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
☒ ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
OR
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
☐ SHELL COMPANY REPORT PURSUANT TO SECTION 13 OR 15(d) of the Securities Exchange Act of 1934
OR
Date of event requiring this shell company report
For the transition period from __________ to __________
Commission file number 001-35223
BioLineRx Ltd.
(Exact name of Registrant as specified in its charter)
Translation of Registrant’s name into English
Israel
(Jurisdiction of incorporation or organization)
2 HaMa’ayan Street
Modi’in 7177871, Israel
(Address of principal executive offices)
Philip A. Serlin
+972 (8) 642-9100
+972 (8) 642-9101 (facsimile)
phils@biolinerx.com
2 HaMa’ayan Street
Modi’in 7177871, Israel
(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 15 ordinary shares, par value
NIS 0.10 per share
Name of each exchange on which registered
Nasdaq Capital Market
Ordinary shares, par value NIS 0.10 per share
Nasdaq Capital Market*
*Not for trading; only in connection with the registration of American Depositary Shares.
Securities registered or to be registered pursuant to Section 12(g) of the Act.
None
(Title of Class)
Securities for which there is a reporting obligation pursuant to Section 15(d) of the Act.
None
(Title of Class)
Indicate the number of outstanding shares of each of the issuer’s classes of capital or common stock as of December 31, 2022: 922,958,942 ordinary shares Indicate by check
mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act.
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 ☒
Note — Checking the box above will not relieve any registrant required to file reports pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934 from their
obligations under those Sections.
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 ☒
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 and post such files).
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 ☐
Accelerated filer ☒
Non-accelerated filer ☐
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. ☐
The term “new or revised financial accounting standard” refers to any update issued by the Financial Accounting Standards Board to its Accounting Standards Codification
after April 5, 2012.
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. ☒
If securities are registered pursuant to Section 12(b) of the Act, indicate by check mark whether the financial statements of the registrant included in the filing reflect the
correction of an error to previously issued financial statements. ☐
Indicate by check mark whether any of those error corrections are restatements that required a recovery analysis of incentive based compensation received by any of the
registrant’s executive officers during the relevant recovery period pursuant to §240.10D-1(b). ☐
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. N/A
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).
☐ Item 17 ☐ Item 18
Yes ☐ No ☒
INTRODUCTION
PART I.
ITEM 1. IDENTITY OF DIRECTORS, SENIOR MANAGEMENT AND ADVISERS
ITEM 2. OFFER STATISTICS AND EXPECTED TIMETABLE
ITEM 3. KEY INFORMATION
ITEM 4. INFORMATION ON THE COMPANY
ITEM 4A UNRESOLVED STAFF COMMENTS
ITEM 5. OPERATING AND FINANCIAL REVIEW AND PROSPECTS
ITEM 6. DIRECTORS, SENIOR MANAGEMENT AND EMPLOYEES
ITEM 7. MAJOR SHAREHOLDERS AND RELATED PARTY TRANSACTIONS
ITEM 8. FINANCIAL INFORMATION
ITEM 9. THE OFFER AND LISTING
ITEM 10. ADDITIONAL INFORMATION
ITEM 11. QUANTITATIVE AND QUALITATIVE DISCLOSURE ON MARKET RISK
ITEM 12. DESCRIPTION OF SECURITIES OTHER THAN EQUITY SECURITIES
ITEM 13. DEFAULTS, DIVIDENDS ARREARAGES AND DELINQUENCIES
ITEM 14. MATERIAL MODIFICATIONS TO THE RIGHTS OF SECURITY HOLDERS AND USE OF PROCEEDS
ITEM 15. CONTROLS AND PROCEDURES
ITEM 16. [RESERVED]
ITEM 16A. AUDIT COMMITTEE FINANCIAL EXPERTS
ITEM 16B. CODE OF ETHICS
ITEM 16C. PRINCIPAL ACCOUNTANT FEES AND SERVICES
ITEM 16D. EXEMPTIONS FROM THE LISTING STANDARDS FOR AUDIT COMMITTEES
ITEM 16E. PURCHASES OF EQUITY SECURITIES BY THE ISSUER AND AFFILIATED PURCHASERS
ITEM 16F. CHANGE IN REGISTRANT’S CERTIFYING ACCOUNTANT
ITEM 16G. CORPORATE GOVERNANCE
ITEM 16H. MINE SAFETY DISCLOSURE
ITEM 16I. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS
ITEM 17. FINANCIAL STATEMENTS
ITEM 18. FINANCIAL STATEMENTS
ITEM 19. EXHIBITS
SIGNATURES
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Certain Definitions
In this Annual Report on Form 20-F, unless the context otherwise requires:
INTRODUCTION
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references to “BioLineRx,” the “Company,” “us,” “we” and “our” refer to BioLineRx Ltd., an Israeli company, and its consolidated subsidiaries;
references to “ordinary shares,” “our shares” and similar expressions refer to the Company’s ordinary shares, NIS 0.10 nominal (par) value per share;
references to “ADS” or “ADSs” refer to the Company’s American Depositary Shares;
references to “dollars,” “U.S. dollars” and “$” are to United States Dollars;
references to “shekels” and “NIS” are to New Israeli Shekels, the Israeli currency;
references to the “Companies Law” are to Israel’s Companies Law, 5759-1999, as amended;
and references to the “SEC” are to the U.S. Securities and Exchange Commission.
Forward-Looking Statements
Some of the statements under the sections entitled “Item 3. Key Information – Risk Factors,” “Item 4. Information on the Company” and “Item 5. Operating and
Financial Review and Prospects” and elsewhere in this Annual Report on Form 20-F constitute forward-looking statements. These statements involve known and unknown
risks, uncertainties and other factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or
achievements expressed or implied by the forward-looking statements. In some cases, you can identify forward-looking statements by terms including “anticipates,”
“believes,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,” “predicts,” “projects,” “should,” “will,” “would,” and similar expressions intended to
identify forward-looking statements. Forward-looking statements reflect our current views with respect to future events and are based on assumptions, and are subject to risks
and uncertainties. In addition, the section of this Annual Report on Form 20-F entitled “Item 4. Information on the Company” contains information obtained from independent
industry and other sources that we have not independently verified. You should not put undue reliance on any forward-looking statements. Our actual results could differ
materially from those discussed in the forward-looking statements. Unless we are required to do so under U.S. federal securities laws or other applicable laws, we do not
intend to update or revise any forward-looking statements. Readers are encouraged to consult the Company’s filings made on Form 6-K, which are periodically filed with or
furnished to the SEC.
Factors that could cause our actual results to differ materially from those expressed or implied in such forward-looking statements include, but are not limited to:
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the initiation, timing, progress and results of our preclinical studies, clinical trials and other therapeutic candidate development efforts;
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our ability to advance our therapeutic candidates into clinical trials or to successfully complete our preclinical studies or clinical trials;
our receipt of regulatory approvals for our therapeutic candidates and the timing of other regulatory filings and approvals;
the clinical development, commercialization and market acceptance of our therapeutic candidates;
our ability to establish and maintain corporate collaborations;
our ability to integrate new therapeutic candidates and new personnel;
the interpretation of the properties and characteristics of our therapeutic candidates and of the results obtained with our therapeutic candidates in preclinical
studies or clinical trials;
the implementation of our business model and strategic plans for our business and therapeutic candidates;
the scope of protection we are able to establish and maintain for intellectual property rights covering our therapeutic candidates and our ability to operate our
business without infringing the intellectual property rights of others;
estimates of our expenses, future revenues, capital requirements and our needs for and ability to access sufficient additional financing;
risks related to changes in healthcare laws, rules and regulations in the United States or elsewhere;
competitive companies, technologies and our industry;
risks related to unfavorable economic and market conditions and adverse developments with respect to financial institutions and associated liquidity risk; and
statements as to the impact of the political and security situation in Israel on our business.
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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. [Reserved]
B. Capitalization and Indebtedness
Not applicable.
C. Reasons for the Offer and Use of Proceeds
Not applicable.
D. Risk Factors
You should carefully consider the risks we describe below, in addition to the other information set forth elsewhere in this Annual Report on Form 20-F, including our
consolidated financial statements and the related notes beginning on page F-1, before deciding to invest in our ordinary shares and ADSs. These material risks could adversely
impact our results of operations, possibly causing the trading price of our ordinary shares and ADSs to decline, and you could lose all or part of your investment.
Summary Risk Factors
Investing in our ordinary shares involves a high degree of risk, as fully described below. The principal factors and uncertainties that make investing in our ordinary
shares risky, include, among others:
Risks Related to Our Financial Condition and Capital Requirements
• We are a pre-commercialization-stage biopharmaceutical development company with a history of operating losses, expect to incur additional losses in the future
and may never be profitable;
• We cannot assure investors that our existing cash and investment balances will be sufficient to meet our future capital requirements.
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If we default under our secured loan agreement with Kreos, all or a portion of our assets could be subject to forfeiture.
Risks Related to Our Business and Regulatory Matters
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If we or our licensees are unable to obtain U.S. and/or foreign regulatory approval for our therapeutic candidates, in a timely manner or at all, we will be unable
to commercialize our therapeutic candidates.
• We are executing on an independent commercialization plan for motixafortide in stem cell mobilization for autologous bone marrow transplantation in multiple
myeloma patients and historically have no experience selling, marketing or distributing products.
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Clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial
results.
Even if we obtain regulatory approvals, our therapeutic candidates will be subject to ongoing regulatory review and if we fail to comply with continuing U.S. and
applicable foreign regulations, we could lose those approvals and our business would be seriously harmed.
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• We may depend on out-licensing arrangements for late-stage development, marketing and commercialization of our therapeutic candidates.
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If we cannot meet requirements under our in-license agreements, we could lose the rights to our therapeutic candidates, which could have a material adverse
effect on our business.
If we do not meet the requirements under our agreement with the Agalimmune selling shareholders, we could lose the rights to the therapeutic candidates in
Agalimmune’s pipeline, including, but not limited to, AGI-134.
• We may seek to partner with third-party collaborators with respect to the development and commercialization of motixafortide, and we may not succeed in
establishing and maintaining collaborative relationships, which may significantly limit our ability to develop and commercialize our product candidates
successfully, if at all.
• Modifications to our therapeutic candidates, or to any other therapeutic candidates that we may develop in the future, may require new regulatory clearances or
approvals or may require us or our licensees, as applicable, to recall or cease marketing these therapeutic candidates until clearances are obtained.
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If our competitors develop and market products that are more effective, safer or less expensive than our current or future therapeutic candidates, our prospects
will be negatively impacted.
Our business could suffer if we are unable to attract and retain key employees.
Our business is subject to risks arising from a widespread outbreak of an illness or any other communicable disease, or any other public health crisis, such as the
COVID-19 pandemic, which has impacted and could in the future impact our business.
Risks Related to Our Industry
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Even if our therapeutic candidates receive regulatory approval or do not require regulatory approval, they may not become commercially viable products.
Healthcare reforms and related reductions in pharmaceutical pricing, reimbursement and coverage by governmental authorities and third-party payors may
adversely affect our business.
If third-party payors do not adequately reimburse customers for any of our therapeutic candidates that are approved for marketing, they might not be purchased
or used, and our revenues and profits will not develop or increase.
Our business has a substantial risk of clinical trial and product liability claims. If we are unable to obtain and maintain appropriate levels of insurance, a claim
could adversely affect our business.
Significant disruptions of our information technology systems or breaches of our data security could adversely affect our business.
• We deal with hazardous materials and must comply with environmental, health and safety laws and regulations, which can be expensive and restrict how we do
business.
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• We are currently party to, and may in the future, become subject to litigation or claims arising in or outside the ordinary course of business that could negatively
affect our business operations and financial condition.
Risks Related to Intellectual Property
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Our access to most of the intellectual property associated with our therapeutic candidates results from in-license agreements with biotechnology companies and
academic institutions, the termination of which would prevent us from commercializing the associated therapeutic candidates.
Patent protection for our products is important and uncertain.
If we are unable to protect the confidentiality of our trade secrets or know-how, such proprietary information may be used by others to compete against us.
Legal proceedings or third-party claims of intellectual property infringement may require us to spend substantial time and money and could prevent us from
developing or commercializing products.
• We may be subject to other patent-related litigation or proceedings that could be costly to defend and uncertain in their outcome.
Risks Related to our Ordinary Shares and ADSs
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Our business, operating results and growth rates may be adversely affected by current or future unfavorable economic and market conditions and adverse
developments with respect to financial institutions and associated liquidity risk.
The market prices of our ordinary shares and ADSs are subject to fluctuation, which could result in substantial losses by our investors.
Future sales of our ordinary shares or ADSs could reduce the market price of our ordinary shares and ADSs.
Raising additional capital by issuing securities may cause dilution to existing shareholders.
If we fail to comply with the continued listing requirements of the Nasdaq Capital Market, our ADSs may be delisted and the price of our ADSs stock and our
ability to access the capital markets could be negatively impacted.
Risks Related to our Operations in Israel
• We conduct our operations in Israel and therefore our results may be adversely affected by political, economic and military instability in Israel and its region.
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Due to a significant portion of our expenses and revenues being denominated in non-dollar currencies, our results of operations may be harmed by currency
fluctuations.
• We have received Israeli government grants for certain research and development expenditures. The terms of these grants may require us to satisfy specified
conditions in order to manufacture products and transfer technologies outside of Israel. We may be required to pay penalties in addition to repayment of the
grants.
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Provisions of Israeli law may delay, prevent or otherwise impede a merger with, or an acquisition of, our company, which could prevent a change of control, even
when the terms of such a transaction are favorable to us and our shareholders.
It may be difficult to enforce a U.S. judgment against us and our officers and directors in Israel or the United States, or to serve process on our officers and
directors.
Your rights and responsibilities as a shareholder will be governed by Israeli law, which may differ in some respects from the rights and responsibilities of
shareholders of U.S. companies.
Risks Related to Our Financial Condition and Capital Requirements
We are a pre-commercialization-stage biopharmaceutical company with a history of operating losses, expect to incur additional losses in the future and may never be
profitable.
We are a pre-commercialization-stage biopharmaceutical company that was incorporated in 2003. Since our incorporation, we have been mainly focused on research
and development. We have incurred losses since inception, principally as a result of research and development and general administrative expenses in support of our
operations. We recorded net losses of $30.0 million in 2020, $27.1 million in 2021 and $25.0 in 2022. As of December 31, 2022, we had an accumulated deficit of $330.0
million. We anticipate that we will incur significant additional losses as we continue to focus our resources on prioritizing, selecting and advancing our most promising
therapeutic candidates. We may never be profitable, and we may never achieve significant sustained revenues.
We cannot assure investors that our existing cash and investment balances will be sufficient to meet our future capital requirements.
As of December 31, 2022, we held cash and short-term investments of $51.1 million. Based on our current projected cash requirements, we believe that our existing
cash and investment balances and other sources of liquidity, not including potential milestone and royalty payments under potential out-licensing and other collaboration
agreements, will be sufficient to meet our capital requirements into the first half of 2024. We have funded our operations primarily through public and private offerings of our
securities, payments received under our strategic licensing and collaboration arrangements and interest earned on investments. The adequacy of our available funds to meet
our operating and capital requirements will depend on many factors, including: the number, breadth, progress and results of our research, product development and clinical
programs; the costs and timing of obtaining regulatory approvals for any of our therapeutic candidates; the costs of commercializing any of our therapeutic candidates; the
terms and conditions of in-licensing and out-licensing therapeutic candidates; and costs incurred in enforcing and defending our patent claims and other intellectual property
rights
While we expect to continue to explore alternative financing sources, including the possibility of future securities offerings and government funding, we cannot be
certain that in the future these liquidity sources will be available when needed on commercially reasonable terms or at all, or that our actual cash requirements will not be
greater than anticipated. We expect to also continue to seek to finance our operations through other sources, including commercialization, if approved, in the United States for
motixafortide, our lead therapeutic candidate, out-licensing arrangements for the development and commercialization of our therapeutic candidates or other partnerships or
joint ventures, as well as grants from government agencies and foundations. If we are unable to obtain future financing through the methods we describe above or through
other means, we may be unable to complete our business objectives and may be unable to continue operations, which would have a material adverse effect on our business and
financial condition.
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If we default under our secured loan agreement with Kreos, all or a portion of our assets could be subject to forfeiture.
In September 2022, we entered into a secured loan agreement, or the Loan Agreement, with Kreos Capital VII Aggregator SCSP, or Kreos VII and together with
Kreos V, Kreos Capital. Under the Loan Agreement, Kreos Capital will provide the Company with access to term loans in an aggregate principal amount of up to $40 million
in three tranches as follows: (a) a loan in the aggregate principal amount of up to $10 million, available for drawdown upon closing of the Loan Agreement and until April 1,
2023, (b) a loan in the aggregate principal amount of up to $20 million, available for drawdown upon achievement of certain milestones and until April 1, 2024, and (c) a loan
in the aggregate principal amount of up to $10 million, available for drawdown upon achievement of certain milestones and until October 1, 2024. We drew down the initial
tranche of $10 million following execution of the agreement in September 2022.
Our ability to make the scheduled payments under the Loan Agreement or to refinance our debt obligations with Kreos Capital depends on numerous factors
including, but not limited to, the amount of our cash reserves, our capital requirements and our ability to raise additional capital. We may be unable to maintain a level of cash
reserves sufficient to permit us to pay the principal and accrued interest on the loan. If our cash reserves, cash flows and capital resources are insufficient to fund our debt
obligations to Kreos Capital, we may be required to seek additional capital, restructure or refinance our indebtedness, or delay or abandon our research and development
projects or other capital expenditures, which could have a material adverse effect on our business, financial condition, prospects or results of operations. There is no assurance
that we would be able to take any of such actions, or that such actions would permit us meet our scheduled debt obligations under the Kreos Capital loan agreements. If we
default on the Loan Agreement and are unable to cure the default pursuant to the terms of the Loan Agreement or are unable to repay or refinance the loan when due, Kreos
could take possession of any or all assets in which it holds a security interest, and dispose those assets to the extent necessary to pay off the debts, which would have a material
adverse effect on our business, financial condition, prospects or results of operations.
Risks Related to Our Business and Regulatory Matters
If we or our licensees are unable to obtain U.S. and/or foreign regulatory approval for our therapeutic candidates in a timely manner or at all, we will be unable to
commercialize our therapeutic candidates.
To date, only one of our products, BL-5010, a legacy asset for the treatment of benign skin lesions, has been approved for marketing and sale. Currently, we have two
clinical-stage therapeutic candidates in development: motixafortide (formerly referred to as BL-8040), a novel peptide for the treatment of stem cell mobilization, solid tumors
and hematological malignancies, and AGI-134, an immuno-oncology agent in development for the treatment of solid tumors. Our therapeutic candidates are subject to
extensive governmental regulations relating to development, clinical trials, manufacturing and commercialization of drugs and devices. In September 2022, we submitted a
New Drug Application, or NDA, for our lead therapeutic candidate, motixafortide, as a novel stem-cell mobilization agent for autologous bone marrow transplantation in
multiple myeloma patients. In November 2022, the US Food and Drug Administration, or FDA, accepted for review and filed our NDA for motixafortide in stem cell
mobilization for autologous transplantation in multiple myeloma patients. Although the FDA has assigned the NDA a Prescription Drug User Fee Act, or PDUFA, target
action date of September 9, 2023, we may not obtain marketing approval of motixafortide for stem cell mobilization from the FDA or for any other of our therapeutic
candidates in a timely manner or at all. In the United States, we are required to submit NDA to obtain FDA approval before marketing motixafortide or any of our therapeutic
candidates. An NDA must include extensive preclinical and clinical data and supporting information to establish the therapeutic candidate’s safety, purity and potency, or
efficacy, for each desired indication. The NDA must also include information regarding the product’s pharmacology, toxicology, chemistry, manufacture and manufacturing
controls. Obtaining approval of an NDA is a lengthy, expensive and uncertain process, and approval may not be obtained. Upon submission of an NDA, the FDA must make
an initial determination that the application is sufficiently complete to accept the submission for filing. Although our NDA for motixafortide in stem cell mobilization for
autologous transplantation in multiple myeloma patients was accepted for review, we cannot be certain that any future submissions will be accepted for filing and review by
the FDA, or ultimately be approved. The FDA may require that we conduct additional clinical or preclinical trials, or take other actions before it will approve or reconsider
any application we make. If the FDA requires additional studies or data, we would incur increased costs and delays in the marketing approval process, which may require us to
expend more resources than we have available. In addition, the FDA may not consider any additional information to be complete or sufficient to support approval.
In addition, in connection with the clinical trials for motixafortide and AGI-134 and other therapeutic candidates that we may seek to develop in the future, either on
our own or through out-licensing or co-development arrangements, we face the risk that:
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a therapeutic candidate or medical device may not prove safe or efficacious;
the results with respect to any therapeutic candidate may not confirm the positive results from earlier preclinical studies or clinical trials;
the results may not meet the level of statistical significance required by the U.S. Food and Drug Administration, or FDA, or other regulatory authorities; and
the results will justify only limited and/or restrictive uses, including the inclusion of warnings and contraindications, which could significantly limit the
marketability and profitability of the therapeutic candidate.
Any delay in obtaining, or the failure to obtain, required regulatory approvals will materially and adversely affect our ability to generate future revenues from a
particular therapeutic candidate. Any regulatory approval to market a product may be subject to limitations on the indicated uses for which we may market the product or may
impose restrictive conditions of use, including cautionary information, thereby limiting the size of the market for the product. We and our licensees, as applicable, also are, and
will be, subject to numerous foreign regulatory requirements that govern the conduct of clinical trials, manufacturing and marketing authorization, pricing and third-party
reimbursement. The foreign regulatory approval process includes all the risks associated with the FDA approval process that we describe above, as well as risks attributable to
the satisfaction of foreign requirements. Approval by the FDA does not ensure approval by regulatory authorities outside the United States. Foreign jurisdictions may have
different approval processes than those required by the FDA and may impose additional testing requirements for our therapeutic candidates.
We are executing on an independent commercialization plan for motixafortide in stem cell mobilization for autologous bone marrow transplantation in multiple myeloma
patients and historically have no experience selling, marketing or distributing products.
We are currently executing on an independent commercialization plan for motixafortide in stem cell mobilization for autologous bone marrow transplantation in
multiple myeloma patients for launch in the U.S., subject to receipt of FDA approval. As part of our plan, we are developing our sales, marketing and distribution capabilities.
Historically we have not had experience in building a sales force or distribution capabilities. To be able to commercialize any of our therapeutic candidates upon approval, if at
all, we must either develop internal sales, marketing and distribution capabilities, which is expensive and time-consuming, or enter into out-licensing arrangements with third
parties to perform these services.
