June
3, 2022 the progress of IPH5201 towards a study of Phase 2 in lung cancers for which the Company will
be the sponsor. In accordance with the amendment signed on June 1, 2022, the Company is eligible for a
milestone payment of $5.0 million by AstraZeneca. This milestone payment was received on August 2,
2022 by the Company.
Upon exercise of its option under the agreement, AstraZeneca is committed to pay an option exercise fee
of $25.0 million and up to $800.0 million in the aggregate upon the achievement of certain development
and regulatory milestones ($300 million) and commercialization milestones ($500 million). The
arrangement also provides for a 50% profit share in Europe if the Company opts into certain co-
promoting and late stage co-funding obligations. In addition, the Company would be eligible to receive
tiered royalties ranging from a high-single digit to mid-teen percentage on net sales of IPH5201, or from a
mid-single digit to low-double digit percentage on net sales of other types of licensed products, outside of
Europe. The royalties payable to the Company under the agreement may be reduced under certain
circumstances, including loss of exclusivity or lack of patent protection. As of December 31, 2020, since
the Company had fulfilled all of its commitments on preclinical work related to the start of Phase 1 of the
IPH5201 program, the initial payment of $50.0 million and the milestone payment of $5.0 million were
fully recognized in revenue. The Company was reimbursed by AstraZeneca for certain research and
development expenses related to IPH5201 for the year ended December 31, 2022. The Company has the
option to co-fund 30% of the shared development expenses related to the Phase 3 clinical trials in order to
acquire co-promotion rights and to share in 50% of the profits and losses of licensed products in Europe.
If the Company does not opt into the co-funding obligations, among other things, its right to share in 50%
of the profits and losses in Europe and right to co-promote in certain European countries will terminate
and will be replaced by rights to receive royalties on net sales at the rates applicable to outside of Europe.
Additionally, certain milestone payments that may be payable to the Company would be materially
reduced.
Refer to Notes 2.p and 13.b for accounting description.
d)
Agreement related to additional preclinical molecules with AstraZeneca
In October 2018, the Company granted to AstraZeneca four exclusive options that are exercisable until
IND approval to obtain a worldwide, royalty-bearing, exclusive license to certain of the Company’s
patents and know-how relating to certain specified pipeline candidates to develop and commercialize
optioned products in all fields of use. Pursuant to the agreement, AstraZeneca paid the Company a
$20.0 million upfront payment (€17.4 million) in October 2018. The Company recognized this upfront
payment in the consolidated statement of financial position as deferred revenue as of December 31, 2018,
until the exercise or the termination of each option at the earliest.
During 2022 first semester, the Company received from AstraZeneca a notice that it will not exercise its
option to license the four preclinical programs covered in the "Future Programs Option Agreement".
Innate has now regained full rights to further develop the four preclinical molecules. Consequently, the
entire initial payment of $20.0 million, or €17.4 million was recognized as revenue as of June 30, 2022
Refer to Notes 2.q and 13.c for accounting description.
F-12
e)
Agreements related to avdoralimab with Novo Nordisk and with AstraZeneca
2017 avdoralimab in-licensing agreement with Novo Nordisk A/S
In July 2017, the Company signed an exclusive license agreement with Novo Nordisk A/S relating to
avdoralimab. Under the agreement, Novo Nordisk A/S granted the Company a worldwide, exclusive
license to develop, manufacture and commercialize pharmaceutical products that contain or comprise an
anti-C5aR antibody, including avdoralimab. The Company made an upfront payment of €40.0 million,
€37.2 million of which was contributed in new shares and €2.8 million of which in cash. In 2020, the
Company made an additional payment of €1.0 million to Novo Nordisk A/S following the launch of the
first Phase 2 trial of avdoralimab. The Company is obligated to pay up to an aggregate of €369.0 million
upon the achievement of development, regulatory and sales milestones and tiered royalties ranging from a
low double-digit to low-teen percentage of net sales.
Refer to Notes 2.h, 2.j and 6 for accounting description.
2018 avdoralimab AstraZeneca agreement
On January 1, 2021, the Company entered into a clinical trial collaboration agreement with AstraZeneca
to sponsor a Phase 1/2 clinical trial (STELLAR-001) to evaluate the safety and efficacy of durvalumab,
an anti-PD-L1 immune checkpoint inhibitor, in combination with avdoralimab, as a treatment for patients
with select solid tumors. The Company is the sponsor of the trial and the costs are equally shared between
the two partners. This collaboration is a non-exclusive agreement and does not include any licensing
rights on avdoralimab to AstraZeneca. In the first half of 2020, and based on data from cohort extensions
in the first two cohorts, the Company decided to stop recruiting in the STELLAR-001 trial.
Refer to Notes 2.p and 13 for accounting description.
Collaboration and license agreements concluded with Sanofi for the development of "NK Cell
f)
engages" in oncology
License and collaboration agreement with Sanofi signed in 2016
On January 2016, the Company entered into a research collaboration and licensing agreement with Sanofi
to apply its proprietary technology to the development of multi-specific antibody formats engaging NK
cells to kill tumor cells through the activating receptor NKp46. The Company granted to Sanofi under
certain of its intellectual property a non-exclusive, worldwide, royalty-free research license, as well as an
exclusive, worldwide license to research, develop and commercialize products directed against two
specified targets, for all therapeutic, prophylactic and diagnostic indications and uses.
The Company had work together with Sanofi on the generation and evaluation to two mulspecific NK cell
engagers (IPH6101/SAR443579 and IPH6401/SAR'514), using its technology and Sanofi’s tumor targets
and technology. Under the terms of the license agreement, Sanofi will be responsible for the development,
manufacturing and commercialization of products resulting from the research collaboration. The
Company will be eligible for up to €400.0 million in payments, primarily upon the achievement of
development and commercial milestones, as well as royalties ranging from a mid to high single-digit
percentage on net sales.
On January 5, 2021, the Company announced that Sanofi has made the decision to progress IPH6101/
SAR443579 into investigational new drug (IND) enabling studies. IPH6101/SAR443579 is a NKp46-
based NK cell engager (NKCE) using Innate’s proprietary multi-specific antibody format. The decision
F-13
triggered a €7.0m milestone payment from Sanofi to Innate. Sanofi will be responsible for all future
development, manufacturing and commercialization of IPH6101/SAR443579. In December 2021, the
Company announced that the first patient was dosed in a Phase 1/2 clinical trial, evaluating IPH6101/
SAR443579, in patients with relapsed or refractory acute myeloid leukemia (R/R AML), B-cell acute
lymphoblastic leukemia (B-ALL) or high risk-myelodysplastic syndrome (HR-MDS). Following the
initiation of the trial, the Company received a €3.0m milestone from Sanofi.
During 2022 first semester, the Company was informed of Sanofi's decision to advance IPH6401/
SAR’514 towards regulatory preclinical studies aimed at studying an investigational new drug. As such,
Sanofi has selected a second multi-specific antibody that engages NK cells as a drug candidate. This
selection triggered a €3.0 million milestone payment from Sanofi to the Company.
Collaboration and research license agreement with Sanofi signed in 2022
On December 19, 2022, the Company announced that it had entered into a research collaboration and
license agreement with Genzyme Corporation, a wholly-owned subsidiary of Sanofi (“Sanofi”) pursuant
to which the Company granted Sanofi an exclusive license on the Innate Pharma's B7H3 ANKET®
program and options on two additional targets. Once selected, Sanofi will be responsible for all
development, manufacturing and marketing.
Under the terms of the research collaboration and license agreement, the Company was eligible for an
initial payment of €25.0 million, received in March 2023. Under the agreement, the Company is eligible
for the duration of the research and collaboration agreement, to milestone payments of up to €1.35 billion
in total, mainly linked to the achievement of preclinical, clinical, regulatory and commercial milestones
(plus royalties on potential net sales).
Refer to Notes 2.p and 13 for accounting description
1.2.
Key events
a)
Key events for the year ended December 31, 2022
On February 14, 2022, the Executive Board carried out a capital increase of €9,301.50 and a net increase
in share premium of €182,141 following (i) the exercise of 750 "BSAAR 2012", and (ii) the creation of
185,280 ordinary shares benefiting the employees of the company, including 138,960 ordinary shares
issued free of charge (subscription). The capital increase carried out can be broken as follow : (i) a
creation of 750 ordinary shares, with a nominal value of €0.05 and an issue price of €2.04 per share (i.e an
increase in share premium of €1,492.50), and (ii) a creation of 138,960 free shares with a nominal value
of €0.05 issued free of charge by deduction from the share premium, with a creation of 46,320 ordinary
shares with a nominal value of €0.05 and an issue price of €4.10 (i.e an increase in share premium of
€180,648.00).
On March 16, 2022, the Company received a tax inspection opinion from the French tax authorities
relating to the 2019 and 2020 financial years as well as to the research tax credit and the accuracy of its
calculation for the 2018 to 2020 financial years. Following the review of the elements for calculating the
research tax credit on 2018 expenses, the administration considered that the company had included
expenses not eligible for the research tax credit. The expenses not included in the calculation of the
research tax credit by the tax authorities mainly relates to depreciation on fixed assets and personnel
costs. As of December 31,2022, and in the absence of a notice of adjustment received, the Company has
assessed the impact on research tax credit claims relating to expenses for the years under review. A
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€1,270 thousand provision was recognized based on estimated amounts and adjustments not disputed by
the Company.
On April 22, 2022, the Executive Board carried out a capital increase of €1,250 thousand following the
definitive acquisition of 25,000 free shares granted on April 29, 2019, under the “AGA New Members
2017 plan. Thus, 25,000 ordinary shares were created with a nominal value of €0.05 issued free of charge
by deduction from the issue premium.
On April 29, 2022, the Company announced the inclusion of the first patient in the “PACIFIC-9” Phase 3
trial evaluating durvalumab in combination with monalizumab or oleclumab in patients with lung cancer.
Under the monalizumab collaboration and license agreement entered into with AstraZeneca in 2015,
AstraZeneca paid on June 17, 2022 a payment of $50.0 million (€47.7 million).
On June 1, 2022, the Company signed an amendment to the collaboration and license option agreement
IPH5201 concluded with AstraZeneca in October 2018. Subsequently, the Company announced on June
3, 2022 the progress of IPH5201 towards a study of Phase 2 in lung cancers for which the Company will
be the sponsor. In accordance with the amendment signed on June 1, 2022, the Company is eligible for a
milestone payment of $5.0 million by AstraZeneca. This milestone payment was received on August 2,
2022 by the Company for an amount of €4.9 million.
During the first half of 2022, the Company received from AstraZeneca a notice that it will not exercise its
option to license the four preclinical programs covered in the "Future Programs Option Agreement". This
option agreement was part of the 2018 multi-term agreement between AstraZeneca and the Company
under which the Company received an upfront payment of $20.0 million ( €17.4 million). Innate has now
regained full rights to further develop the four preclinical molecules. Consequently, the entire initial
payment of $20.0 million, or €17.4 million was recognized as revenue during 2022 fiscal year.
During the first half of 2022, the Company was informed of Sanofi's decision to advance IPH6401/
SAR’514 towards regulatory preclinical studies aimed at studying an investigational new drug. As such,
Sanofi has selected a second multi-specific antibody that engages NK cells as a drug candidate. This
selection triggered a €3.0 million milestone payment from Sanofi to the Company. This amount was
received by the Company on September 9, 2022.
On July 13, 2022, the Executive Board carried out a capital increase of 680.70 following the definitive
acquisition of 13,614 free shares granted on July 13, 2020, under the “AGA Bonus 2020-2" plan. Thus,
13,614 ordinary shares were created with a nominal value of €0.05 issued free of charge by deduction
from the issue premium.
On July 27, 2022, the Executive Board carried out a capital increase of €6,287.70 following the definitive
acquisition of 125,748 free shares granted on July 22, 2021, under the “AGA Bonus 2021-1" plan. Thus,
125,748 ordinary shares were created with a nominal value of €0.05 issued free of charge by deduction
from the issue premium.
On August 2022, the Company requested the extension repayment of the non-dilutive financing of
€28.7 million obtained in December 2021 in the form of two State Guaranteed Loans ( “PGE”),
respectively for 20.0 and 8.7 million euros for an additional period of five years starting in 2022 and
including a one-year grace period. Consequently, the Company has obtained agreements from Société
Générale and BNP Paribas. The effective interest rates applied to these contracts during the additional
period are 1.56% and 0.95% for Société Générale and BNP Paribas loans, respectively, excluding
insurance and guarantee fees, with an amortization exemption for the entire year 2023. During this grace
F-15
period, the Company will only be liable for the payment of interest and the guarantee fees, with
amortization of the two loans starting in 2024 over a period of four years. Consequently, financial
liabilities linked to the PGEs loans are presented as "financial liabilities - current" and "financial liabilities
- non-current" in view of the new amortization plan of extended loans.
On November 7, 2022 the Executive Board approved the final performance relating to the "AGA Perf
Employees 2019-1" and "AGA Perf Management 2019-1" free performances shares plans, granted on
November 4, 2019. The definitive performance was 50%. Consequently, the Executive Board carried out
a capital increase of €15,952.50 following (i) the definitive acquisition of 147,500 free performance
shares under the "AGA Perf Employee 2019-1" plan and (ii) the definitive acquisition of 171,550 free
performance shares under the "AGA Perf Management 2019-1" plan. Thus, 319,050 ordinary shares were
created with a nominal value of €0.05 issued free of charge by deduction from the issue premium.
On December 2022, the Executive Board granted 1,371,500 free performances shares to employees of the
Company (“AGA Perf Employees 2022-1”), and 550,000 free performances shares to members of the
management (“AGA Perf Management 2022-1”).
On December 2022, the Company decided to stop avdoralimab development in bullous pemphigoid
("BP") indication in inflammation, following decision taken by sponsor to stop the Phase 2 clinical trial in
said indication during the 2022 fourth semester. Consequently, and on the date of the decision to stop
avdoralimab development in "BP" indication, avdoralimab rights were fully impaired for their net
accounting value, i.e €41.0 million
2) Accounting policies and statement of compliance
a)
Basis of preparation
Consolidated financial statements of the Company for the years ended December 31, 2020, 2021 and
2022 (the “Consolidated Financial Statements”) have been prepared under the responsibility of the
management of the Company in accordance with the underlying assumptions of going concern as the
Company’s loss-making situation is explained by the innovative nature of the products developed,
therefore involving a multi-year research and development Phase.
The general accounting conventions were applied in compliance with the principle of prudence, in
accordance with the underlying assumptions namely (i) going concern, (ii) permanence of accounting
methods from one year to the next and (iii) independence of financial years, and in conformity with the
general rules for the preparation and presentation of consolidated financial statements in accordance with
IFRS, as defined below.
Except for share data and per share amounts, the Consolidated Financial Statements are presented in
thousands of euro. Amounts are rounded up or down to the nearest whole number for the calculation of
certain financial data and other information contained in these accounts. Accordingly, the total amounts
presented in certain tables may not be the exact sum of the preceding figures
b)
Statement of compliance
The Consolidated Financial Statements have been prepared in accordance with International Financial
Reporting Standards (“IFRS”) as issued by the International Accounting Standard Board (“IASB”) and
F-16
were approved and authorized for issuance by the Board of Directors of the Company on March 22, 2023.
They will be approved by the General Meeting of the Company on May 12, 2023, which has the right to
modify them.
Due to the listing of ordinary shares of the Company on Euronext Paris and in accordance with the
European Union’s regulation No. 1606/2002 of July 19, 2002, the Consolidated Financial Statements of
the Company for the years ended December 31, 2020, 2021 and 2022 are also prepared in accordance
with IFRS, as adopted by the European Union (EU). For the years ended December 31, 2020, 2021 and
2022, all IFRS that the IASB had published and that are mandatory are the same as those endorsed by the
EU and mandatory in the EU. As a result, the Consolidated Financial Statements comply with
International Financial Reporting Standards as published by the IASB and as adopted by the EU.
IFRS include International Financial Reporting Standards (IFRS), International Accounting Standards
(“IAS”), as well as the interpretations issued by the Standing Interpretations Committee (“SIC”), and the
International Financial Reporting Interpretations Committee (“IFRIC”). The main accounting methods
used to prepare the Consolidated Financial Statements are described below. These methods were used for
all periods presented.
c)
Recently issued accounting standards and interpretations
Application of the following new and amended standards is mandatory for the first time for the financial
period beginning on January 1, 2020 and, as such, they have been adopted by the Company:
• Amendments to IFRS 3 "Definition of a company", published on October 22, 2018.
• Amendment to IFRS 16: "Covid-19-Adjustments to tenants' rents". The entry into force of this
amendment had no impact on the Company's financial statements.
• Amendments to IAS 1 and IAS 8 relating to the modification of the definition of the term
“significant”, published on October 31, 2018.
• Amendments to IAS 39, IFRS 7 and IFRS 9 relating to the reform of benchmark interest rates.
• Conceptual framework for financial reporting and modification of references to Conceptual
Framework in IFRS.
Application of the following new and amended standards is mandatory for the first time for the financial
period beginning on January 1, 2021 and, as such, they have been adopted by the Company:
• Amendments to IFRS 16 : Covid-19-Related Rent Concessions, published on May 22, 2020.
• Amendments to IFRS 9, IAS 39, IFRS 7, IFRS 4 and IFRS 16 : Interest Rate Benchmark Reform
— Phase 2, published on September 26, 2019.
•
IFRS IC opinion (IFRS / IAS Standards Interpretation Committee) addressed to the IASB in May
2021 and validated in June 2021 proposing to modify the way in which the commitments relating
to certain defined benefit plans including an obligation of attendance at the retirement, a ceiling
on rights from a certain number of years of seniority and depending on the seniority of the
employee on the date of retirement. The changes in the calculation method presented in this
opinion have been adopted by the Company from the financial year ended beginning on January
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1, 2021 in the assessment of its commitments relating to retirement benefits. The details relating
to this change in calculation method are presented in note 10) "Employee benefits"
Those standards and interpretations have no impact on the Consolidated Financial statements, except as
noted below following IFRS IC opinion addressed to IASB and validated in June 2021.
The following new standards, amendments to existing standards and interpretations have been published
but are not applicable in 2021 or have not yet been adopted by the European Union, and have not been
applied early:
• Amendment to IFRS 3 "Update of a reference to the conceptual framework"
• Amendment to IAS16 "Products generated before their intended use"
• Amendment to IAS37 "Onerous contracts - Costs of performing a contract"
• Amendment to IAS1 "Classification of current or non-current liabilities"
The accounting rules and valuation principles used for the financial statements at December 31, 2022 are
identical to those used for the previous comparative year.
Application of the following new and amended standards is mandatory for the first time for the financial
period beginning on January 1, 2022 and, as such, they have been adopted by the Company:
• Amendment to IFRS 3 "Update of a reference to the conceptual framework"
• Amendment to IAS16 "Products generated before their intended use"
• Amendment to IAS37 "Onerous contracts - Costs of performing a contract"
The following new standards, amendments to existing standards and interpretations have been published
but are not applicable in 2022 or have not yet been adopted by the European Union, and have not been
applied early:
• Amendment to IAS1 "Classification of current or non-current liabilities"
d)
Change in accounting policies
Except for the adoption of IFRS 16 as of IFRS IC opinion on certain defined benefit plans validated by
the IASB as of January, 2021 (see details in note 10), there has been no change in accounting policies for
any of the years presented.
e)
Translation of transactions denominated in foreign currency
Pursuant to IAS 21 The effects of changes in foreign exchange rates, transactions performed by
consolidated entities in currencies other than their functional currency are translated at the prevailing
exchange rate on the transaction date.
Trade receivables and payables and liabilities denominated in a currency other than the functional
currency are translated at the period-end exchange rate. Unrealized gains and losses arising from
translation are recognized in net operating income.