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There are risks involved with establishing our own sales, marketing and distribution capabilities. We must commit significant financial and managerial resources to
develop a marketing and sales force with technical expertise and with supporting distribution capabilities. Factors that may inhibit our efforts to commercialize our products
directly and without strategic partners include:
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our inability to recruit and retain adequate numbers of effective sales and marketing personnel;
the inability of sales personnel to obtain access to or persuade adequate numbers of physicians to prescribe our therapeutic candidates;
the inability to price our products at a sufficient price point to ensure an adequate and attractive level of profitability;
the difficulty of obtaining reimbursement from governmental and commercial payers;
the lack of complementary products to be offered by sales personnel, which may put us at a competitive disadvantage relative to companies with more extensive
product lines; and
unforeseen costs and expenses associated with creating and sustaining an independent sales and marketing organization.
We may not be successful in recruiting the sales and marketing personnel necessary to sell any of our therapeutic candidates upon approval, if at all, and, even if we
do build a sales force, we may not be successful in marketing our therapeutic candidates, which would have a material adverse effect on our business, financial condition and
results of operations.
If we are unable to establish our own sales, marketing and distribution capabilities or enter into successful arrangements with third parties to perform these services,
any future product revenues and our profitability, may be materially adversely affected.
Clinical trials involve a lengthy and expensive process with an uncertain outcome, and results of earlier studies and trials may not be predictive of future trial results.
We have limited experience in conducting and managing the clinical trials necessary to obtain regulatory approvals, including FDA approval. Clinical trials are
expensive and complex, can take many years and have uncertain outcomes. We cannot necessarily predict whether we or any licensee will encounter problems with any of the
completed, ongoing or planned clinical trials that will cause us, any licensee or regulatory authorities to delay or suspend clinical trials, or to delay the analysis of data from
completed or ongoing clinical trials. In addition, because some of our clinical trials are investigator-initiated studies (i.e., we are not the study sponsor), we may have less
control over these studies. We estimate that clinical trials of certain of our advanced therapeutic candidates will continue for several years, but they may take significantly
longer to complete. Failure can occur at any stage of the testing, and we may experience numerous unforeseen events during, or as a result of, the clinical trial process that
could delay or prevent commercialization of our current or future therapeutic candidates, including, but not limited to:
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delays in securing clinical investigators or trial sites for the clinical trials;
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delays in obtaining institutional review board and other regulatory approvals to commence a clinical trial;
slower-than-anticipated patient recruitment and enrollment;
negative or inconclusive results from clinical trials;
unforeseen safety issues;
uncertain dosing issues;
an inability to monitor patients adequately during or after treatment; and
problems with investigator or patient compliance with the trial protocols.
A number of companies in the pharmaceutical, medical device and biotechnology industries, including those with greater resources and experience than us, have
suffered significant setbacks in advanced clinical trials, even after seeing promising results in earlier clinical trials. Despite the results reported in earlier clinical trials for our
therapeutic candidates, we do not know whether any Phase 3 or other clinical trials we or our licensees may conduct will demonstrate adequate efficacy and safety to result in
regulatory approval to market our therapeutic candidates. If later-stage clinical trials of any therapeutic candidate do not produce favorable results, our ability to obtain
regulatory approval for the therapeutic candidate may be adversely impacted, which will have a material adverse effect on our business, financial condition and results of
operations.
Even if we obtain regulatory approvals, our therapeutic candidates will be subject to ongoing regulatory review and if we fail to comply with continuing U.S. and
applicable foreign regulations, we could lose those approvals and our business would be seriously harmed.
Even if products we or any licensee develops receive regulatory approval or clearance, we or any licensee, as applicable, will be subject to ongoing reporting
obligations, and the products and the manufacturing operations will be subject to continuing regulatory review, including FDA inspections. The outcome of this ongoing
review may result in the withdrawal of a product from the market, the interruption of the manufacturing operations and/or the imposition of labeling and/or marketing
limitations. Since many more patients are exposed to drugs and medical devices following their marketing approval, serious but infrequent adverse reactions that were not
observed in clinical trials may be observed during the commercial marketing of the product. In addition, the manufacturer and the manufacturing facilities we or our licensees,
as applicable, will use to produce any therapeutic candidate will be subject to periodic review and inspection by the FDA and other, similar foreign regulators. Later discovery
of previously unknown problems with any product, manufacturer or manufacturing process, or failure to comply with regulatory requirements, may result in actions such as:
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restrictions on such product, manufacturer or manufacturing process;
warning letters from the FDA or other regulatory authorities;
withdrawal of the product from the market;
suspension or withdrawal of regulatory approvals;
refusal to approve pending applications or supplements to approved applications that we or our licensees submit;
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voluntary or mandatory recall;
fines;
refusal to permit the import or export of our products;
product seizure or detentions;
injunctions or the imposition of civil or criminal penalties; or
adverse publicity.
If we, or any licensee, supplier, third-party contractor, partner or clinical investigator is slow to adapt, or are unable to adapt, to changes in existing regulatory
requirements or the adoption of new regulatory requirements or policies, we or any licensee may lose marketing approval for any of our products, if any of our therapeutic
products are approved, resulting in decreased or lost revenue from milestones, product sales or royalties.
We generally rely on third parties to conduct our preclinical studies and clinical trials and to provide other services, and those third parties may not perform satisfactorily,
including by failing to meet established deadlines for the completion of such services.
We do not have the ability to conduct certain preclinical studies and clinical trials independently for our therapeutic candidates, and we rely on third parties, such as
contract laboratories, contract research organizations, medical institutions and clinical investigators to conduct these studies and clinical trials. Our reliance on these third
parties limits our control over these activities. The third-party contractors may not assign as great a priority to our clinical development programs or pursue them as diligently
as we would if we were undertaking such programs directly. Accordingly, these third-party contractors may not complete activities on schedule, or may not conduct the studies
or our clinical trials in accordance with regulatory requirements or with our trial design. If these third parties do not successfully carry out their contractual duties or meet
expected deadlines, or if their performance is substandard, we may be required to replace them or add more sites to the studies. Although we believe that there are a number of
other third-party contractors that we could engage to continue these activities, replacement of these third parties will result in delays and/or additional costs. As a result, our
efforts to obtain regulatory approvals for, and to commercialize, our therapeutic candidates may be delayed. The third-party contractors may also have relationships with other
commercial entities, some of whom may compete with us. If the third-party contractors assist our competitors, our competitive position may be harmed.
In addition, our ability to bring future products to market depends on the quality and integrity of data that we present to regulatory authorities in order to obtain
marketing authorizations. Although we attempt to audit and control the quality of third-party data, we cannot guarantee the authenticity or accuracy of such data, nor can we
be certain that such data has not been fraudulently generated. The failure of these third parties to carry out their obligations would materially adversely affect our ability to
develop and market new products and implement our strategies.
9
We have in the past and may in the future rely on out-licensing arrangements for late-stage development, marketing and commercialization of our therapeutic candidates.
Although we are executing on an independent commercialization plan for motixafortide in stem cell mobilization for autologous bone marrow transplantation in
multiple myeloma patients, we have in the past and may in the future rely on out-licensing arrangements for late-stage development, marketing and commercialization of our
therapeutic candidates. Dependence on out-licensing arrangements subjects us to a number of risks, including the risk that:
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we have limited control over the amount and timing of resources that a licensee devotes to our therapeutic candidates;
a licensee may experience financial difficulties;
a licensee may fail to secure adequate commercial supplies of our therapeutic candidates upon marketing approval, if at all;
our future revenues depend heavily on the efforts of a licensee;
business combinations or significant changes in a licensee’s business strategy may adversely affect the licensee’s willingness or ability to complete its obligations
under any arrangement with us;
a licensee could move forward with a competing therapeutic candidate developed either independently or in collaboration with others, including our competitors;
and
out-licensing arrangements are often terminated or allowed to expire, which would delay the development and may increase the development costs of our
therapeutic candidates.
If we or any licensee breaches or terminates its agreement with us, or if any licensee otherwise fails to conduct its development and commercialization activities in a
timely manner or there is a dispute about their obligations, we may need to seek other licensees, or we may have to develop our own internal sales and marketing capability for
our therapeutic candidates. Our dependence on a licensee’s experience and the rights of a licensee will limit our flexibility in considering alternative out-licensing
arrangements for our therapeutic candidates. Any failure to successfully develop these arrangements or failure by a licensee to successfully develop or commercialize any of
our therapeutic candidates in a competitive and timely manner will have a material adverse effect on the commercialization of our therapeutic candidates.
We depend on our ability to identify and in-license technologies and therapeutic candidates.
We employ a number of methods to identify therapeutic candidates that we believe are likely to achieve commercial success. In certain instances, disease-specific
third-party advisors evaluate therapeutic candidates as we deem necessary. However, there can be no assurance that our internal research efforts or our screening system will
accurately or consistently select among various therapeutic candidates those that have the highest likelihood to achieve, and that ultimately achieve, commercial success. As a
result, we may spend substantial resources developing therapeutic candidates that will not achieve commercial success, and we may not advance those therapeutic candidates
with the greatest potential for commercial success.
An important element of our strategy is maintaining relationships with universities, medical institutions and biotechnology companies in order to in-license potential
therapeutic candidates. We may not be able to maintain relationships with these entities, and they may elect not to enter into in-licensing agreements with us or to terminate
existing agreements. The existence of global companies with significantly greater resources than we have may increase the competition with respect to the in-licensing of
promising therapeutic candidates. We may not be able to acquire licenses on commercially reasonable terms or at all. Failure to license or otherwise acquire necessary
technologies could materially and adversely affect our business, financial condition and results of operations.
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If we cannot meet requirements under our in-license agreements, we could lose the rights to our therapeutic candidates, which could have a material adverse effect on our
business.
We depend on in-licensing agreements with third parties to maintain the intellectual property rights to our therapeutic candidates. We have in-licensed rights from
Biokine Therapeutics Ltd., or Biokine, with respect to our motixafortide therapeutic candidate; from the University of Massachusetts and from Kode Biotech Limited, or Kode
Biotech, with respect to our AGI-134 therapeutic candidate; and from Innovative Pharmaceutical Concepts, Inc., or IPC, with respect to our BL-5010 therapeutic candidate.
See “Item 4. Information on the Company — Business Overview — In-Licensing Agreements.” Our in-license agreements require us to make payments and satisfy
performance obligations in order to maintain our rights under these agreements. The royalty rates and revenue sharing payments vary from case to case but range from 20% to
29.5% of the consideration we receive from sublicensing the applicable therapeutic candidate and a substantially lower percentage (generally less than 5%) if we elect to
commercialize the subject therapeutic candidate independently. Due to the relatively advanced stage of development of the compound licensed from Biokine, our license
agreement with Biokine provides for royalty payments of 10% of net sales, subject to certain limitations, should we independently sell products. These in-license agreements
last either throughout the life of the patents that are the subject of the agreements, or with respect to other licensed technology, for a number of years after the first commercial
sale of the relevant product.
In addition, we are responsible for the cost of filing and prosecuting certain patent applications and maintaining certain issued patents licensed to us. If we do not
meet our obligations under our in-license agreements in a timely manner, we could lose the rights to our proprietary technology, which could have a material adverse effect on
our business, financial condition and results of operations.
If we do not meet the requirements under our agreement with the Agalimmune selling shareholders, we could lose the rights to the therapeutic candidates in
Agalimmune’s pipeline, including, but not limited to, AGI-134.
In March 2017, we acquired substantially all the outstanding shares of Agalimmune Ltd., or Agalimmune, a privately held company incorporated in the United
Kingdom. In conjunction with the acquisition, we entered into a development agreement with Agalimmune and its selling shareholders, or the Agalimmune Development
Agreement, which, among other things, grants us an option to purchase any remaining Agalimmune shares. If we do not exercise this option within a certain period of time
after achieving certain milestones or we commit a material breach of the Agalimmune Development Agreement, the selling shareholders have a reversionary option to acquire
all the Agalimmune shares we hold for nominal consideration. If the exercise of this reversionary option is completed and our development work subsequently generates
revenues for Agalimmune, we will only be entitled to a percentage of Agalimmune’s net proceeds, until such time as we have recouped the expenses we incurred in
connection with the Agalimmune Development Agreement. Completion of the exercise of the reversionary option would result in the loss of our rights in the proprietary
technology held by Agalimmune, which could have a material adverse effect on our business, financial condition and results of operations.
We may seek to partner with third-party collaborators with respect to the development and commercialization of motixafortide and for any other therapeutic candidate and
we may not succeed in establishing and maintaining collaborative relationships, which may significantly limit our ability to develop and commercialize our product
candidates successfully, if at all.
Although we are currently executing on an independent commercialization plan for motixafortide in stem cell mobilization for autologous bone marrow
transplantation in multiple myeloma patients, we collaborate with third parties with respect to the development of motixafortide in other indications and may in the future seek
a partner for any other therapeutic candidate. We compete with many other companies as we seek partners for motixafortide and for any other therapeutic candidate and we
may not be able to compete successfully against those companies. If we are not able to enter into collaboration arrangements for motixafortide and for any other therapeutic
candidate, we would be required to undertake and fund further development, clinical trials, manufacturing and commercialization activities solely at our own expense and risk,
as is the case with motixafortide in stem cell mobilization for autologous bone marrow transplantation in multiple myeloma patients. If we are unable to finance and/or
successfully execute those expensive activities, or we delay such activities due to capital availability, our business could be materially and adversely affected, and potential
future product launch could be materially delayed, be less successful, or we may be forced to discontinue clinical development of these product candidates. Furthermore, if we
are unable to enter into a commercial agreement for the development and commercialization of motixafortide and for any other therapeutic candidate, then this could have a
material adverse effect on our business, financial condition or results of operations.
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The process of establishing and maintaining collaborative relationships is difficult, time-consuming and involves significant uncertainty, including:
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a collaboration partner may shift its priorities and resources away from our therapeutic candidates due to a change in business strategies, or a merger, acquisition,
sale or downsizing;
a collaboration partner may seek to renegotiate or terminate their relationships with us due to unsatisfactory clinical results, manufacturing issues, a change in
business strategy, a change of control or other reasons;
a collaboration partner may cease development in therapeutic areas which are the subject of our strategic collaboration;
a collaboration partner may not devote sufficient capital or resources towards our therapeutic candidates;
a collaboration partner may change the success criteria for a therapeutic candidate thereby delaying or ceasing development of such candidate;
a significant delay in initiation of certain development activities by a collaboration partner will also delay payment of milestones tied to such activities, thereby
impacting our ability to fund our own activities;
a collaboration partner could develop a product that competes, either directly or indirectly, with our therapeutic candidate;
a collaboration partner with commercialization obligations may not commit sufficient financial or human resources to the marketing, distribution or sale of a
product;
a collaboration partner with manufacturing responsibilities may encounter regulatory, resource or quality issues and be unable to meet demand requirements;
a partner may exercise a contractual right to terminate a strategic alliance;
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a dispute may arise between us and a partner concerning the research, development or commercialization of a therapeutic candidate resulting in a delay in
milestones, royalty payments or termination of an alliance and possibly resulting in costly litigation or arbitration which may divert management attention and
resources; and
a partner may use our products or technology in such a way as to invite litigation from a third party.
Any collaborative partners we enter into agreements with may in the future shift their priorities and resources away from our therapeutic candidates or seek to
renegotiate or terminate their relationships with us. If any collaborator fails to fulfill its responsibilities in a timely manner, or at all, our research, clinical development,
manufacturing or commercialization efforts related to that collaboration could be delayed or terminated, or it may be necessary for us to assume responsibility for expenses or
activities that would otherwise have been the responsibility of our collaborator. If we are unable to establish and maintain collaborative relationships on acceptable terms or to
successfully transition terminated collaborative agreements, we may have to delay or discontinue further development of one or more of our product candidates, undertake
development and commercialization activities at our own expense or find alternative sources of capital.
Modifications to our therapeutic candidates, or to any other therapeutic candidates that we may develop in the future, may require new regulatory clearances or approvals
or may require us or our licensees, as applicable, to recall or cease marketing these therapeutic candidates until clearances are obtained.
Modifications to our therapeutic candidates, after they have been approved for marketing, if at all, or to any other pharmaceutical product or medical device that we
may develop in the future, may require new regulatory clearance or approvals, and, if necessitated by a problem with a marketed product, may result in the recall or suspension
of marketing of the previously approved and marketed product until clearances or approvals of the modified product are obtained. The FDA requires pharmaceutical products
and device manufacturers to initially make and document a determination of whether a modification requires a new approval, supplement or clearance. A manufacturer may
determine in conformity with applicable regulations and guidelines that a modification may be implemented without pre-clearance by the FDA; however, the FDA can review
a manufacturer’s decision and may disagree. The FDA may also on its own initiative determine that a new clearance or approval is required. If the FDA requires new
clearances or approvals of any pharmaceutical product or medical device for which we or our licensees receive marketing approval, if any, we or our licensees may be required
to recall such product and to stop marketing the product as modified, which could require us or our licensees to redesign the product and will have a material adverse effect on
our business, financial condition and results of operations. In these circumstances, we may be subject to significant enforcement actions.
If a manufacturer determines that a modification to an FDA-cleared device could significantly affect the safety or efficacy of the device, would constitute a major
change in its intended use, or otherwise requires pre-clearance, the modification may not be implemented without the requisite clearance. We or our licensees may not be able
to obtain those additional clearances or approvals for the modifications or additional indications in a timely manner, or at all. For those products sold in the European Union,
or EU, we or our licensees, as applicable, must notify the applicable EU Notified Body, an organization appointed by a member state of the EU either for the approval and
monitoring of a manufacturer’s quality assurance system or for direct product inspection, if significant changes are made to the product or if there are substantial changes to
the quality assurance systems affecting the product. Delays in obtaining required future clearances or approvals would materially and adversely affect our ability to introduce
new or enhanced products in a timely manner, which in turn would have a material adverse effect on our business, financial condition and results of operations.
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If our competitors develop and market products that are more effective, safer or less expensive than our current or future therapeutic candidates, our prospects will be
negatively impacted.
The life sciences industry is highly competitive, and we face significant competition from many pharmaceutical, biopharmaceutical and biotechnology companies
that are researching and marketing products designed to address the indications for which we are currently developing therapeutic candidates or for which we may develop
therapeutic candidates in the future. Specifically, we are aware of other companies that currently market and/or are in the process of developing products that address stem cell
mobilization and solid malignancies and skin lesions.
An important element of our strategy for identifying future products is maintaining relationships with universities, medical institutions and biotechnology companies
in order to in-license potential therapeutic candidates, and we compete with respect to this in-licensing with a number of global pharmaceutical companies. The presence of
these global companies with significantly greater resources than we have may increase the competition with respect to the in-licensing of promising therapeutic candidates.
Our failure to license or otherwise acquire necessary technologies could materially and adversely affect our business, financial condition and results of operations.
Our contract manufacturers are, and will be, subject to FDA and other comparable agency regulations.
Our contract manufacturers are, and will be, required to adhere to FDA regulations setting forth current good manufacturing practices, or cGMP, for drugs and
Quality System Regulations, or QSR, for devices. These regulations cover all aspects of the manufacturing, testing, quality control and recordkeeping relating to our
therapeutic candidates. Our manufacturers may not be able to comply with applicable regulations. Our manufacturers are and will be subject to unannounced inspections by
the FDA, state regulators and similar regulators outside the United States. The failure of our third-party manufacturers to comply with applicable regulations could result in the
imposition of sanctions on us, including fines, injunctions, civil penalties, failure of regulatory authorities to grant marketing approval of our therapeutic candidates, delays,
suspension or withdrawal of approvals, license revocation, seizures or recalls of our candidates or products, operating restrictions and criminal prosecutions, any of which
could significantly and adversely affect regulatory approval and supplies of our therapeutic candidates, and materially and adversely affect our business, financial condition
and results of operations.
Our business could suffer if we are unable to attract and retain key employees.
Our success depends upon the continued service and performance of our senior management and other key personnel. The loss of the services of these personnel
could delay or prevent the successful completion of our planned clinical trials or the commercialization of our therapeutic candidates or otherwise affect our ability to manage
our company effectively and to carry out our business plan. We do not maintain key-man life insurance. Although we have entered into employment agreements with all of the
members of our senior management team, members of our senior management team may resign at any time. High demand exists for senior management and other key
personnel in the pharmaceutical industry. There can be no assurance that we will be able to continue to retain and attract such personnel.
Our growth and success also depend on our ability to attract and retain additional highly qualified scientific, technical, sales, managerial and finance personnel. We
experience intense competition for qualified personnel, and the existence of non-competition agreements between prospective employees and their former employers may
prevent us from hiring those individuals or subject us to suit from their former employers. In addition, if we elect to independently commercialize any therapeutic candidate,
we will need to expand our marketing and sales capabilities. While we attempt to provide competitive compensation packages to attract and retain key personnel, many of our
competitors are likely to have greater resources and more experience than we have, making it difficult for us to compete successfully for key personnel. If we cannot attract
and retain sufficiently qualified technical employees on acceptable terms, we may not be able to develop and commercialize competitive products. Further, any failure to
effectively integrate new personnel could prevent us from successfully growing our company.
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We rely upon third-party manufacturers to produce therapeutic supplies for the clinical trials, and commercialization, of our therapeutic candidates. If we manufacture
any of our therapeutic candidates in the future, we will be required to incur significant costs and devote significant efforts to establish and maintain manufacturing
capabilities.
We do not currently have laboratories that are compliant with cGMP and therefore cannot independently manufacture drug products for our current clinical trials. We
rely on third-party manufacturers to produce the therapeutic supplies that will enable us to perform clinical trials and, if we choose to do so, commercialize therapeutic
candidates ourselves. We have limited personnel with experience in drug or medical device manufacturing and we lack the resources and capabilities to manufacture any of
our therapeutic candidates on a commercial scale. The manufacture of pharmaceutical products and medical devices requires significant expertise and capital investment,
including the development of advanced manufacturing techniques and process controls. Manufacturers of pharmaceutical products and medical devices often encounter
difficulties in production, particularly in scaling up initial production. These problems include difficulties with production costs and yields and quality control, including
stability of the therapeutic candidate.
We do not currently have any long-term agreements with third-party manufacturers that guarantee the supply of any of our therapeutic candidates. When we require
additional supplies of our therapeutic candidates to complete our clinical trials or if we elect to commercialize our products independently, we may be unable to enter into
agreements for clinical or commercial supply, as applicable, with third-party manufacturers, or may be unable to do so on acceptable terms. Even if we enter into these
agreements, it is likely that the manufacturers of each therapeutic candidate will be single-source suppliers to us for a significant period of time.
Reliance on third-party manufacturers entails risks to which we would not be subject if we manufactured therapeutic candidates ourselves, including:
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reliance on the third party for regulatory compliance and quality assurance;
limitations on supply availability resulting from capacity and scheduling constraints of the third parties;
impact on our reputation in the marketplace if manufacturers of our products, once commercialized, fail to meet customer demands;
the possible breach of the manufacturing agreement by the third party because of factors beyond our control; and
the possible termination or nonrenewal of the agreement by the third party, based on its own business priorities, at a time that is costly or inconvenient for us.
The failure of any of our contract manufacturers to maintain high manufacturing standards could result in injury or death of clinical trial participants or patients being
treated with our products. Such failure could also result in product liability claims, product recalls, product seizures or withdrawals, delays or failures in testing or delivery,
cost overruns or other problems, which would have a material adverse effect on our business, financial condition and results of operations.
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Increasing scrutiny of, and evolving expectations for, sustainability and environmental, social, and governance, or ESG, initiatives could increase our costs or otherwise
adversely impact our business.
Public companies are facing increasing scrutiny related to ESG practices and disclosures from certain investors, capital providers, shareholder advocacy groups, other
market participants and other stakeholder groups. With this increased focus, public reporting regarding ESG practices is becoming more broadly expected. Such increased
scrutiny may result in increased costs, enhanced compliance or disclosure obligations, or other adverse impacts on our business, financial condition or results of operations. If
our ESG practices and reporting do not meet investor or other stakeholder expectations, which continue to evolve, we may be subject to investor or regulator engagement
regarding such matters. In addition, new sustainability rules and regulations have been adopted and may continue to be introduced in various states and other jurisdictions. For
example, the SEC has published proposed rules that would require companies to provide significantly expanded climate-related disclosures in their periodic reporting, which
may require us to incur significant additional costs to comply and impose increased oversight obligations on our management and board of directors. Our failure to comply
with any applicable rules or regulations could lead to penalties and adversely impact our reputation, access to capital and employee retention. Such ESG matters may also
impact our third-party contract manufacturers and other third parties on which we rely, which may augment or cause additional impacts on our business, financial condition, or
results of operations.
Our business is subject to risks arising from a widespread outbreak of an illness or any other communicable disease, or any other public health crisis, such as the
COVID-19 pandemic and other pandemics, which has impacted and could in the future impact our business.
The novel coronavirus outbreak, or COVID-19, has affected segments of the global economy. Due to clinical operating issues associated with the COVID-19
pandemic, during 2020, we temporarily suspended enrollment to the phase 1/2a study for AGI-134, our second lead compound. If there is a resurgence, COVID-19 could
impact our future operations, including potential interruptions to supply chains, clinical trials, commercialization activities and regulatory reviews and approvals. COVID-19
may also affect our employees and employees and operations at suppliers that may result in delays or disruptions in supply. In addition, a recession or market correction
resulting from any resurgence of COVID-19 could materially affect our business and the value of our shares. Additionally, if the COVID-19 pandemic has a significant impact
on our business and financial results for an extended period of time, our liquidity and cash resources could be negatively impacted. Capital and credit markets have been
disrupted by the crisis and exchanges have experienced increased volatility. As a result, access to additional financing may be challenging and is largely dependent upon
evolving market conditions and other factors. We have in the past taken precautionary measures, including, for example, a Company-wide salary reduction related to the
COVID-19 pandemic carried out in the second and third quarters of 2020, and may take additional measures, intended to minimize the risk of COVID-19 to our employees
and operations. The extent of the impact of any resurgence of COVID-19 or other pandemics on our operational and financial performance, including our ability to execute
our business strategies in the expected time frame or at all, will depend on future developments, such as the duration and spread of the COVID-19 and other pandemics and
related restrictions and implications and the effectiveness of actions taken to contain and treat the diseases, all of which are uncertain and cannot be predicted. The impact of
any resurgence of the COVID-19 pandemic or another pandemic may also have the effect of heightening many of the other risks described in the “Risk Factors” section of this
Annual Report on Form 20-F
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Risks Related to Our Industry
Even if our therapeutic candidates receive regulatory approval or do not require regulatory approval, they may not become commercially viable products.
Even if our therapeutic candidates are approved for commercialization, they may not become commercially viable products. For example, if we or any licensee
receive regulatory approval to market a product, approval may be subject to limitations on the indicated uses or subject to labelling or marketing restrictions, which could
materially and adversely affect the marketability and profitability of the product. In addition, a new product may appear promising at an early stage of development or after
clinical trials but never reach the market, or it may reach the market but not result in sufficient product sales, if any. A therapeutic candidate may not result in commercial
success for various reasons, including:
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difficulty in large-scale manufacturing;
low market acceptance by physicians, healthcare payors, patients and the medical community as a result of lower demonstrated clinical safety or efficacy
compared to other products, prevalence and severity of adverse side effects, or other potential disadvantages relative to alternative treatment methods;
insufficient or unfavorable levels of reimbursement from government or third-party payors;
infringement on proprietary rights of others for which we or our licensees have not received licenses;
incompatibility with other therapeutic products;
other potential advantages of alternative treatment methods;
ineffective marketing and distribution support;
significant changes in pricing due to pressure from public opinion, non-governmental organizations or governmental authorities;
lack of cost-effectiveness; or
timing of market introduction of competitive products.
If we are unable to develop commercially viable products, either on our own or through licensees, our business, results of operations and financial condition will be
materially and adversely affected.
Healthcare reforms and related reductions in pharmaceutical pricing, reimbursement and coverage by governmental authorities and third-party payors may adversely
affect our business.
The continuing increase in expenditures for healthcare has been the subject of considerable government attention, particularly as public resources have been stretched
by financial and economic crises in the United States, Western Europe and elsewhere. Both private health insurance funds and government health authorities continue to seek
ways to reduce or contain healthcare costs, including by reducing or eliminating coverage for certain products and lowering reimbursement levels. In many countries and
regions, including the United States, Western Europe, Israel, Russia, certain countries in Central and Eastern Europe and several countries in Latin America, pharmaceutical
prices are subject to new government policies designed to reduce healthcare costs. These changes frequently adversely affect pricing and profitability and may cause delays in
market entry. We cannot predict which additional measures may be adopted or the impact of current and additional measures on the marketing, pricing and demand for our
approved products, if any of our therapeutic products are approved.
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Significant developments that may adversely affect pricing in the United States include (i) the enactment of federal healthcare reform laws and regulations, including
the Medicare Prescription Drug Improvement and Modernization Act of 2003 and the Patient Protection and Affordable Care Act of 2010, or PPACA, and (ii) trends in the
practices of managed care groups and institutional and governmental purchasers, including the impact of consolidation of our customers. In 2022, the Inflation Reduction Act
of 2022, or IRA, establishes the Medicare Drug Price Negotiation Program which permits the government to negotiate “maximum fair” drug prices for certain high
expenditure, single source drugs and biologics. It is estimated that over the next seven years, 60 drugs covered under Medicare B and D will have negotiated a “maximum fair
price.”
Changes to the healthcare system enacted as part of healthcare reform in the United States, as well as the increased purchasing power of entities that negotiate on
behalf of Medicare, Medicaid, and private sector beneficiaries, may result in increased pricing pressure by influencing, for instance, the reimbursement policies of third-party
payors. Healthcare reform legislation has increased the number of patients who would have insurance coverage for our approved products, if any of our therapeutic products
are approved, but provisions such as the assessment of a branded pharmaceutical manufacturer fee and an increase in the amount of the rebates that manufacturers pay for
coverage of their drugs by Medicaid programs may have an adverse effect on us. It is uncertain how current and future reforms in these areas will influence the future of our
business operations and financial condition, as federal, state and foreign governmental authorities are likely to continue efforts to control the price of drugs and reduce overall
healthcare costs. These efforts could have an adverse impact on our ability to market products and generate revenues in the United States and foreign countries.
If third-party payors do not adequately reimburse customers for any of our therapeutic candidates that are approved for marketing, they might not be purchased or used,
and our revenues and profits will not develop or increase.
Our revenues and profits will depend heavily upon the availability of adequate reimbursement for the use of our approved candidates, if any, from governmental or
other third-party payors, both in the United States and in foreign markets. Reimbursement by a third-party payor may depend upon a number of factors, including the third-
party payor’s determination that the use of an approved 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.
Obtaining reimbursement approval for a product from each government or other third-party payor is a time-consuming and costly process that could require us or our
licensees to provide supporting scientific, clinical and cost-effectiveness data for the use of our products to each payor. Even when a payor determines that a product is eligible
for reimbursement, the payor may impose coverage limitations that preclude payment for some uses that are approved by the FDA or comparable foreign regulatory
authorities. Reimbursement rates may vary according to the use of the product and the clinical setting in which it used, may be based on payments allowed for lower-cost
products that are already reimbursed, may be incorporated into existing payments for other products or services, and may reflect budgetary constraints and/or imperfections in
Medicare, Medicaid or other data used to calculate these rates.
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Regardless of the impact of the PPACA on us, the U.S. government, other governments and commercial payors have shown significant interest in pursuing healthcare
reform and reducing healthcare costs. Any government-adopted reform measures, such as the IRA, could cause significant pressure on the pricing of healthcare products and
services, including those biopharmaceuticals currently being developed by us or our licensees, in the United States and internationally, as well as the amount of reimbursement
available from governmental agencies or other third-party payors. The continuing efforts of the U.S. and foreign governments, insurance companies, managed care
organizations and other payors to contain or reduce healthcare costs may compromise our ability to set prices at commercially attractive levels for our products that we may
develop, which in turn could adversely impact how much or under what circumstances healthcare providers will prescribe or administer our products, if approved. Changes in
healthcare policy, such as the creation of broad limits for diagnostic products, could substantially diminish the sale of or inhibit the utilization of diagnostic tests, increase
costs, divert management’s attention and adversely affect our ability to generate revenues and achieve consistent profitability. This could materially and adversely impact our
business by reducing our ability to generate revenue, raise capital, obtain additional collaborators and market our products, if approved.
Further, the Centers for Medicare and Medicaid Services, or CMS, frequently change product descriptors, coverage policies, product and service codes, payment
methodologies and reimbursement values. The IRA will modify 60 drugs and biologics through negotiation of a fair maximum pricing for CMS. Third-party payors often
follow Medicare coverage policy and payment limitations in setting their own reimbursement rates, and both CMS and other third-party payors may have sufficient market
power to demand significant price reductions.
Our business has a substantial risk of clinical trial and product liability claims. If we are unable to obtain and maintain appropriate levels of insurance, a claim could
adversely affect our business.
Our business exposes us to significant potential clinical trial and product liability risks that are inherent in the development, manufacturing and sales and marketing of
human therapeutic products. Claims could be made against us based on the use of our therapeutic candidates in clinical trials and in marketed products. We currently carry life
science liability insurance covering general liability with an annual coverage amount of $30.0 million per occurrence and product liability and clinical trials coverage with an
annual coverage amount of $30.0 million each claim and in the aggregate. The annual aggregate as well as the maximum indemnity for a single occurrence, claim or
circumstances under this insurance is $30.0 million. However, our insurance may not provide adequate coverage against potential liabilities. Furthermore, clinical trial and
product liability insurance is becoming increasingly expensive. As a result, we may be unable to maintain current amounts of insurance coverage or to obtain additional or
sufficient insurance at a reasonable cost to protect against losses that could have a material adverse effect on us. If a claim is brought against us, we might be required to pay
legal and other expenses to defend the claim, as well as damages awards beyond the coverage of our insurance policies resulting from a claim brought successfully against us.
Furthermore, whether or not we are ultimately successful in defending any claims, we might be required to direct significant financial and managerial resources to such
defense, and adverse publicity is likely to result.
Significant disruptions of our information technology systems or breaches of our data security could adversely affect our business.
A significant invasion, interruption, destruction or breakdown of our information technology systems and/or infrastructure by persons with authorized or
unauthorized access could negatively impact our business and operations. We could experience business interruption, information theft and/or reputational damage from cyber-
attacks or cyber-intrusions over the Internet, computer viruses, malware, natural disasters, terrorism, war, telecommunication and electrical failures, and attachments to emails.
Any of the foregoing may compromise our systems and lead to data leakage either internally or at our third-party providers. The risk of a security breach or disruption,
particularly through cyber-attacks or cyber-intrusion, including by computer hackers, foreign governments and cyber terrorists, has generally increased as the number,
intensity and sophistication of attempted attacks and intrusions from around the world have increased. If such an event were to occur and cause interruptions in our operations,
it could result in a material disruption of our product development programs. For example, the loss of clinical trial data from completed or ongoing or planned clinical trials
could result in delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. Our systems have been, and are expected to
continue to be, the target of malware and other cyber-attacks. Although we have invested in measures to reduce these risks, we cannot assure you that these measures will be
successful in preventing compromise and/or disruption of our information technology systems and related data.
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We deal with hazardous materials and must comply with environmental, health and safety laws and regulations, which can be expensive and restrict how we do business.
Our activities and those of our third-party manufacturers on our behalf involve the controlled storage, use and disposal of hazardous materials, including microbial
agents, corrosive, explosive and flammable chemicals, as well as cytotoxic, biologic, radio-labeled and other hazardous compounds. We and our manufacturers are subject to
U.S. federal, state, local, Israeli and other foreign laws and regulations governing the use, manufacture, storage, handling and disposal of these hazardous materials. Although
we believe that our safety procedures for handling and disposing of these materials comply with the standards prescribed by these laws and regulations, we cannot eliminate
the risk of accidental contamination or injury from these materials. In addition, if we develop a manufacturing capacity, we may incur substantial costs to comply with
environmental regulations and would be subject to the risk of accidental contamination or injury from the use of hazardous materials in our manufacturing process.
In the event of an accident, government authorities may curtail our use of these materials and interrupt our business operations. In addition, we could be liable for any
civil damages that result, which may exceed our financial resources and may seriously harm our business. Although our Israeli insurance program covers certain unforeseen
sudden pollutions, we do not maintain a separate insurance policy for any of the foregoing types of risks. In addition, although the general liability section of our life sciences
policy covers certain unforeseen, sudden environmental issues, pollution in the United States and Canada is excluded from the policy. In the event of environmental discharge
or contamination or an accident, we may be held liable for any resulting damages, and any liability could exceed our resources. In addition, we may be subject to liability and
may be required to comply with new or existing environmental laws regulating pharmaceuticals or other medical products in the environment.
We are currently part to, and may in the future, become subject to litigation or claims arising in or outside the ordinary course of business that could negatively affect our
business operations and financial condition.
We are currently party to, and may in the future, become subject to litigation or claims arising in or outside the ordinary course of business (other than intellectual
property infringement actions) that could negatively affect our business operations and financial condition, including securities class actions which are typically expensive to
defend. Such claims and litigation proceedings may be brought by third parties, including our competitors, advisors, service providers, partners or collaborators, employees,
and governmental or regulatory bodies. For information on legal proceedings, please see “Item 8. Financial Information – A. Financial Statements and Other Financial
Information – Legal Proceedings.” Any claims and lawsuits, and the disposition of such claims and lawsuits, could be time-consuming and expensive to resolve, divert
management attention and resources, and lead to attempts on the part of other parties to pursue similar claims. We may not be able to determine the amount of any potential
losses and other costs we may incur due to the inherent uncertainties of litigation and settlement negotiations. In the event we are required or decide to pay amounts in
connection with any claims or lawsuits, such amounts could be significant and could have a material adverse impact on our liquidity, business, financial condition and results
of operations. In addition, depending on the nature and timing of any such dispute, a resolution of a legal matter could materially affect our future operating results, our cash
flows or both. Additionally, we may be unable to maintain our existing directors’ and officers’ liability insurance in the future at satisfactory rates or adequate coverage
amounts and may incur significant increases in insurance costs.
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Risks Related to Intellectual Property
Our access to most of the intellectual property associated with our therapeutic candidates results from in-license agreements with biotechnology companies and a
university, the termination of which would prevent us from commercializing the associated therapeutic candidates.
We do not conduct our own initial research with respect to the identification of our therapeutic candidates. Instead, we rely upon research and development work
conducted by third parties as the primary source of our therapeutic candidates. As such, we have obtained our rights to our therapeutic candidates through in-license
agreements entered into with biotechnology companies and a university that invent and own the intellectual property underlying our candidates. There is no assurance that
such in-licenses or rights will not be terminated or expire due to a material breach of the agreements, such as a failure on our part to achieve certain progress milestones set
forth in the terms of the in-licenses or due to the loss of the rights to the underlying intellectual property by any of our licensors. There is no assurance that we will be able to
renew or renegotiate an in-licensing agreement on acceptable terms if and when the agreement terminates. We cannot guarantee that any in-license is enforceable or will not be
terminated or converted into a non-exclusive license in the future. The termination of any in-license or our inability to enforce our rights under any in-license would materially
and adversely affect our ability to commercialize certain of our therapeutic candidates.
We currently have in-licensing agreements relating to our therapeutic candidates that are in development or being commercialized. In 2012, we in-licensed the rights
to motixafortide under a license agreement from Biokine. Under the license agreement for motixafortide, we are obligated to make commercially reasonable, good faith efforts
to sublicense or commercialize motixafortide for fair consideration. Agalimmune in-licensed rights to AGI-134 under a license from the University of Massachusetts in 2013
and under a license from Kode Biotech in 2015. Under each of those license agreements, Agalimmune is obligated to use diligent efforts or cause its affiliates and sublicensees
to use diligent efforts to develop the respective licensed technology and introduce licensed products into the commercial market. In 2007, we in-licensed the rights to BL-5010
under a license agreement with IPC. Under the BL-5010 license agreement, we are obligated to use commercially reasonable efforts to develop the licensed technology in
accordance with a specified development plan, including meeting certain specified diligence goals.
Each of the foregoing in-licensing agreements, or the obligation to pay royalties thereunder, will generally remain in effect until the expiration, under the applicable
agreement, of all the licensing, royalty and sublicense revenue obligations to the applicable licensors, determined on a product-by-product and country-by-country basis. We
may terminate the motixafortide in-licensing agreement upon 90 days’ prior written notice to Biokine. Agalimmune may terminate each of the in-licensing agreements with
University of Massachusetts and Kode Biotech relating to AGI-134, on 90 days’ notice. We may terminate the BL-5010 in-licensing agreement upon 30 days’ prior written
notice to IPC.
Any party to any of the foregoing in-licensing agreements may terminate the respective agreement for material breach by the other party if the breaching party is
unable to cure the breach within an agreed-upon period, generally 30 days to 90 days, after receiving written notice of the breach from the non-breaching party.
Patent protection for our products is important and uncertain.
Our success depends, in part, on our ability, and the ability of our licensees and licensors to obtain patent protection for our therapeutic candidates, maintain the
confidentiality of our trade secrets and know-how, operate without infringing on the proprietary rights of others and prevent others from infringing our proprietary rights.
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We try to protect our proprietary position by, among other things, filing U.S., European, Israeli and other patent applications related to our proprietary products,
technologies, inventions and improvements that may be important to the continuing development of our therapeutic candidates. As of March 21, 2023, we owned or
exclusively licensed for uses within our field of business 33 patent families that collectively contain 129 issued patents, 10 allowed patent applications and over 80 pending
patent applications relating to our therapeutic candidates.
Because the patent position of biopharmaceutical companies involves complex legal and factual questions, we cannot predict the validity and enforceability of patents
with certainty. Our issued patents and the issued patents of our licensees or licensors may not provide us with any competitive advantages or may be held invalid or
unenforceable as a result of legal challenges by third parties. Thus, any patents that we own or license from others may not provide any protection against competitors. Our
pending patent applications, those we may file in the future or those we may license from third parties may not result in patents being issued. If these patents are issued, they
may not provide us with proprietary protection or competitive advantages against competitors with similar technology. The degree of future protection to be afforded by our
proprietary rights is uncertain because legal means afford only limited protection and may not adequately protect our rights or permit us to gain or keep our competitive
advantage.
Patent rights are territorial; thus, the patent protection we do have will only extend to those countries in which we have issued patents. Even so, the laws of certain
countries do not protect our intellectual property rights to the same extent as do the laws of the United States. For example, the patent laws of China and India are relatively
new and are not as developed as are older, more established patent laws of other countries. Competitors may successfully challenge our patents, produce similar drugs or
products that do not infringe our patents, or produce drugs in countries where we have not applied for patent protection or that do not respect our patents. Furthermore, it is not
possible to know the scope of claims that will be allowed in published applications and it is also not possible to know which claims of granted patents, if any, will be deemed
enforceable in a court of law.
Our technology may infringe the rights of third parties. The nature of claims contained in unpublished patent filings around the world is unknown to us and it is not
possible to know which countries patent holders may choose for the extension of their filings under the Patent Cooperation Treaty, or other mechanisms. Any infringement by
us of the proprietary rights of third parties may have a material adverse effect on our business, financial condition and results of operations.
If we are unable to protect the confidentiality of our trade secrets or know-how, such proprietary information may be used by others to compete against us.
We rely on a combination of patents, trade secrets, know-how, technology, trademarks and regulatory exclusivity to maintain our competitive position. We generally
try to protect trade secrets, know-how and technology by entering into confidentiality or non-disclosure agreements with parties that have access to it, such as our licensees,
employees, contractors and consultants. We also enter into agreements that purport to require the disclosure and assignment to us of the rights to the ideas, developments,
discoveries and inventions of our employees, advisors, research collaborators, contractors and consultants while we employ or engage them. However, these agreements can
be difficult and costly to enforce or may not provide adequate remedies. Any of these parties may breach the confidentiality agreements and willfully or unintentionally
disclose our confidential information, or our competitors might learn of the information in some other way. The disclosure to, or independent development by, a competitor of
any trade secret, know-how or other technology not protected by a patent could materially adversely affect any competitive advantage we may have over any such competitor.
To the extent that any of our employees, advisors, research collaborators, contractors or consultants independently develop, or use independently developed,
intellectual property in connection with any of our projects, disputes may arise as to the proprietary rights to this type of information. If a dispute arises with respect to any
proprietary right, enforcement of our rights can be costly and unpredictable, and a court may determine that the right belongs to a third party.
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Legal proceedings or third-party claims of intellectual property infringement may require us to spend substantial time and money and could prevent us from developing or
commercializing products.
The development, manufacture, use, offer for sale, sale or importation of our therapeutic candidates may infringe on the claims of third-party patents. A party might
file an infringement action against us. The cost to us of any patent litigation or other proceeding, even if resolved in our favor, could be substantial. Some of our competitors
may be able to sustain the costs of such litigation or proceedings more effectively because of their substantially greater financial resources. Uncertainties resulting from the
initiation and continuation or defense of a patent litigation or other proceedings could have a material adverse effect on our ability to compete in the marketplace. Patent
litigation and other proceedings may also absorb significant management time. Consequently, we are unable to guarantee that we will be able to manufacture, use, offer for
sale, sell or import our therapeutic candidates in the event of an infringement action. At present, we are not aware of pending or threatened patent infringement actions against
us.
In the event of patent infringement claims, or to avoid potential claims, we may choose or be required to seek a license from a third party and would most likely be
required to pay license fees or royalties or both. These licenses may not be available on acceptable terms, or at all. Even if we were able to obtain a license, the rights may be
non-exclusive, which could potentially limit our competitive advantage. Ultimately, we could be prevented from commercializing a therapeutic candidate or be forced to cease
some aspect of our business operations if, as a result of actual or threatened patent infringement claims, we are unable to enter into licenses on acceptable terms. This inability
to enter into licenses could harm our business significantly. At present, we have not received any written demands from third parties that we take a license under their patents
nor have we received any notice form a third party accusing us of patent infringement.