Foreign exchange gains and losses arising from the translation of inter-Group transactions or receivables
or payables denominated in currencies other than the functional currency of the entity are recognized in
the line “net financial income (loss)” of the consolidated statements of income (loss).
F-18
Foreign currency transactions are translated into the presentation currency using the following exchange
rates:
December 31, 2020
December 31, 2021
December 31, 2022
€1 EQUALS TO
AVERAGE
RATE
CLOSING
RATE
AVERAGE
RATE
CLOSING
RATE
AVERAGE
RATE
CLOSING
RATE
USD
1.1422
1.2271
1.1827
1.1326
1.0530
1.0666
f)
Consolidation method
The Group applies IFRS 10 Consolidated financial statements. IFRS 10 presents a single consolidation
model identifying control as the criteria for consolidating an entity. An investor controls an investee if it
has the power over the entity, is exposed or has rights to variable returns from its involvement with the
entity and has the ability to use its power over the entity to affect the amount of the investor’s returns.
Subsidiaries are entities over which the Company exercises control. They are fully consolidated from the
date the Group obtains control and are deconsolidated from the date the Group ceases to exercise control.
Intercompany balances and transactions are eliminated.
g)
Financial instruments
Financial assets
Financial assets are initially measured at fair value plus directly attributable transaction costs in the case
of instruments not measured at fair value through profit or loss. Directly attributable transaction costs of
financial assets measured at fair value through profit or loss are recorded in the consolidated statement of
income (loss).
Under IFRS 9, financial assets are classified in the following three categories:
•
•
•
Financial assets at amortized cost;
Financial assets at fair value through other comprehensive income (“FVOCI”); and
Financial assets at fair value through profit or loss.
The classification of financial assets depends on:
•
•
The characteristics of the contractual cash flows of the financial assets; and
The business model that the entity follows for the management of the financial asset.
Financial assets at amortized cost
Financial assets are measured at amortized cost when (i) they are not designated as financial assets at fair
value through profit or loss, (ii) they are held within a business model whose objective is to hold assets in
order to collect contractual cash flows and (iii) they give rise to cash flows that are solely payments of
principal and interest on the principal amount outstanding (“SPPI” criterion). They are subsequently
measured at amortized cost, determined using the effective interest method (“EIR”), less any expected
impairment losses in relation to the credit risk. Interest income, exchange gains and losses, impairment
losses and gains and losses arising on derecognition are all recorded in the consolidated statement of
income (loss).
This category primarily includes trade receivables, as well as other loans and receivables. Long-term
loans and receivables that are not interest-bearing or that bear interest at a below-market rate are
discounted when the amounts involved are material.
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Financial assets at fair value through other comprehensive income
Financial assets at fair value through other comprehensive income is mainly comprised is composed of
debt instruments whose contractual cash flows represent payments of interest or repayments of principal,
and which are managed with a view to collecting cash flows and selling the asset. Gains and losses arising
from changes in fair value are recognized in equity within the statement of comprehensive income in the
period in which they occur. When such assets are derecognized, the cumulative gains and losses
previously recognized in equity are reclassified to profit or loss for the period within the line items
Financial income or Financial expenses. The Company did not hold this type of instrument as of January
1, 2022 or as of December 31, 2022.
Financial assets at fair value through profit or loss
Financial assets at fair value through profit or loss is comprised of:
•
•
financial assets that are not part of the above categories; and
instruments that management has designated as “fair value through profit or loss” on initial
recognition.
Gains and losses arising from changes in fair value are recognized in profit or loss within the line items
financial income or financial expenses.
Impairment of financial assets measured at amortized cost
The main assets involved are trade receivables and others. Trade receivables are recognized when the
Company has an unconditional right to payment by the customer. Impairment losses on trade receivables
and others are estimated using the expected loss method, in order to take account of the risk of payment
default throughout the lifetime of the receivables. The expected credit loss is estimated collectively for all
accounts receivable at each reporting date using an average expected loss rate, determined primarily on
the basis of historical credit loss rates. However, that average expected loss rate may be adjusted if there
are indications of a likely significant increase in credit risk. If a receivable is subject to a known credit
risk, a specific impairment loss is recognized for that receivable. The amount of expected losses is
recognized in the balance sheet as a reduction in the gross amount of accounts receivable. Impairment
losses on accounts receivable are recognized within Operating expenses in the consolidated statement of
income (loss).
Financial liabilities
Financial liabilities comprise deferred revenue, collaboration liabilities, loans and trade and other
payables.
Financial liabilities are initially recognized on the transaction date, which is the date that the Company
becomes a party to the contractual provisions of the instrument. They are derecognized when the
Company’s contractual obligations are discharged, cancelled or expire.
Loans are initially measured at fair value of the consideration received, net of directly attributable
transaction costs. Subsequently, they are measured at amortized cost using the EIR method. All costs
related to the issuance of loans, and all differences between the issuance proceeds net of transaction costs
and the value on redemption, are recognized within financial expenses in the consolidated statement of
income (loss) over the term of the debt using the EIR method.
Other financial liabilities include trade accounts payable, which are measured at fair value (which in most
cases equates to face value) on initial recognition, and subsequently at amortized cost.
F-20
Cash and cash equivalents
Cash equivalents are short-term, highly liquid investments, that are readily convertible to known amounts
of cash and which are subject to an insignificant risk of changes in value. Cash and cash equivalents
comprise the cash that is held at the bank and petty cash as well as the short-term fixed deposits for which
the maturity is less than three months.
For the purpose of establishing the statement of cash flows, cash and cash equivalents include cash in
hand, demand deposits and short fixed-term deposits with banks and short-term highly liquid investments
with original maturities of three months or less, net of bank overdrafts.
Cash and cash equivalents are initially recognized at their purchase costs on the transaction date, and are
subsequently measured at fair value. Changes in fair value are recognized in profit or loss.
Fair value of financial instruments
Under IFRS 13 Fair value measurement and IFRS 7 Financial instruments: disclosures, or IFRS 7, fair
value measurements must be classified using a hierarchy based on the inputs used to measure the fair
value of the instrument. This hierarchy has three levels:
•
•
•
level 1: fair value calculated using quoted prices in an active market for identical assets and
liabilities;
level 2: fair value calculated using valuation techniques based on observable market data such
as prices of similar assets and liabilities or parameters quoted in an active market; and
level 3: fair value calculated using valuation techniques based wholly or partly on unobservable
inputs such as prices in an inactive market or a valuation based on multiples for unlisted
securities.
h)
Intangible assets
Research and development (R&D) expenses
In accordance with IAS 38 Intangible assets, or IAS 38, expenses on research activities are recognized as
an expense in the period in which it is incurred.
An internally generated intangible asset arising from the Company’s development activities is recognized
only if all of the following conditions are met:
•
•
•
•
Technically feasible to complete the intangible asset so that it will be available for use or sale;
The Company has the intention to complete the intangible assets and use or sell it;
The Company has the ability to use or sell the intangible assets;
The intangible asset will generate probable future economic benefits, or indicate the existence
of a market;
• Adequate technical, financial and other resources to complete the development are available;
and
•
The Company is able to measure reliably the expenditure attributable to the intangible asset
during its development.
Because of the risks and uncertainties related to regulatory approval, the R&D process and the availability
of technical, financial and human resources necessary to complete the development Phases of the product
candidates, the six criteria for capitalization are usually considered not to have been met until the product
candidate has obtained marketing approval from the regulatory authorities. Consequently, internally
F-21
generated development expenses arising before marketing approval has been obtained, mainly the cost of
clinical trials, are generally expensed as incurred within Research and development expenses.
However, some clinical trials, for example those undertaken to obtain a geographical extension for a
molecule that has already obtained marketing approval in a major market, may in certain circumstances
meet the six capitalization criteria under IAS 38, in which case the related expenses are recognized as an
intangible asset. These related costs are capitalized when they are incurred and amortized on a straight
line basis over their useful lives beginning when marketing approval is obtained.
Licenses
Payments for separately acquired research and development are capitalized within “Other intangible
assets” provided that they meet the definition of an intangible asset: a resource that is (i) controlled by the
Group, (ii) expected to provide future economic benefits for the Group and (iii) identifiable (i.e. it is
either separable or arises from contractual or legal rights).
In accordance with paragraph 25 of IAS 38 standard, the first recognition criterion, relating to the
likelihood of future economic benefits generated by the intangible asset, is presumed to be achieved for
research and development activities when they are acquired separately.
In this context, amounts paid to third parties in the form of initial payments or milestone payments
relating to product candidates that have not yet obtained a regulatory approval are recognized as
intangible assets. These rights are amortized on a straight-line basis:
(i) after obtaining the regulatory approval, over their useful life; or
(ii) after entering in an out-license collaboration agreement with a third-party partner, over their
estimated useful life. This estimated useful life takes into consideration the period of protection
of the out-licensed exclusivity rights and the anticipated period over which the Company will
receive the economic benefits of the asset.
Unamortized rights (before marketing authorization) are subject to impairment tests in accordance with
the method defined in Note 6.
When intangible assets acquired separately are acquired through variable or conditional payments, these
payments are recognized as an increase of the carrying amount of the intangible asset when they become
due. Royalties due by the Company related to acquired licenses are recognized as operating expenses
when the Company recognizes sales subject to royalties.
Estimate of the useful life of the acquired licenses: intangible assets are amortized on a straight line basis
over their anticipated useful life. The estimated useful life is the period over which the asset provides
future economic benefits. It is estimated by management and is regularly revised by taking into
consideration the period of development over which it expects to receive economic benefits such as
collaboration revenues, royalties, product of sales, etc. However, given the uncertainty surrounding the
duration of the R&D activities for the programs in development and their likelihood to generate future
economic benefits to the Company, the estimated useful life of the rights related to these programs is
rarely longer than the actual development Phase of the product candidate. When a program is in
commercialization Phases, the useful life takes into account the protection of the exclusivity rights and the
anticipated period of commercialization without taking into account any extension or additional patents.
The prospective amendment of the amortization plan of the monalizumab intangible asset, which is
modified according to the estimate ending date of the Phase 2 clinical trial is described in Note 6.
F-22
Other intangible assets
Other intangible assets consist of acquired software. Costs related to the acquisition of software licenses
are recognized as assets based on the costs incurred to acquire and set up the related software. Software is
amortized using the straight-line method over a period of one to three years depending on the anticipated
period of use.
i)
Property and equipment
Property and equipment are carried at acquisition cost. Major renewals and improvements are capitalized
while repairs and maintenance are expensed as incurred.
Property and equipment are depreciated over their estimated useful lives using the straight-line
depreciation method. Leasehold improvements are depreciated over the life of the improvement or the
remaining lease term, whichever is shorter.
The headquarters of the Company was split into several components (e.g., foundations, structure,
electricity, heating and ventilation systems) which are depreciated over different useful lives according to
the anticipated useful life of these elements.
Depreciation periods are as follows:
Buildings and improvements on buildings .......................................................................... 20 to 40 years
Installations .........................................................................................................................
5 to 20 years
Technical installations and equipment ................................................................................
8 years
Equipment and office furniture ...........................................................................................
5 years
Computers and IT equipment ..............................................................................................
3 years
j)
Impairment of intangible assets, property, and equipment
The Group assesses at the end of each reporting period whether there is an indication that intangible
assets, property and equipment may be impaired. If any indication exists, the Group estimates the
recoverable amount of the related asset.
Whether or not there is any indication of impairment, intangible assets not yet available for use are tested
for impairment annually by comparing their carrying amount with their recoverable amount.
Pursuant to IAS 36—Impairment of Assets, criteria for assessing indication of loss in value may notably
include performance levels lower than forecast, a significant change in market data and/or the regulatory
environment, the asset development strategy approved by management, or obsolescence or physical
damage of the asset not included in the amortization/depreciation schedule. The recognition of an
impairment loss alters the amortizable/depreciable amount and potentially, the amortization/depreciation
schedule of the relevant asset.
Impairment losses on intangible assets, property and equipment shall be reversed subsequently if the
impairment loss no longer exists or has decreased. In such case, the recoverable amount of the asset is to
be determined again so that the reversal can be quantified. The asset value after reversal of the
impairment loss may not exceed the carrying amount net of depreciation/amortization that would have
been recognized if no impairment loss had been recognized in prior periods.
The Group does not have any intangible assets with an indefinite useful life. However, as explained in
Note 2.h, the Group recognized intangible assets in progress, which will be amortized once marketing
authorization is received.
F-23
k)
Employee benefits
Long-term pension benefits
Company employees are entitled to pension benefits required by French law:
•
•
Pension benefit, paid by the Company upon retirement (i.e. defined benefit plan); and
Pension payments from social security entities, financed by contributions from businesses and
employees (i.e. defined contribution plan”).
In addition, the Company has implemented an additional, non-mandatory, pension plan (“Article 83”),
initially for the benefit of executives only. This plan was extended to the non-executive employees
starting on January 1, 2014. This plan meets the definition of defined contribution plan and is financed
through a contribution that corresponds to 2.2% of the employee’s annual wage, with the Company
paying 1.4% and the employee paying 0.8%.
For the defined benefit plan, the costs of the pension benefit are estimated using the “projected unit
credit” method. According to this method, the pension cost is accounted for in the consolidated statement
of income (loss), so that it is distributed uniformly over the term of the services of the employees. The
pension benefit commitments are valued using the actual present value of estimated future payments,
adopting the rate of interest of long-term bonds in the private sector (i.e. Euro zone AA or higher rated
corporate bonds + 10 years). The difference between the amount of the provision at the beginning of a
period and at the close of that period is recognized in the consolidated statement of income (loss) for the
portion representing the costs of services rendered and the net interest costs, and through other
comprehensive income for the portion representing the actuarial gains and losses. The Company’s
commitments under the defined benefit plan are not covered by any plan assets.
Payments made by the Company for defined contribution plans are accounted for as expenses in the
consolidated statement of income (loss) in the period in which they are incurred.
Other long-term benefits
The Company pays seniority bonuses to employees reaching 10, 15 and 20 years of seniority. These
bonuses represent long-term employee benefits. Under IAS 19R “Employee benefits”, they are recording
as a defined benefit obligation in the consolidated statement of financial position, but their
remeasurements is not recognized in the consolidated statement of other comprehensive income (loss).
Other short-term benefits
An accrued expense is recorded for the amount the Company expects to pay its eligible employees in
relation to services rendered during the reporting period (actual legal or implicit obligation to make to
these payments on a short-term basis).
l)
Leases
The Company assesses whether a contract is or contains a lease, at inception of the contract. The
Company recognizes a right-of-use asset and a corresponding lease liability with respect to all lease
arrangements in which it is the lessee, except for short-term leases (defined as leases with a lease term of
12 months or less) and leases of low value assets (such as tablets and personal computers, small items of
office furniture and telephones). For these leases, the Company recognizes the lease payments as an
operating expense on a straight-line basis over the term of the lease unless another systematic basis is
more representative of the time pattern in which economic benefits from the leased assets are consumed.
F-24
The lease liability is initially measured at the present value of the lease payments that are not paid at the
commencement date, discounted by using the rate implicit in the lease. If this rate cannot be readily
determined, the Company uses its incremental borrowing rate. Lease payments included in the
measurement of the lease liability comprise:
•
•
•
•
•
fixed lease payments (including in-substance fixed payments), less any lease incentives
receivable;
variable lease payments that depend on an index or rate, initially measured using the index or
rate at the commencement date;
the amount expected to be payable by the lessee under residual value guarantees;
the exercise price of purchase options, if the lessee is reasonably certain to exercise the options;
and
payment of penalties for terminating the lease, if the lease term reflects the exercise of an
option to terminate the lease.
The lease liability is included in the financial liabilities in the consolidated statement of financial position
and is subsequently measured by increasing the carrying amount to reflect interest on the lease liability
(using the effective interest method) and by reducing the carrying amount to reflect the lease payments
made.
The right-of-use assets comprise the initial measurement of the corresponding lease liability, lease
payments made at or before the commencement day, less any lease incentives received and any initial
direct costs. They are subsequently measured at cost less accumulated depreciation and impairment
losses.
Whenever the Company incurs an obligation for costs to dismantle and remove a leased asset, restore the
site on which it is located or restore the underlying asset to the condition required by the terms and
conditions of the lease, a provision is recognized and measured under IAS 37. To the extent that the costs
relate to a right-of-use asset, the costs are included in the related right-of-use asset, unless those costs are
incurred to produce inventories.
Right-of-use assets are depreciated over the shorter period of lease term and useful life of the underlying
asset. If a lease transfers ownership of the underlying asset or the cost of the right-of-use asset reflects
that the Company expects to exercise a purchase option, the related right-of-use asset is depreciated over
the useful life of the underlying asset. The depreciation starts at the commencement date of the lease.
The right-of-use assets are included in the property and equipment line item in the consolidated statement
of financial position.
The Company applies IAS 36 to determine whether a right-of-use asset is impaired and accounts for any
identified impairment loss.
m)
Provisions and contingent liabilities
In the course of its business, the Company could be exposed to certain risks and litigations, notably in
relation to contractual arrangements. Provisions are recognized when the Company has a present legal or
constructive obligation as a result of past events, it is probable that the Company is subject to a release of
outflow representatives of economic benefits to settle the obligation and a reliable estimate of the amount
of the obligation can be made. Management of the Company estimates the probability and the expected
amount of a cash outflow associated with risks, together with the other information to be provided on
possible liabilities. Where the Company expects a provision to be reimbursed, for example under an
F-25
insurance contract, the reimbursement is recognized as a separate asset but only when the reimbursement
is certain.
In addition, the Company may assess a potential obligation towards a third party resulting from events the
existence of which will only be confirmed by the occurrence, or not, of one or more events. uncertain
futures which are not totally under the control of the Company; or an obligation to a third party for which
it is not probable or certain that it will result in an outflow of resources without at least equivalent
consideration expected from the latter. These elements are mentioned in note 18 of the group's
consolidated financial statements as contingent liabilities.
n)
Capital
Ordinary shares are classified in shareholders’ equity. Costs associated with the issuance of new shares
are directly accounted for in shareholders’ equity in diminution of issuance premium.
The Company’s own shares bought in the context of a brokering/liquidity agreement are presented as a
reduction in shareholders’ equity until their cancellation, their reissuance or their disposal.
o)
Share-based compensation
Since its inception, the Company has established several plans for compensation paid in equity
instruments in the form of free shares (“Attributions gratuites d’actions,” or “AGA”), free preferred
shares convertible into ordinary shares (“Attributions gratuites d’actions de préférence convertibles en
actions ordinaires,” or “AGAP”), free performance shares (“Attributions gratuites d’actions de
performance,” or “AGA Perf”), share subscription warrants (“Bons de souscription d’actions,” or
“BSA”), redeemable share subscription warrants (“Bons de Souscription et/ou d’Acquisition d’Actions
Remboursables,” or “BSAAR”), granted to its employees, executives, members of the Executive Board
and scientific consultants.
Pursuant to IFRS 2—Share-based Payment, these awards are measured at their fair value on the date of
grant. The fair value is calculated with the most relevant formula regarding the conditions and the
settlement of each plan.
For share-based compensation granted to employees, executives, members of the Executive Board and
scientific consultants, the Company uses the Black-Scholes and Monte Carlo approach pricing models to
determine the fair value of the share-based compensation. For scientific consultants providing similar
services, as the Company cannot estimate reliably the fair value of the goods or services received, it
measures the value of share-based compensation and the corresponding increase in equity, indirectly, by
reference to the fair value of the equity instruments granted also using the Black-Scholes option pricing
model. The fair value of free shares included in the model is determined using the value of the shares at
the time of their distribution.
In calculating the fair value of share-based compensation, the Company also considers the vesting period
and the employee turnover weighted average probability as described in Note 11. Other assumptions used
are also detailed in Note 11.
The Company recognizes the fair value of these awards as a share-based compensation expense over the
period in which the related services are received with a corresponding increase in shareholders’ equity.