Our license agreements with our licensees contain, and any contract that we enter into with licensees in the future will likely contain, indemnity provisions that
obligate us to indemnify the licensee against any losses arising from infringement of third-party intellectual property rights. In addition, our in-license agreements contain
provisions that obligate us to indemnify the licensors against any damages arising from the development, manufacture and use of products developed on the basis of the in-
licensed intellectual property.
We may be subject to other patent-related litigation or proceedings that could be costly to defend and uncertain in their outcome.
In addition to infringement claims against us, we may in the future become a party to other patent litigation or proceedings, including interference or re-examination
proceedings filed with the U.S. Patent and Trademark Office or opposition proceedings in other foreign patent offices regarding intellectual property rights with respect to our
products and technology, as well as other disputes regarding intellectual property rights with licensees, licensors or others with whom we have contractual or other business
relationships. Post-issuance oppositions are not uncommon and we, our licensee or our licensor will be required to defend these opposition procedures as a matter of course.
Opposition procedures may be costly, and there is a risk that we may not prevail.
We may be subject to damages resulting from claims that we or our employees or contractors have wrongfully used or disclosed alleged trade secrets of their former
employers.
Many of our employees and contractors were previously employed at universities or other biotechnology or pharmaceutical companies, including our competitors or
potential competitors. Although no claims against us are currently pending, we may be subject to claims that we or any employee or contractor has inadvertently or otherwise
used or disclosed trade secrets or other proprietary information of his or her former employers. Litigation may be necessary to defend against these claims. If we fail in
defending such claims, in addition to paying monetary damages, we may lose valuable intellectual property rights or personnel. A loss of key research personnel or their work
product could hamper or prevent our ability to commercialize certain therapeutic candidates, which could severely harm our business, financial condition and results of
operations. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management.
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Risks Related to our Ordinary Shares and ADSs
We may be a passive foreign investment company, or PFIC, for U.S. federal income tax purposes for our taxable year ending December 31, 2023 or in any subsequent
year. There may be negative tax consequences for U.S. taxpayers that are holders of our ordinary shares or our ADSs if we are a PFIC.
We will be treated as a PFIC for U.S. federal income tax purposes in any taxable year in which either (i) at least 75% of our gross income is “passive income” or (ii)
on average at least 50% of our assets by value produce passive income or are held for the production of passive income. Passive income for this purpose generally includes,
among other things, certain dividends, interest, royalties, rents and gains from commodities and securities transactions and from the sale or exchange of property that gives rise
to passive income. Passive income also includes amounts derived by reason of the temporary investment of funds, including those raised in a public offering. In determining
whether a non-U.S. corporation is a PFIC, a proportionate share of the income and assets of each corporation in which it owns, directly or indirectly, at least a 25% interest (by
value) is taken into account. We believe that we were a PFIC during certain prior taxable years, although we believe that we were not a PFIC for the year ended December 31,
2022. Although we have not determined whether we will be a PFIC for our taxable year ending December 31, 2023, or in any subsequent year, our operating results for any
such years may cause us to be a PFIC. Because PFIC status is determined annually and is based on our income, assets and activities for the entire taxable year, it is not
possible to determine with certainty whether we will be characterized as a PFIC for the 2023 taxable year until after the close of the year, and there can be no assurance that
we will not be classified as a PFIC in any future year. If we are a PFIC for our taxable year ending December 31, 2023, or any subsequent year, and a U.S. Investor (as defined
below) does not make an election to treat us as a “qualified electing fund,” or QEF, or make a “mark-to-market” election, then “excess distributions” to a U.S. Investor, and
any gain realized on the sale or other disposition of our ordinary shares or ADSs will be subject to special rules. Under these rules: (i) the excess distribution or gain would be
allocated ratably over the U.S. Investor’s holding period for the ordinary shares (or ADSs, as the case may be); (ii) the amount allocated to the current taxable year and any
period prior to the first day of the first taxable year in which we were a PFIC would be taxed as ordinary income; and (iii) the amount allocated to each of the other taxable
years would be subject to tax at the highest rate of tax in effect for the applicable class of taxpayer for that year, and an interest charge for the deemed deferral benefit would
be imposed with respect to the resulting tax attributable to each such other taxable year. In addition, if the U.S. Internal Revenue Service, or the IRS, determines that we are a
PFIC for a year with respect to which we have determined that we were not a PFIC, it may be too late for a U.S. Investor to make a timely QEF or mark-to-market election.
U.S. Investors who hold our ordinary shares or ADSs during a period when we are a PFIC will be subject to the foregoing rules, even if we cease to be a PFIC in subsequent
years, subject to exceptions for U.S. Investors who made a timely QEF or mark-to-market election. A U.S. Investor can make a QEF election by completing the relevant
portions of and filing IRS Form 8621 in accordance with the instructions thereto. A QEF election generally may not be revoked without the consent of the IRS. Upon request,
we intend to annually furnish U.S. Investors with information needed in order to complete IRS Form 8621 (which form would be required to be filed with the IRS on an
annual basis by the U.S. Investor) and to make and maintain a valid QEF election for any year in which we or any of our subsidiaries are a PFIC. See also “Item 10. Additional
Information—E. Taxation—U.S. Federal Income Tax Considerations.”
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If a United States person is treated as owning at least 10% of our shares, such holder may be subject to adverse U.S. federal income tax consequences.
If a United States person is treated as owning (directly, indirectly or constructively) at least 10% of the value or voting power of our shares, such person may be
treated as a “United States shareholder” with respect to each “controlled foreign corporation” in our group (if any). 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, whether or not we make any distributions, and may be subject to tax reporting obligations. 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. A failure to comply with these reporting obligations may subject you to significant monetary penalties and
may prevent the statute of limitations with respect to your U.S. federal income tax return for the year for which reporting was due from starting. We cannot provide any
assurances that we will assist any shareholder in determining whether such shareholder is treated as a United States shareholder with respect to any “controlled foreign
corporation” in our group (if any) or furnish to any United States shareholders information that may be necessary to comply with the aforementioned reporting and tax paying
obligations. A United States investor should consult its tax advisors regarding the potential application of these rules to its investment in the shares.
Our business, operating results and growth rates may be adversely affected by current or future unfavorable economic and market conditions and adverse developments
with respect to financial institutions and associated liquidity risk.
Our business depends on the economic health of the global economies. If the conditions in the global economies remain uncertain or continue to be volatile, or if they
deteriorate, including as a result of the impact of military conflict, such as the war between Russia and Ukraine, terrorism or other geopolitical events, our business, operating
results and financial condition may be materially adversely affected. Economic weakness, inflation and increases in interest rates, limited availability of credit, liquidity
shortages and constrained capital spending have at times in the past resulted, and may in the future result, in challenging and delayed sales cycles, slower adoption of new
technologies and increased price competition, and could negatively affect our ability to forecast future periods, which could result in an inability to satisfy demand for our
products and a loss of market share.
In addition, increases in inflation raise our costs for commodities, 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 our financial condition. Additionally, increases in inflation, along with the uncertainties surrounding COVID-19,
geopolitical developments and global supply chain disruptions, have caused, and may in the future cause, global economic uncertainty and uncertainty about the interest rate
environment, which may make it more difficult, costly or dilutive for us to secure additional financing. A failure to adequately respond to these risks could have a material
adverse impact on our financial condition, results of operations or cash flows.
More recently, the closures of SVB and Signature Bank and their placement into receivership with the FDIC created bank-specific and broader financial institution
liquidity risk and concerns. Although the Department of the Treasury, the Federal Reserve and the FDIC jointly released a statement that depositors at SVB and Signature
Bank would have access to their funds, even those in excess of the standard FDIC insurance limits, under a systemic risk exception, future adverse developments with respect
to specific financial institutions or the broader financial services industry may lead to market-wide liquidity shortages, impair the ability of companies to access near-term
working capital needs, and create additional market and economic uncertainty. There can be no assurance that future credit and financial market instability and a deterioration
in confidence in economic conditions will not occur. Our general business strategy may be adversely affected by any such economic downturn, liquidity shortages, volatile
business environment or continued unpredictable and unstable market conditions. If the current equity and credit markets deteriorate, or if adverse developments are
experienced by financial institutions, it may cause short-term liquidity risk and also make any necessary debt or equity financing more difficult, more costly, more onerous
with respect to financial and operating covenants and more dilutive. Failure to secure any necessary financing in a timely manner and on favorable terms could have a material
adverse effect on our growth strategy, financial performance and stock price and could require us to alter our operating plans. In addition, there is a risk that one or more of our
service providers, financial institutions, manufacturers, suppliers and other partners may be adversely affected by the foregoing risks, which could directly affect our ability to
attain our operating goals on schedule and on budget.
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The market prices of our ordinary shares and ADSs are subject to fluctuation, which could result in substantial losses by our investors.
The stock market in general and the market prices of our ordinary shares on the TASE and ADSs on Nasdaq, in particular, are subject to fluctuation, and changes in
these prices may be unrelated to our operating performance. We expect that the market prices of our ordinary shares and ADSs will continue to be subject to wide fluctuations.
The market price of our ordinary shares and ADSs are and will be subject to a number of factors, including:
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announcements of technological innovations or new products by us or others;
announcements by us of significant acquisitions, strategic partnerships, in-licensing, out-licensing, joint ventures or capital commitments;
expiration or terminations of licenses, research contracts or other collaboration agreements;
public concern as to the safety of drugs we, our licensees or others develop;
general market conditions;
the volatility of market prices for shares of biotechnology companies generally;
success of research and development projects;
departure of key personnel;
developments concerning intellectual property rights or regulatory approvals;
variations in our and our competitors’ results of operations;
changes in earnings estimates or recommendations by securities analysts, if our ordinary shares or ADSs are covered by analysts;
statements about the Company made in the financial media or by bloggers on the Internet;
statements made about drug pricing and other industry-related issues by government officials;
changes in government regulations or patent decisions;
developments by our licensees; and
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general market conditions and other factors, including factors unrelated to our operating performance.
These factors and any corresponding price fluctuations may materially and adversely affect the market price of our ordinary shares and ADSs, and result in
substantial losses by our investors. See also Risk Factors—Risks Related to our Ordinary Shares and ADSs—“ Our business, operating results and growth rates may be
adversely affected by current or future unfavorable economic and market conditions and adverse developments with respect to financial institutions and associated liquidity
risk.”
Additionally, market prices for securities of biotechnology and pharmaceutical companies historically have been very volatile. The market for these securities has
from time to time experienced significant price and volume fluctuations for reasons unrelated to the operating performance of any one company. A significant outbreak of
contagious diseases could result in a widespread health crisis that could adversely affect the economies and financial markets of many countries, resulting in an economic
downturn. Following periods of market volatility, shareholders have often instituted securities class action litigation and we are currently party to two purported securities
class action litigation. See “Item 8.A—Financial Information—Legal Proceedings” for additional information. Such securities litigation or any additional securities litigation
could have a substantial cost and divert resources and attention of management from our business, even if we are successful.
Our ordinary shares are traded on the TASE and our ADSs are listed on Nasdaq. Trading in our securities on these markets takes place in different currencies (dollars
on Nasdaq and NIS on the TASE), and at different times (resulting from different time zones, different trading days and different public holidays in the United States and
Israel). The trading prices of our securities on these two markets may differ due to these factors, the factors listed above, or other factors. Any decrease in the price of our
securities on one of these markets could cause a decrease in the trading price of our securities on the other market.
Future sales of our ordinary shares or ADSs could reduce the market price of our ordinary shares and ADSs.
Substantial sales of our ordinary shares or ADSs, either on the TASE or on Nasdaq, may cause the market price of our ordinary shares or ADSs to decline. Sales by us
or our securityholders of substantial amounts of our ordinary shares or ADSs, or the perception that these sales may occur in the future, could cause a reduction in the market
price of our ordinary shares or ADSs.
As of March 21, 2023, as a result of previous financings, we had warrants outstanding (i) for the purchase of 63,837 ADSs at an exercise price of $14.10 per ADS, (ii)
for the purchase of 1,866,667 ADSs at an exercise price of $11.25 per ADS, (iii) for the purchase of 718,750 ADSs at an exercise price of $3.00 per ADS, (iv) for the purchase
for the purchase of 13,636,365 ADSs at an exercise price of $1.15 per ADS and (vi) for the purchase of 681,818 ADSs at an exercise price of $1.375 per ADS.
On September 25, 2020, we entered into an offering agreement, or the Original HCW Offering Agreement, with HCW. Pursuant to Original HCW Offering
Agreement, we were able to offer and sell, from time to time, at our option, up to $25.0 million of our ADSs through an “at-the-market” equity offering program under which
HCW agreed to act as sales agent. From the effective date of the Original HCW Offering Agreement through September 3, 2021, we had sold an aggregate of 7,381,101 ADSs
for an aggregate offering price of $24.5 million. On September 3, 2021, the Original HCW Offering Agreement was terminated.
On September 3, 2021, we entered into a new offering agreement, or the New HCW Offering Agreement, with HCW, pursuant to which we may offer and sell, at our
option, up to $25.0 million of our ADSs through an “at-the-market” equity program under which HCW agreed to act as sales agent. As of March 21, 2023, we have sold
608,651 of our ADSs for total gross proceeds of approximately $1.4 million under the New HCW Offering Agreement.
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As of March 21, 2023, in the framework of our Share Incentive Plan, there are outstanding stock options, restricted stock units and performance stock units (granted
to directors, employees and consultants) for the purchase of 92.1 million ordinary shares with a weighted average exercise price of $0.13 per ordinary share.
The issuance of any additional ordinary shares, any additional ADSs, or any securities that are exercisable for or convertible into our ordinary shares or ADSs, may
have an adverse effect on the market price of our ordinary shares and ADSs and will have a dilutive effect on our shareholders.
Raising additional capital by issuing securities may cause dilution to existing shareholders.
We may need to raise substantial future capital to continue to complete clinical development and commercialize our products and therapeutic candidates and to
conduct the research and development and clinical and regulatory activities necessary to bring our therapeutic candidates to market. Our future capital requirements will
depend on many factors, including:
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the failure to obtain regulatory approval, in a timely manner or at all, or achieve commercial success of our therapeutic candidates;
our success in effecting out-licensing arrangements with third parties;
our success in establishing other out-licensing or co-development arrangements;
the success of our licensees in selling products that utilize our technologies;
the results of our preclinical studies and clinical trials for our earlier stage therapeutic candidates, and any decisions to initiate clinical trials if supported by the
preclinical results;
the costs, timing and outcome of regulatory review of our therapeutic candidates that progress to clinical trials;
the costs of establishing or acquiring specialty sales, marketing and distribution capabilities, if any of our therapeutic candidates are approved, and we decide to
commercialize them ourselves;
the costs of preparing, filing and prosecuting patent applications, maintaining and enforcing our issued patents and defending intellectual property-related claims;
the extent to which we acquire or invest in businesses, products or technologies and other strategic relationships; and
the costs of financing unanticipated working capital requirements and responding to competitive pressures.
If we raise additional funds through licensing arrangements with third parties, we may have to relinquish valuable rights to our therapeutic candidates or grant
licenses on terms that are not favorable to us. If we raise additional funds by issuing equity or convertible debt securities, we will reduce the percentage ownership of our then-
existing shareholders, and these securities may have rights, preferences or privileges senior to those of our existing shareholders. See also “— Future sales of our ordinary
shares or ADSs could reduce the market price of our ordinary shares and ADSs.”
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As a foreign private issuer, we are permitted to follow certain home country corporate governance practices instead of applicable SEC and Nasdaq requirements, which
may result in less protection than is accorded to investors under rules applicable to domestic issuers.
As a foreign private issuer, we are permitted to follow certain home country corporate governance practices instead of those otherwise required under the Listing
Rules of the Nasdaq Stock Market, or the Nasdaq Rules, for U.S. domestic issuers. For instance, we may follow home country practice in Israel with regard to, among other
things, composition of the board of directors, director nomination procedure, composition of the compensation committee, approval of compensation of officers, and quorum
at shareholders’ meetings. In addition, we will follow our home country law, instead of the Nasdaq Rules, which require that we obtain shareholder approval for certain
dilutive events, such as for the establishment or amendment of certain equity-based compensation plans, an issuance that will result in a change of control of the company,
certain transactions other than a public offering involving issuances of a 20% or more interest in the company and certain acquisitions of the stock or assets of another
company. Following our home country governance practices as opposed to the requirements that would otherwise apply to a U.S. company listed on Nasdaq may provide less
protection than is accorded to investors under the Nasdaq Rules applicable to U.S. domestic issuers. See “Item 16G — Corporate Governance — Nasdaq Listing Rules and
Home Country Practices.”
In addition, as a foreign private issuer, we are exempt from the rules and regulations under the U.S. Securities Exchange Act of 1934, as amended, or the Exchange
Act, related to the furnishing and content of proxy statements, and our 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, we are not required under the Exchange Act to file annual, quarterly and current reports and
financial statements with the SEC as frequently or as promptly as domestic companies whose securities are registered under the Exchange Act.
If we fail to comply with the continued listing requirements of the Nasdaq Capital Market, our ADSs may be delisted and the price of our ADSs stock and our ability to
access the capital markets could be negatively impacted.
Nasdaq has established certain standards for the continued listing of a security on the Nasdaq Capital Market. The standards for continued listing include, among
other things, that the minimum bid price for the listed securities not fall below $1.00 per share for a period of 30 consecutive trading days.
On November 2, 2022, we were notified in a letter, or the Notification Letter, by the Nasdaq Listing Qualifications that we are not in compliance with the minimum
bid price requirements set forth in Nasdaq Listing Rule 5550(a)(2), or the Rule, for continued listing on The Nasdaq Capital Market.
The Notification Letter provides that the Company has 180 calendar days, or until May 1, 2023, to regain compliance with the Rule. To regain compliance, the bid
price of our ADSs must have a closing bid price of at least $1.00 per share for a minimum of 10 consecutive business days. In the event we do not regain compliance by May
1, 2023, we may then be eligible for additional 180 days if we meet the continued listing requirement for market value of publicly held shares and all other initial listing
standards for The Nasdaq Capital Market, with the exception of the bid price requirement, and will need to provide written notice of our intention to cure the deficiency during
the second compliance period. If we do not qualify for the second compliance period or fail to regain compliance during the second compliance period, then Nasdaq will
notify us of its determination to delist our ADSs, at which point we will have an opportunity to appeal the delisting determination to a Hearings Panel
No assurance can be given that we will be able to regain compliance with the Rule. Failure to meet applicable Nasdaq continued listing standards could result in a
delisting of our ADSs. A delisting of our ADSs from Nasdaq could materially reduce the liquidity of our ADSs and result in a corresponding material reduction in the price of
our ADSs. In addition, delisting could harm our ability to raise capital through alternative financing sources on terms acceptable to us, or at all, and may result in the potential
loss of confidence by investors, employees and fewer business development opportunities.
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Risks Related to our Operations in Israel
We conduct our operations in Israel and therefore our results may be adversely affected by political, economic and military instability in Israel and its region.
Our headquarters, our operations and some of our suppliers and third-party contractors are located in central Israel and our key employees, officers and most of our
directors are residents of Israel. Accordingly, political, economic and military conditions in Israel and the surrounding region may directly affect our business. Since the
establishment of the State of Israel in 1948, a number of armed conflicts have taken place between Israel and its Arab neighbors. Any hostilities involving Israel or the
interruption or curtailment of trade within Israel or between Israel and its trading partners could adversely affect our operations and results of operations and could make it
more difficult for us to raise capital. From time to time and most recently in May and June of 2021, Israel has been engaged in armed conflicts with Hamas, a militia group and
political party operating in the Gaza Strip; These conflicts involved missile strikes against civilian targets in various parts of Israel, as well as civil insurrection of Palestinians
in the West Bank, on the border with the Gaza Strip and in Israeli cities, and negatively affected business conditions in Israel. In addition, Israel faces threats from more distant
neighbors, in particular Iran. Iran is also believed to have a strong influence among extremist groups in the region, such as Hamas in Gaza, Hezbollah (a Lebanese Islamist
Shiite militia group and political party), and various rebel militia groups in Syria, as well as having a limited military presence in Syria. Additionally, Iran has threatened to
attack Israel and may be developing nuclear weapons. These threats may escalate in the future to more violent events that may affect Israel and us. Among other things, this
instability may affect the global economy and marketplace through changes in oil and gas prices. Any armed conflicts, terrorist activities or political instability in the region
could adversely affect business conditions and could harm our results of operations. For example, any major escalation in hostilities in the region could result in a portion of
our employees being called up to perform military duty for an extended period of time. Parties with whom we do business have sometimes declined to travel to Israel during
periods of heightened unrest or tension, forcing us to make alternative arrangements when necessary. In addition, the political and security situation in Israel may result in
parties with whom we have agreements involving performance in Israel claiming that they are not obligated to perform their commitments under those agreements pursuant to
force majeure provisions in the agreements.
Our commercial insurance does not cover losses that may occur as a result of events associated with the security situation in the Middle East. Although the Israeli
government currently covers the reinstatement value of direct damages that are caused by terrorist attacks or acts of war, we cannot assure you that this government coverage
will be maintained. Any losses or damages incurred by us could have a material adverse effect on our business. Any armed conflicts or political instability in the region would
likely negatively affect business conditions and could harm our results of operations.
Further, in the past, the State of Israel and Israeli companies have been subjected to an economic boycott. Several countries still restrict business with the State of
Israel and with Israeli companies. These restrictive laws and policies may have an adverse impact on our operating results, financial condition or the expansion of our
business. If the BDS Movement, the movement for boycotting, divesting and sanctioning Israel and Israeli institutions (including universities) and products become
increasingly influential in the United States and Europe, this may also adversely affect our financial condition.
Israel’s most recent general elections were held on April 9, 2019, September 17, 2019, March 2, 2020, March 23, 2021 and November 1, 2022. In addition, proposed
judicial reform has sparked widespread protests across Israel. Uncertainty surrounding future elections and the outcome of the judicial reform in Israel may continue and the
political situation in Israel may further deteriorate. Actual or perceived political instability in Israel or any negative changes in the political environment, may individually or
in the aggregate adversely affect the Israeli economy and, in turn, our business, financial condition, results of operations and growth prospects.
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Due to a significant portion of our expenses and revenues being denominated in non-dollar currencies, our results of operations may be harmed by currency fluctuations.
Our reporting and functional currency is the dollar. However, we pay a significant portion of our expenses in NIS and in euro, and we expect this to continue. If the
dollar weakens against the NIS or the euro in the future, there may be a negative impact on our results of operations. Although we expect our revenues from future licensing
arrangements to be denominated primarily in dollars, we are exposed to the currency fluctuation risks relating to the recording of our revenues in currencies other than dollars.
For example, if the euro strengthens against the dollar, our reported revenues in dollars may be lower than anticipated. From time to time, we engage in currency hedging
transactions to decrease the risk of financial exposure from fluctuations in the exchange rates of the currencies mentioned above in relation to the dollar. These measures,
however, may not adequately protect us from material adverse effects.
We have received Israeli government grants for certain research and development expenditures. The terms of these grants may require us to satisfy specified conditions in
order to manufacture products and transfer technologies outside of Israel. We may be required to pay penalties in addition to repayment of the grants.
Our research and development efforts were previously financed, in part, through grants that we received from the Israel Innovation Authority, or the IIA (formerly the
Office of the Chief Scientist of Israel’s Ministry of Economy and Industry, or the OCS). In addition, before we in-licensed motixafortide, Biokine had received funding for the
project from the IIA, and as a condition to IIA consent to our in-licensing of motixafortide, we were required to agree to abide by any obligations resulting from such funding.
We therefore must comply with the requirements of the Israeli Law for the Encouragement of Industrial Research, Development and Technological Innovation, 1984, and
related regulations, as amended, or the Research Law, with respect to these projects. Through December 31, 2022, we received approximately $22.0 million in funding from
the IIA and paid the IIA approximately $7.0 million in royalties under our approved programs. As of December 31, 2022, we have no contingent obligation to the IIA other
than for motixafortide as agreed when we in-licensed the project. The contingent liability to the IIA assumed by us relating to this transaction (which liability has no relation to
the funding actually received by us) amounts to $3.7 million as of December 31, 2022. We have a full right of offset for amounts payable to the IIA from payments that we
may owe to Biokine in the future.
The transfer or licensing to third parties of know-how or technologies developed under the programs submitted to the IIA and derivatives thereof and as to which we
or our licensors received grants, or manufacturing or rights to manufacture based on and/or incorporating such know-how to third parties, might require the consent of the IIA,
and may require certain payments to the IIA. There is no assurance that we will be able to obtain such consent on terms acceptable to us, or at all. Although such restrictions
do not apply to the export from Israel of our products developed with such know-how, without receipt of the aforementioned consent, such restrictions may prevent or limit us
from engaging in transactions with our affiliates, customers or other third parties outside Israel, involving transfer or licensing of manufacturing rights or other know-how or
assets that might otherwise be beneficial to us.
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Provisions of Israeli law may delay, prevent or otherwise impede a merger with, or an acquisition of, our company, which could prevent a change of control, even when
the terms of such a transaction are favorable to us and our shareholders.
Israeli corporate law regulates mergers, requires tender offers for acquisitions of shares above specified thresholds, requires special approvals for transactions
involving directors, officers or significant shareholders and regulates other matters that may be relevant to these types of transactions. For example, a merger may not be
consummated unless at least 50 days have passed from the date that a merger proposal was filed by each merging company with the Israel Registrar of Companies and at least
30 days from the date that the shareholders of both merging companies approved the merger. In addition, a majority of each class of securities of the target company must
approve a merger. Moreover, a full tender offer can only be completed if the acquirer receives the approval of at least 95% of the issued share capital (provided that a majority
of the offerees that do not have a personal interest in such tender offer shall have approved the tender offer, except that if the total votes to reject the tender offer represent less
than 2% of the company’s issued and outstanding share capital, in the aggregate, approval by a majority of the offerees that do not have a personal interest in such tender offer
is not required to complete the tender offer), and the shareholders, including those who indicated their acceptance of the tender offer, may, at any time within six months
following the completion of the tender offer, claim that the consideration for the acquisition of the shares did not reflect their fair market value and petition the court to alter
the consideration for the acquisition accordingly (unless the acquirer stipulated in the tender offer that a shareholder that accepts the offer may not seek appraisal rights, and
the acquirer or the company published all required information with respect to the tender offer prior to the date indicated for response to the tender offer).
Furthermore, Israeli tax considerations may make potential transactions unappealing to us or to our shareholders whose country of residence does not have a tax
treaty with Israel exempting such shareholders from Israeli tax. For example, Israeli tax law does not recognize tax-free share exchanges to the same extent as U.S. tax law.
With respect to mergers, Israeli tax law allows for tax deferral in certain circumstances but makes the deferral contingent on the fulfilment of numerous conditions, including a
holding period of two years from the date of the transaction during which sales and dispositions of shares of the participating companies are restricted. Moreover, with respect
to certain share swap transactions, the tax deferral is limited in time, and when such time expires, the tax becomes payable, even if no actual disposition of the shares has
occurred.
These and other similar provisions could delay, prevent or impede an acquisition of us or our merger with another company, even if such an acquisition or merger
would be beneficial to us or to our shareholders.
We have received Israeli government grants for certain research and development expenditures. The terms of these grants may require us to satisfy specified
conditions in order to manufacture products and transfer technologies outside of Israel. We may be required to pay penalties in addition to repayment of the grants. Such grants
may be terminated or reduced in the future, which would increase our costs. See “Business — Government Regulation and Funding — Israeli Government Programs.”
It may be difficult to enforce a U.S. judgment against us and our officers and directors in Israel or the United States, or to serve process on our officers and directors.
We are incorporated in Israel. All of our executive officers and the majority of our directors reside outside of the United States, and all of our assets and most of the
assets of our executive officers and directors are located outside of the United States. Therefore, a judgment obtained against us or any of our executive officers and directors
in the United States, including one based on the civil liability provisions of the U.S. federal securities laws, may not be collectible in the United States and may not be
enforced by an Israeli court. It also may be difficult for you to effect service of process on these persons in the United States or to assert U.S. securities law claims in original
actions instituted in Israel.
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Your rights and responsibilities as a shareholder will be governed by Israeli law, which may differ in some respects from the rights and responsibilities of shareholders of
U.S. companies.
We are incorporated under Israeli law. The rights and responsibilities of the holders of our ordinary shares are governed by our Articles of Association and Israeli law.
These rights and responsibilities differ in some respects from the rights and responsibilities of shareholders in typical U.S.-based corporations. In particular, a shareholder of
an Israeli company has a duty to act in good faith toward the company and other shareholders and to refrain from abusing its power in the company, including, among other
things, in voting at the general meeting of shareholders on matters such as amendments to a company’s articles of association, increases in a company’s authorized share
capital, mergers and acquisitions and interested party transactions requiring shareholder approval. In addition, a shareholder who knows that it possesses the power to
determine the outcome of a shareholder vote or to appoint or prevent the appointment of a director or executive officer in the company has a duty of fairness toward the
company. There is limited case law available to assist us in understanding the implications of these provisions that govern shareholders’ actions. These provisions may be
interpreted to impose additional obligations and liabilities on holders of our ordinary shares that are not typically imposed on shareholders of U.S. corporations.
ITEM 4. INFORMATION ON THE COMPANY
A. History and Development of the Company
Our legal and commercial name is BioLineRx Ltd. We are a company limited by shares organized under the laws of the State of Israel. Our principal executive
offices are located at 2 HaMa’ayan Street, Modi’in 7177871, Israel, and our telephone number is +972 (8) 642-9100. Our wholly owned subsidiary, BioLineRx USA, Inc., was
incorporated in Delaware on January 4, 2008, and is located at 77 Fourth Ave, Waltham, Massachusetts 02451, and its telephone number is (617) 859-6409.
We were founded in 2003 by leading institutions in the Israeli life sciences industry. We completed our initial public offering in Israel in February 2007 and our
ordinary shares are traded on the TASE under the symbol “BLRX.” In July 2011, we listed our ADSs on Nasdaq and they are traded under the symbol “BLRX.”
In March 2017, we acquired Agalimmune Ltd., a private U.K.-based company, and its U.S. subsidiary, Agalimmune Inc. Agalimmune Inc. was dissolved on
December 31, 2017.
Our capital expenditures for the years ended December 31, 2020, 2021 were immaterial and 0.3 million for the year ended December 31, 2022. Our current capital
expenditures involve acquisitions of laboratory equipment, computers and communications equipment.
The SEC maintains an Internet site that contains reports, proxy and information statements, and other information regarding issuers like BioLineRx that file
electronically with the SEC. The address of that site is www.sec.gov. We maintain a corporate website at www.biolinerx.com. Information contained on or accessible through
our website is not a part of this Annual Report on Form 20-F, and the inclusion of our website address herein is an inactive textual reference only.
We use our website (http://www.biolinerx.com) as a channel of distribution of Company information. The information we post through this channel may be deemed
material. Accordingly, investors should monitor our website, in addition to following our press releases, SEC filings and public conference calls and webcasts. The contents of
our website are not, however, a part of this Annual Report on Form 20-F.
We have not had any material commitments for capital expenditures, including any anticipated material acquisition of plant and equipment or interests in other
companies.
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B. Business Overview
We are a pre-commercial-stage biopharmaceutical company focused on oncology. Our current development and commercialization pipeline consists of two clinical-
stage therapeutic candidates – motixafortide (BL-8040), a novel peptide for the treatment of stem-cell mobilization and solid tumors, and AGI-134, an immuno-oncology
agent in development for solid tumors. In addition, we have an off-strategy, legacy therapeutic product called BL-5010 for the treatment of skin lesions. We have generated our
pipeline by systematically identifying, rigorously validating and in-licensing therapeutic candidates that we believe exhibit a high probability of therapeutic and commercial
success. To date, except for BL-5010, none of our therapeutic candidates have been approved for marketing or sold commercially. Our strategy includes commercializing our
therapeutic candidates through out-licensing arrangements with biotechnology and pharmaceutical companies and evaluating, on a case-by-case basis, the commercialization
of our therapeutic candidates independently. In this regard, we are currently executing on an independent commercialization plan for motixafortide in stem cell mobilization
for autologous bone marrow transplantation in multiple myeloma patients.
Our Product Development Approach
We seek to develop a pipeline of promising therapeutic candidates that exhibit distinct advantages over currently available therapies or address unmet medical needs.
Our resources are focused on advancing our therapeutic candidates through development and toward commercialization. Our current drug development pipeline consists of
two clinical-stage therapeutic candidates.
We have established close relationships with various universities, academic and research institutions and biotechnology companies that permit us to identify and
select compounds at various stages of clinical and pre-clinical development. Our approach is consistent with our objective of proceeding only with therapeutic candidates that
we believe exhibit a relatively high probability of therapeutic and commercial success.
Our Product Pipeline
The table below summarizes our current pipeline of therapeutic candidates, including the target indications and status of each candidate and our development
partners:
Motixafortide
Motixafortide, is a novel, short peptide that functions as a high-affinity antagonist for CXCR4, which we are developing for the treatment of stem cell mobilization
and solid tumors. CXCR4 is expressed by normal hematopoietic cells and overexpressed in various human cancers where its expression correlates with disease severity.
CXCR4 is a chemokine receptor that mediates the homing and retention of hematopoietic stem cells, or HSCs, in the bone marrow, and also mediates tumor progression,
angiogenesis (growth of new blood vessels in the tumor), metastasis (spread of tumor to other organs) and survival. Before “motixafortide” was approved by the World Health
Organization, or WHO, in 2019 as an International Nonproprietary Name, this therapeutic candidate was known as “BL-8040”. In October 2021, we received WHO approval
of the United States Adopted Name, or USAN, “motixafortide”.
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Inhibition of CXCR4 by motixafortide leads to the mobilization of HSCs from the bone marrow to the peripheral blood, enabling their collection for subsequent
autologous or allogeneic transplantation in cancer patients. Clinical data has demonstrated the ability of motixafortide to mobilize higher numbers of long-term engrafting
HSCs (CD34+CD38-CD45RA-CD90+CD49f+) as compared to G-CSF.
Motixafortide also mobilizes cancer cells from the bone marrow, detaching them from their survival signals and sensitizing them to chemotherapy. In addition,
motixafortide has demonstrated a direct anti-cancer effect by inducing apoptosis (cell death) and inhibiting proliferation in various cancer cell models (multiple myeloma, non-
Hodgkin’s lymphoma, leukemia, non-small-cell lung carcinoma, neuroblastoma and melanoma).
In the field of immuno-oncology, motixafortide mediates infiltration of T-cells while reducing immune regulatory cells in the tumor microenvironment, or TME. In
clinical studies, the combination of motixafortide with immune checkpoint inhibitors, such as anti PD-1, has shown T-cell activation and a reduction in tumor cell numbers.
The following is a summary of the clinical trials being carried out with motixafortide.
Stem cell mobilization
In March 2015, we reported successful top-line results from a Phase 1 safety and efficacy trial for the use of motixafortide as a novel stem cell mobilization treatment
for allogeneic bone marrow transplantation at Hadassah Medical Center in Jerusalem.
In March 2016, we initiated a Phase 2 trial for motixafortide in allogeneic stem cell transplantation, conducted in collaboration with the Washington University
School of Medicine, Division of Oncology and Hematology. In May 2018, we announced positive top-line results of this study showing, among other things, that a single
injection of motixafortide mobilized sufficient amounts of CD34+ cells required for transplantation at a level of efficacy similar to that achieved by using 4-6 injections of G-
CSF, the current standard of care.
In December 2017, we commenced a randomized, placebo-controlled Phase 3 registrational trial for motixafortide, known as the GENESIS trial, for the mobilization
of HSCs, for autologous transplantation in patients with multiple myeloma. The trial began with a lead-in period for dose confirmation, which was to include 10-30 patients
and then progress to the placebo-controlled main part, which was designed to include 177 patients in more than 25 centers. Following review of the positive results from
treatment of the first 11 patients, the Data Monitoring Committee, or DMC, recommended that the lead-in part of the study be stopped and that we should move immediately
to the second part. Additional positive results from the lead-in period were reported at the annual meeting of the European Society for Blood and Marrow Transplantation held
in March 2019, where it was announced that HSCs mobilized by motixafortide in combination with G-CSF were successfully engrafted in all 11 patients.
In August 2020, we announced a decision to perform an interim analysis on approximately 65% of the original study sample size, primarily based on a significantly
lower-than-anticipated patient-dropout rate in the study. In October 2020, we announced positive results from the interim analysis. Based on the statistically significant
evidence favoring treatment with motixafortide, the study’s independent DMC issued a recommendation to us that patient enrollment may be ceased immediately, without the
need to recruit all 177 patients originally planned for the study. In accordance with the DMC’s recommendation, study enrollment was complete at 122 patients. In May 2021,
we announced positive top-line results from the Phase 3 trial. Based on an analysis of data on all 122 enrolled patients (the intent to treat population) we found highly
statistically significant evidence across all primary and secondary endpoints favoring motixafortide in addition to G-CSF, as compared to placebo plus G-CSF (p<0.0001). The
addition of motixafortide to G-CSF also allowed 88.3% of patients to undergo transplantation after only one apheresis session, compared to 10.8% in the G-CSF arm – an 8.2-
fold increase. The combination was also found to be safe and well tolerated.
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We continue to follow-up on the GENESIS study patients for relapse-free and overall survival. In addition, we continue to perform detailed analyses of the data
according to the statistical analysis plan agreed-upon with the FDA, as well as certain post hoc analyses. In December 2021, we held a pre-NDA meeting with the FDA. The
purpose of the meeting was to obtain agreement from the FDA on the content of the proposed NDA, and, in particular, to confirm that our single Phase 3 pivotal study,
GENESIS, is sufficient to support an NDA submission. During the pre-NDA meeting, the FDA agreed that the proposed data package is sufficient to support an NDA
submission. In September 2022, we submitted an NDA to the FDA for motixafortide in stem cell mobilization for autologous bone marrow transplantation for multiple
myeloma patients and in November 2022, the FDA accepted for review the NDA and assigned the NDA a PDUFA target action date of September 9, 2023.
In October 2021, we announced positive results from a pharmacoeconomic study evaluating the cost-effectiveness of using investigational drug motixafortide as a
primary stem cell mobilization agent on top of granulocyte colony stimulating factor (G-CSF), versus G-CSF alone, in multiple myeloma patients undergoing autologous
stem-cell transplantation (ASCT). The study was performed by the Global Health Economics and Outcomes Research (HEOR) team of IQVIA, and was a pre-planned study
conducted in parallel with the GENESIS Phase 3 trial. The study concluded that the addition of motixafortide to G-CSF (the current standard of care) is associated with a
statistically significant decrease in health resource utilization (HRU) during the ASCT process, compared to G-CSF alone. Based on the significantly higher number of
mobilized cells and the lower number of apheresis sessions, lifetime estimates show quality-adjusted-life-year benefits and net cost savings of ~$19,000 (not including the cost
of motixafortide), versus G-CSF alone.
In March 2022, we announced results from a follow-on pharmacoeconomic study performed by the HEOR team of IQVIA. This study indirectly evaluated the cost-
effectiveness of using motixafortide as a primary stem cell mobilization agent in combination with G-CSF, against plerixafor in combination with G-CSF, in multiple myeloma
patients undergoing ASCT. The additional study results show that motixafortide in combination with G-CSF, versus plerixafor in combination with G-CSF, demonstrates a
statistically significant decrease in HRU during the ASCT process. Based on the significantly higher number of mobilized cells and the lower number of apheresis sessions,
lifetime estimates show QALY benefits and net cost savings of ~$30,000 (not including the cost of motixafortide), versus plerixafor plus G-CSF. The study findings strengthen
the assessment that the use of motixafortide in combination with G-CSF, as the potential new standard of care in mobilization for ASCT, would be a cost-effective option in
the US, based on accepted willingness-to-pay (WTP) values for healthcare payers.
We believe these results, together with the highly significant and clinically meaningful data from the GENESIS trial, strongly support the potential use of
motixafortide, on top of G-CSF, as the standard of care in stem cell mobilization for autologous stem cell transplantation. In this regard, in June 2022, we appointed
biopharmaceutical veteran executive, Holly W. May as our Chief Commercial Officer and in September 2022 we announced our U.S. commercialization plan for
APHEXDA® (motixafortide) in stem cell mobilization for autologous bone marrow transplantation for multiple myeloma patients and appointed Ms. May as President of our
U.S. subsidiary, who is responsible for the commercial planning, positioning, and launch oversight for motixafortide in the stem cell mobilization indication across the U.S.
market, assuming FDA approval. If approved, we intend to commercialize APHEXDA in the U.S. independently in order to accelerate its availability to patients and to
maximize the value of this innovative therapeutic candidate.
In March 2023, we entered into a clinical collaboration with Washington University School of Medicine in St. Louis to advance a Phase 1 clinical trial in which
motixafortide will be tested as monotherapy and in combination with natalizumab (VLA-4 inhibitor) as novel regimens to mobilize CD34+ hematopoietic stem cells for gene
therapies in Sickle Cell Disease (SCD). The study will enroll five adults with a diagnosis of SCD who are receiving automated red blood cell exchanges via apheresis. The
trial’s primary objective is to assess the safety and tolerability of motixafortide alone and the combination of motixafortide + natalizumab in SCD patients, defined by dose-
limiting toxicities. Secondary objectives include determining the number of CD34+ hematopoietic stem and progenitor cells (HSPCs) mobilized via leukapheresis; and
determining the kinetics of CD34+ HSPCs mobilization to peripheral blood in response to motixafortide alone and motixafortide + natalizumab in SCD patients. The study is
anticipated to begin enrollment in 2023 (although timelines are ultimately controlled by the independent investigator and are therefore subject to change).
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Solid tumors
In January 2016, we entered into a clinical collaboration with MSD (a tradename of Merck & Co., Inc., Kenilworth, New Jersey) in the field of cancer
immunotherapy. Based on this collaboration, in September 2016 we initiated a Phase 2a study, known as the COMBAT/KEYNOTE-202 study, focusing on evaluating the
safety and efficacy of motixafortide in combination with KEYTRUDA® (pembrolizumab), MSD’s anti-PD-1 therapy, in 37 patients with metastatic pancreatic
adenocarcinoma, or PDAC. The study was an open-label, multicenter, single-arm trial designed to evaluate the clinical response, safety and tolerability of the combination of
these therapies as well as multiple pharmacodynamic parameters, including the ability to improve infiltration of T-cells into the tumor and their reactivity. Top-line results
showed that the dual combination demonstrated encouraging disease control and overall survival in patients with metastatic pancreatic cancer. In addition, assessment of
patient biopsies supported motixafortide’s ability to induce infiltration of tumor-reactive T-cells into the tumor, while reducing the number of immune regulatory cells.
In July 2018, we announced the expansion of the COMBAT/KEYNOTE-202 study under the collaboration to include a triple combination arm investigating the
safety, tolerability and efficacy of motixafortide, KEYTRUDA ® and chemotherapy. We initiated this arm of the trial in December 2018. In December 2019, we announced
that preliminary data from the study indicated that the triple combination therapy showed a high level of disease control, including seven partial responders and 10 patients
with stable disease out of 22 evaluable patients. In February 2020, we completed recruiting a total of 43 patients for the study and in December 2020, we announced the final
results of the study. The results of the study showed substantial improvement as compared to comparable historical results of other pancreatic cancer studies across all study
endpoints. Of the 38 evaluable patients, median overall survival was 6.5 months, median progression free survival was 4.0 months, confirmed overall response rate was
13.2%, overall response rate was 21.2% and disease control rate was 63.2%. The combination was generally well tolerated, with a safety profile consistent with the individual
safety profile of each component alone; adverse event and severe adverse event profiles were as expected with chemotherapy-based treatment regimens.
In August 2016, in the framework of an agreement with MD Anderson Cancer Center, or MD Anderson, we entered into an additional collaboration for the
investigation of motixafortide in combination with KEYTRUDA in pancreatic cancer. The focus of this study, in addition to assessing clinical response, was the mechanism of
action by which both drugs might synergize, as well as multiple assessments to evaluate the biological anti-tumor effects induced by the combination. We supplied
motixafortide for this Phase 2b study, which commenced in January 2017. Final results from this study (based on a cut-off in July 2019 from 20 enrolled patients out of which
15 were evaluable) showed that the dual combination demonstrated clinical activity and encouraging overall survival in patients with metastatic pancreatic cancer. In addition,
assessment of patient biopsies supported motixafortide’s ability to induce infiltration of tumor-reactive T-cells into the tumor.
In October 2020, we announced that motixafortide will be tested in combination with the anti-PD-1 cemiplimab (LIBTAYO®) and standard-of-care chemotherapy
(gemcitabine and nab-paclitaxel) in first-line PDAC. This investigator-initiated Phase 2 study, led by Columbia University, will initially enroll 10-12 PDAC patients, and will
be expanded to a total of 40 patients following an evaluation of the initial 10-12 patients based on pre-defined criteria. The primary endpoint of the study is the overall
response rate. Secondary endpoints include safety and tolerability, progression free survival, duration of clinical benefit and overall survival. Data from the study is anticipated
in 2023 (although timelines are ultimately controlled by the independent investigator and are therefore subject to change).