Share-based compensation is recognized using the straight-line method. The share compensation expense
is based on awards ultimately expected to vest and is reduced by expected forfeitures.
F-26
p)
Revenue
Revenue from collaboration and license agreements
To date, the Company’s revenue results primarily from payments received in relation to research,
collaboration and licensing agreements signed with pharmaceutical companies. These contracts generally
provide for components such as:
•
•
non-refundable upfront payments upon signature;
payments for the exercise of the option to acquire licenses of drug candidates;
• milestones payments triggered following stages of development (scientific results obtained by
the Company or by the partner, obtaining regulatory marketing approvals);
•
•
payments related to the Company’s R&D activities;
payments triggered by the start of the commercialization of products resulting from
development work or by crossing cumulative thresholds of product sales, as well as the
allocation of royalties on future sales of products or a sharing of profits on sales.
Under collaboration and license agreements, the Company may promise its partners licenses on
intellectual property, as well as research and development services. According to IFRS 15, the Company
has to determine if the promises included in the contract are distinct (therefore recognized separately as
revenue) or if they have to be combined as a single performance obligation.We conclude that the license
is not distinct from the research and development services when the research and development services
involve the Company's own expertise, so that the customer cannot benefit from the license alone or in
combination with services provided by third parties, or when the intellectual property is at such a stage of
development that the research and development work significantly modifies the initial purpose of the
license.
When promises in a collaboration and license agreement are considered as a single performance
obligation, the Company has to determine if the combined performance obligation is satisfied over time or
at point in time. If the combined performance obligation is satisfied over time, revenue recognition is
based on the percentage of completion of the costs to be incurred. Non-refundable initial payments are
deferred and recognized as revenue during the period the Company is engaged to deliver services to the
customer on the basis of the corresponding costs.
When promises in a collaboration and license agreement are considered as separate performance
obligations, revenue is allocated to each obligation proportionally to its transaction price, which
corresponds to a price each performance obligation would have been sold in the context of a separate
transaction.
In accordance with IFRS 15, variable considerations cannot be included in the estimated transaction price
as long as it not highly probable that the related revenue will not reversed in the future. According to the
level of uncertainty relating to the results of preclinical and clinical trials and the decisions relating to the
regulatory approvals, variable considerations depending on these events are excluded from the transaction
price as long as the trigger event is not highly probable. When the trigger event occurs, the corresponding
milestone is added to the transaction price. Such adjustments are recorded on a cumulative catch-up basis,
which would affect revenues and net income (loss) in the period of adjustment.
Revenues based on royalties, completion of commercialization steps or co-sharing profit from sales are
recognized when the corresponding sales of products are carried out by the partner.
When a collaboration contract grants a partner an option to acquire a licensed intellectual property (“IP”),
the Company determines the date of the transfer of control over the licensed IP. Depending on the
F-27
Company analysis, revenue related to the option fee will be recognized (i) when control over the licensed
IP transfers (payment related to the exercise of the option being therefore considered as a variable
consideration), or, (ii) deferred until the exercise of the option or its expiration period.
When an agreement only promises development services, the Company will recognize the related revenue
when the costs are incurred.
Up-front and milestones payments and fees are recorded as deferred revenue upon receipt or when due,
and may require deferral of revenue recognition to a future period until the Company performs its
obligations under these arrangements. Amounts due by the Company in relation to cost-sharing are
recorded as collaboration liability. Amounts payable to the Company are recorded as accounts receivable
when the Company’s right to consideration is unconditional.
See Note 13 for accounting description of significant agreements.
q)
Government financing for research expenditures
Research tax credit
The research tax credit (Crédit d’Impôt Recherche) (the “Research Tax Credit” or “CIR”) granted by the
French tax authorities in order to encourage Companies to conduct technical and scientific research.
Companies that can justify that these expenses meet the required criteria receive such grants in the form
of a refundable tax credit that can be used for the payment of taxes due for the period in which the
expense was incurred and for the next three years. These grants are presented under other income, in
“government financing for research expenditures” line item in the consolidated statements of income
(loss), as soon as these eligible expenses were conducted.
The Company has benefited from a Research Tax Credit since its inception.
The reimbursements are made under the European Community tax rules for small and medium sized
enterprises (“SME”) in compliance with the applicable regulations in effect. Only companies that meet
the definition of SME according to European Union criteria are eligible for early reimbursement of their
CIR. Management ensured that the Company was a SME according to European Union criteria and can
therefore benefit from this early reimbursement until as of December 31, 2019. As of December 31, 2019,
the Company no longer met the eligibility criteria for this status (criteria not met as of December 31, 2018
and 2019). Thus, the CIR for the years 2019 and 2020 represent a receivable against the French Treasury
which will in principle be offset against the French corporate income tax due by the company with respect
to the three following years. The remaining portion of tax credit not being offset upon expiry of such a
period may then be refunded to the Company.
For the 2021 and 2022 financial year, the Company met again the definition of an SME according to the
criteria of the European Union. As a result, the Company was eligible for the early repayment by the
French treasury of the 2021 Research Tax Credit during the fiscal year 2022. The Company will also be
eligible to the early repayment by the French treasury of the 2022 Research Tax Credit during the fiscal
year 2023.
The CIR is presented under other income, in “government financing for research expenditures” line item
in the consolidated statements of income (loss) as it meets the definition of government grant as defined
in IAS 20 Accounting for government grants and disclosure of government assistance.
F-28
Subsidies
Government grants are recognized when there is a reasonable assurance that:
•
•
The Company will comply with the conditions attached to the grants; and that
The grants will be received.
A government grant that becomes receivable as compensation for expenses or losses already incurred, or
for the purpose of providing immediate financial support to the Company with no future related costs, is
recognized as other income of the period in which it becomes receivable.
Government grants to subsidize capital expenditures are presented in the statement of financial position as
deferred income and are recognized as income on a straight line basis over the useful life of those assets
that have been financed through the grants.
A non-repayable loan from the government is treated as a government grant when there is a reasonable
assurance that the Company will meet the terms for non-repayment of the loan. When there is no such
assurance, the loan is recorded as a liability under borrowings.
r)
Income tax
Deferred income tax is provided in full, using the liability method, on temporary differences arising
between the tax bases of assets and liabilities and their carrying amounts in the financial statements. Main
temporary differences are generally associated with the depreciation of property and equipment,
provisions for pension benefits and tax losses carried forward and also with the deferred tax liabilities /
assets generated by the application of IFRS 15. Currently enacted tax rates are used in the determination
of deferred income tax.
Deferred tax assets are recognized to the extent that it is probable that future taxable profit will be
available against which the temporary differences can be utilized. Due to Company’s early stage of
development, it is not probable that future taxable profit will be available against which the unused tax
losses can be utilized. As a consequence, deferred tax assets are recognized up to deferred tax liabilities.
s)
Earnings (loss) per share
In accordance with IAS 33 Earnings per share, basic income (loss) per share is calculated by dividing the
income (loss) attributable to equity holders of the Group by the weighted average number of outstanding
shares for the period.
Diluted income (loss) per share is measured by dividing the income (loss) attributable to holders of equity
and dilutive instruments by the weighted average number of outstanding shares and dilutive instruments
for the period.
If in the calculation of diluted income (loss) per share, instruments giving deferred rights to capital such
as warrants generates an antidilutive effect, then these instruments are not taken into account.
t)
Other comprehensive income
Items of income and expenses for the period that are recognized directly in equity are presented under
“other comprehensive income.” The items mainly include :
•
Foreign currency translation gain (loss); and
• Actuarial gains and (losses) related to defined benefit obligations.
F-29
u)
Segment information
For internal reporting purposes, and in order to comply with IFRS 8 Operating segments, the Company
performed an analysis of operating segments. Following this analysis, the Company considers that it
operates within a single operating segment being the R&D of pharmaceutical products in order to market
them in the future. All R&D activities of the Company are located in France. Key decision makers (the
executive committee of the Company) monitor the Company’s performance based on the cash
consumption of its activities. For these reasons, the Management of the Group considers it not appropriate
to set up separate business segments in its internal reporting.
In 2020 revenue was entirely generated by one customer (AstraZeneca). In 2021 and 2022, revenue
consisted of revenue from collaboration agreements with AstraZeneca and Sanofi as well as sales of
Lumoxiti in the U.S. Lumoxiti sales are also now included in the consolidated statement of income (loss)
in the line "net income (loss) from discontinued operations" following the signing of the termination and
transition agreement with AstraZeneca in 2021 (see notes 1.1, 2.w and 17).
v)
Non-current assets held for sale and discontinued operations
A discontinued operation is a component of an entity that either has been disposed of, or that is classified
as held for sale. It must either: represent a major separate line of business or geographical area of
operations; be part of a single coordinated disposal plan; or be a subsidiary acquired exclusively with a
view to resale. Intercompany transactions between continuing and discontinued operations are eliminated
against discontinuing operations. Non-current assets and disposal groups are classified as assets held for
sale if their carrying amount is to be recovered principally through a sale transaction rather than through
continuing use. This condition is regarded as met only when the sale is highly probable and the asset (or
disposal group) is available for immediate sale in its present condition. They are stated at the lower of
carrying amount and fair value less costs to sell with any resulting impairment recognized. Assets related
to discontinued operations and assets of disposal group held for sale are not depreciated. The prior-year
consolidated balance sheet is not restated.
Further to the decision to terminate the Lumoxiti Agreement and termination notice sent in December
2020, a Termination and Transition Agreement was discussed and executed, effective as of June 30, 2021
terminating the Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply
agreement, the quality agreement and other related agreements) and transferring of the U.S. marketing
authorization and distribution rights of Lumoxiti back to AstraZeneca. Consecutively, the activities
related to Lumoxiti are presented as a discontinued operation as of October 1, 2021.
Consequently, in accordance with IFRS5 "non-current assets held for sale and discontinued operations",
the Lumoxiti operations are presented in the consolidated statement of income (loss) and the notes to the
consolidated financial statements as a discontinued operation for the 2021 financial year. The 2019 and
2020 comparatives have been restated compared to previous publications (where applicable), in
accordance with the same standard.
w)
Critical accounting estimates and assumptions
The preparation of the consolidated financial statements under IFRS requires management to make
estimates, assumptions and judgments that affect the reported amounts of assets, liabilities, income and
expenses during the reporting period. The Company bases estimates and assumptions on historical
experience when available and on various factors that it believes to be reasonable under the
circumstances. The Company’s actual results may differ from these estimates under different assumptions
or conditions.
F-30
These estimates and judgments involve mainly:
•
•
the accounting for collaboration and licensing agreements: the revenue results primarily
from payments based on several components (e.g., upfront payments, milestone payments)
received in relation to research, collaboration and licensing agreements signed with
pharmaceutical or other companies. When the Company is committed to perform R&D
services, revenue is spread over the period the Company is engaged to deliver these services,
more particularly on the basis of the Company’s inputs to the satisfaction of a performance
obligation relative to the total expected inputs to the satisfaction of that performance obligation.
Milestone payments are dependent upon the achievement of certain scientific, regulatory, or
commercial milestones. These variable payments are recognized when the triggering event has
occurred, there are no further contingencies or services to be provided with respect to that
event, and the counterparty has no right to refund of the payment. The changes in estimate
regarding the completion of the works and the variable consideration relating to the contracts
signed with customers are described in Note 13. As of December 31, 2022, given the significant
progress of the work to be performed (94.5%) and the level of budget consumption, the impact
of accounting estimates is no longer a determining factor in the calculation of revenue related to
the monalizumab agreement.
the estimate of the recoverable amount of the acquired and under progress licenses:
impairment tests are performed on a yearly basis for the intangible assets which are not
amortized (such as intangible assets in progress). Amortizable intangible assets are tested for
impairment when there is an indicator of impairment. Impairment tests involve comparing the
recoverable amount of the licenses to their net book value. The recoverable amount of an asset
is the higher of its fair value less costs to sell and its value in use. If the carrying amount of any
asset is below its recoverable amount, an impairment loss is recognized to reduce the carrying
amount to the recoverable amount. The main assumptions used for the impairment test include
(a) the amount of cash flows that are set on the basis of the development and commercialization
plans and budgets approved by Management, (b) assumptions related to the achievement of the
clinical trials and the launch of the commercialization, (c) the discount rate, (d) assumptions on
risk related to the development and (e) for the commercialization, selling price and volume of
sales, Any change in these assumptions could lead to the recognition of an impairment charge
that could have a significant impact on the Company’s consolidated financial statements. As of
December 31, 2022, given the Company's decision in December 2022 to discontinue the
development of avdoralimab in the indication of bullous pemphigoid supporting the recoverable
amount of the asset as of December 31, 2021 and June 30, 2022, the rights related to the
intangible asset have been fully impaired for the net carrying amount of the intangible asset, of
€41,000 thousand , without using the historical assumptions described above (see note 6). As a
result, the Company considers that there are no longer any critical estimates in line with
intangible assets in 2022. There are therefore no longer any critical assumptions that could call
into question the recoverable amount of the asset.
3)
Management of financial risks and fair value
The principal financial instruments held by the Company are cash, cash equivalents and marketable
securities. The purpose of holding these instruments is to finance the ongoing business activities of the
Company. It is not the Company’s policy to invest in financial instruments for speculative purposes. The
Company does not utilize derivatives.
F-31
The principal risks to which the Company is exposed are liquidity risk, foreign currency exchange risk,
interest rate risk and credit risk.
Liquidity risk
The Company’s cash management is performed by the Finance department, in charge of monitoring the
day-to-day financing and the short-term forecast and enabling the Company to face its financial
commitments by maintaining an amount of available cash consistent with the maturities of its liabilities.
As of December 31, 2022, cash, cash equivalents and short-term investments were €101,485 thousand,
which represents more than a year of cash consumption.
The company's assets are fairly split between top-rated banks (S&P A+ rating).
The main characteristics of the financial instruments owned by the Company (including liquidity) are
presented in Note 4.
Foreign currency exchange risk
The Company is exposed to foreign exchange risk inherent in certain subcontracting activities relating to
its operations in the United States, which have been invoiced in U.S. dollars. The Company does not
currently have recurring revenues in euros, dollars or in any other currency.
The revenue denominated in U.S. dollars has represented approximately 88%, 78% and 92% of revenue
in the years ended December 31, 2020, 2021 and 2022, respectively. Payments in U.S dollars represented
approximately 48%, 50%, and 50% of the payments in the years ended December 31, 2020, 2021 and
2022, respectively. In order to cover this risk, the Company kept in U.S. dollars a part of the consideration
received from AstraZeneca in June 2015, January 2019 and December 2020. The Company entirely kept
the U.S dollars portion of the proceeds received from our Global Offering in October 2019.
The Company’s foreign exchange policy does not include the use of hedging instruments in its current
operations.
Interest rate risk
The Company has very low exposure to interest rate risk. Such exposure primarily involves money
market funds and time deposit accounts. Changes in interest rates have a direct impact on the rate of
return on these investments and the cash flows generated. The Company has no credit facilities. The
repayment flows of the advances from Banque Publique d’Investissement (“BPI France”), the borrowings
subscribed in 2017 and the two State Guaranteed Loans obtained in 2021 and extended in 2022, are not
subject to interest rate risk.
Credit risk
The credit risk related to the Company’s cash equivalents, short-term investments and non-current
financial assets is not significant in light of the quality of the issuers. The Company deemed that none of
the instruments in its portfolio are exposed to credit risk.
Fair value
The fair value of financial instruments traded on an active market is based on the market rate as of
December 31, 2022. The market prices used for the financial assets owned by the Company are the bid
prices in effect on the market as of the valuation date.
F-32
4) Cash, cash equivalents and financial assets
(in thousands of euro)
Cash and cash equivalents
Short-term investments
Cash and cash equivalents and short-term investments
Non-current financial assets
Total cash, cash equivalents and financial assets
2020
136,792
14,845
151,637
38,934
190,570
December 31
2021
103,756
16,080
119,836
39,878
159,714
2022
84,225
17,260
101,485
35,119
136,604
Cash and cash equivalents are mainly composed of current bank accounts, interest-bearing accounts and
fixed-term accounts.
Other non-current financial assets generally include a guarantee of capital at the maturity date (which is
always longer than one year). These instruments are defined by the Company as financial assets at fair
value through profit or loss and classified as non-current due to their maturity.
As of December 31, 2020, 2021 and 2022 the amount of cash, cash equivalents and financials assets
denominated in U.S. dollars amounted respectively to €64,654 thousand , €47,164 thousand and €34,735
thousand
The variation of short-term investments and non-current financial assets for the periods presented, are the
following:
December 31,
2020
Additions(1)
Deductions
(2)
Variance of
fair value
through the
consolidated
statement of
income (loss)
14,845
38,934
53,779
—
—
—
—
—
—
99
888
987
Variance of
accrued
interests
Foreign
currency
effect
December
31, 2021
—
1,136
16,080
55
55
—
39,878
1,136
55,958
December 31,
2021
Additions(1)
Deductions
(2)
Variance of
fair value
through the
consolidated
statement of
income (loss)
Variance of
accrued
interests
Foreign
currency
effect
December
31, 2022
16,080
39,878
55,958
—
—
—
—
268
—
912
17,260
(3,000)
(1,640)
(118)
(3,000)
(1,372)
(118)
—
912
35,119
52,379
(in thousands of
euro)
Short-term
investments
Non-current
financial assets
Total
(in thousands of
euro)
Short-term
investments
Non-current
financial assets
Total
F-33
5) Trade receivables and others
Trade receivables and others are analyzed as follows:
(in thousands of euro)
Other receivables
Research tax credit(1)
Other tax credits
Prepaid expenses (2)
VAT refund
Trade account receivables (3)
Prepayments made to suppliers
Receivables and others - current
Research tax credit(1)
Prepaid expenses (2)
Receivables and others - non-current
Trade receivables and others - excluding rebate related to
capital expenditures
Year ended December 31,
2020
741
—
333
6,833
2,208
10,585
1,114
21,815
29,821
—
29,821
51,635
2021
814
10,310
333
2,582
1,170
846
2,364
18,420
29,821
—
29,821
48,241
2022
61
25,904
361
4,672
1,614
3,080
2,652
38,345
13,018
1,081
14,099
52,445
(1) In accordance with the principles described in Note 2.q, the research tax credit (Crédit d’Impôt Recherche or “CIR”) is recognized as other
operating income in the year to which the eligible research expenditure relates. The amount of €13,018 thousand recognized in non-current
receivables corresponds to the CIR for the 2020 tax year following the fact that the Company no longer met the eligibility criteria for the
SME status as of December 31, 2019. Thus, the CIR for the 2020 represented a non-current receivable which will in principle be offset
against the French corporate income tax due by the Company with respect to the three following years, or refunded if necessary upon
expiry of such a period. Since December 2020, the Company has ensured that the eligibility criteria for the SME status are met again. As a
result, the CIR related to the 2021 tax year which amounted €10,302 thousand has been refunded in advance by the French Treasury to the
Company. This amount was received by the Company on November 16, 2022. The Company is also eligible for the early repayment by
the French treasury of the 2022 Research Tax Credit during the fiscal year 2023 for an amount of €9,167 thousand and also the CIR
related to the 2019 tax year for an amount of €16,737 thousand given the expiry of the three-year period (see note 2.q).
(2) As of December 31, 2022, the prepaid expenses include an amount of €1,256 thousand relating to the guarantee fees in line with the two
State Guaranteed Loans from Société Générale and BNP Paribas. Following the extension of these two loans repayment for an additional
period, the full amount of the guarantee fee over the additional five-year period has been recognized as an operating expense in 2022. As
of December 31, 2022, an adjustment is made through the prepaid accounts to reflect the fact that the expenses are related to the fiscal year
(see note 9).