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In June 2022, we entered into a collaboration agreement with GenFleet Therapeutics, or GenFleet, an immuno-oncology focused biopharmaceutical company based
in China, to advance motixafortide through a randomized Phase 2b clinical trial in PDAC. Under the terms of the agreement, GenFleet will fully fund, design and execute a
randomized Phase 2b clinical trial that will enroll approximately 200 first-line metastatic PDAC patients in China. This randomized controlled study will aim to evaluate the
superiority of motixafortide in combination with an anti-PD-1 and chemotherapy compared to chemotherapy alone, the current standard of care and is expected to commence
in 2023 (although timelines are ultimately controlled by the independent investigator and are therefore subject to change). As part of the collaboration, we will supply
motixafortide, while GenFleet will supply the other study drugs for the trial. Trial oversight will be administered by a Joint Development Committee. GenFleet will be eligible
to receive low-to-mid-single digit tiered percentage royalties on future motixafortide sales, if approved.
ARDS secondary to COVID-19 and other viral infections
During the first half of 2020, we initiated the evaluation of motixafortide as a potential therapy for acute respiratory distress syndrome, or ARDS, resulting from
COVID-19 and other viral infections In this regard, substantial data is emerging regarding the involvement of neutrophils, neutrophil extracellular traps (NETs), monocytes
and macrophages in the development of ARDS secondary to COVID-19 and other viral infections; as well as the key involvement of CXCR4 as a mediator of those cells in
the inflamed pulmonary tissue. Based on the scientific data indicating the importance of blocking the CXCR4/CXCL12 axis during ARDS, we believe that motixafortide may
be of potential benefit for patients with ARDS. Following our initial evaluation, in November 2020, we announced initiation of a Phase 1b study in patients with ARDS
secondary to COVID-19 and other respiratory viral infections. The study is an investigator-initiated study, led by Wolfson Medical Center, in Israel, to evaluate motixafortide
in patients hospitalized with ARDS. The primary endpoint of the study is to assess the safety of motixafortide in these patients; respiratory parameters and inflammatory
biomarkers will be assessed as exploratory endpoints. Up to 25 patients will be enrolled in the study, with a preliminary analysis planned after ten patients have completed the
initial treatment period. Results of the preliminary analysis are expected in 2023 (although timelines are ultimately controlled by the independent investigator and are therefore
subject to change).
Other matters
In addition to the above, we are currently conducting, or planning to conduct, a number of investigator-initiated, open-label studies in a variety of indications to
support the interest of the scientific and medical communities in exploring additional uses for motixafortide. These studies serve to further elucidate the mechanism of action
for motixafortide. The results of studies such as these are presented from time to time at relevant professional conferences.
Motixafortide has been granted three Orphan Drug Designations by the FDA: for use to mobilize HSCs from the bone marrow to peripheral blood for collection in
autologous or allogeneic transplantation (granted in July 2012); for the treatment of AML (granted in September 2013); and for the treatment of pancreatic cancer (granted in
February 2019). In January 2020, the European Medicines Agency, or EMA, granted Orphan Drug Designation to motixafortide for the treatment of pancreatic cancer.
In September 2022, the FDA approved APHEXDA as motixafortide’s trade name.
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AGI-134
AGI-134, a clinical therapeutic candidate in-licensed by our subsidiary, Agalimmune Ltd., is a synthetic alpha-Gal glycolipid immunotherapy in development for
solid tumors. AGI-134 harnesses the body’s pre-existing, highly abundant, anti-alpha-Gal antibodies to induce a hyper-acute, systemic, specific anti-tumor response to the
patient’s own tumor neo-antigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on, anti-metastatic immune
response. In August 2018, we initiated a Phase 1/2a clinical study for AGI-134 that is primarily designed to evaluate the safety and tolerability of AGI-134 in unresectable
metastatic solid tumors and to validate AGI-134’s mechanism of action using a wide array of biomarkers. The multi-center, open-label study was carried out in the United
Kingdom, Spain and Israel. Initial safety results from the first part of the study were announced at the beginning of September 2019; at the end of the same month, the second
part of the study was commenced. Due to clinical operating issues associated with the COVID-19 pandemic, in April 2020, enrollment to the clinical trial was temporarily
suspended. In August 2020, we renewed study enrollment, and in January 2022, we completed enrollment. In December 2022, we announced results from the study. The study
met its primary endpoint of AGI-134’s safety and tolerability. Generation of an immune response and markers of clinical efficacy were assessed as secondary endpoints. Most
patients analyzed showed an increase in Alpha-Gal antibodies, indicating increased overall immune activity. Additionally, increases in antigen presenting cells (APCs) were
observed in most tissue samples analyzed, and T cell and macrophage tumor infiltration was seen in approximately one-third of evaluable patients’ injected tumors, and in
approximately half of evaluable patients’ un-injected lesions. Radiological assessments found that 29 percent of patients in the trial achieved best overall response of stable
disease. We plan to seek publication of our data at a medical congress in 2023, and in consultation with our scientific advisory board, we will determine the next steps for the
program in the first half of 2023.
Establishment of Scientific Advisory Board
In December 2021, we established a Scientific Advisory Board (SAB) to provide insight and guidance on our activities in the field of immuno-oncology. The SAB is
comprised of recognized leaders in cancer immunology, intra-tumoral injections and clinical development.
Listed in alphabetical order, the founding SAB members are: Ronald Levy, MD, the Robert K. and Helen K. Summy Professor and Director of the Lymphoma
Program at Stanford University School of Medicine, Palo Alto, CA; Aurélien Marabelle, MD, PhD, Clinical Director, Cancer Immunotherapy Program, Gustave Roussy,
Paris, France and Director, Translational Research Laboratory in Immunotherapy, INSERM, Paris, France; Ignacio Melero MD, PhD, Professor of Immunology at the
Academic Hospital of Navarra, Spain and at the Center for Applied Medical Research (CIMA) of the University of Navarra, Spain; Jon Wigginton, MD, Chair of the SAB and
Senior Advisor at Cullinan Oncology, former Chief Medical Officer of MacroGenics, and former Therapeutic Area Head, Immuno-Oncology, Early Clinical Research at
Bristol-Myers Squibb; and Leisha Emens, MD, PhD, Professor of Medicine, Director of Translational Immunotherapy for the Women's Cancer Research Center 15213 Co-
Leader, Hillman Cancer Immunology/Immunotherapy Program at the UPMC Hillman Cancer Center, Pittsburgh, PA.
BL-5010
Our commercialized, legacy therapeutic product, BL-5010, is a customized, proprietary pen-like applicator containing a novel, acidic, aqueous solution for the non-
surgical removal of skin lesions. In December 2014, we entered into an exclusive out-licensing arrangement with Perrigo Company plc, or Perrigo, for the rights to BL-5010
for over-the-counter, or OTC, indications in Europe, Australia and additional selected countries. In March 2016, Perrigo received CE Mark approval for BL-5010 as a novel
OTC treatment for the non-surgical removal of warts. The commercial launch of products for treatment of this first OTC indication (warts/verrucas) commenced in Europe in
the second quarter of 2016. Since then, Perrigo has invested in improving the product and during 2019 launched an improved version of the product in several European
countries. In March 2020, we agreed that Perrigo could relinquish its license rights for certain countries that had been included in its territory according to the original license
agreement and was also no longer obligated to develop, obtain regulatory approval for and commercialize products for a second OTC indication. In turn, in March 2020, we
agreed with our licensor of the rights to BL-5010, Innovative Pharmaceutical Concepts (IPC) Inc., or IPC, to return to IPC those license rights no longer out-licensed to
Perrigo as a result of the agreement described in the preceding sentence, in consideration of the payment to us of royalties or fees on sublicense receipts.
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Our Strategy
Our objective is to become a leader in the development of novel therapeutics for the treatment of cancer. We have successfully advanced a number of therapeutic
candidates into clinical development. We intend to commercialize our two clinical candidates, motixafortide and AGI-134, and any future candidates either on our own or
through out-licensing or co-development arrangements with third parties that may perform any or all of the following tasks: completing development, securing regulatory
approvals, securing reimbursement codes from insurance companies and health maintenance organizations, manufacturing and/or marketing. If appropriate, we may also enter
into co-development and similar arrangements with respect to any therapeutic candidate with third parties or commercialize a therapeutic candidate ourselves.
Therapeutic Candidates
Motixafortide
The following paragraphs are a high-level summary of the therapeutic areas we are currently investigating for motixafortide:
Stem cell mobilization. High-dose chemotherapy followed by stem cell transplantation has become an established treatment modality for a variety of hematologic
malignancies, including multiple myeloma (MM), as well as various forms of lymphoma and leukemia. Stem cells are mobilized from the bone marrow of the patient (i.e.,
autologous transplant) or donor (i.e., allogeneic transplant) using granulocyte-colony stimulating factor (G-CSF), harvested from the peripheral blood by apheresis, and
infused to the patient after intensive myeloablation (chemo/radiotherapy). In 2019, approximately 45,000 autologous transplants were conducted in the US and EU. The goal
of collection is approximately 5-6M cells/kg for MM patients. Plerixafor (in combination with G-CSF) can be used upfront, or as a rescue therapy for those patients that did
not achieve the target collection. Today, it is estimated that approximately 55-60% of patients undergoing autologous transplantation in the US receive plerixafor on top of G-
CSF. A recent market assessment which we commissioned through a third-party vendor estimates the value of the U.S. stem cell mobilization market at ~$360M in 2021.
Solid tumors. Novel, emerging therapeutic approaches for targeting solid tumors are being developed and tested. Combinational therapies of immune checkpoint
inhibitors with immuno-oncology supporting agents, with or without chemotherapy, are among the most promising experimental treatments for solid malignancies.
Pancreatic cancer has a low rate of early diagnosis, a high mortality rate and a poor five-year survival prognosis. Symptoms are usually non-specific and as a result,
pancreatic cancer is often not diagnosed until it reaches an advanced stage. Once the disease has metastasized, or spread to other organs, it becomes especially hard to treat.
Each year, about 185,000 individuals globally are diagnosed with this condition; and in 2022, the Surveillance, Epidemiology and End Results program, or SEER, of the
National Cancer Institute estimated that in the United States there would be approximately 62,000 individuals diagnosed with pancreatic cancer. The overall five-year survival
rate among pancreatic cancer patients is 11-12%, which constitutes the highest mortality rate among solid tumor malignancies; among those diagnosed with metastatic disease,
the overall five-year survival rate is only 3%. Recent developments that have improved the survival in many cancer types have not been effective for pancreatic cancer
patients, highlighting the need for the development of new therapeutic options.
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Furthermore, second-line patients that were diagnosed already with metastatic disease have very few therapeutic options. The only approved regimen for second-line
patients is Onivyde® in combination with 5FU and LV. For these Stage IV at diagnosis patients reaching second-line therapy, median overall survival is only 4.7 months
(Macarulla et al, Pancreas 2020).
Regulatory Approvals.
United States
In September 2013, the FDA granted an Orphan Drug Designation to motixafortide as a therapeutic for the treatment of AML. In January 2014, the FDA granted an
Orphan Drug Designation to motixafortide for use, in combination with G-CSF, in mobilizing human stem cells from the bone marrow to the peripheral blood for collection
for autologous or allogeneic (donor-based) transplantation. In January 2015, the FDA modified this Orphan Drug Designation for motixafortide for use either as a single agent
or in combination with G-CSF. In February 2019, the FDA granted Orphan Drug Designation to motixafortide for use in the treatment of pancreatic cancer. Orphan Drug
Designation is granted to therapeutics intended to treat rare diseases that affect not more than 200,000 people in the United States. Orphan Drug Designation entitles the
sponsor to a seven-year marketing exclusivity period and clinical protocol assistance with the FDA, as well as federal grants and tax credits and an exemption from the
Prescription Drug User Fee so long as the revenue is below $50,000,000.
European Union
In January 2020, the EMA granted an Orphan Drug Designation to motixafortide for the treatment of pancreatic cancer. The EMA grants orphan medicinal product
designation to investigational drugs intended to treat, prevent or diagnose a life-threatening or chronically debilitating disease affecting fewer than five in 10,000 people in the
EU and for which no satisfactory treatment is available or, if such treatment exists, the medicine must be of significant benefit to those affected by the condition. Orphan
medicinal product designation provides regulatory and financial incentives for companies to develop and market therapies, including ten years of market exclusivity, protocol
assistance, fee reductions and EU-funded research.
Preclinical Results.
In vitro and in vivo studies have shown that motixafortide binds CXCR4 with high affinity (7.9 pM) and occupies it for prolonged periods of time (>48h). Animal
cancer models have shown that motixafortide mobilizes cancer cells from the bone marrow and may therefore detach these cells from survival signals in the bone marrow
microenvironment as well as sensitize them to chemo- and bio-based anti-cancer therapies. In addition, motixafortide directly induces apoptosis of cancer cells. Motixafortide
was efficient, both alone and in combination with chemotherapy, in reducing malignant bone marrow cells and stimulating their cell death.
In August 2013, we announced that motixafortide has been shown in preclinical trials to be effective for the treatment of thrombocytopenia, or reduced platelet
production.
In December 2013, we presented preclinical data at the annual meeting of the American Society of Hematology (ASH), showing that motixafortide directly inhibits
AML, cell growth and induces cell death, both in cell cultures and in mice engrafted with human AML cells. In addition, motixafortide showed the ability to induce
mobilization of AML cells from the bone marrow into the blood circulation, thereby enhancing the chemotherapeutic effect of ARA-C (one of the standard-of-care
chemotherapies for AML). The data also showed that motixafortide’s effects were even more robust in cells harboring the FLT3 mutation, and a synergistic effect was
observed when motixafortide was combined with the FLT3 inhibitor AC220 (Quizartinib).
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At the annual meeting of ASH in December 2016, detailed preclinical data on the mechanism-of-action by which motixafortide directly induces apoptosis of AML
cells was presented by Prof. Amnon Peled of the Hadassah Medical Center and Biokine. The results of the preclinical studies showed that motixafortide treatment in vivo
triggered mobilization of AML blasts from their protective bone marrow microenvironment and induced their terminal differentiation, further supporting the data we presented
at the American Association for Cancer Research (AACR) annual conference earlier in 2016. In addition, the studies illustrate how motixafortide increases the expression and
activity of a special class of microRNA precursors termed miR-15a/16-1. These microRNA molecules have been previously linked to cancer and shown to suppress the
activity of several tumor-related pro-survival proteins. Therefore, by increasing the expression of miR-15a/16-1 microRNA molecules, motixafortide decreases the expression
of tumor-survival proteins and promotes tumor cell death. Importantly, in both in vitro and in vivo experiments, motixafortide was found to synergize with a selective Bcl-2
inhibitor (Venetoclax) and an FLT3 inhibitor (Quizartinib, also known as AC220) in inducing AML cell death, pointing at potential drug combination treatments.
At the ASCO-SITC Clinical Immuno-Oncology Symposium, or ASCO-SITC, in January 2018, we presented preclinical data showing that motixafortide augments
the ability of the immune system to fight cancer by increasing the infiltration of anti-tumor-specific T-cells into the TME, resulting in decreased tumor growth and prolonged
survival in a murine model of cancer. In the preclinical study, a murine model of cancer was used to assess the effects of motixafortide in combination with a cancer vaccine
that primes the immune system against the tumor. The results of the study show that combining motixafortide with the cancer vaccine leads to a significantly enhanced anti-
tumor immune response, which attenuates tumor growth and prolongs mouse survival better than either agent administered alone. The results go on to demonstrate that
motixafortide significantly increases the abundance of tumor-specific T-cells in the TME, suggesting an explanation for the enhanced efficacy of the combination over either
agent when administered alone.
At the annual meeting of SITC in November 2019, we presented positive preclinical results further elucidating the mechanism of action of motixafortide in
combination with an anti PD-1 and chemotherapy. The pre-clinical study assessed the effects of motixafortide, anti-PD-1 and chemotherapy (Irinotecan, Fluorouracil and
Leucovorin), both alone and in various combinations, on tumor growth and immune cell constitution in a mouse model for pancreatic cancer. The key findings were that the
triple combination of motixafortide+anti-PD-1+chemotherapy (a) had a significantly better effect on tumor growth compared to chemotherapy alone or any dual combination
with chemotherapy and (b) showed the best effect in modulation of the TME, resulting in reduction in immunosuppressive cells, and accompanied by increase of activated T
effector cells.
At the annual meeting of ASH in December 2021, we presented findings from in vivo and in vitro pre-clinical studies demonstrating that motixafortide acts as an
immunomodulator by affecting the biology of regulatory T-cells (Tregs), and immunosuppressive T-cells, supporting biomarker findings from our COMBAT Phase 2 study in
pancreatic cancer patients.
Clinical Trials
Stem cell mobilization
Phase 1/2a and Phase 1 study
In a Phase 1/2a, open-label, dose escalation, safety and efficacy clinical trial in 18 multiple myeloma patients, motixafortide demonstrated a good safety profile at all
doses tested and was highly effective in combination with G-CSF, in the mobilization of hematopoietic stem cells from the bone marrow to the peripheral blood for autologous
transplantation. All patients receiving transplants (n=17) exhibited rapid engraftment, with median time to neutrophil and platelet recovery of 12 and 14 days, respectively, at
the highest dose given (0.9 mg/kg).
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In March 2015, we announced successful top-line results from a Phase 1 trial for motixafortide as a novel treatment for the mobilization of stem cells from the bone
marrow to the peripheral blood circulation in healthy volunteers, where they can be potentially harvested for allogeneic transplant supporting the treatment of hematological
indications. The study was conducted at the Hadassah Medical Center in Jerusalem and consisted of two parts. The first part of the study was a randomized, double-blind,
placebo-controlled, dose-escalation study in three cohorts of eight participants each, with each participant receiving two consecutive injections of motixafortide. Results show
that motixafortide is safe and well tolerated up to the maximal tested dose of one mg/kg, and that dramatic mobilization of CD34+ hematopoietic stem and progenitor cells, or
HSPCs, was observed across all doses tested. The robust mobilization supports the further use of a single injection of motixafortide for HSPC collection.
In the second part of the Phase 1 study, eight healthy participants received a single injection of motixafortide at the highest tested dose of 1 mg/kg, and four hours
later underwent a single, standard leukapheresis procedure. Robust and rapid stem cell mobilization was evident in all treated participants, supporting a novel approach to stem
cell collection. The median level of collected stem cells was higher than 11 x 106 cells per kg, which is more than two-fold higher than the target concentration, and five-fold
higher than the minimum concentration, necessary for transplantation. In addition, the level of HPSCs in the peripheral blood circulation 24 hours after injection of
motixafortide enabled an additional apheresis on Day 2, if needed. These data support the use of motixafortide as a single-agent, single-injection, one-day regimen for the
collection of stem cells.
Phase 2 study
In March 2016, we initiated a Phase 2 trial for motixafortide as a novel approach for the mobilization and collection of bone marrow stem cells from the peripheral
blood circulation for allogeneic bone marrow transplantation. The open-label study was conducted in collaboration with the Washington University School of Medicine,
Division of Oncology and Hematology, and enrolled up to 24 donor/recipient pairs, aged 18-70. The trial was designed to evaluate the ability of motixafortide, as a single
agent, to promote stem cell mobilization for allogeneic transplantation. On the donor side, the primary endpoint of the study was the ability of a single injection of
motixafortide to mobilize 2x106 CD34 cells for transplantation following up to two apheresis collections. On the recipient side, the study aimed to evaluate the functionality
and engraftment following transplantation of the motixafortide collected graft. The study also evaluated the safety and tolerability of motixafortide in healthy donors, as well
as graft durability, the incidence of grade 2-4 acute graft versus host disease, or GVHD, chronic GVHD, relapse and other recipient-related parameters in patients who have
undergone transplantation of hematopoietic cells mobilized with motixafortide.
In May 2018, we announced positive results from the study. Single-agent treatment with motixafortide showed efficacy similar to standard of care (currently, a four-
to five-day treatment cycle with G-CSF and a one- to two-day apheresis procedure) in only one administration of motixafortide. In addition, motixafortide showed results that
were comparable to the standard of care in recipient engraftment, with all transplanted recipients successfully engrafting with motixafortide-mobilized grafts.
Phase 3 study
In December 2017, we initiated a Phase 3 registration study for motixafortide in autologous stem cell mobilization. The trial, known as the GENESIS study, is a
randomized, placebo-controlled, multicenter study, evaluating the safety, tolerability and efficacy of motixafortide and G-CSF, compared to placebo and G-CSF, for the
mobilization of HSCs for autologous transplantation in multiple myeloma patients. The study began with an open-label, single-arm lead-in period, which was to include 10-30
patients in order to assess safety and efficacy following treatment with motixafortide plus G-CSF. Results of the first 11 patients showed that motixafortide in combination
with standard G-CSF treatment is safe, tolerable and efficacious, demonstrating the potential of motixafortide treatment to reduce the number of administrations and apheresis
sessions, as well as hospitalization costs, related to the preparation of multiple myeloma patients for autologous HSC transplantation. Following its review of the positive
lead-in results, the DMC recommended that the lead-in part of the study be stopped and that we move immediately to the placebo-controlled main part, which was designed to
include 177 patients in more than 15 centers. Additional positive results from the lead-in period were reported at the annual meeting of the European Society for Blood and
Marrow Transplantation held in March 2019, where it was announced that HSCs mobilized by motixafortide in combination with G-CSF were successfully engrafted in all 11
patients. Treatment in the main part of the study included five to eight days of G-CSF, with a single dose of motixafortide or placebo on Day 4 and an optional additional dose
of motixafortide or placebo on Day 6. Apheresis for stem cell collection was performed on day 5. Further apheresis sessions were conducted if needed in order to reach the
benchmark of ≥ 6 million mobilized CD34+ cells. The primary objective of the study was to demonstrate that motixafortide on top of G-CSF is superior to G-CSF alone in the
ability of mobilize ≥ 6 million CD34+ cells in up to two apheresis sessions. Secondary objectives included time to engraftment of neutrophils and platelets and durability of
engraftment, as well as other efficacy and safety parameters.
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In August 2020, we announced a decision to perform an interim analysis on approximately 65% of the original study sample size, primarily based on a significantly
lower-than-anticipated patient-dropout rate in the study. In October 2020, we announced positive results from the interim analysis. Based on the statistically significant
evidence favoring treatment with motixafortide, the study’s independent DMC issued a recommendation to us that patient enrollment may be ceased immediately, without the
need to recruit all 177 patients originally planned for the study. In accordance with the DMC’s recommendation, study enrollment was complete at 122 patients.
In May 2021, we announced positive top-line results from the Phase 3 trial. An analysis of data on all 122 enrolled patients (the intent to treat, or ITT, population)
found highly statistically significant evidence across all primary and secondary endpoints favoring motixafortide in addition to G-CSF, as compared to placebo plus G-CSF. In
addition, the combination was found to be safe and well tolerated. The primary endpoint of the study demonstrated a 4.9-fold increase and treatment effect of 54.6% (95% CI
39.7-69.5%; p<0.0001) in the proportion of patients in the treatment arm, as compared to the control arm, mobilizing ≥ 6 million CD34+ cells/kg in up to two apheresis
sessions, and after only one administration of motixafortide. This translated to an odds-ratio of 12.9. The study also achieved its main secondary endpoint, demonstrating a
14.1-fold increase and treatment effect of 61.7% (95% CI 49.5-73.8%; p<0.0001) in the proportion of patients in the treatment arm, as compared to the control arm, who
mobilized ≥ 6 million CD34+ cells/kg in just one apheresis session. This translated to an odds-ratio of 56.0. Other important data from the study include median number of
CD34+ cells collected on the first day of apheresis (~11 million in the treatment arm vs ~2 million in the control arm) – a >5-fold increase. The addition of motixafortide to G-
CSF also allowed 88.3% of patients to undergo transplantation after only one apheresis session, compared to 10.8% in the G-CSF arm – an 8.2-fold increase. Engraftment
endpoints, including the number of days needed for engraftment, success of engraftment and the durability of engraftment 100 days post-transplant, further support the study's
success.
We continue to follow-up on the GENESIS study patients for relapse-free and overall survival. In addition, we continue to perform detailed analyses of the data
according to the statistical analysis plan agreed-upon with the FDA, as well as certain post hoc analyses. In December 2021, we held a pre-NDA meeting with the FDA. The
purpose of the meeting was to obtain agreement from the FDA on the content of the proposed NDA, and, in particular, to confirm that our single Phase 3 pivotal study,
GENESIS, is sufficient to support an NDA submission. During the pre-NDA meeting, the FDA agreed that the proposed data package is sufficient to support an NDA
submission. In September 2022, we submitted an NDA to the FDA for motixafortide in stem cell mobilization for autologous bone marrow transplantation for multiple
myeloma patients and in November 2022, the FDA accepted for review the NDA and assigned the NDA a PDUFA target action date of September 9, 2023.
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Phase I study (SCD)
In March 2023, we entered into a clinical collaboration with Washington University School of Medicine in St. Louis to advance a Phase 1 clinical trial in which
motixafortide will be tested as monotherapy and in combination with natalizumab (VLA-4 inhibitor) as novel regimens to mobilize CD34+ hematopoietic stem cells for gene
therapies in Sickle Cell Disease (SCD). The study will enroll five adults with a diagnosis of SCD who are receiving automated red blood cell exchanges via apheresis. The
trial’s primary objective is to assess the safety and tolerability of motixafortide alone and the combination of motixafortide + natalizumab in SCD patients, defined by dose-
limiting toxicities. Secondary objectives include determining the number of CD34+ hematopoietic stem and progenitor cells (HSPCs) mobilized via leukapheresis; and
determining the kinetics of CD34+ HSPCs mobilization to peripheral blood in response to motixafortide alone and motixafortide + natalizumab in SCD patients. The study is
anticipated to begin enrollment in 2023 (although timelines are ultimately controlled by the independent investigator and are therefore subject to change).
Solid tumors
COMBAT-KEYNOTE-202 Dual Combination Study
In January 2016, we entered into a clinical collaboration with MSD in the field of cancer immunotherapy. In the framework of this collaboration, in September 2016
we initiated a Phase 2a study, known as the COMBAT/KEYNOTE-202 study, focusing on evaluating the safety and efficacy of motixafortide in combination with
KEYTRUDA, MSD’s anti-PD-1 therapy, in patients with metastatic PDAC. Findings in the field of immuno-oncology suggest that CXCR4 antagonists such as motixafortide
may be effective in inducing the migration of anti-tumor T-cells into the TME. KEYTRUDA is a humanized monoclonal antibody that works by blocking co-inhibitory T-cell
activation signals, thereby increasing the ability of the body’s immune system to help detect and fight tumor cells. KEYTRUDA blocks the interaction between PD-1 and its
ligands, PD-L1 and PD-L2, thereby activating T lymphocytes, which may affect both tumor cells and healthy cells. The study was an open-label, multicenter, single-arm trial
designed to evaluate the clinical response, safety and tolerability of the combination of motixafortide and KEYTRUDA as well as multiple pharmacodynamic parameters,
including the ability to improve infiltration of T-cells into the tumor and their reactivity. According to the terms of our collaboration agreement with MSD, we sponsored and
performed the COMBAT/KEYNOTE-202 study and MSD supplied its compound for purposes of the study. Upon completion of the study, or at any earlier point, both parties
will have the option to expand the collaboration to include a pivotal registration study.
Partial results from the motixafortide monotherapy portion of this trial were presented at ASCO-GI in January 2018. These results showed that motixafortide was safe
and well-tolerated, and that it induced an increase in the number of total immune cells in the peripheral blood, while the frequency of peripheral blood Tregs, known to impede
the anti-tumor immune response, was decreased. In addition, analysis of available biopsies (N=7) showed infiltration of effector T-cells, known to attack cancer cells, into the
tumor periphery and TME. In this regard, the results show up to a 15-fold increase in CD3+ T-cells, and up to a two-fold increase in CD8+ T-cells, in the TME of 43% (3/7) of
the patients, after five days of motixafortide monotherapy.
In October 2018, we announced encouraging top-line results from the dual combination arm of the COMBAT/KEYNOTE-202 study at the European Society for
Medical Oncology 2018 Congress. The data showed that the treatment regimen was safe and well tolerated. The disease control rate (patients exhibiting a response or stable
disease) was 34.5% for the evaluable population (N=29), including one patient (3.4%) with a partial response showing a 40% reduction in tumor burden, as well as nine
patients (31%) with stable disease, with a median treatment time of 72 days (37-267). Median overall survival (OS) in all patients (N=37) was 3.3 months with a six-month
survival rate of 34.4%. A significant observation was made in the subpopulation of patients receiving the study drugs as a second-line treatment (N=17), where the median
overall survival was 7.5 months, with a six-month survival rate of 51.5%. This compared favorably with historical median overall survival data of 6.1 months for the only
currently approved second-line PDAC treatment (a chemotherapy combination of Onivyde®, 5-FU and leucovorin). Additional data from in-depth analyses of biopsies taken
at screening and following monotherapy or combination treatment of motixafortide and KEYTRUDA demonstrate that in 75% of the available biopsies, motixafortide
treatment promotes an increase in the number of infiltrating CD4+, CD8+ and CD8+Granzyme B+ cytotoxic T-cells. The greatest improvement in T-cell infiltration was
observed following combination treatment of motixafortide and KEYTRUDA and was correlated with stable disease for eight cycles of treatment. Furthermore, increased
infiltration of activated CD4 and CD8 T-cells was accompanied by a pronounced decrease in the number of tumor cells, as well as by a decrease in myeloid-derived suppressor
cells, a cell type known to impede the antitumor immune response.
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COMBAT-KEYNOTE-202 Triple Combination Study
As a result of the encouraging data, the collaboration with MSD was expanded to include an additional cohort that tested the effect of the triple combination of
motixafortide, KEYTRUDA and chemotherapy (Onivyde®/5-fluorouracil/leucovorin). We initiated this additional arm of the trial in December 2018 to investigate the safety,
tolerability and efficacy of this triple combination. The triple combination arm focused on second-line pancreatic cancer patients and included approximately 40 patients with
unresectable metastatic PDAC who have progressed following first-line therapy prior to enrollment. Patients received motixafortide monotherapy priming treatment for five
days, followed by repeat cycles of the combination of chemotherapy, KEYTRUDA and motixafortide until progression. The primary endpoint of the study was the objective
response rate (ORR) assessed by RECIST v1.1 criteria. Secondary endpoints included overall survival, progression free survival, and the disease control rate.
At the European Society of Medical Oncology Immuno-Oncology Congress (ESMO IO) 2019 in December 2019, we presented partial results from the triple
combination arm of the study. Out of 36 enrolled patients, 30 patients were evaluable for safety and 22 were evaluable for efficacy. The best response for the evaluable
population of 22 patients showed 7 partial response (PR) and 10 stable disease (SD) patients, resulting in an overall response rate (ORR) of 32% and a disease control rate
(DCR) of 77%. These data compared favorably with the current chemotherapy standard-of-care treatment (Onivyde®/5-fluorouracil/leucovorin) in second-line patients with
ORR of 17% and DCR of 52%. The combination showed continuity of effect, in that 5 patients with stable disease became partial responders as treatment continued. Out of
the 7 partial responders, 5 were still on treatment as of the presentation date, with a current maximum treatment time of 330+ days; and 4 responders showed a reduction in
tumor burden of >50%. The median duration of clinical benefit until progression for the 17 patients with disease control (7 PR and 10 SD patients) was 7.8 months. The
combination was generally well tolerated, with a safety profile consistent with the individual safety profile of each component alone; adverse event and severe adverse event
profiles were as expected with chemotherapy-based treatment regimens.
In February 2020, we completed recruiting a total of 43 patients for the triple combination study and in December 2020, we announced the final results of the study.
The results of the study showed substantial improvement as compared to comparable historical results of other pancreatic cancer studies across all study endpoints. Of the 38
evaluable patients, median overall survival was 6.5 months (versus comparable historical data of 4.7 months), median progression free survival was 4.0 months (versus
comparable historical data of 2.7-3.1 months), confirmed overall response rate was 13.2% (versus comparable historical data of 7.7%), overall response rate was 21.2%
(versus comparable historical data of 16%) and disease control rate was 63.2% (versus comparable historical data of 29-52%). The combination was generally well tolerated,
with a safety profile consistent with the individual safety profile of each component alone; adverse event and severe adverse event profiles were as expected with
chemotherapy-based treatment regimens.
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MD Anderson Cancer Center Study
In August 2016, we entered into an agreement with MD Anderson in regard to an additional collaboration for the investigation of motixafortide in combination with
KEYTRUDA in pancreatic cancer. The study was conducted as an investigator-sponsored study, as part of a strategic clinical research collaboration between Merck and MD
Anderson aimed at evaluating KEYTRUDA in combination with various treatments and novel drugs, including motixafortide. The open-label, single center, single-arm Phase
2b study focused on the mechanism of action by which both drugs might synergize. In addition to assessing clinical response, the study included multiple assessments to
evaluate the biological anti-tumor effects induced by the combination. We supplied motixafortide for the study, which commenced in January 2017.
Final results of the MD Anderson study were presented at the SITC annual meeting in November 2019. Of the 20 patients enrolled, 15 were evaluable for the primary
endpoint of radiologic response. Of these 15 evaluable patients, one patient showed a partial response, two patients had stable disease and 12 patients experienced disease
progression, resulting in a disease control rate of 20%. The overall median time to progression was two months, while the median time to progression for patients showing
disease control was seven months. Median overall survival was seven months, while median survival for the patients showing disease control was 12 months. The combination
was generally well tolerated with injection site discomfort being the most commonly reported adverse event. Four patients experienced grade 3 toxicities and one patient had a
grade 4 dyspnea.
Investigator-Initiated LIBTAYO Study
In October 2020, we announced that motixafortide will be tested in combination with the anti-PD-1 cemiplimab (LIBTAYO®) and standard-of-care chemotherapy
(gemcitabine and nab-paclitaxel) in first-line PDAC. This investigator-initiated Phase 2 study, led by Columbia University, will initially enroll 10-12 PDAC patients, and will
be expanded to a total of 40 patients following an evaluation of the initial 10-12 patients based on pre-defined criteria. The primary endpoint of the study is the overall
response rate. Secondary endpoints include safety and tolerability, progression free survival, duration of clinical benefit and overall survival. Data from the study is anticipated
in 2023 (although timelines are ultimately controlled by the independent investigator and are therefore subject to change).
GenFleet Study
In June 2022, we entered into a collaboration agreement with GenFleet Therapeutics, or GenFleet, an immuno-oncology focused biopharmaceutical company based
in China, to advance motixafortide through a randomized Phase 2b clinical trial in PDAC. Under the terms of the agreement, GenFleet will fully fund, design and execute a
randomized Phase 2b clinical trial that will enroll approximately 200 first-line metastatic PDAC patients in China. This randomized controlled study will aim to evaluate the
superiority of motixafortide in combination with an anti-PD-1 and chemotherapy compared to chemotherapy alone, the current standard of care and is expected to commence
in 2023. As part of the collaboration, we will supply motixafortide, while GenFleet will supply the other study drugs for the trial. Trial oversight will be administered by a
Joint Development Committee. GenFleet will be eligible to receive low-to-mid-single digit tiered percentage royalties on future motixafortide sales, if approved.
AML
Phase 2a Study
During 2016, we completed and reported on the results of a Phase 2a clinical trial studying the use of motixafortide for the treatment of relapsed/refractory AML, or
r/r AML. The study was conducted at six sites in the United States, including MD Anderson in Houston, Memorial Sloan-Kettering Cancer Center in New York, Mayo Clinic
in Jacksonville, Johns Hopkins University in Baltimore, Northwestern Memorial Hospital in Chicago and Washington University in St. Louis, as well as at five well-known
sites in Israel. The study was an open-label study under an IND, designed to evaluate the safety and efficacy profile of repeated escalating doses of motixafortide in
combination with HiDAC in adult subjects with r/r AML. The study was comprised of two parts – a dose escalation Phase and an expansion Phase at the highest tolerated dose
found during the escalation Phase. The primary endpoints of the study were the safety and tolerability of the drug. Secondary endpoints included the pharmacokinetic profile
of the drug and an efficacy evaluation, indicated by the extent of mobilization of cancer cells from the bone marrow to the peripheral blood, the level of cancer cell death
(apoptosis) and clinical responses.
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Final results for the Phase 2a trial were presented at the annual meetings of the Society of Hematologic Oncology and ASH in September and December 2016,
respectively. The reported data set includes 45 patients, including three compassionate-use patients treated at the study sites under the identical treatment protocol. The
majority of patients in the study were heavily pretreated, with 45% of patients being refractory to one or two remission induction treatments, 19% of patients having relapsed
after a short first remission of less than 12 months, and 17% of patients having undergone two or more relapses. In addition, the treated patient population included patients
that had relapsed post allogeneic stem cell transplantation (17%), as well as secondary AML patients (24%), both conditions which represent difficult-to-treat populations with
poor prognoses.
The results showed that treatment with motixafortide in combination with HiDAC, was safe and well tolerated at all doses tested up to and including the highest dose
level of 2.0 mg/kg. Response to treatment was associated with efficient CXCR4 inhibition, resulting in high mobilization of blasts. The composite complete remission rate,
including both CR and CRi, was 38% in subjects receiving up to two cycles of motixafortide treatment at doses of 1 mg/kg and higher (n=39). In the 1.5 mg/kg dose selected
for the expansion Phase of the study (n=23), the composite complete remission rate was 39%. These response rates were superior to the historical response rate of
approximately 19% reported for high-risk AML patients treated with Ara-C alone in Phase 3 randomized trials. The ongoing follow-up of patients participating in the study’s
expansion Phase and responding to the combination treatment suggests long durability of the remissions achieved. Results further showed that motixafortide monotherapy had
a substantial therapeutic effect. Treatment with motixafortide as a single agent triggered robust mobilization of AML blasts from the bone marrow to the peripheral blood
stream, and the extent of mobilization was correlated with a positive response to treatment. The preferential mobilization of AML blasts over normal cells (4.7-fold vs. 1.4-
fold, respectively) was further confirmed by analysis using the fluorescence in situ hybridization, or FISH, technique in a subset of patients. In addition, motixafortide
monotherapy resulted in a 40% increase in AML blast apoptosis.
In June 2018, at the 23rd Congress of the EHA in Stockholm, Sweden, we reported long-term survival data from the study that showed significantly enhanced overall
survival of r/r AML patients treated with a combination of motixafortide and HiDAC. The response rate for all dosing levels was 29% and median overall survival was 9.1
months, compared with historical data on overall survival of 6.1 months for HiDAC alone. In addition, a statistically significant correlation between patient response and the
mobilization of AML blasts was reported. Responding patients demonstrated a clear and significant increase in the number of AML blasts in the peripheral blood following
motixafortide treatment, whereas non-responding patients were largely unaffected. In patients receiving the 1.5 mg/kg dose selected for expansion (n=23), the response rate
was 39% and median overall survival was 10.7 months with one-year, two-year and three-year survival rates of 38.1%, 23.8% and 23.8%, respectively. Furthermore, median
overall survival for responding patients at the 1.5 mg/kg dose (n=9) was 21.8 months, with one-year, two-year and three-year survival rates of 66.7%, 44.4% and 44.4%,
respectively. Responding patients also demonstrated a statistically significant mean 6.3-fold increase (p=0.003) in the number of AML blasts in the peripheral blood following
motixafortide monotherapy treatment, whereas in non-responding patients the mean-fold increase was minor and non-significant (1.66-fold; p=0.21).
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BLAST Study
We also investigated a second AML treatment line – consolidation therapy – in a large randomized, controlled Phase 2b trial in Germany, known as the BLAST study.
This study examined motixafortide as part of a second-stage treatment, termed consolidation therapy (cytarabine), to improve outcomes for the approximately 70% of AML
patients who achieved remission after the standard initial treatment regimen, known as induction therapy. The consolidation therapy was aimed at eliminating the minimal
residual disease left in the bone marrow after induction therapy that can lead to relapse in 40-60% of the patients within 12-18 months after entering remission.
The Phase 2b trial, which was conducted in collaboration with the University of Halle as sponsor and with the participation of two large leukemia study groups in
Germany, was a double-blind, placebo-controlled, randomized, multi-center study aimed at assessing the efficacy of motixafortide in addition to standard consolidation
therapy in AML patients. The primary endpoint of the study was to compare the RFS time in AML subjects in their first remission during a minimum follow-up time of 18
months after randomization. In addition, pharmacodynamic measurements were conducted in order to assess the minimal residual disease, and biomarker analyses was
performed to identify predictors of motixafortide response. The study, which was carried out at 29 sites in Germany. AML patients between 18 and 75 years of age with
documented first remission were randomized in a 1:1 ratio to receive HiDAC, either with motixafortide or with a matching placebo, as consolidation therapy.
During 2020, we finalized plans with our collaboration partners to conduct an interim analysis on 2/3 (N=128) of the 194 patients originally planned in the study, all
of which had already completed treatment. In November 2020, we announced that based on the interim analysis, the investigational arm of motixafortide combined with
cytarabine did not demonstrate a statistically significant effect in the study’s primary endpoint, and therefore, the DMC recommended not to continue the study. Based on the
DMC’s recommendation, we terminated the study. We continue to believe in the relevance of CXCR4 as a viable target in other AML treatment lines, such as rr/AML and
induction treatment.
Other clinical results
At the annual meeting of ASH in December 2017, clinical data supporting motixafortide as a robust mobilizer of HSCs associated with long-term engraftment was
presented by Prof. Amnon Peled. HSCs are cells found in the bone marrow, peripheral blood or umbilical cord blood that are responsible for generation and replenishment of
all blood cell progenitors and eventually mature cells. It is therefore believed to be beneficial for a variety of therapeutic purposes, such as transplantation for people with
hematological malignancies or for the therapy of blood or immune system disorders. The success of long-term HSC engraftment depends largely on the amount and quality of
HSCs (CD34+ CD38- CD45RA- CD90+ CD49f+). The data presented demonstrate that human CD34+ cells from motixafortide-mobilized grafts contain high numbers of
HSC (CD34+, CD38-, CD45RA-, CD90+, CD49f+) associated with long-term engraftment, compared to cells mobilized by granulocyte colony stimulating factor (G-CSF).
An associated in vivo study further showed that motixafortide-mobilized HSCs can successfully engraft the bone marrow and spleen of immunodeficient mice. In addition, a
robust long-term engraftment of motixafortide-mobilized human CD34+ cells was seen in these mice in primary and secondary transplants.
AGI-134
AGI-134 entered our pipeline following our acquisition of Agalimmune in March 2017. The compound is a synthetic alpha-gal immunotherapy in development for
solid tumors. AGI-134 harnesses the body’s pre-existing, highly abundant, anti-alpha-gal, or anti-Gal, antibodies to induce a systemic, specific anti-tumor response to the
patient’s own tumor neo-antigens. This response not only kills the tumor cells at the site of injection, but also brings about a durable, follow-on, anti-metastatic immune
response. Alpha-gal is a cell-surface carbohydrate antigen that is not expressed by humans, unlike virtually all other mammals and bacteria. Therefore, humans universally
produce and maintain high levels of anti-Gal antibodies, due to exposure to alpha-gal on bacteria in the digestive system.
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AGI-134 is injected into the tumor, where it coats the tumor cell membranes, resulting in alpha-gal being exposed on the tumor cell surface. Anti-Gal antibodies bind
to the alpha-gal part of AGI-134 to produce an initial immune response that activates complement-dependent and antibody-dependent cellular cytotoxicity (cell death). This
cytotoxicity generates immune-tagged cells and cellular debris that trigger an uptake of tumor-associated antigens by antigen-presenting cells (APCs). These APCs induce a
follow-on systemic immune response by the activation and clonal expansion of T-cells to the patient’s own neo-antigens. This approach not only targets the primary injectable
tumor but has also demonstrated efficacy against existing distant secondary tumors. Furthermore, the mechanism of action suggests the potential of long-term protection
against future metastases.
AGI-134 has completed numerous proof-of-concept studies, demonstrating regression of established primary tumors after injection with AGI-134 and robust
protection against the development of secondary tumors in a model of melanoma with a single dose only. Synergy has also been demonstrated in the same model when
combined with a PD-1 immune checkpoint inhibitor, offering the potential to broaden the utility of such immunotherapies and improve the rate and duration of responses in
multiple cancer types. A 28-day, repeated-administration GLP toxicology study in monkeys with AGI-134 has also been successfully completed.
At ASCO-SITC in January 2018, we presented preclinical findings demonstrating successful results in the treatment of primary tumors. Intratumoral administration
of AGI-134 induced regression of established tumors in two murine melanoma models. Moreover, treatment with AGI-134 showed a beneficial effect on survival, compared to
the control group, with fewer mice dying or requiring euthanasia due to tumor burden. In addition, the results show that injection of AGI-134 into the tumors induces
activation of the complement system, an important component of the innate immune system. Activation of the complement system within tumors by AGI-134 is predicted to
destroy tumor cells and create a pro-inflammatory TME that attracts and activates other immune cells, ultimately resulting in adaptive anti-tumor immunity.
In August 2018, we initiated a Phase 1/2a clinical study for AGI-134 that is primarily designed to evaluate the safety and tolerability of AGI-134 given as
monotherapy in unresectable metastatic solid tumors. Additional objectives are to perform a wide array of biomarker studies, to demonstrate the mechanism of AGI-134 and to
assess its efficacy by clinical and pharmacodynamic parameters. The multicenter, open-label study is being carried out in the United Kingdom, Spain and Israel.