(3) As of December 31, 2022, the amount is entirely comprised of the receivables from AstraZeneca for an amount of €1,775 thousand and
€1,303 thousand in line with the performance of research and development services under the monalizumab and IPH5201 collaboration
agreements, respectively. As a reminder, as of December 31, 2020, the amount included a receivable of €8,400 thousands (including
€1,400 thousand of value added tax) linked to the collaboration and licensing agreement signed with Sanofi in January 2016. This
receivable resulted from the decision taken by Sanofi to advance IPF6101/SAR443579 towards regulatory preclinical studies for the study
of a new investigational drug. This payment was received by the Company in January 2021.
Trade receivables and others have payment terms of less than one year. No valuation allowance was
recognized on trade receivables and others as the credit risk of each of debtors was considered as not
significant.
F-34
6)
Intangible assets
Intangible assets can be broken down as follows:
(in thousands of euro)
January 1, 2020
Acquisitions
Additional considerations
Disposals
Depreciation
Impairment
Transfers
December 31, 2020
(in thousands of euro)
January 1, 2021
Acquisitions
Additional considerations
Disposals
Depreciation
Transfers
December 31, 2021
(in thousands of euro)
January 1, 2022
Acquisitions
Additional considerations
Disposals
Depreciation
Impairment
Transfers
December 31, 2022
Purchased
licenses
56,851
—
2,685 (1)
—
(10,904) (3)
(43,529) (4)
—
5,103
Other intangible
assets
116
264
—
—
(195)
—
—
185
Purchased
licenses
5,103
—
368 (5)
—
(2,310) (3)
—
3,161
Other intangible
assets
185
13
—
(39)
(130)
—
29
Other intangible
assets
29
Purchased
licenses
3,161
—
587 (6)
—
(2,195) (3)
—
—
1,553
—
(29)
—
—
—
In progress
40,000
—
1,000 (2)
—
—
—
—
41,000
In progress
41,000
—
—
—
—
—
41,000
In progress
41,000
—
—
—
—
(41,000) (7)
—
—
Total
96,968
264
3,685
—
(11,099)
(43,529)
—
46,289
Total
46,289
13
368
(39)
(2,440)
—
44,192
Total
44,192
—
587
—
(2,224)
(41,000)
—
1,556
(1) This amount of 2,685 thousand euros included two additional payments made to Orega Biotech in April 2020 (2,500 thousand euros) and
June 2020 (185 thousand euros) relating to IPH5201 rights following the first patient dosed in Phase 1 clinical trial in Mars 2020.
(2) This amount of €1,000 thousand was paid in October 2020 to Novo Nordisk A / S following the launch of the first Phase 2 trial regarding
avdoralimab.
(3) As of December 31, 2020, this amount included the amortization of rights relating to monalizumab (€2,844 thousand), IPH5201
(€4,314 thousand) and Lumoxiti (€3,746 thousand). The amortization relating to Lumoxiti rights related to the period prior to the decision
to return the commercial rights to AstraZeneca. Impact of the decision on the book value of said rights is presented in note 6 below. As of
December 31, 2021, the amount includes the amortization of rights relating to monalizumab (€1,942 thousand) and IPH5201
(€368 thousand). As of December 31, 2022, this amount includes the amortization of rights relating to monalizumab (€1,604 thousand)
and IPH5201 (€587 thousand).
F-35
(4) Following the Company's decision to return the commercial rights to Lumoxiti in the United States and in Europe at the end of November
2020, the rights relating to the intangible asset were fully impaired for the carrying amount of the intangible asset to the date of the
decision, amounting to €43,529 thousand.
(5) This amount relates to an additional consideration paid to Orega Biotech in January 2022 following the arbitration decision rendered in
December 2021 relating to the joint ownership of certain patents relating to IPH5201. This additional payment is fully amortized as of
December 31, 2021.
(6) This amount corresponds to the additional payment made to Orega Biotech in October 2022 for the rights relating to IPH5201, following
the amendment to the collaboration and license option agreement IPH5201 concluded with AstraZeneca in October 2018 and the
announcement by the Company on June 3, 2022, of the progression of IPH5201 towards a Phase 2 study in lung cancers of which the
Company will be a sponsor.
(7) Following the Company's decision in December 2022 to stop the development of avdoralimab in bullous pemphigoid ("BP") indication in
inflammation, only indication supporting the recoverable amount of the asset as of December 31, 2021 (as well that as of June 30, 2022),
the rights relating to the intangible asset have been fully impaired for their net book value on the date of the decision, i.e.
€41,000 thousand (see below "Avdoralimab (IPH5401) (anti-C5aR) rights acquired from Novo Nordisk A/S')
Monalizumab rights under the 2014 monalizumab (NKG2A) Novo Nordisk agreement
At the agreement inception, acquired rights were recorded as intangible asset for an amount of
€7,000 thousand. The Company recorded an additional consideration of €6,325 thousand in 2015 and a
final consideration of $15,000 thousand (€13,050 thousand) due in 2018 (see Note 1.1.a).
Since their acquisition by the Company, monalizumab rights are amortized on a straight-line basis over
the anticipated residual duration of the Phase 2 trials. The Company has reassessed the anticipated
residual duration of the Phase 2 trials as of December 31, 2022 and estimated that it would be fully
amortized by 2023, which is the same estimation as of December 31, 2021, as a result of the completion
of some trials and by modifying the estimated end dates relating to certain cohorts.
The net book values of the monalizumab rights were €1,551 thousand and €3,155 thousand as of
December 31, 2022 and December 31, 2021, respectively.
IPH5201 (Anti-CD39) rights acquired from Orega Biotech
On January 4, 2016, the Company and Orega Biotech entered into an exclusive licensing agreement by
which Orega Biotech granted the Company full worldwide rights to its program of first-in-class anti-
CD39 checkpoint inhibitors. The undisclosed upfront payment paid by the Company to Orega Biotech has
been recognized as an intangible asset in the consolidated financial statements for the year ended
December 31, 2016. Criteria relating to the first development milestone were reached in December 2016.
Consequently, the amount of this milestone was recognized as an intangible asset in addition to the initial
payment, for a total of €1.8 million as of December 31, 2021. In June 2019, the Company also paid Orega
Biotech €7.0 million in relation to the anti-CD39 program as consideration following the collaboration
and option agreement signed on October 22, 2018 with AstraZeneca regarding IPH5201. Under this
agreement, the Company also paid in April and June 2020, respectively €2.5 and €0.2 million to Orega
Biotech following the first Phase 1 dosing relating to IPH5201.
This asset was amortized on a straight-line basis since November 1, 2018 (corresponding to the effective
beginning date of the collaboration) until the date the Company expected to fulfill its commitment (end of
fiscal year 2020). As a reminder, these collaboration commitments have all been fulfilled. Thus, the rights
relating to IPH5201 are fully amortized since December 31, 2020.
Orega Biotech claimed joint ownership of certain patents relating to IPH5201. the Company and Orega
Biotech have resolved these claims in an arbitration proceeding, which decision was rendered in
December 2021. As a result of this decision, the Company will be required to pay a low-teen percentage
of sub-licensing revenues received by the Company pursuant to its agreement with AstraZeneca regarding
F-36
IPH5201 Following this arbitration decision, the Company paid in January 2022 an additional amount of
0.4 million euros to Orega Biotech.
The Company announced on June 3, 2022 the progress of IPH5201 towards a study of Phase 2 in lung
cancer, of which the Company will be a sponsor. In accordance with the amendment signed on June 1,
2022, the Company was eligible for a milestone payment of $5 million by AstraZeneca, received in
August 2022 by the Company. In October 2022, the Company therefore paid an additional €0.6 million to
Orega Biotech.
The Company may also be obligated to pay Orega Biotech up to €48.2 million upon the achievement of
development and regulatory milestones.
Avdoralimab (IPH5401) (anti-C5aR) rights acquired from Novo Nordisk A/S
At the agreement inception, an upfront payment of €40 million for acquired rights were recorded as
intangible asset. As part of this agreement, an additional amount of €1.0 million was paid in October 2020
to Novo Nordisk A / S following the launch of the first avdoralimab Phase 2 trial. As avdoralimab is still
in clinical trial, the acquired rights are classified as intangible asset in progress. They were subject to
annual impairment test. No impairment were recorded since inception.
According to the agreement, the Company will pay additional payments according to the reach of specific
steps. As of December 31, 2022, according to the uncertainty of these potential future payments, no
liability was recognized.
Development costs incurred by the Company are recognized as research and development expenses.
During 2022 fourth quarter, the Company was informed by the sponsor of the Phase 2 clinical trial
evaluating avdoralimab in inflammation in bullous pemphigoid ("BP") indication of its decision to
discontinue said trial. Consequently, the Company decided in December 2022 to stop the development of
avdoralimab in bullous pemphigoid ("BP") indication in inflammation, only indication supporting the
recoverable amount of the asset as of December 31, 2021 (as well that as of June 30, 2022).
Following that decision, the Company applied IAS 36 "Impairment of assets" and assessed that there was
an indication of impairment sufficiently significant to result in the full impairment of the intangible asset.
This depreciation was recognized with regard to the estimate of the recoverable value of avdoralimab's
intangible assets, based on expected future cash flows, as of December 2022, date of the decision. Thus,
on decision date to stop the development of avdoralimab in bullous pemphigoid ("BP") indication in
inflammation, avdoralimab rights were fully written down to their net book value, i.e €41,000 thousand.
Lumoxiti rights acquired from AstraZeneca under the 2018 AstraZeneca multi-term agreement
The license by which the Company acquired Lumoxiti rights was initially amortized on a straight-line
basis through July 31, 2031, which corresponds to the expiration of the current composition of matter
patent, not including any additional patent extensions or patents. The net book value of the Lumoxiti
rights was €47,276 thousand as of December 31, 2019.
End of November 2020, the Company decided to return the marketing rights of Lumoxiti in the United
States and in Europe. Following this decision, the Company applied IAS 36 "Impairment of assets" and
assessed that there was an indication of impairment sufficiently significant to result in the full impairment
of the intangible asset. This depreciation was recognized with regard to the estimate of the recoverable
value of Lumoxiti's intangible assets, based on expected future cash flows, determined using the
marketing plan and budget approved by management, and future expenses to be exposed in particular as
part of the transition plan, which was under negotiation as of December 31, 2020. Thus, on the date of the
decision to return the rights, the Lumoxiti rights were fully written down to their net book value as of
October 31, 2020, i.e. €43,529 thousand.
F-37
As a reminder, as part of the communication of its 2020 consolidated financial statements, the Company
had communicated on a contingent liability estimated at a maximum of $12.8 million related to the
sharing of certain manufacturing costs. As part of the termination and transition agreement signed in
2021, Innate and AstraZeneca have agreed to share manufacturing costs, and Innate will pay $6.2 million
on April 30, 2022 (see note 8 and 17).
7) Property and equipment
(in thousands of euro)
January 1, 2020
Acquisitions
Disposals
Transfers
Depreciation
December 31, 2020
(in thousands of euro)
January 1, 2021
Acquisitions
Disposals
Depreciation
Transfers
December 31, 2021
(in thousands of euro)
January 1, 2022
Acquisitions
Disposals
Depreciation
Transfers
December 31, 2022
Land and
buildings
Laboratory
equipment
and other
In progress
Total
5,356
1,152
—
—
(757)
5,751
5,947
944
(9)
134
(1,440)
5,576
369
132
—
(134)
—
367
Of which
finance leases
6,270
1,195
—
(1,042)
—
6,423
11,672
2,228
(9)
—
(2,197)
11,694
Land and
buildings
Laboratory
equipment
and other
In progress
Total
Of which
right of use
assets
5,751
11
(781)
4,981
5,576
987
(7)
(1,373)
4
5,187
367
—
—
—
(361)
6
11,694
998
(7)
(2,154)
(357)
10,174
6,423
—
—
—
—
6,423
Land and
buildings
Laboratory
equipment
and other
In progress
Total
Of which
right of use
assets
4,981
20
(759)
—
4,242
5,187
535
(11)
(1,413)
—
4,298
6
(6)
—
—
10,174
556
(17)
(2,171)
—
8,542
6,423
—
—
—
—
6,423
F-38
8) Trade payables and others
This line item is analyzed as follows:
(in thousands of euro)
Suppliers (excluding payables related to capital expenditures)
Tax and employee-related payables
Other payables (1)
Trade payables and others excluding payables related to capital
expenditures
Payables related to capital expenditures
Payables and others
2020
December 31,
2021
2022
20,730
8,325
463
29,519
20
29,539
14,729
7,463
6,380
28,573
—
28,573
13,656
5,978
1,260
20,894
17
20,911
(1) As of December 31, 2022, this amount mainly includes the liability related to the payment of the guarantee fees on the two State
Guaranteed Loans obtained from Société Générale and BNP Paribas in 2021 (see note 9). As a reminder, this amount included, as of
December 31, 2021, the liability of $6,200 thousand (€5,474 thousand as of December 31, 2021) to be paid to AstraZeneca on April 30,
2022 under the Lumoxiti termination and transition agreement effective June 30, 2021 (see note 17).
The book value of trade payables and others is considered to be a reasonable approximation of their fair
value.
9) Financial liabilities
This line item was broken down per maturity and is analyzed as follows:
In thousand euros
BPI PTZI IPH41 (1)
BPI Refundable advance -
FORCE (2)
Lease liabilities – Real estate
property
Property transaction (down-
payment)
Lease liabilities – Building
"Le Virage"
Lease liabilities – Premises
Innate Inc
Lease liabilities – Laboratory
equipment
Lease liabilities – Vehicles
Lease liabilities - Printers
Loans – Equipment
Loans – Building (4)
Total
December 31,
2019
Proceeds from
borrowing
Proceeds from
lease liabilities
and other non
cash effects
Repayments of
borrowings
and lease
liabilities
December 31,
2020
450
—
418
(74)
1,437
496
815
37
—
319
14,826
18,723
—
1,360
—
—
—
—
—
—
—
1,360
F-39
—
94
—
—
(300)
150
—
1,454
(418)
74
—
—
1,114
(164)
2,387
—
—
—
41
—
—
1,249
(49)
447
(176)
639
(16)
—
(57)
(1,139)
(2,245)
21
41
262
13,687
19,087
In thousand euros
BPI PTZI IPH41 (1)
BPI Refundable advance -
FORCE (2)
State guaranteed loan Société
Générale (3)
State guaranteed loan BNP
Paribas (3)
Lease liabilities – Building
"Le Virage"
Lease liabilities – Premises
Innate Inc
Lease liabilities – Laboratory
equipment
Lease liabilities – Vehicles
Lease liabilities - Printers
Loans – Equipment
Loans – Building (4)
Total
December 31,
2020
Proceeds from
borrowing
Proceeds from
lease liabilities
and other non
cash effects
Repayments of
borrowings
and lease
liabilities
December 31,
2021
150
1,454
—
—
2,387
447
639
21
41
262
13,687
19,087
—
—
20,000
8,700
—
—
—
—
—
—
—
28,700
(150)
—
—
—
—
—
20,000
8,700
(512)
1,875
(1,454)
—
—
—
(16)
(40)
—
(175)
62
—
—
—
(1,408)
(30)
(6)
(53)
(1,162)
(2,128)
391
464
53
35
209
12,525
44,251
F-40
In thousand euros
State guaranteed loan Société
Générale (3)
State guaranteed loan BNP
Paribas (3)
State guaranteed loans -
accrued interest
Lease liabilities – Building
"Le Virage"
Lease liabilities – Premises
Innate Inc
Lease liabilities – Laboratory
equipment
Lease liabilities – Vehicles
Lease liabilities - Printers
Loans – Equipment
Loans – Building (4)
Total
December 31,
2021
Proceeds from
borrowing
Proceeds from
lease liabilities
and other non
cash effects
Repayments of
borrowings
and lease
liabilities
December 31,
2022
20,000
8,700
—
1,875
391
464
53
35
209
12,525
44,251
—
—
—
—
—
—
—
—
—
—
—
—
—
15
—
15
—
12
—
—
—
42
—
—
—
20,000
8,700
15
(522)
1,353
(61)
(177)
(32)
(8)
(55)
(1,187)
(2,042)
345
287
33
27
154
11,338
42,251
(1) In 2013, the Company was granted an interest-free loan for innovation (“PTZI”) by BPI France
relating to the program lacutamab IPH4102 for an amount of €1,500 thousand.
(2) As a reminder, on August 11, 2020, the Company signed a financing contract with Bpifrance
Financement as part of the program set up by the French government to help develop a therapeutic
solution with a preventive or curative aim against COVID-19. This funding, for a maximum amount of €
6.8m, consisted of (i) an advance repayable only in the event of technical and commercial success and (ii)
a non-repayable grant. This funding should have been received in four successive installments. The first
tranche of 1.7 million euros was paid at signing, and the other three tranches should be received after
successful completion of certain clinical milestones, particularly around Phase 2 of the FORCE trial. The
portion relating to the repayable advance included in this first tranche amounted to €1,454 thousand as of
December 31, 2020 (including actualization). As of December 31, 2021, this financing is considered by
the Company to be non-refundable, in accordance with the terms of the agreement, in light of the
technical and commercial failure of the project based on the results of the Phase 2 "Force" trial evaluating
avdoralimab in COVID-19, published on July 6, 2021 (see note 13.2).
(3) On January 5, 2022, the Company announced that it had obtained €28.7 million in non-dilutive
financing in the form of two State Guaranteed Loans from Société Générale (€20.0 million) and BNP
Paribas (€8.7 million). The Company received the funds related to these two loans on December 27 and
30, 2021 respectively. Both loans have an initial maturity of one year with an option to extend to five
years from August 2022. They are 90% guaranteed by the French government as part of the package of
measures put in place by the French government to support companies during the COVID-19 pandemic.
In August 2022, the Company has requested the extension of these two loans repayment for an additional
period of five years starting in 2022 and including a one-year grace period. Consequently, the Company
has obtained agreements from Société Générale and BNP Paribas. The effective interest rates applied to
F-41
these contracts during the additional period are 1.56% and 0.95% for Société Générale and BNP Paribas
loans, respectively, excluding insurance and guarantee fees, with an amortization exemption for the entire
year 2023. During this grace period, the Company will only be liable for the payment of interest and the
guarantee fees, with amortization of the two loans starting in 2024 over a period of four years. The state
guarantee fees amounts to €877 thousand and €379 thousand for Société Générale and BNP Paribas loans
respectively.
(4) On July 3, 2017, the Company borrowed from the Bank “Société Générale” in order to finance the
construction of its future headquarters. This loan amounting to a maximum of €15,200 thousand will be
raised during the period of the construction in order to pay the supplier payments as they become due. As
of December 31, 2018 and 2019, the loan was raised at an amount of €1,300 thousand.
The loan release period was limited to August 30, 2019. On August 30, 2019, the Company drew down
the remaining portion of the €15,200 thousand loan granted, for an amount of €13,900 thousand. The
reimbursement of the capital has begun in August 30, 2019 and will proceed until August 30, 2031 (12
years). Given the development of its portfolio and in particular the refocusing of its activities on research
and development, the Company has for the time being suspended the project to build its new head office
on the land acquired in Luminy. In the meantime, the loan will be used to finance several structuring
projects (improvement of the information system, development of a commercial platform, development of
additional premises rented, etc.). As of December 31, 2022, the remaining capital of the loan amounted to
€11,338 thousand. The Company authorized collateral over financial “Société Générale” instruments
amounting to €15,200 thousand. The security interest on the pledge financial instruments will be released
in accordance with the following schedule: €4,200 thousand in July 2024, €5,000 thousand in August
2027 and €6,000 thousand in August 2031.
This loan bears a fixed interest rate of 2.01%. It is subject to a covenant based on the assumption that the
total cash, cash equivalents and current and non-current financial assets are at least equal to principal as of
financial year end.
The table below shows the schedule for the contractual flows (principal only) as of December 31, 2020,
2021 and 2022 respectively :
In thousand euros
Current financial liabilities
BPI PTZI IPH41
BPI Refundable advance - FORCE
State guaranteed loan Société Générale
State guaranteed loan BNP Paribas
State guaranteed loans - accrued interest
Lease finance obligations – Rent Le Virage
Lease liabilities – Premises Innate Inc
Lease finance obligations – Laboratory equipment
Lease liabilities – Vehicles
Lease liabilities - Printers
Loans - Equipment
Loans - Building
Total – Current financial liabilities
Year ended December 31,
2021
2022
2020
150
—
—
—
—
511
72
175
13
6
55
1,161
2,142
—
—
20,000
8,700
—
522
74
177
23
8
55
1,187
30,748
—
—
—
—
15
532
90
177
16
9
55
1,210
2,102
In thousand euros
Non-Current financial liabilities
BPI PTZI IPH41(1)
Year ended December 31,
2021
2022
2020
—
—
—
F-42
BPI Refundable advance - FORCE
State guaranteed loan Société Générale
State guaranteed loan BNP Paribas
State guaranteed loans - accrued interest
Lease finance obligations – Building Le Virage
Lease liabilities – Premises Innate Inc
Lease finance obligations – Laboratory equipment
Lease finance obligations – Vehicles
Lease liabilities - Printers
Loans - Equipment
Loans - Building
Total – Non-Current financial liabilities
1,454
—
—
—
1,876
375
463
8
35
208
12,526
16,945
—
—
—
—
1,352
317
287
30
26
154
11,338
13,503
—
20,000
8,700
—
820
255
110
17
18
99
10,128
40,149
The table below shows the schedule for the contractual flows (being principal and interest payments):
(in thousands of euro)
State guaranteed loan Société Générale
State guaranteed loan BNP Paribas
State guaranteed loans - accrued interest
Lease finance obligations – Rent Le Virage
Lease liabilities – Premises Innate Inc.
Lease liabilities – Laboratory equipment
Lease liabilities – Vehicles
Lease liabilities - Printers
Loans – Equipment
Loan – Building
Total
10) Employee benefits
Defined benefit obligations
(in thousands of euro)
Allowance for retirement defined benefit
Allowance for seniority awards
Total Defined benefit obligations
≤ 1 year
2 to 5 years
included
≥ 5 years
Total
312
86
15
558
96
179
19
9
57
1,427
2,758
20,670
8,884
—
838
312
110
20
18
100
5,706
36,658
—
—
—
—
—
—
—
—
—
5,112
5,112
20,982
8,970
15
1,396
408
289
39
27
157
12,245
44,528
Year ended December 31,
2020
2021
2022
3,713
463
4,177
2,544
432
2,975
2,184
366
2,550
French law requires payment of a lump sum retirement indemnity to employees based on years of service,
the rights guaranteed by the collective agreements and annual compensation at retirement. Benefits do not
vest prior to retirement. The Company pays for this defined benefit plan. It is calculated as the present
value of estimated future benefits to be paid, applying the projected unit credit method whereby each
period of service is seen as giving rise to an additional unit of benefit entitlement, each unit being
measured separately to build up the final. As a reminder, in April 2021, the IFRIC ( or "IFRS
Interpretations Committee") sent a proposal to the IAS Board (International Accounting Standards Board)
to change the way in which the liabilities for certain defined benefit plans are calculated. The IAS Board
endorsed this position in June 2021. The impacts of this change in valuation method are detailed below.
F-43
On March 24, 2016, the Company entered into an internal labor agreement with the employees
representatives whereby the Company is committed to paying a seniority award after 15 years and 20
years of employment. This award is paid on the anniversary date. A similar award existed for employees
having a seniority of 10 years but was not booked due to its insignificant amount. As such, in 2016 the
Company recorded a provision for seniority awards and a corresponding charge included in “Personnel
costs other than share-based payments” (see Note 14) other than payments in shares. These awards meet
the definition of other long-term benefits under IAS 19. This provision is determined by an external
actuary firm based on the assumptions disclosed hereafter and amounts to €366 thousand as of December
31, 2022 (€432 thousand as of December 31, 2021).
The main actuarial assumptions used to evaluate retirement benefits are the following:
Economic assumptions
Discount rate (iBoxx Corporate AA) for retirement
Annual rate of increase in wages
Demographical assumptions
Type of retirement
Annual mobility rate
Rate of contributions
Rate of wages costs
Age at retirement
- Executives
- Non executives
Mortality table
Annual turnover by tranche of age
16-24 years
25-29 years
30-34 years
35-39 years
40-44 years
45-49 years
+50 years
Year ended December 31,
2021
2022
2020
0.50%
3.00%
0.95%
3.00%
3.75%
4.00%
At the initiative
of the employee
2.6%
45.17%
22.06%
At the initiative
of the employee
4.2%
48.39%
24.18%
At the initiative
of the employee
4.3%
47.07%
23.46%
64 years
62 years
TH-TF 00-02
All personnel
6.0%
5.0%
3.7%
3.0%
2.0%
1.0%
0%
64 years
62 years
TH-TF 00-02
All personnel
12.0%
9.0%
7.0%
4.5%
3.0%
1.5%
0%
64 years
62 years
TH-TF 00-02
All personnel
12.0%
10.0%
7.0%
5.0%
3.0%
1.5%
0%
Changes in the projected benefit obligation for the periods presented were as follows (in thousands of
euro):
As of January 1, 2020
Service cost
Interest costs
Actuarial loss
As of December 31, 2020
IAS19 Restatement related to the change in calculation method - IFRIC (1)
Service cost
Interest costs
F-44
3,760
252
(35)
200
4,177
(1,054)
484
(47)
Actuarial gain
As of December 31, 2021
Service cost
Interest costs
Actuarial loss
As of December 31, 2022
(584)
2,976
427
(62)
(790)
2,550
(1) In its April 2021 Update, the IFRS IC published a final agenda decision clarifying how to calculate the
obligation relating to certain defined benefit plans under which the retirement benefit is (i) contingent on
the employee being employed by the entity at the time of retirement; (ii) capped at a specified number of
years of service; and (iii) linked to the employee's length of service at the date of retirement. In that
decision, the IFRS IC took the view that the obligation should be recognized only over the years of
service preceding the date of retirement in respect of which the employee generates entitlement to the
benefit. The application of this decision has led to a change in accounting method, the effects of which
should be taken into account retrospectively in accordance with IAS 8. However, as the Company
considers the impact of this change of method on defined benefit obligation and the income statement to
be insignificant, these impacts have not been restated for years prior to January 1, 2021. The effects of
this change of method are therefore taken into account retrospectively as of January 1, 2021 in respect of
2020's and prior years defined benefit obligation. The adjustment at that date corresponds to a reduction
in the 2020 commitments in the amount of €1,054 thousand. This reversal has been offset against
previous reserves and retained earnings.
There is no asset covering the defined benefit obligations.
An increase/decrease of +/- 50 basis point of the discount rate would result in a decrease/increase of the
total benefit obligation of €174 thousand.
The amounts recognized as an expense linked to defined contributions plans amounted to €1,420
thousand, €1,434 thousand and €1,432 thousand in the years ended December 31, 2020, 2021 and 2022,
respectively.
11) Share capital and share based payments
a)
Share capital
The Company manages its capital to ensure that the Company will be able to continue as a going concern
while maximizing the return to shareholders through the optimization of the debt and equity balance.
The Company has never declared or paid any dividends on its ordinary shares. The Company does not
anticipate paying cash dividends on its equity securities in the foreseeable future and intend to retain all
available funds and any future earnings for use in the operation and expansion of its business, given our
state of development.
As of December 31, 2022, the Company’s share capital amounted to €4,011,308 divided into (i)
79,542,627 ordinary shares, each with a nominal value of €0.05, (ii) 6,881 “2016” free preferred shares,
each with a nominal value of €0.05 and (iii) 7,581 “2017” free preferred shares, each with a nominal
value of €0.05, respectively fully paid up.
Share capital does not include BSAs, BSAAR,AGAs and AGAPs that have been granted to certain
investors or natural persons, both employees and non-employees of the Company, but not yet exercised.
In October 21, 2019 and December 30, 2019, the retention period for the “2016 free preferred shares” has
ended. The number of ordinary shares to which the conversion of one preferred share entitle has been
F-45
determined according to the fulfillment of the performance criteria. Holders of “2016” preferred shares”
are entitled to vote at our shareholders’ meetings, to dividends and to preferential subscription rights, on
the basis of the number of ordinary shares to which they are entitled if they convert their preferred shares.
In April 3, 2021, the retention period for the "2017 free preferred shares" has ended. The number of
ordinary shares to which the conversion of one preferred share entitle has been determined according to
the fulfillment of the performance criteria. According to these same performance criteria, the Executive
Board of April 7, 2021 noted that the "2017 preferred shares" did not give right to any ordinary shares.
The “2017 preferred shares” will not be redeemed by the Company and will remain incorporated into the
capital, unless subsequently decided by the Executive Board. As the conversion is void, the "2017
preferred shares" no longer give the right to vote at our general meetings, nor to receive dividends.
The table below presents the historical changes in the share capital of the Company as of December 31,
2020, 2021 and 2022, respectively:
Nature of the Transactions
Balance as of January 1, 2020
Capital increase by issuance of
common shares (exercise of
share warrants)
Capital increase by issuance of
common shares (definitive
acquisition of free shares )
Capital increase by issuance of
common shares (exercise of
share warrants)
Capital increase by issuance of
common shares (definitive
acquisition of free shares )
Capital increase by issuance of
common shares (conversion of
preferred shares in common
shares)
Capital increase by issuance of
common shares (conversion of
preferred shares in common
shares)
Capital increase by issuance of
common shares (conversion of
preferred shares in common
shares)
Number of
Share
Capital
3,941,281
Share
premium
369,617,017
Common
shares
78,811,114
Preferred
shares
Nominal
value
14,507
€0.05
75
2,985
1,500
4,283
(4,283)
85,650
1,250
43,000
25,000
2,869
(2,869)
57,376
€0.05
€0.05
€0.05
€0.05
32
(32)
650
(5)
€0.05
226
(226)
4,550
(35)
—
32
(32)
650
(5)
€0.05
Share based payments
—
2,475,422
—
€0.05
Date
January 15, 2020
January 27, 2020
July 7, 2020
July 13, 2020
September 11,
2020
September 24,
2020
December 31, 2020
December 31, 2020
December 31, 2020
3,950,048
372,130,982
78,986,490
14,462
€0.05
(1) Share issuance costs representing incremental expenses directly attributable to the offering of new shares in the IPO on the Nasdaq and in
the European Private Placement (together the “Global Offering”) were recorded through equity for an amount of €621 thousand. They
F-46
consist mainly of legal, financial, accounting and printing fees associated with drafting and filing the registration statement of Innate
Pharma. The other incremental costs incurred in the Global Offering were expensed for an amount of €2,150 thousand.
Nature of the Transactions
Balance as of January 1, 2021
Capital increase by issuance of
common shares (exercise of
share warrants)
Capital increase by issuance of
common shares (exercise of
share warrants)
Capital increase by issuance of
common shares (conversion of
preferred shares in common
shares)
Capital increase by issuance of
common shares (definitive
acquisition of free shares )
Capital increase by issuance of
common shares (exercise of
share warrants)
Capital increase by issuance of
common shares (exercise of
share warrants)
Number of
Share
Capital
3,950,048
Share
premium
372,130,982
Common
shares
78,986,490
Preferred
shares
Nominal
value
14,462
€0.05
1,500
59,700
30,000
—
€0.05
222
7,637
4,440
—
€0.05
548
(548)
11,050
(85)
€0.05
2,418
(2,418)
48,362
—
€0.05
625
21,500
12,500
—
€0.05
10,000
398,000
200,000
—
€0.05
Date
June 4, 2021
July 7, 2021
July 19, 2021
July 22, 2021
July 22, 2021
August 6, 2021
December 31, 2021
Capital increase by issuance of
common shares (conversion of
preferred shares in common
shares)
Capital increase by issuance of
common shares (definitive
acquisition of free shares )
December 31, 2021
December 31, 2021 Share based payments
December 31, 2021
1,819
(1,819)
36,660
(282)
€0.05
10,656
(10,656)
213,125
—
€0.05
—
3,977,836
2,617,289
375,219,667
—
79,542,627
—
14,095
€0.05
F-47
Date
February 14, 2022
February 14, 2022
February 14, 2022
April 22, 2022
July 13, 2022
Nature of the Transactions
Balance as of January 1, 2022
Capital increase by issuance of
common shares (exercise of
share warrants)
Capital increase by issuance of
common shares
Capital increase by issuance of
common shares (definitive
acquisition of free shares )
Capital increase by issuance of
common shares (definitive
acquisition of free shares )
Capital increase by issuance of
common shares (definitive
acquisition of free shares )
Capital increase by issuance of
common shares (exercise of
share warrants)
July 25, 2022
December 16, 2022 Subsciption of share warrants
Capital increase by issuance of
common shares (conversion of
preferred shares in common
shares)
November 7, 2022
December 31, 2022 Share based payments
December 31, 2022
Number of
Share
Capital
3,977,836
Share
premium
375,219,667
Common
shares
79,542,627
Preferred
shares
Nominal
value
14,095
€0.05
38
1,493
750
—
€0.05
2,316
187,596
46,320
—
€0.05
6,948
(6,948)
138,960
—
€0.05
1,250
(1,250)
25,000
—
€0.05
681
(681)
13,614
—
€0.05
6,287
(6,287)
125,748
—
9,995
—
15,953
(15,953)
319,050
—
—
—
—
4,011,308
4,249,113
379,636,744
—
80,212,069
—
14,095
€0.05
€—
€0.05
—
€0.05
Holding by the Company of its own shares
The Company held 18,575 of its own shares as of December 31, 2022.
b)
Share based payments
The Company has issued BSAs, BSAARs, stock options, AGAs and AGAPs as follows as of December
31, 2020, 2021 and 2022, respectively: :
F-48
Date
Types
Sept. 9, 2011
May 27, 2013
July 1, 2015
October 21, 2016
October 21, 2016
October 21, 2016
December 30, 2016
December 30, 2016
April 3, 2018
April 3, 2018
April 3, 2018
July 3, 2018
November 20, 2018
November 20, 2018
January 14, 2019
April 29, 2019
July 3, 2019
November 4, 2019
November 4, 2019
July 13, 2020
August 5, 2020
August 5, 2020
July 21, 2020
July 29, 2011
July 17, 2013
July 16, 2014
April 27, 2015
July 1, 2015
BSAAR 2011
BSAAR 2012
BSAAR 2015
AGAP
Management
2016-1
AGAP Employees
2016-1
AGA Management
2016-1
AGAP
Management
2016-2
AGA Management
2016-2
AGAP Employees
2017-1
AGAP Management
2017-1
AGA Employees
2017
AGA Bonus 2018-1
AGAP Perf
Employees 2018-1
AGAP Perf
Management
2018-1
AGA Employees
2018
AGA New
Members 2017-1
AGA Bonus 2019-1
AGAP 2019
Employees 2019
AGAP 2019
Management 2019
AGA Bonus 2020-1
AGA Perf
Employees 2020-1
AGA Perf
Management
2020-1
Stock Options
2020-1
BSA 2011-2
BSA 2013
BSA 2014
BSA 2015-1
BSA 2015-2
September 20, 2017 BSA 2017
Total as of
December 31,
2020
Number of
warrants
issued as of
12/31/2020
Number of
warrants
void as of
12/31/2020
Number of
warrants
exercised as
of
12/31/2020
Number of
warrants
outstanding
as of
12/31/2020
Maximum
number of
shares to be
issued as of
12/31/2020
Exercise
price per
share (in €)
650,000
146,050
1,050,382
—
—
2,720
395,000
85,950
1,940
255,000
60,100
255,000
60,100
1,045,722
1,045,722
2,000
2,486
50,000
3,000
250,000
5,725
2,400
550
251
—
—
—
833
800
—
50
1,450
188,500
2,185
284,050
50,000
—
—
—
3,000
333,000
250,000
—
—
—
—
4,892
489,200
1,600
160,000
114,500
4,000
110,500
67,028
469
66,559
327,500
85,000
260,000
60,000
—
—
—
—
—
—
242,500
242,500
200,000
200,000
90,650
5,000
85,650
—
—
—
25,000
25,000
57,376
—
—
25,000
57,376
—
—
546,700
86,100
355,000
30,000
79,861
—
766,650
70,540
710,000
—
102,000
72,000
225,000
237,500
150,000
70,000
14,200
37,000
—
—
—
—
—
—
183,060
191,140
75,000
—
—
—
—
—
—
—
—
—
460,600
460,600
325,000
325,000
79,861
79,861
696,110
696,110
710,000
710,000
30,000
41,940
46,360
75,000
70,000
14,200
37,000
30,000
41,940
46,360
75,000
70,000
14,200
37,000
6,398,008
418,263
1,552,225
4,427,520
5,869,143
F-49
€2.04
€2.04
€7.20
€—
€—
€—
€—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
€1.77
€2.36
€8.65
€9.59
€14.05
€11.00
Date
Types
Number of
warrants
issued as of
12/31/2021
Number of
warrants
void as of
12/31/2021
Number of
warrants
exercised as
of
12/31/2021
Number of
warrants
outstanding
as of
12/31/2021
Maximum
number of
shares to be
issued as of
12/31/2021
Exercise
price per
share (in €)
650,000
146,050
1,050,382
25,000
—
2,720
625,000
85,950
1,940
—
60,100
—
60,100
1,045,722
1,045,722
Sept. 9, 2011
May 27, 2013
July 1, 2015
October 21, 2016
October 21, 2016
October 21, 2016
December 30, 2016
December 30, 2016
April 3, 2018
April 3, 2018
April 3, 2018
July 3, 2018
November 20, 2018
November 20, 2018
January 14, 2019
April 29, 2019
July 3, 2019
November 4, 2019
November 4, 2019
July 13, 2020
August 5, 2020
August 5, 2020
July 22, 2021
October 1, 2021
October 1, 2021
July 21, 2020
July 29, 2011
July 17, 2013
July 16, 2014
April 27, 2015
July 1, 2015
BSAAR 2011
BSAAR 2012
BSAAR 2015
AGAP
Management
2016-1
AGAP Employees
2016-1
AGA Management
2016-1
AGAP
Management
2016-2
AGA Management
2016-2
AGAP Employees
2017-1
AGAP Management
2017-1
AGA Employees
2017
AGA Bonus 2018-1
AGAP Perf
Employees 2018-1
AGAP Perf
Management
2018-1
AGA Employees
2018
AGA New
Members 2017-1
AGA Bonus 2019-1
AGAP 2019
Employees 2019
AGAP 2019
Management 2019
AGA Bonus 2020-1
AGA Perf
Employees 2020-1
AGA Perf
Management
2020-1
AGA Bonus 2021-1
AGA Perf
Employees 2021-1
AGA Perf
Management
2021-1
Stock Options
2020-1
BSA 2011-2
BSA 2013
BSA 2014
BSA 2015-1
BSA 2015-2
2,000
2,486
50,000
3,000
250,000
5,725
2,400
550
251
—
—
—
5,725
2,400
250,000
—
—
114,500
4,000
110,500
67,028
469
66,559
327,500
224,375
103,125
260,000
150,000
110,000
90,650
5,000
85,650
250
167
1,200
156,000
2,068
268,840
50,000
—
—
—
3,000
333,000
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
25,000
25,000
57,376
—
—
—
—
356,800
356,800
325,000
325,000
48,362
13,614
13,614
—
—
—
—
—
—
200,000
191,140
75,000
—
—
516,824
516,824
680,000
680,000
125,748
125,748
1,049,100
1,049,100
580,000
580,000
—
—
46,360
75,000
70,000
14,200
—
—
46,360
75,000
70,000
14,200
25,000
57,376
—
—
546,700
189,900
355,000
79,861
30,000
17,885
766,650
249,826
710,000
30,000
125,748
—
1,066,600
17,500
610,000
30,000
102,000
102,000
225,000
237,500
150,000
70,000
14,200
25,000
—
—
—
—
F-50
€2.04
€2.04
€7.20
€—
€—
€—
€—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
€1.77
€2.36
€8.65
€9.59
€14.05
September 20, 2017 BSA 2017
37,000
—
—
37,000
37,000
€11.00
Total as of
December 31, 2021
8,200,356
1,112,601
2,061,019
5,026,736
5,778,308
Date
Types
Sept. 9, 2011
May 27, 2013
July 1, 2015
October 21, 2016
October 21, 2016
October 21, 2016
December 30, 2016
December 30, 2016
April 3, 2018
April 3, 2018
April 3, 2018
July 3, 2018
November 20, 2018
November 20, 2018
January 14, 2019
April 29, 2019
July 3, 2019
November 4, 2019
November 4, 2019
July 13, 2020
August 5, 2020
August 5, 2020
July 22, 2021
October 1, 2021
October 1, 2021
February 12, 2022
BSAAR 2011
BSAAR 2012
BSAAR 2015
AGAP
Management
2016-1
AGAP Employees
2016-1
AGA Management
2016-1
AGAP
Management
2016-2
AGA Management
2016-2
AGAP Employees
2017-1
AGAP Management
2017-1
AGA Employees
2017
AGA Bonus 2018-1
AGAP Perf
Employees 2018-1
AGAP Perf
Management
2018-1
AGA Employees
2018
AGA New
Members 2017-1
AGA Bonus 2019-1
AGAP 2019
Employees 2019
AGAP 2019
Management 2019
AGA Bonus 2020-1
& 2
AGA Perf
Employees 2020-1
AGA Perf
Management
2020-1
AGA Bonus 2021-1
AGA Perf
Employees 2021-1
AGA Perf
Management
2021-1
AGA "Plan Epargne
Entreprise" 2022
Number of
warrants
issued as of
12/31/2022
Number of
warrants
void as of
12/31/2022
Number of
warrants
exercised as
of
12/31/2022
Number of
warrants
outstanding
as of
12/31/2022
Maximum
number of
shares to be
issued as of
12/31/2022
Exercise
price per
share (in €)
650,000
146,050
1,050,382
25,000
—
2,720
625,000
86,700
1,940
—
59,350
—
59,350
1,045,722
1,045,722
250
167
1,200
156,000
2,068
268,840
50,000
—
—
—
3,000
333,000
2,000
2,486
50,000
3,000
250,000
5,725
2,400
550
251
—
—
—
5,725
2,400
250,000
—
—
114,500
4,000
110,500
67,028
469
66,559
327,500
224,375
103,125
260,000
150,000
110,000
90,650
5,000
85,650
25,000
57,376
—
—
25,000
57,376
546,700
375,150
171,550
355,000
207,500
147,500
79,861
17,885
61,976
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
766,650
286,306
710,000
60,000
—
—
480,344
480,344
650,000
650,000
125,748
—
125,748
—
—
1,066,600
95,600
610,000
90,000
—
—
971,000
971,000
520,000
520,000
138,960
—
138,960
—
—
F-51
€2.04
€2.04
€7.20
€—
€—
€—
€—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
October 3, 2022
December 12, 2022
December 12, 2022
July 21, 2020
July 29, 2011
July 17, 2013
July 16, 2014
April 27, 2015
July 1, 2015
AGA Bonus 2022-1
AGA Perf
Employees 2022-1
AGA Perf
Management
2022-1
Stock Options
2020-1
BSA 2011-2
BSA 2013
BSA 2014
BSA 2015-1
BSA 2015-2
September 20, 2017 BSA 2017
December 16, 2022
BSA 2022-1
Total as of
December 31, 2022
128,061
1,371,500
550,000
—
—
—
102,000
102,000
225,000
237,500
150,000
70,000
14,200
37,000
40,000
25,000
—
—
—
—
—
31,740
—
—
—
—
200,000
191,140
75,000
—
—
—
—
128,061
128,061
1,371,500
1,371,500
550,000
550,000
—
—
46,360
75,000
70,000
14,200
37,000
8,260
—
—
46,360
75,000
70,000
14,200
37,000
8,260
10,428,877
1,711,671
2,684,141
6,033,065
6,784,637
€—
€—
€—
€—
€1.77
€2.36
€8.65
€9.59
€14.05
€11.00
€2.31
AGA
Details of AGA
Date of grant
(Board of
Directors)
Vesting period
(years)
Non
transferability
period
Number of free
shares granted
Share entitlement
per free share
Grant date share
fair value
Expected
dividends
Performance
conditions
Expected
turnover (yearly
basis)
AGAP
Management
2016-1
AGAP
Employees
2016-1
AGA
Management
2016-1
AGA Employees
2016-1
AGAP
Management
2016-2
October 21,
2016
October 21,
2016
October 21,
2016
October 21,
2016
October 21,
2016
1 year
1 year
3 years
1 year
1 year
2 years after the
vesting period
end
2 years after the
vesting period
end
None
2 years after the
vesting period
end
2 years after the
vesting period
end
2,000
2,486
50,000
99,932
3,000
(1)
130
(1)
130
1
1
111
€10.87
€10.87
€10.87
€10.87
€12.73
None
Yes
5%
None
Yes
5%
None
None
None
None
None
Yes
—
5%
9%
F-52
Volatility
Fair value per
AGA
40%
€911
40%
€911
—
—
€10.55
€10.55
40%
€956
In October 21, 2019 and December 30, 2019, the retention period for the “2016 free preferred shares” has
ended. The number of ordinary shares to which the conversion of one preferred share entitle has been
determined according to the fulfilment of the performance criteria. Holders of “2016” preferred shares”
are entitled to vote at our shareholders’ meetings, to dividends and to preferential subscription rights, on
the basis of the number of ordinary shares to which they are entitled if they convert their preferred shares.
Date of grant (Board of
Directors)
Vesting period (years)
Non transferability
period
Number of free shares
granted
Share entitlement per
free share
Grant date share fair
value
Expected dividends
Performance conditions
Expected turnover
(yearly basis)
Volatility
Fair value per AGA
AGA
Management
2016-2
December 30,
2016
3 years
None
AGA Employees
2016-2
AGA Bonus
2017
AGA Employee
2017
AGAP
Employees
2017-1
December 30,
2016
1 year
2 years after the
vesting period
end
September 20,
2017
1 year
1 year after the
vesting period
end
April 3, 2018
April 3, 2018
1 year
1 year after the
vesting period
end
1 year
2 years after the
vesting period
end
250,000
149,943
114,500
28,556
5,725
1
1
1
1
100
€12.73
€12.73
None
None
—
—
€14.61
None
None
5%
—
€10.55
€5.52
None
Yes
4
55
€5.83
€10.90
€5.52
None
None
—%
—%
€10.30
None
Yes
5%
55%
€90
F-53
Date of grant (Board of
Directors)
Vesting period (years)
Non transferability
period
Number of free shares
granted
Share entitlement per
free share
Grant date share fair
value
Expected dividends
Performance conditions
Expected turnover
(yearly basis)
Volatility
Fair value per AGA
Date of grant (Board of
Directors)
Vesting period (years)
Non transferability
period
Number of free shares
granted
Share entitlement per
free share
Grant date share fair
value
Expected dividends
Performance conditions
Expected turnover
(yearly basis)
Volatility
Fair value per AGA
AGAP
Management
2017
AGA Bonus
2018
AGA Perf
Employees 2018
April 3, 2018
July 3, 2018
1 year
2 years after the
vesting period
end
1 year
1 year after the
vesting period
end
AGA Perf
Management
2018
November 20,
2018
3 years
AGA New
Members 2017-1
April 29, 2019
3 years
November 20,
2018
3 years
None
None
None
2,400
100
€5.52
None
Yes
11%
55%
€90
67,028
327,500
260,000
25,000
1
1
1
1
€5.06
None
Yes
—
—
€4.69
€8.00
€8.00
€5.74
None
Yes
4%
45%
None
Yes
10%
45%
€3.81
€3.81
None
No
10%
—
€5.74
AGA Employees
2018
AGA Bonus
2019-1
AGA Perf
Employees 2019
January 14,
2019
1 year
1 year after the
vesting period
end
July 3, 2019
1 year
1 year after the
vesting period
end
AGA Perf
Management
2019
November 4,
2019
3 years
November 4,
2019
3 years
None
None
AGA Bonus
2020
July 13, 2020
1 year
1 year after the
vesting period
end
90,650
57,376
546,700
355,000
79,861
1
€7.31
None
No
4.03%
N/A
€7.31
1
1
1
1
€3.13
€3.13
€6.40
None
Yes
10%
45%
None
Yes
10%
45%
€3.13
€3.13
None
No
—%
—%
€6.40
€5.90
None
No
—
—
€5.72
F-54
Date of grant (Board of
Directors)
Vesting period (years)
Non transferability
period
Number of free shares
granted
Share entitlement per
free share
Grant date share fair
value
Expected dividends
Performance conditions
Expected turnover
(yearly basis)
Volatility
Fair value per AGA
AGA Perf
Employees
2020-1
AGA Perf
Management
2020-1
AGA Bonus
2021-1
August 5, 2020 August 5, 2020
July 22, 2021
3.5 years
3.5 years
None
None
1 year
1 year
AGA Perf
Employees
2021-1
October 1,
2021
3.5 years
AGA Perf
Management
2021-1
October 1,
2021
3.5 years
None
None
769,202
710,000
125,748
1,066,600
610,000
1
€2.94
None
Yes
10.00%
45.00%
€2.94
1
€2.94
None
Yes
10.00
45.00
€2.94
1
€3.43
None
No
—
—
€3.43
1
€1.76
None
Yes
13.32
50.00
€1.76
1
€1.76
None
Yes
13.32
50.00
€1.76
AGA "Plan
Epargne
Entreprise"
2022
AGA Bonus
2022-1
AGA Perf
Employees
2022-1
AGA Perf
Management
2022-1
Date of grant (Board of
Directors)
February 12,
2022
October 3,
2022
December 12,
2022
December 12,
2022
Vesting period (years)
Non transferability
period
Number of free shares
granted
Share entitlement per
free share
Grant date share fair
value
Expected dividends
Performance conditions
Expected turnover
(yearly basis)
Volatility
Fair value per AGA
None
None
1 year
3.1 years
3.1 years
None
None
None
138,960
128,061
1,371,500
550,000
1
€1.39
None
Yes
10.50
50.00
€1.39
1
€1.39
None
Yes
10.50
50.00
€1.39
1
€4.10
None
No
—%
—%
€4.10
1
€3.89
None
No
—
—
€3.89
F-55
Change in Number of AGAs Outstanding
Number of AGAs
Balance at beginning of period
Granted during the period
Forfeited during the period
Exercised during the period
Expired during the period
Balance at end of period
Breakdown of the Closing Balance
Number of AGAs
AGAP Management 2016-1
AGAP Employees 2016-1
AGAP 2016-2
AGAP Management 2017
AGAP Perf Employees 2018
AGAP Perf Management 2018
AGA New Members 2017-1
AGA Perf Employees 2019-1
AGA Perf Management 2019-1
AGA Bonus 2020-1
AGA Perf Employees 2020-1
AGA Perf Management 2020-1
AGA Bonus 2021-1
AGA Perf Employees 2021-1
AGA Perf Management 2021-1
AGA Bonus 2022-1
AGA Perf Employees 2022-1
AGA Perf Management 2022-1
TOTAL
Year ended December 31,
2020
1,607,345
1,556,511
(268,587)
(143,071)
—
2,752,198
2021
2,752,198
1,802,348
(614,338)
(261,854)
—
3,678,354
2022
3,678,354
2,188,521
(567,330)
(622,372)
—
4,677,173
Year ended December 31,
2020
2021
2022
Outstanding
Outstanding
Outstanding
1,450
2,185
3,000
1,600
242,500
200,000
25,000
460,600
325,000
79,861
696,110
710,000
—
—
—
—
—
—
2,752,198
1,200
2,068
3,000
—
—
—
25,000
356,800
325,000
13,614
516,824
680,000
125,748
1,049,100
580,000
—
—
—
3,678,354
1,200
2,068
3,000
—
—
—
—
—
—
—
480,344
650,000
—
971,000
520,000
128,061
1,371,500
550,000
4,677,173
The fair value of granted free shares is based on the closing price of the Company’s share at grant date,
reduced when necessary by an estimated turn-over rate. This estimated fair value is recognized as
operating expenses on a straight-line basis over the vesting period.
F-56
Free performance shares 2018 (AGA Perf Employees 2018-1 and AGA Perf Management 2018-1)
Free performance shares granted in 2018 are subject to share price conditions and a vesting kicker
triggered by the performance of an internal condition, which is the success of certain clinical trials.
The fair value of these free performance shares is based on a third-party valuation report. The valuation
method used to estimate the fair value of these free performance shares is presented below:
•
Estimation of the expectation of gain associated with internal and share price conditions, made
on the basis of a CAPM model of the share price using a Monte Carlo approach;
• Adjustment of the estimation by applying expected turnover rates.
Changes in internal conditions are taken into account in the revision of the estimated number of free
performance shares expected to vest during the vesting period.
On January 3, 2022, the Executive Board determined the achievement of the performance conditions and
the final vesting of the free performance shares 2018 as of November 20, 2021. The underlying
performance conditions were thus achieved at 55%, noting on November 20, 2021 the final acquisition of
103,125 “AGA Perf Employees 2018-1” as well as 110,000 “AGA Perf Management 2018-1”.
Expenses were €618 thousand, €(232) thousand (income) the financial years ended December 31, 2020,
and 2021 respectively. These instruments were definitively acquired during the 2021 financial year.
Consequently, no expense relating to these plans was recognized during the financial year ended
December 31, 2022.
AGA 2018-1 (Employees)
Expenses were €23 thousand for the financial year ended December 31, 2020, and respectively. These
instruments were definitively acquired during the 2020 financial year. Consequently, no expense relating
to these plans was recognized during the financial year ended December 31, 2021 and 2022, respectively.
AGA 2017-1 Management (New Members)
Expenses were €43 thousand, €71 thousand and nil for the financial years ended December 31, 2020 2021
and 2022, respectively.
Free performance shares 2019 (AGA Perf Employees 2019-1 / AGA Perf Management 2019)
Free performance shares granted in 2019 are subject to share price conditions and a vesting kicker
triggered by the performance of an internal condition, which is Lumoxiti's market penetration rate in the
United States.
The fair value of these free performance shares is based on a third-party valuation report. The valuation
method used to estimate the fair value of these free performance shares is presented below:
•
Estimation of the expectation of gain associated with internal and share price conditions, made
on the basis of a CAPM model of the share price using a Monte Carlo approach;
• Adjustment of the estimation by applying expected turnover rates.
On November 7, 2022, the Executive Board determined the achievement of the performance conditions
and the final vesting of the 2019 free performance shares as of November 4, 2022. The underlying
performance conditions were thus achieved at 50%. Consequently, on November 7, 2022, the Executive
Board carried out the definitive acquisition of 171,550 free performance shares under the "AGA Perf
Management 2019-1" plans.
F-57
.
Expenses were €867 thousand, €649 thousand and €(181) thousand (income) for the financial years ended
December 31, 2020, 2021 and 2022, respectively. Income relating to the 2022 financial year is explained
by the review of the performance conditions during the 2022 financial year with regard to the definitive
achievement of the vesting.
Free performance shares 2020 (AGA Perf Employees 2020-1 / AGA Perf Management 2020)
Free performance shares granted in 2020 are subject to share price conditions and two vesting kickers
triggered by the performance of internal conditions, which are :
• A commercial break-even point for Lumoxiti in the U.S. reached at the end of fiscal year 2023
(this criterion will not be met given the return of the commercial rights notified to AstraZeneca in
December 2020).
• Revenue from collaborative and licensing agreements accrued between the attribution and
definitive acquisition date (excluding payment by AstraZeneca for the first patient in Phase 3 for
monalizumab), reaching $100 million.
The fair value of these free performance shares is based on a third-party valuation report. The valuation
method used to estimate the fair value of these free performance shares is presented below:
•
Estimation of the expectation of gain associated with internal and share price conditions, made
on the basis of a CAPM model of the share price using a Monte Carlo approach;
• Adjustment of the estimation by applying expected turnover rates.
Expenses were €502 thousand, €1,253 thousand and €1,738 thousand for the financial year ended
December 31, 2020 2021 and 2022, respectively
AGA Bonus 2020-1
AGA Bonus 2020 were granted to the Executive members Committee who opted for these compensation
plans. For each recipient, the number of shares definitely acquired is equal to the cash equivalent of 50%
of the annual variable compensation increased by a 30% premium. In the event of an over-performance
(i.e. achieved target above 100%), the surplus is paid in cash.
Expenses were €394 thousand for the financial year ended December 31, 2020. These instruments were
definitively acquired during the 2021 financial year. Consequently, no expense relating to these plans
were recognized during the financial years ended December 31, 2021 and 2022, respectively.
Free performance shares 2021 (AGA Perf Employees 2021-1 / AGA Perf Management 2021-1)
Free performance shares granted in 2021 are subject to share price conditions and two vesting kickers
triggered by the performance of internal conditions, which are :
• An interim analysis demonstrates a predefined threshold of clinical activity in the INTERLINK-1
study (phase 3 study evaluating monalizumab in combination with cetuximab in patients with
squamous cell carcinoma of the head and neck and previously treated with chemotherapy).
• Obtaining positive Phase 2 results for a product in the Company's portfolio.
•
The start of a first clinical trial for a product in the Company's portfolio
F-58
The fair value of these free performance shares is based on a third-party valuation report. The valuation
method used to estimate the fair value of these free performance shares is presented below:
•
Estimation of the expectation of gain associated with internal and share price conditions, made
on the basis of a CAPM model of the share price using a Monte Carlo approach;
• Adjustment of the estimation by applying expected turnover rates.
Expenses were €473 thousand and €1,577 thousand for the financial years ended December 31, 2021 and
2022, respectively.
AGA Bonus 2021-1
AGA Bonus 2021 were granted to the Executive members Committee who opted for these compensation
plans. For each recipient, the number of shares definitely acquired is equal to the cash equivalent of 50%
of the annual variable compensation increased by a 50% premium. In the event of an over-performance
(i.e. achieved target above 100%), the surplus is paid in cash.
Expenses were €432 thousand for the financial year ended December 31, 2021.
Free performance shares 2022 (AGA Perf Employees 2022-1 / AGA Perf Management 2022-1)
Free performance shares granted in 2022 are subject to share market capitalization and three vesting
kickers triggered by the performance of internal conditions, which are :
•
•
•
The filing and approval of a BLA (Biologic License Application) application filed with the Food
and Drug Administration ("FDA") in the United States or the European Medicine Agency
("EMEA") in Europe for one of the Company's products.
The start of a first clinical trial for a product from the Company's portfolio.
The conclusion of a collaboration or license agreement.
The fair value of these free performance shares is based on a third-party valuation report. The valuation
method used to estimate the fair value of these free performance shares is presented below:
•
Estimation of the expectation of gain associated with internal and share price conditions, made
on the basis of a CAPM model of the share price using a Monte Carlo approach;
• Adjustment of the estimation by applying expected turnover rates.
Expenses were €46 thousand for the financial year ended December 31, 2022.
AGA Bonus 2022-1
AGA Bonus 2022 were granted to the Executive members Committee who opted for these compensation
plans. For each recipient, the number of shares definitely acquired is equal to the cash equivalent of 50%
of the annual variable compensation increased by a 50% premium. In the event of an over-performance
(i.e. achieved target above 100%), the surplus is paid in cash.
Expenses were €499 thousand for the financial year ended December 31, 2022.
F-59
BSA 2013
BSA 2014
BSA 2015-1
BSA 2015-2
BSA 2017
July 17, 2013
July 16, 2014
April 27, 2015
July 1, 2015 September 20, 2017
2 years
June 30,
2025
14,200
1
€14.05
Black &
Scholes
€13.64
47.83%
5.5 years
0.25%
None
None
€4.73
2 years
September 20, 2027
37,000
1
€11.00
Black & Scholes
€10.41
61.74%
6 years
0.20%
None
None
€0.57
BSA
Details of BSA
Date of grant (Board of
directors)
Vesting period (years)
2 years
2 years
2 years
Plan expiration date
July 17, 2023
July 16, 2024
April 26, 2025
Number of BSA granted
Share entitlement per BSA
Exercise price
Valuation method used
Grant date share fair value
Expected volatility
Average life of BSA
Risk-free interest rate
Expected dividends
Performance conditions
Fair value per BSA
237,500
1
€2.36
Black &
Scholes
€2.45
31.83%
5.5 years
2.42%
None
None
€0.87
150,000
1
€8.65
Black &
Scholes
€6.85
46.72%
5.5 years
1.00%
None
None
€2.51
70,000
1
€9.59
Black & Scholes
€13.65
54.08%
5.5 years
0.25%
None
None
€6.59
Date of grant (Board of
directors)
Vesting period (years)
Plan expiration date
BSA 2022-1
December 16,
2022
2 years
October 3,
2032
Number of BSA granted
Share entitlement per BSA
Exercise price
Valuation method used
Grant date share fair value
Expected volatility
Average life of BSA
Risk-free interest rate
Expected dividends
Performance conditions
Fair value per BSA
40,000
1
€2.31
Black &
Scholes
€1.31
50.00%
5.5 years
2.40%
None
None
€1.21
F-60
Change in Number of BSA Outstanding
Number of BSA
Balance at beginning of period
Granted during the period
Forfeited during the period
Exercised during the period
Expired during the period
Balance at end of period
Breakdown of the Closing Balance
2020
Year ended December 31,
2021
2022
309,500
—
—
(25,000)
—
284,500
284,500
—
—
(16,940)
(25,000)
242,560
242,560
40,000
(31,740)
—
—
250,820
2020
Year ended December 31,
2021
2022
Outstanding
Exercisable
Outstanding
Exercisable
Outstanding
Exercisable
41,940
46,360
75,000
70,000
14,200
37,000
—
284,500
41,940
46,360
75,000
70,000
14,200
37,000
—
284,500
—
46,360
75,000
70,000
14,200
37,000
—
242,560
—
46,360
75,000
70,000
14,200
37,000
—
242,560
—
46,360
75,000
70,000
14,200
37,000
8,260
250,820
—
46,360
75,000
70,000
14,200
37,000
8,260
250,820
Number of BSA
BSA 2011-2
BSA 2013
BSA 2014
BSA 2015-1
BSA 2015-2
BSA 2017
BSA 2022-1
TOTAL
BSAAR
BSAAR are securities whose subscription price and exercise price are fixed at their fair value as
determined by an expert. The BSAAR subscription therefore represents an investment on the part of the
beneficiary. At the end of the exercise period, if they have not been exercised, the BSAAR becomes void.
The Company benefits from a clause called «forcing» making it possible to encourage holders to exercise
their redeemable equity warrants when the market price exceeds the exercise price and reaches a threshold
defined in the BSAAR issuance agreement. The Company may, then, subject to a time period for
notifying holders that will permit them to exercise the BSAAR, decide to reimburse the warrants not
exercised at a unit price equal to the BSAAR acquisition price paid by its holder.
Details of BSAAR
BSAAR. The methodology used to estimate the fair value of the BSAAR is similar to the one used to
estimate the fair value of the BSA, except for the following:
Expected Term. Unlike the BSA, the Company does not have sufficient historical experience for the
BSAAR. Consequently, the expected term used for the valuation of the fair value is the legal maturity of
the instrument (10 years).
No share-based payment compensation expense was recognized relating to the BSAAR since the amount
paid by the beneficiaries is equal to the fair value.
Date of grant (Board of directors)
Vesting period (years)
Plan expiration date
BSAAR 2015
July 1, 2015
2 years
June 30, 2025
F-61
Number of BSAAR granted
Share entitlement per BSAAR
Exercise price
Valuation method used
Grant date share fair value
Expected volatility
Average life of BSAAR
Risk-free interest rate
Expected dividends
Performance conditions
Fair value per BSA
Change in Number of BSAAR Outstanding
Number of BSAAR
Balance at beginning of period
Granted during the period
Forfeited during the period
Exercised during the period
Expired during the period
Balance at end of period
Breakdown of the Closing Balance
1,050,382
1
€7.20
Black & Scholes
€13.77
41%
10 years
1.22%
None
No
€1.15
Year ended December 31,
2021
1,360,822
—
—
(230,000)
(25,000)
1,105,822
2020
1,362,322
—
—
(1,500)
—
1,360,822
2022
1,105,822
—
—
(750)
—
1,105,072
Number of
BSAAR
BSAAR 2011
BSAAR 2012
BSAAR 2015
TOTAL
2020
Outstanding
255,000
60,100
1,045,722
1,360,822
Year ended December 31,
2021
Exercisable
255,000
60,100
1,045,722
1,360,822
Outstanding
—
60,100
1,045,722
1,105,822
Exercisable
—
60,100
1,045,722
1,105,822
2022
Outstanding
—
59,350
1,045,722
1,105,072
Exercisable
—
59,350
1,045,722
1,105,072
F-62
Breakdown of expenses per financial year
The share-based compensation expenses are broken down as follows (in thousands of euro):
(in thousands of euro)
AGA Perf Management 2018 / AGA Perf Employees 2018
AGA 2018-1 Employees
AGA 2017-1 Management (New Members)
AGAP Employee 2019 / AGAP Management 2019
AGA Bonus 2019-1
AGA Bonus 2020
AGAP Employee 2020 / AGAP Management 2020
Stock Options 2020
AGA Bonus 2021-1
AGAP Employee 2021 / AGAP Management 2021
AGA "Plan Epargne Entreprise" 2022
AGA Bonus 2022-1
AGAP Employee 2022 / AGAP Management 2022
Share based compensation
Year ended December 31,
2021
2022
2020
618
23
43
867
—
394
502
28
—
—
—
—
—
2,475
(232)
—
71
649
—
—
1,253
(28)
432
473
—
—
—
2,617
—
—
—
(181)
—
—
1,738
—
—
1,577
570
499
46
4,249
12) Financial instruments recognized in the statement of financial position and related effect on the
income statement
The following tables show the carrying amounts and fair values of financial assets and financial liabilities.
The tables do not include fair value information for financial assets and financial liabilities not measured
at fair value if the carrying amount is a reasonable approximation of fair value.
As of December 31, 2020 (in thousands of
euro)
Book value on the
statement of
financial position
Fair value through
profit and loss(1)
Receivables
Fair value
Financial assets
Non-current financial assets
Trade receivables and others
Short-term investments
Cash and cash equivalents
Total financial assets
As of December 31, 2020 (in thousands of
euro)
Financial liabilities
Financial liabilities—non-current portion
Financial liabilities—current portion
Trade payables and others
Total financial liabilities
38,934
51,635
14,845
136,792
242,206
38,934
—
14,845
136,792
190,571
51,635
—
—
51,635
38,934
51,635
14,845
136,792
242,206
Book value on the
statement of
financial position
Fair value through
profit and loss(1)
Debt at
amortized
cost(3)
Fair value
—
—
—
—
16,945
2,142
29,539
48,624
16,945
2,142
29,539
48,624
16,945
2,142
29,539
48,624
F-63
As of December 31, 2021 (in thousands of
euro)
Financial assets
Non-current financial assets
Trade receivables and others
Short-term investments
Cash and cash equivalents
Total financial assets
As of December 31, 2021 (in thousands of
euro)
Financial liabilities
Financial liabilities—non-current portion
Financial liabilities—current portion
Trade payables and others
Total financial liabilities
As of December 31, 2022 (in thousands of
euro)
Financial assets
Non-current financial assets
Trade receivables and others
Short-term investments
Cash and cash equivalents
Total financial assets
As of December 31, 2022 (in thousands of
euro)
Financial liabilities
Financial liabilities—non-current portion
Financial liabilities—current portion
Trade payables and others
Total financial liabilities
Book value on the
statement of
financial position
Fair value through
profit and loss(1)
Receivables
Fair value
39,878
48,241
16,080
103,756
207,955
39,878
—
16,080
103,756
159,714
—
48,241
—
—
48,241
39,878
48,241
16,080
103,756
207,955
Book value on the
statement of
financial position
Fair value through
profit and loss(1)
Debt at
amortized
cost(3)
Fair value
13,503
30,748
28,573
72,824
—
—
—
—
13,503
30,748
28,573
72,822
13,503
30,748
28,573
72,822
Book value on the
statement of
financial position
Fair value through
profit and loss(1)
Receivables
Fair value
35,119
52,445
17,260
84,225
189,049
35,119
—
17,260
84,225
136,604
—
52,445
—
—
52,445
35,119
52,445
17,260
84,225
189,049
Book value on the
statement of
financial position
Fair value through
profit and loss(1)
Debt at
amortized
cost(3)
Fair value
40,149
2,102
20,911
63,162
—
—
—
—
40,149
2,102
20,911
63,162
40,149
2,102
20,911
63,162
(1) The fair value of financial assets classified as fair value through profit and loss corresponds to the market value of the assets, which are
primarily determined using level 2 measurements.
(2) The fair value of financial assets classified as fair value through comprehensive income corresponds to the market value of the assets,
which are primarily determined using level 1 measurements.
(3) The book amount of financial assets and liabilities measured at amortized cost was deemed to be a reasonable estimation of fair value.
In accordance with the amendments to IFRS 7, financial instruments are presented in three categories
based on a hierarchy of methods used to determine fair value:
Level 1: fair value determined based on quoted prices in active markets for assets or liabilities;
Level 2: fair value determined on the observable database for the asset or liability concerned either
directly or indirectly;
F-64
Level 3: fair value determined on the basis of evaluation techniques based in whole or in part on
unobservable data.
13) Revenue and government financing for research expenditures
Revenue from collaboration and licensing agreements
The Company’s revenue from collaboration and licensing agreements amounts to €56,155, €12,112 and
€49,580 for the fiscal year ended December 31, 2020, 2021 and 2022, respectively.
(in thousands of euro)
Proceeds from collaboration and licensing agreements
of which monalizumab agreement - AstraZeneca
of which IPH5201 agreement - AstraZeneca
of which preclinical molecules agreement - AstraZeneca
of which Sanofi agreement
of which other agreements
Invoicing of research and development costs (IPH5201)
Exchange gains (loss) on collaboration agreements
Others
Revenue from collaboration and licensing agreements
Year ended December 31,
2021
2020(1)
2022
54,038
33,620
13,418
—
7,000
—
2,531
(602)
188
56,155
10,497
7,497
—
—
3,000
—
1,613
—
—
12,112
48,806
22,376
4,677
17,400
4,000
353
1,391
(627)
10
49,580
(1) The 2020 comparatives have been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17.
a)
Revenue recognition related to monalizumab AstraZeneca agreements and amendments
The Company identified the following promises under the monalizumab AstraZeneca agreements and
amendments: (1) a non-exclusive license related to monalizumab restricted to two applications, with an
option for an exclusive license related to monalizumab including all applications, (2) the performance of
certain initial studies related to Phases 1/2 trials, and participation in certain studies of Phases 1/2 trials
and Phase 3 clinical trials through a co-financing.
The Company considered the license has a standalone functionality and is capable of being distinct.
However the Company determined that the license is not distinct from the performance of initial studies
and participation to Phase 3 clinical trials because they increased the utility of the licensed IP. Thus, the
licensed IP, the performance of initial studies and participation to Phase 3 clinical trials are combined into
a single performance obligation.
This performance obligation was considered as satisfied over time as AstraZeneca controls the licensed IP
which is being enhanced during the agreement. The revenue is recognized over time, based on the input
method (costs incurred). As a result, the Company recognizes the price of the transaction as a revenue on
the basis of the progress of studies that the Company has undertaken to carry out under the agreement.
Progression is assessed following to actual costs incurred relative to the total budgeted costs to fulfill the
obligation.
The transaction price was initially estimated to the initial payment of $250,000 thousand, less the amounts
that the Company expected to pay to AstraZeneca for co-financing Phase 1/2 clinical studies. The
additional payment of $100,000 thousand triggered by AstraZeneca’s exercise of the exclusivity option
was treated as a change in the price estimate of the transaction. In addition, the amendment of the
contract, which modified the scope and budget of the studies to be carried out by the Company as well as
F-65
the arrangements for sharing the cost of the other studies, led to a revision of the degree of progress and
the price of the transaction. Thus, the exercise of the option and the amendment of the contract resulted in
the recognition of a favourable cumulative adjustment of €38,321 thousand in revenue for the year ended
December 31, 2019.
The additional payment of $50,000 thousand triggered by the dosing of the first patient in the Phase 3 trial
evaluating monalizumab was treated in full as a collaboration commitment ("collaboration liability" in the
consolidated balance sheet) in view to the commitment linked to the contract for the Phase 1/2 (co-
financing) and Phase 3 studies (amendment signed in September 2020). Consequently, this additional
payment has no impact on the transaction price.
In addition to these amounts, AstraZeneca made an additional payment of $50.0 million (€47.7 million) in
June 2022 and triggered by the treatment of the first patient in a second Phase 3 trial “PACIFIC-9”
evaluating monalizumab in April 2022. This additional payment has been treated as an increase of the
collaboration commitment ("collaboration liabilities" in the consolidated statements of financial position)
for an amount of $36.0 million (€34.3 million) in connection to the Phase 3 study co-funding commitment
made by the Company and notified to AstraZeneca in July 2019. The remaining amount of $14.0 million
(€13.4 million) has been treated as an increase of the transaction price, recognized in the income
statement in line with the progress of the Phase 1/2 studies.
The subsequent milestones and potential royalty payments are excluded from the transaction price due to
the uncertainties of clinical trials results.
The Company used the most likely amount to determine variable consideration. Variable consideration
for cost-sharing payments related to certain studies of Phases 1/2 trials and Phase 3 clinical trials when
applicable are included in the transaction price.
As a reminder, the expected payments to AstraZeneca are classified as collaboration liability in the
consolidated statement of financial position. Quarterly invoices received from AstraZeneca reduce the
collaboration liability and have no impact on the consolidated statement of income.
Change in monalizumab deferred revenue (in thousands of euro):
As of December 31, 2019
Revenue for the 2020 financial year
Transfer from collaboration liabilities
As of December 31, 2020
Revenue for the 2021 financial year
Transfer from collaboration liabilities
As of December 31, 2021
Increase in deffered revenu resulting from the $50m milestone relating to the dosage of the first
patent in the Phase 3 trial PACIFIC-9 (1)
Revenue for the 2022 financial year
Transfer from collaboration liabilities
As of December 31, 2022
62,657
(33,620)
(2,465)
26,572
(7,497)
1,084
20,159
47,687
(22,376)
(30,989)
14,481
(1) The increase in deferred revenue relating to monalizumab agreement between December 31, 2021 and
December 31, 2022 is explained by the additional payment of €47,687 thousand ($50,000 thousand)
made by AstraZeneca in June 2022 and triggered by the launch of the “PACIFIC-9” Phase 3 trial on April
28, 2022. This increase has led to a simultaneous increase in collaboration commitment ("collaboration
liability"- see below) of €34,335 thousand ($36,000 thousand) in accordance with the Company’s July
2019 option concerning the co-financing of Phase 3 trials in the field of collaboration.
F-66
Change in monalizumab collaboration liablities (in thousands of euro):
As of December 31, 2019 (1)
Additions (2)
Deductions
As of December 31, 2020 (3)
Additions
Deductions
As of December 31, 2021 (4)
Additions (5)
Deductions
As of December 31, 2022(6)
21,304
46,320
(20,938)
46,686
4,262
(10,534)
40,415
37,564
(14,768)
63,211
(1) Of which €21,304 thousand of current portion.
(2) Including €41,227 thousand euros ($ 50,000 thousand) relating to the collaboration commitment following the milestone payment related
to the treatment of the first patient in the Phase 3 trial evaluating monalizumab.
(3) Of which €1,832 thousand of current portion and €44,854 of non-current portion.
(4) Of which €7,418 thousand of current portion and €32,997 thousand of non-current portion.
(5) The increase in collaboration liabilities relating to monalizumab agreement between December 31, 2021 and December 31, 2022 mainly
results from (i) a €34,335 thousand ($36,000 thousand) increase in collaboration commitments in connection with the launch of the
“PACIFIC-9” Phase 3 trial on April 28, 2022, and (ii) a €2,145 thousand net increase in the collaboration commitments in connection with
exchange rate fluctuations over the period.
(6) Of which €10,223 thousand of current portion and €52,988 thousand of non-current portion.
b)
Revenue recognition related to IPH5201 AstraZeneca collaboration and option agreement
Revenue related to IPH5201 for the year ended December 31, 2022 is €4,677 million and results from the
entire recognition in revenue of the $5.0 million (€4.7 million) milestone payment received from
AstraZeneca following the signature on June 1, 2022 of an amendment to the initial contract signed in
October 2018. This amendment sets the terms of the collaboration following AstraZeneca’s decision to
advance IPH5201 to a Phase 2 study. The Company will conduct the study. Both parties will share the
external cost related to the study and incurred by the Company and AstraZeneca will provide products
necessary to conduct the clinical trial.
Revenue related to collaboration and option agreement related to four to-be-agreed upon
c)
molecules (preclinical molecules)
Change in deferred revenue relating to the 2018 future programs option agreement
(in thousands of euro)
As of December 31, 2021
Augmentation
Deductions
As of December 31, 2022
Total
17,400
—
(17,400)
—
During the first half of 2022, the Company received from AstraZeneca a notice that it will not exercise its
option to license the four preclinical programs covered in the "Future Programs Option Agreement". This
license option was part of the 2018 multi-term agreement between AstraZeneca and the Company under
which the Company had received an upfront payment of $20,000 thousand (€17,400 thousand). As the
F-67
rights related to these four preclinical programs have been returned to the Company, the entire upfront
payment of $20,000 thousand (€17,400 thousand) was recognized as revenue as of June 30, 2022.
d)
Revenue recognition related to collaboration and license agreement signed with Sanofi in 2016
Revenues under the collaboration and license agreement signed with Sanofi in 2016 amounted to €4,000
thousand for the year ended December 31, 2022 as compared to €3,000 thousand for the year ended
December 31, 2021. During the period, the Company announced, notably, the decision taken by Sanofi to
advance IPH6401/SAR'514 towards regulatory preclinical studies for a new investigational drug. This
decision triggered a milestone payment of €3,000 thousand fully recognized in revenue. This amount was
received by the Company on September 9, 2022.
e)
Schedule of variance of deferred revenue
The main variance of the global deferred revenue is presented in the following schedule:
(in thousands of euro)
Monalizumab
IPH5201
Preclinical molecules
Total
December 31,
2019
Recognition in
P&L
Proceeds
62,657
9,054
17,400
89,112
(33,620)
(13,418)
—
(47,038)
—
4,365
—
4,365
Transfer from
collaboration
liabilities
December 31, 2020
26,572
—
17,400
43,973 (1)
(2,465)
—
—
(2,465)
(1) Of which €11,299 thousand of current deferred revenue and €32,674 thousand of non-current deferred revenue.
(in thousands of euro)
Monalizumab
IPH5201
Preclinical molecules
Others
Total
December 31,
2020
Recognition in
P&L
Proceeds
26,572
—
17,400
—
43,973
(7,497)
—
—
—
(7,497)
—
—
—
353
353
Transfer from
collaboration
liabilities
1,084
—
—
—
1,084
December 31, 2021
20,159
—
17,400
353
37,913 (2)
(2) Of which €12,500 thousand of current deferred revenue and €25,413 thousand of non-current deferred revenue.
(in thousands of euro)
Monalizumab
Preclinical molecules
Others
Total
December 31,
2021
Recognition in
P&L
20,159
17,400
(22,376)
(17,400)
353
(353)
Proceeds and
other increase
47,687
Transfer from
collaboration
liabilities
(30,989)
December 31, 2022
14,481
—
—
—
—
—
—
37,913
(39,776)
47,687
(30,989)
14,481 (3)
(3) Of which €6,560 thousand of current deferred revenue and €7,921 thousand of non-current deferred revenue.
F-68
Government financing for research expenditures
The Company receives grants from the European Commission and the French government and state
organizations in several different forms:
•
Investment and operating grants; and
• Research Tax Credits.
The total amount for government financing for research expenditures recorded as other income in the
income statement can be analyzed as follows:
(in thousands of euro)
Research Tax Credit(1)
Grant and other tax credit(2)
Government financing for research expenditures
Year ended December 31,
2020
2021
2022
13,084
534
13,618
10,310
2,281
12,591
7,925
110
8,035
(1) As of December 31, 2022, the amount is mainly composed of (i) the research tax credit calculated and
recognized for the 2022 financial year for an amount of €9,167 thousand from which is subtracted (ii) a
provision amounting to €1,270 thousand following the tax inspection carried out in 2022 by the French
tax authorities and relating to the 2019 and 2020 financial years as well as to the research tax credit and
the accuracy of its calculation for the 2018 to 2020 financial years. This provision was recognized as a
deduction from the 2022 research tax credit, based on estimated amounts and adjustments not disputed by
the Company. On March 3, 2023, the Company received from the tax authorities the rectification
proposal, confirming the amount of the provision recognized on the amounts of the rectifications not
disputed by the Company.
(2) As a reminder, as of December 31, 2021, the total amount of grants recognized in the income
statement included all installments of the refundable advance received and remaining to be received as of
December 31, 2021 for a total amount of €1,988 thousand. The Company considered that the initial
payment of €1,360 thousand euros and an amount to be received of €628 thousand as of December 31,
2021 as non-refundable in accordance with the terms of the agreement and in light of the technical and
commercial failure of the project.
F-69
14) Operating expenses
(in thousands of euro)
2020 (1)
Year ended December 31,
2021
2022
Subcontracting costs(2)
Cost of supplies and
consumable materials
Personnel expenses other
than share-based
compensation
Share-based
compensation
Personnel expenses
Non-scientific advisory
and consulting(3)
Leasing and maintenance
Travel expenses and
meeting attendance
Marketing,
communication and
public relations
Scientific advisory and
consulting(4)
Other purchases and
external expenses
Depreciation and
amortization
Intellectual property
expenses
Other income and
(expenses), net
Impairment of intangible
assets (5)
Total net operating
expenses
R&D
G&A
Total
R&D
G&A
Total
R&D
G&A
(19,866)
4
(19,862) (24,189)
(101) (24,290) (24,432)
—
Impair
ment
—
Total
(24,432)
(3,590)
32
(3,558) (2,533)
(532) (3,065) (3,051)
(531) —
(3,582)
(13,825) (6,611) (20,436) (14,859) (8,616) (23,475) (14,329) (8,025) —
(22,354)
(836) (1,639) (2,475)
(349) (2,267) (2,617) (2,044) (2,204) —
(4,249)
(14,661) (8,250) (22,911) (15,208) (10,883) (26,092) (16,373) (10,229)
—
(26,603)
(342) (4,441) (4,783)
(161) (5,108) (5,269) (1,441) (4,244) —
(5,685)
(559) (1,605) (2,164)
(260) (1,754) (2,014)
(200) (1,798) —
(1,998)
(146)
(138)
(284)
(103)
(170)
(273)
(466)
(252) —
(718)
(96)
(408)
(504)
(79)
(393)
(472)
(130)
(530) —
(660)
(962)
—
(962)
(288)
—
(288) (1,263)
—
—
(1,263)
(46) (2,007) (2,053)
(30) (2,395) (2,425)
(91) (2,557) —
(2,648)
(8,231) (1,154) (9,385) (3,153) (1,416) (4,569) (2,928) (1,496) —
(4,424)
(877)
(393) (1,270) (1,279)
(305) (1,584)
(996)
(296) —
(1,292)
(332)
(626)
(958)
279
(2,467) (2,188)
(292)
(503) —
(795)
—
—
—
—
—
—
—
—
(41,000) (41,000)
(49,708) (18,986) (68,694) (47,004) (25,524) (72,528) (51,663) (22,436) (41,000) (115,099)
(1) The 2020 comparative have been restated to consider the impact of classifying the Lumoxiti business as discontinued operations in 2021.
See note 2.v and 17.
(2) The Company subcontracts a significant part of its preclinical (pharmaceutical development, tolerance studies and other model
experiments, etc.) and clinical operations (coordination of trials, hospital costs, etc.) to third parties. Associated costs are recorded in
subcontracting on the basis of the level of completion of the clinical trials.
(3) Non-scientific advisory and consulting are services performed to support the selling, general and administration activities of the Company,
such as legal, accounting and audit fees as well as business development support.
(4) Scientific advisory and consulting expenses relate to consulting services performed by third parties to support the research and
development activities of the Company.
(5) Following the Company's decision in December 2022 to stop the development of avdoralimab in bullous pemphigoid ("BP") indication in
inflammation, only indication supporting the recoverable amount of the asset as of December 31, 2021 (as well as of June 30, 2022), the
rights relating to the intangible asset have been fully impaired for their net book value on the date of the decision, i.e. €41,000 thousand
(see note 6)
F-70
2020
Year ended December 31,
2021
2022
Deloitte &
Associés
Total
Deloitte &
Associés
Total
Deloitte &
Associés
Total
684
115
799
684
115
799
702
78
780
702
78
780
855
248
1,103
855
248
1,103
(in thousands of euro)
Audit fees
Non-audit fees
Total
* Non-audit fees: these fees correspond to services performed by the auditors related to the production of certification in the context of the
declaration of expenses for the obtention of grants; to the verification report of social and environmental information, special reports
within the framework of operations on the Company’s capital
Personnel expenses other than share-based compensation
The line item amounted to €20,436 thousand, €23,475 thousand and €22,354 thousand for the years ended
December 31, 2020, 2021 and 2022 respectively. These items do not include personnel expenses relating
to the Lumoxiti discontinued operation (see note 17). The Company had 214 employees as of December
31, 2021, compared to 208 as of December 31, 2022.
Depreciation and amortization
The line item is mainly composed of the amortization of the monalizumab, IPH5201 intangible assets (see
Note 6).
Cost of supplies and consumable materials
Cost of supplies and consumable materials consists mainly of the cost of procurement of the Company’s
drug substance and/or drug product that is manufactured by third-parties. This line item amounts to
€3,558 thousand €3,065 thousand and €3,582 thousand for the years ended December 31, 2020, 2021 and
2022, respectively.
15) Net financial loss
Net financial loss can be analyzed as follows:
(in thousands of euro)
Interests and gains on financial assets
Unrealized gains on financials assets
Foreign exchange gains
Other financial income
Financial income
Foreign exchange losses
Unrealized losses on financial assets
Interest on financial liabilities
Other financial expenses
Financial expenses
Net financial income (loss)
Year ended December 31,
2021
2022
2020
564
313
3,978
—
4,855
(5,557)
(865)
(341)
—
(6,763)
(1,908)
327
1,177
4,839
—
6,344
(3,591)
(95)
(312)
—
(3,997)
2,347
546
418
3,810
—
4,775
(2,983)
(2,050)
(288)
—
(5,321)
(546)
For the financial years ended December 31, 2021 and 2022, the foreign exchange gains and losses mainly
result from the variance of the exchange rate between the Euro and the U.S. dollar on U.S. dollars
denominated cash and cash equivalent and financial assets accounts.
F-71
Unrealized losses on financial assets relate to unquoted instruments, the fair value of which is determined
using level 2 measurements.
16) Income Tax
Due to the Company’s early stage of development, it is not probable that future taxable profit will be
available against which the unused tax losses can be utilized. As a consequence, deferred tax assets are
recognized up to deferred tax liabilities.
Temporary differences mainly result from leases, provision for defined benefit obligation and tax losses
carryforwards.
As of December 31, 2022, the accumulated tax losses carryforwards of Innate Pharma SA were €466,153
thousand with no expiration date (€339,274 and €392,633 thousand as of December 31, 2020 and 2021).
As of December 31, 2022, the accumulated tax losses carryforwards of Innate Pharma Inc. was €15,419
thousand, or $16,446 thousand, (€11,955 thousand, or $14,670 thousand and €14,198 thousand, or
$16,081 thousand as of December 31, 2020 and 2021, respectively), with a 20-year period expiration.
Tax rate reconciliation
(in thousands of euro)
Net income (loss) before tax
Statutory tax rate
Income tax benefit / (expense) calculated at statutory tax rate
Increase / (decrease) in income tax benefit / (expenses) arising
from:
Differences in tax rates
Research tax credit
Provision for defined benefit obligations
Share-based compensation
Revenue from collaboration agreements
Non-recognition of deferred tax assets related to tax losses and
temporary differences
Carry-back
Impact linked to intra-group merger operations
Impact linked to the exercise of a real estate leasing option
Others differences
Income tax benefit / (expense) (a)
Effective tax rate
Deferred tax income / (loss) (b)
Income tax benefit / (expense) (a) + (b)
Year ended December 31,
2020
(63,984)
28.00%
17,916
2021
(52,809)
26.50%
13,994
2022
(58,103)
25.00%
14,526
128
3,961
(117)
(693)
8,824
62
3,091
39
(694)
(3,313)
—
1,971
106
(1,062)
2,210
(15,746)
(14,433)
(18,290)
—
(16,288)
(1,103)
3,118
—
0%
—
—
—
—
—
1,254
—
0%
—
—
—
—
—
539
—
0%
—
—
17)
Discontinued Operations
Further to the decision to terminate the Lumoxiti Agreement and termination notice sent in December
2020, a Termination and Transition Agreement was discussed and executed, effective as of June 30, 2021
terminating the Lumoxiti Agreement as well as Lumoxiti related agreements (including the supply
agreement, the quality agreement and other related agreements) and transferring of the U.S. marketing
F-72
authorization and distribution rights of Lumoxiti back to AstraZeneca. Consecutively, the activities
related to Lumoxiti are presented as a discontinued operation as of October 1, 2021.
As part of the communication of its 2020 consolidated financial statements, the Company had
communicated on a contingent liability estimated at a maximum of $12.8 million related to the sharing of
certain manufacturing costs. As part of the termination and transition agreement, Innate and AstraZeneca
agreed to share manufacturing costs, and Innate had to pay $6.2 million on April 30, 2022. This amount
was paid by the Company as part of the agreement in April 2022 for an amount of €5.9 millions
($6.2 million).
a) Financial Performance
Revenue and other income
Revenue from collaboration and licensing agreements
Sales
Total revenue and other income
Operating expenses
Research and development expenses
Selling, general and administrative expenses
Impairment of intangible assets
Total operating expenses
Net income (loss) from distribution agreements
Operating income (loss)
Financial income
Financial expenses
Net financial income (loss)
Net income (loss) before tax
Income tax expense
Year ended December 31,
2020
2021
2022
—
678
678
926
874
1,800
(8,905)
(624)
(12,260)
(8,507)
(43,529)
—
(21,165)
(9,131)
861
—
194
22
216
—
(346)
—
(346)
—
(63,155)
(7,331)
(131)
—
—
—
—
—
—
(63,155)
(7,331)
—
—
—
—
—
(131)
—
(131)
Net income (loss) from discontinued operations
(63,155)
(7,331)
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b) Cash-Flows
Year ended December 31,
2020
2021
2022
Net cash generated from / (used in) operating activities
(22,391)
(3,552)
(5,097)
Net cash generated from / (used in) investing activities
Net cash generated from / (used in) financing activities
(6,620)
—
—
—
—
—
Net cash flows from discontinued operations
(29,011)
(3,552)
(5,097)
18)
Commitments, contingencies and litigations
Commitments
The Company has identified the following off-balance sheet commitments as of December 31, 2022:
•
non-cancellable purchase commitments as of December 31, 2022 for a total of €8,774 thousand
with various suppliers notably contract research organizations (CRO) or contract manufacturing
organizations (CMO). These commitments are comprised of non-cancellable purchase orders
placed over the period with CRO and CMO for the supply of various services in relation with
preclinical work for an amount of €7,421 thousand and clinical work for an amount of
€1,353 thousand. The execution and billing of these has not yet started as of December 31, 2022;
• On July 3, 2017, Innate Pharma borrowed from the bank Société Générale in order to finance the
construction of its future headquarters. As security for the loan, Innate pledged collateral in the
form of financial instruments held at Société Générale amounting to €15.2 million. The security
interest on the pledged financial instruments will be released in accordance with the following
schedule: €4,200 thousand in July 2024, €5,000 thousand in August 2027 and €6,000 thousand in
August 2031. Furthermore, under the loan, Innate is subject to a covenant that its total cash, cash
equivalents and current and non-current financial assets as of each fiscal year end will be at least
equal to the amount of outstanding principal under the loan. As of December 31, 2022, the
remaining capital of this loan amounted to €11,338 thousand. The Company was in compliance
with this covenant as of December 31, 2022;
•
The Company has entered into indemnification agreements with its directors & officers (the «
Beneficiaries »), under which (1) Company will provide to the Beneficiaries the benefit of one or
more director and officer (“D&O”) insurance policies and (2) if not indemnifiable under the D&O
insurance policy, the Beneficiary shall be compensated for any indemnifiable claim by the
Company to the fullest extent permitted by law.
Licensing and collaboration agreements
Commitments related the Company’s licensing and collaboration agreements are disclosed in Note 1.1.
Contingencies and litigations
The Company is exposed to contingent liabilities relating to legal actions before the labor court or
intellectual property issues happening in the ordinary course of its activities. Each pre-litigation, known
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litigation or procedure in ordinary course the Company is involved in was analyzed at the closing date
after consultation of advisors.
Provisions
Provisions amounted to €897 thousand, €900 thousand and €1,740 thousand as of December 31, 2020,
2021 and 2022, respectively. As of December 31, 2022, they mainly consist of (i) a provision amounting
to €1,270 thousand following the tax inspection carried out in 2022 by the French tax authorities and
relating to the 2019 and 2020 financial years as well as to the research tax credit and the accuracy of its
calculation for the 2018 to 2018 financial years 2020. This provision was based on estimated amounts and
adjustments not disputed by the Company. On March 3, 2023, the Company received from the tax
authorities the rectification proposal, confirming the amount of the provision recognized on the amounts
of the rectifications not disputed by the Company, and (ii) provisions for employee departures and
provision for charges relating and the employer contribution in respect of the grants of employee equity
instruments
In accordance with IFRS 2, when a Company decides to provide its employees with shares bought back
on the market, a provision has to be recognized upon the decision to allocate free shares that are spread
over the vesting period when the plan conditions actions for employees when they join the Company at
the end of the plan.
19) Related party transactions
Members of the Executive Board and Executive Committee
For each of the periods presented, the following compensation was granted to the members of the
Executive Committee of the Company and were recognized as expense:
(in thousands of euro)
Personnel expenses and other short-term employee benefits
Extra pension benefits
Share-based compensation
Advisory fees
Executive Committee members compensation
Year ended December 31,
2021
2022
2020
3,131
—
1,363
—
4,494
3,456
11
2,067
—
5,534
2,176
43
1,989
661
4,869
As of December 31, 2022, two members of the Executive Committee were also members of the Executive
Board.
Calculation of share-based compensation is detailed in Note 11.b.
Members of the Supervisory Board
The Company recognized a provision of €348 thousand for attendance fees (jetons de presence) relating
to the year ended December 31, 2022 which should be paid in 2023. This amount includes the
compensation for the Chairman of the Supervisory Board. The company recognized a provision of €274
thousand and €338 thousand as of December 31, 2020 and 2021, respectively.
Related parties
AstraZeneca is a shareholder and is related to the Company through several collaboration and option
licensing or license agreements for different drug candidates (monalizumab, avdoralimab, IPH5201) and a
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termination and transition agreement relating to Lumoxiti. The payments between the two companies as
well as the liabilities and receivables as of 31 December 2021 are as follows:
(in thousands of euros)
Collection (AstraZeneca towards the Company) / Receivables
Payments (the Company towards AstraZeneca) / Liabilities
Total(1)
As of December 31, 2022
Payments
Assets/Liabilities
54,774
(17,745)
37,029
3,078
(7,298)
(4,220)
As a reminder, BPI France is a board member and has granted the Company a €1,500 thousand interest-
free loan (Prêt à Taux Zéro Innovation, or “PTZI”) and a free-interest advance repayable. PTZI loan is
fully repaid as of December 31, 2021. Regarding the repayable advance, this is considered non-repayable
by the Company as of December 31, 2021 in accordance with the terms specified in the financing contract
signed with BPI in August 2020, in view of the technical and commercial failure of the project, in view of
the results of the “FORCE” Phase 2 trial evaluating avdoralimab in COVID-19, published on July 6, 2021
(see notes 9 and 13.2).
Subsidiaries
The business relationships between the Company and its subsidiary Innate Pharma Inc are governed by
intra-group agreements, conducted at standard conditions on an arm’s length basis.
20)
Income (loss) per share
Basic income (loss) per share
Basic income (loss) per share is calculated by dividing the net income (loss) attributable to equity holders
of the Company by the weighted average number of ordinary shares in circulation during the
corresponding period.
(in thousands of euro, except for data share)
Net income (loss)
Weighted average number of ordinary shares in circulation
Basic income (loss) per share (€ per share)
Year ended December 31.
2020
2021
2022
(63,984)
(52,809)
78,934,960
79,542,627
(0.81)
(0.66)
(58,103)
79,639,826
(0.73)
The instruments that entitle their holders to a portion of the share capital on a deferred basis (BSAs,
BSAAR, AGAs and AGAPs) are considered to be anti-dilutive (1,564,662 instruments in 2020, 2,166,829
instruments in 2021 and 2,265,301 instruments in 2022). These instruments are presented in detail in Note
11.
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Diluted income (loss) per share
Diluted income (loss) per share is calculated by dividing the net income (loss) attributable to equity
holders of the Company by the weighted average number of ordinary shares in circulation during the
corresponding period, increased by all dilutive potential ordinary shares.
(in thousands of euro, except for data share)
Net income (loss)
Weighted average number of ordinary shares in circulation
Adjustment for share instruments
Diluted income (loss) per share (€ per share)
Year ended December 31,
2020
2021
2022
(63,984)
(52,809)
78,934,960
—
(0.81)
79,542,627
—
(0.66)
(58,103)
79,639,826
—
(0.73)
21) Events after the reporting date
On December 19, 2022, the Company announced that it had entered into a research collaboration and
license agreement with Genzyme Corporation, a wholly-owned subsidiary of Sanofi (“Sanofi”) pursuant
to which the Company granted Sanofi an exclusive license on the Innate Pharma's B7H3 ANKET®
program and options on two additional targets. Once selected, Sanofi will be responsible for all
development, manufacturing and marketing. The closing of the transaction was subject to the
authorization of the American authorities in accordance with the Hart Scott Rodino Act of 1976. This
authorization was obtained on January 24, 2023, the date on which the collaboration was effective. Under
the terms of the collaboration and research license agreement, the Company is eligible from the effective
date of the contract for an initial payment of €25.0 million. This amount was collected by the Company in
March 2023.
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117 avenue de Luminy 13009 Marseille - France
www.innate-pharma.com