The study is comprised of two parts: (i) an accelerated dose-escalation part to assess the safety and tolerability of intratumorally injected AGI-134 as a monotherapy,
as well as to determine the maximum tolerated dose and the recommended dose for part 2 of the study and (ii) a dose expansion part at the recommended dose, designed to
assess the safety, tolerability and anti-tumor activity of AGI-134 as a monotherapy in a basket cohort of multiple solid tumor types. The first part of the study was completed
in September 2019, with AGI-134 being found to be safe and well tolerated, with no serious drug-related adverse events or dose-limiting toxicities reported. The maximal
tolerated dose was not reached and the recommended dose for the second part of the study was determined. We commenced the second part of the study in September 2019.
Due to clinical operating issues associated with the COVID-19 pandemic, in April 2020, the clinical trial was temporarily suspended. In August 2020, we renewed study
enrollment, and in January 2022, we completed enrollment. In December 2022, we announced results from the study. The study met its primary endpoint of AGI-134’s safety
and tolerability. Generation of an immune response and markers of clinical efficacy were assessed as secondary endpoints. Most patients analyzed showed an increase in
Alpha-Gal antibodies, indicating increased overall immune activity. Additionally, increases in antigen presenting cells (APCs) were observed in most tissue samples analyzed,
and T cell and macrophage tumor infiltration was seen in approximately one-third of evaluable patients’ injected tumors, and in approximately half of evaluable patients’ un-
injected lesions. Radiological assessments found that 29 percent of patients in the trial achieved best overall response of stable disease. We plan to seek publication of our data
at a medical congress in 2023, and in consultation with our scientific advisory board, we will determine the next steps for the program in the first half of 2023.
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In November 2018, the FDA granted the Biological Product Designation for AGI-134. This designation provides us with eligibility to obtain 12 years of market
exclusivity upon approval of the product for commercial use by the FDA. This regulatory market exclusivity adds an incremental layer of protection in addition to that
afforded by existing patents granted in the United States and Europe, and pending in other countries, covering the use of AGI-134 for the treatment of solid cancer tumors.
Commercialized Product
BL-5010
BL-5010 is a novel medical device containing an acidic, aqueous solution and applicator for the non-surgical removal of benign skin lesions. It offers an alternative to
painful, invasive and expensive removal treatments including cryotherapy, laser treatment and surgery. Since the treatment is non-invasive, it poses minimal infection risk and
eliminates the need for anesthesia, antiseptic precautions and bandaging. The pre-filled device controls and standardizes the volume of solution applied to a lesion, ensuring
accurate administration directly on the lesion and preventing both accidental exposure of the healthy surrounding tissue and unintentional dripping. It has an ergonomic
design, making it easy to handle, and has been designed with a childproof cap. BL-5010 is applied topically on a skin lesion in a treatment lasting a few minutes with the pen-
like applicator and causes the lesion to gradually dry out and fall off within one to four weeks. We received European confirmation from British Standards Institute of the
regulatory pathway classification of BL-5010 as a Class IIa medical device. We in-licensed the exclusive, worldwide rights to develop, market and sell BL-5010 from IPC in
November 2007.
Development and Commercialization Arrangement. In December 2014, we entered into an exclusive out-licensing arrangement with Perrigo for the rights to BL-5010
for OTC indications in Europe, Australia and additional selected countries. We retain the OTC rights to BL-5010 in the United States and the rest of the world, as well as the
non-OTC rights on a global basis. Under the original terms of our out-licensing arrangement with Perrigo, Perrigo was obligated to use commercially reasonable best efforts to
obtain regulatory approval in the licensed territory for at least two OTC indications and to commercialize BL-5010 for those two OTC indications. In addition, Perrigo agreed
to sponsor and manufacture BL-5010 in the relevant regions. Compensation by Perrigo for the exclusive license includes the payment to us of an agreed percentage of the
gross revenue of sales of licensed products. We agreed to pay a portion of all net consideration we receive from Perrigo, within our standard range of sublicense receipt
consideration, to IPC, the company from which we initially in-licensed the development rights to BL-5010. We have the right to prosecute and maintain the patents for BL-
5010 in the licensed territories, and Perrigo agreed to bear the cost of all renewal fees for patents and the other costs of prosecution and maintenance up to an agreed limit. In
addition, we were granted full access to all clinical and research and development data generated during the performance of the development plan and may use these data in
order to develop or license the product in other territories and fields of use where we retain the rights. Our agreement with Perrigo will continue in effect until the cessation of
all commercialization in the licensed territory. After the fifth anniversary of the first commercial sale of a licensed product, either party may terminate the agreement by giving
at least 18 months’ prior written notice to the other party. Either party may terminate the agreement (a) by providing 60 days’ written notice of a material breach of the
agreement by the other party if the breaching party does not cure the breach during that time or (b) with immediate effect on written notice to the other party if there is a
change of control of the other party. The parties have agreed that the announced acquisition of Perrigo by Perrigo Company Plc is a change of control event that will not give
rise to a right on our part to terminate the license agreement. In addition, we have the right to terminate the agreement if Perrigo does not fulfill any of its obligations of
diligence with respect to launching a licensed product or obtaining regulatory approval for, and commercializing, licensed products as described above.
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In March 2016, Perrigo received CE Mark approval for BL-5010 as a novel OTC treatment for the non-surgical removal of warts. The commercial launch of products
for treatment of this first OTC indication (warts/verrucas) commenced in Europe in the second quarter of 2016. Since then, Perrigo has invested in improving the product and
during 2019 launched an improved version of the product in several European countries.
In March 2020, we agreed that Perrigo could relinquish its license rights for certain countries that had been included in its territory according to the original license
agreement and was also no longer obligated to develop, obtain regulatory approval for and commercialize products for a second OTC indication. In turn, in March 2020, we
agreed with our licensor of the rights to BL-5010, IPC, to return to IPC those license rights no longer out-licensed to Perrigo as a result of the agreement described in the
preceding sentence, in consideration of the payment to us of royalties or fees on sublicense receipts.
Collaboration and Out-Licensing Agreements
Collaboration Agreement with MSD
See “—Therapeutic Candidates — Motixafortide — Clinical Trials — Solid tumors” for details regarding our collaboration with MSD.
Collaboration Agreement with GenFleet
See “—Therapeutic Candidates — Motixafortide — Clinical Trials — Solid tumors” for details regarding our collaboration with GenFleet.
Out-Licensing Agreement with Perrigo
See “—Commercialized Product— BL-5010— Development and Commercialization Arrangement” for details regarding our out-licensing agreement with Perrigo.
In-Licensing Agreements
We have in-licensed and intend to continue to in-license development, production and marketing rights from selected research and academic institutions in order to
capitalize on the capabilities and technology developed by these entities. We also seek to obtain technologies that complement and expand our existing technology base by
entering into license agreements with pharmaceutical and biotechnology companies. When entering into in-license agreements, we generally seek to obtain unrestricted
sublicense rights consistent with our primarily partner-driven strategy. We are generally obligated under these agreements to diligently pursue product development, make
development milestone payments, pay royalties on any product sales and make payments upon the grant of sublicense rights. We generally insist on the right to terminate any
in-license for convenience upon prior written notice to the licensor.
The scope of payments we are required to make under our in-licensing agreements is comprised of various components that are paid commensurate with the
progressive development and commercialization of our drug products.
Our in-licensing agreements generally provide for the following types of payments:
•
Revenue sharing payments. These are payments to be made to licensors with respect to revenue we receive from sub-licensing to third parties for further
development and commercialization of our drug products. These payments are generally fixed at a percentage of the total revenues we earn from these
sublicenses.
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• Milestone payments. These payments are generally linked to the successful achievement of milestones in the development and approval of drugs, such Phases 1,
2 and 3 of clinical trials and approvals of NDAs.
•
•
Royalty payments. To the extent we elect to complete the development, licensing and marketing of a therapeutic candidate, we are generally required to pay our
licensors royalties on the sales of the end drug product. These royalty payments are generally based on the net revenue from these sales. In certain instances, the
rate of the royalty payments decreases upon the expiration of the drug’s underlying patent and its transition into a generic drug. Certain of our agreements
provide that if a licensed drug product is developed and sold through a different corporate entity, the licensors may elect to receive shares in such company
instead of a portion of the royalties.
Additional payments. In addition to the above payments, certain of our in-license agreements provide for a one-time or periodic payment that is not linked to
milestones. Periodic payments may be paid until the commercialization of the product, either by direct sales or sublicenses to third parties. Other agreements
provide for the continuation of these payments even following the commercialization of the licensed drug product.
The royalty and revenue-sharing rates we agree to pay in our in-licensing agreements vary from case to case but in most cases range from 20% to 29.5% of the
consideration we receive from sublicensing the applicable therapeutic candidate. We are required to pay a substantially lower percentage, generally less than 5%, if we elect to
commercialize the subject therapeutic candidate independently. Due to the relatively advanced stage of development of the compound licensed from Biokine, our license
agreement with Biokine provides for royalty payments of 10% of net sales, subject to certain limitations, should we independently sell products. In addition, milestone
payments are not generally payable if the revenue-sharing from an out-licensing transaction is greater than any relevant payments due under our in-licensing agreements.
The following are descriptions of our in-licensing agreements associated with our therapeutic candidates. In addition to the in-licensing agreements discussed herein,
we have entered into other in-licensing arrangements in connection with our therapeutic candidates in clinical, advanced preclinical and feasibility stages.
Motixafortide
In September 2012, we in-licensed the rights to motixafortide under a license agreement with Biokine. Pursuant to the agreement, Biokine granted us an exclusive,
worldwide, sublicensable license to develop, manufacture, market and sell certain technology relating to a short peptide that functions as a high-affinity antagonist for CXCR4
and the uses thereof.
There were no upfront payments due under the agreement. We are obligated to pay a monthly development fee of $27,500 for certain development services that
Biokine has committed to provide to us under the agreement. The payment of this monthly fee will continue until the completion of the last clinical trial in which
motixafortide is planned to be tested, or is being tested with, at least 20 subjects.
We are responsible for paying all development costs incurred by the parties in carrying out the development plan.
Should we independently develop manufacture and sell products (excluding sublicensing) containing the licensed technology, we are obligated to make royalty
payments of 10% of net sales, subject to certain limitations.
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The agreement also grants us the right to grant sublicenses for the licensed technology. Initially, we were required to pay Biokine a royalty payment of 40% of the
amounts we receive as consideration in connection with any sublicensing, development, manufacture, marketing, distribution or sale of the licensed technology. In October
2018, Biokine agreed to reduce the royalty payment for sublicensing to 20% in return for the payment by us of $10 million in cash plus $5 million in our restricted shares.
Biokine is also eligible to receive up to a total of $5 million in future milestone payments.
Before we in-licensed motixafortide, Biokine had received funding for the project from the IIA, and as a condition to IIA giving its consent to our in-licensing of
motixafortide, we were required to agree to abide by any obligations resulting from such funding. However, if we become legally required to make payments to the IIA in
respect of grants made to Biokine, we have the right to offset the full amount of such grants from any payments otherwise due to Biokine as sublicensing royalties as described
above.
We are obligated under the agreement with Biokine to make commercially reasonable, good faith efforts to sublicense or commercialize motixafortide for fair
consideration. If we do not fulfill this obligation within 24 months after completion of the development plan, all of the rights and responsibilities with respect to
commercialization of the licensed technology will revert to Biokine, and our obligation to pay royalties for sales of any licensed products or sublicensing as described above
will revert to Biokine.
We have the first right to prepare, file, prosecute and maintain any patent applications and patents, in respect of the licensed technology and any part thereof, at our
expense, provided that we are required to consult with Biokine regarding patent prosecution and patent maintenance. In addition, we have the right to take action in the
prosecution, prevention, or termination of any patent infringement of the licensed technology. We are responsible for all the expenses of any patent infringement suit that we
bring, including any expenses incurred by Biokine in connection with such suits, with such expenses reimbursable from any sums recovered in such suit or in the settlement
thereof for. After such reimbursement, if any funds remain, both we and Biokine are each entitled to a certain percentage of any remaining sums.
The agreement will remain in effect until the expiration of all of our royalty and sublicense revenue obligations to Biokine, determined on a product-by-product and
country-by-country basis. We may terminate the agreement for any reason on 90 days’ prior written notice to Biokine. Either party may terminate the agreement for a material
breach by the other party if the breaching party is unable to cure the breach within 30 days after receiving written notice of the breach from the non-breaching party. With
respect to any termination for a material breach, if the breach is not susceptible to cure within the stated period and the breaching party uses diligent, good faith efforts to cure
such breach, the stated period will be extended by an additional 30 days. In addition, either party may terminate the agreement upon the occurrence of certain bankruptcy
events.
Termination of the agreement will result in a loss of all of our rights to the drug and the licensed technology, which will revert to Biokine. In addition, any sublicense
of ours will terminate provided that, upon such termination and at the request of the sublicensee, Biokine will be required to enter into a separate license agreement with the
sublicensee on substantially the same terms as those contained in the applicable sublicense agreement.
AGI-134
Acquisition Agreements with Agalimmune
In March 2017, we acquired substantially all of the outstanding shares of Agalimmune and entered into the Agalimmune Development Agreement with the selling
shareholders. We control the Agalimmune board of directors, and subject to the protections in favor of the selling shareholders, we will direct and be responsible for the
planning, execution and day-to-day management of Agalimmune and its pipeline, including AGI-134.
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The Agalimmune Development Agreement provides the selling shareholders with a reversionary option, in the event of a breach of that agreement and certain other
limited triggering events, that permits the selling shareholders to re-acquire our equity interests in Agalimmune for nominal consideration. See “Risk Factors — Risks Related
to Our Business Regulatory Matters — If we do not meet the requirements under our agreement with the Agalimmune selling shareholders, we could lose the rights to the
therapeutic candidates in Agalimmune’s pipeline, including but not limited to AGI-134.”
License from the University of Massachusetts
In 2013, Agalimmune entered into an exclusive license agreement with the University of Massachusetts, which was amended and restated in February 2017, for rights
to intellectual property related to AGI-134. Pursuant to the agreement, Agalimmune has an exclusive, worldwide, royalty-bearing, sublicensable license to develop,
manufacture, use, import and sell licensed products. Agalimmune is obligated to use diligent efforts to develop the licensed products and to introduce them into the
commercial market. The agreement sets forth specific development milestones that Agalimmune is required to fulfill. In consideration of the grant of the license, Agalimmune
is obligated to pay upfront license fees, annual maintenance fees, milestone payments, and low, single digit royalty payments on the net sales of licensed products. In addition,
the agreement provides that following a change of control event, Agalimmune will allot to the University 6% of its shares on a fully diluted basis. The agreement will remain
in full effect until the later of expiration or abandonment of all valid claims in the licensed patents or 10 years from the date of first sale of a licensed product. Agalimmune
may terminate the agreement for any reason on 90 days’ prior written notice to the University.
License from Kode Biotech
In March 2015, Agalimmune entered into an evaluation license and option agreement with Kode Biotech for the rights to intellectual property related to certain water
dispersible glycan-lipid conjugates (the “KODETM Constructs”), including AGI-134. Pursuant to the agreement, Agalimmune had an exclusive license to pursue preclinical
assessment of the use of the KODETM Constructs in Agalimmune’s method of promoting tumor anticancer therapy, and the exclusive right to require Kode Biotech to grant
Agalimmune an exploitation license to pursue clinical development and commercialization of the use of the KODETM Constructs in its method.
In September 2017, Agalimmune exercised its option to enter into the exploitation license agreement with Kode Biotech that grants Agalimmune a worldwide,
exclusive, royalty-bearing transferable license to develop, manufacture, use, import and sell licensed products, including AGI-134. Agalimmune is obligated to use reasonable,
diligent efforts to develop licensed products and to introduce licensed products into the commercial market. In consideration of the grant of the license, Agalimmune paid a
license issue fee and is obligated to pay annual maintenance fees, milestone payments and low, single-digit royalty payments on the net sales of the licensed products.
Agalimmune also has the right to grant sublicenses for the licensed technology and is required to pay Kode Biotech a payment based on the revenues from sublicense net
sales. The agreement will remain in effect, unless terminated earlier in accordance with its terms, until the later of expiration or abandonment of all enforceable patent claims
within the licensed patents.
BL-5010
In November 2007, we in-licensed the rights to develop and commercialize BL-5010 under a license agreement with IPC. Under the agreement, IPC granted us an
exclusive, worldwide, sublicensable license to develop, manufacture, market and sell certain technology relating to an acid-based formulation for the non-surgical removal of
skin lesions and the uses thereof. We are obligated to use commercially reasonable efforts to develop the licensed technology in accordance with a specified development plan,
including meeting certain specified diligence goals. We are required to make low, single-digit royalty payments on the net sales of the licensed technology if we manufacture
and sell it on our own, subject to certain limitations. Our royalty payment obligations are payable on a product-by-product and country-by-country basis, until the last to expire
of any patent included within the licensed technology in such country. We also have the right to grant sublicenses for the licensed technology and are required to pay IPC a
payment, within our standard range of sublicense receipt consideration, based on the revenues we receive as consideration in connection with any sublicensing, development,
manufacture, marketing, distribution or sale of the licensed technology.
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The license agreement remains in effect until the expiration of all of our license, royalty and sublicense revenue obligations to IPC, determined on a product-by-
product and country-by-country basis, unless we terminate the license agreement earlier. We may terminate the license agreement for any reason on 30 days’ prior written
notice. Either party may terminate the agreement for material breach if the breach is not cured within 30 days after written notice from the non-breaching party. If the breach is
not susceptible to cure within the stated period and the breaching party uses diligent, good faith efforts to cure such breach, the stated period will be extended by an additional
30 days. In addition, either party may terminate the agreement upon the occurrence of certain bankruptcy events.
Termination of the agreement will result in a loss of all of our rights to the licensed technology, which would revert to IPC. In addition, any sublicense of the licensed
technology will terminate provided that, upon termination, at the request of the sublicensee, IPC is required to enter into a license agreement with the sublicensee on
substantially the same terms as those contained in the sublicense agreement.
Intellectual Property
Our success depends in part on our ability to obtain and maintain proprietary protection for our therapeutic candidates, technology and know-how, to operate without
infringing the proprietary rights of others and to prevent others from infringing our proprietary rights. Our policy is to seek to protect our proprietary position by, among other
methods, filing U.S. and foreign patent applications related to our proprietary technology, inventions and improvements that are important to the development of our business.
We also rely on trade secrets, know-how and continuing technological innovation, as well as on regulatory exclusivity, such as Orphan Drug designation or new chemical
entity, or NCE, protection to develop and maintain our proprietary position.
Patents
As of March 21, 2023, we owned or exclusively licensed for uses within our field of business 33 patent families that collectively contain 129 issued patents, 10
allowed patent applications and over 80 pending patent applications relating to the three candidates listed below. We are also pursuing patent protection for other drug
candidates in our pipeline. Patents related to our therapeutic candidates may provide future competitive advantages by providing exclusivity related to the composition of
matter, formulation, and method of administration of the applicable compounds and could materially improve the value of our therapeutic candidates. The patent positions for
our three therapeutic candidates are described below and include both issued patents and pending patent applications we exclusively license. We vigorously defend our
intellectual property to preserve our rights and gain the benefit of our investment.
•
The motixafortide drug product candidate is covered as a composition of matter by a pending international patent application. Corresponding patents, if granted,
will expire in December 2041, not including any applicable patent term extension, which may add an additional term of up to five years on the patent. We also
have an exclusive license to a patent family that covers the active ingredient molecule per se. Patents of this family have been granted in the U.S., Europe, Japan
and Canada. The patents will expire in August 2023, not including any applicable patent term extension. We have an exclusive license to a patent family that
covers motixafortide combined with a PD1 antagonist for the treatment of cancer. Four patents of this family have been granted in the U.S., and member patent
applications are pending in the U.S., Europe, Japan, China, Canada, Australia, India, Korea, Mexico, Brazil and Israel. The granted U.S. patent and patents to
issue in the future based on pending patent applications in this family will expire in 2036, not including any applicable patent term extension. In addition, we
have an exclusive license to nineteen other patent families pending or granted worldwide directed to methods of synthesis of motixafortide and methods of use of
motixafortide either alone or in combination with other drugs for the treatment of certain types of cancer and other indications. Furthermore, we have Orphan
Drug status for AML, pancreatic cancer and stem cell mobilization, as well as data exclusivity protection afforded to motixafortide as an NCE.
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• With respect to AGI-134, Agalimmune owns or has an exclusive license to three patent families that cover the AGI-134 compound and its use for treating cancer.
The use of AGI-134 for treating solid tumors is covered by patents granted in the U.S., Europe, China, Japan and other countries. The patents will expire in 2035,
not including any applicable patent term extensions. The compound AGI-134 is covered by patents granted in the United States, Europe, Japan and other
countries. The patents will expire in 2025, not including any applicable patent term extensions. In addition, the future drug product is eligible for obtaining
regulatory Biological Product exclusivity (12 years of market exclusivity in the U.S.).
• With respect to BL-5010, we have an exclusive license to a patent family directed to a novel applicator uniquely configured for applying the BL-5010
composition to targeted skin tissue safely and effectively. Patents in this family have been granted in the U.S., Europe, Israel, Japan and China. The patents will
expire in 2034.
The patent positions of companies like ours are generally uncertain and involve complex legal and factual questions. Our ability to maintain and solidify our
proprietary position for our technology will depend on our success in obtaining effective claims and enforcing those claims once granted. We do not know whether any of our
patent applications or those patent applications that we license will result in the issuance of any patents. Our issued patents and those that may issue in the future, or those
licensed to us, may be challenged, narrowed, circumvented or found to be invalid or unenforceable, which could limit our ability to stop competitors from marketing related
products or the length of term of patent protection that we may have for our products. Neither we nor our licensors can be certain that we were the first to invent the inventions
claimed in our owned or licensed patents or patent applications. In addition, our competitors may independently develop similar technologies or duplicate any technology
developed by us, and the rights granted under any issued patents may not provide us with any meaningful competitive advantages against these competitors. Furthermore,
because of the extensive time required for development, testing and regulatory review of a potential product, it is possible that, before any of our products can be
commercialized, any related patent may expire or remain in force for only a short period following commercialization, thereby reducing any advantage of the patent.
Trade Secrets
We may rely, in some circumstances, on trade secrets to protect our technology. However, trade secrets can be difficult to protect. We seek to protect our proprietary
technology and processes, in part, by confidentiality agreements and assignment of invention agreements with our employees, consultants, scientific advisors and contractors.
We also seek to preserve the integrity and confidentiality of our data and trade secrets by maintaining physical security of our premises and physical and electronic security of
our information technology systems. While we have confidence in these individuals, organizations and systems, such agreements or security measures may be breached, and
we may not have adequate remedies for any breach. In addition, our trade secrets may otherwise become known or be independently discovered by competitors.
Trademarks
We also rely on protection available under trademark laws. As of March 21, 2023, we have registered trademarks for “APHEXDA” in Israel and also have the same
pending trademarks in the EU and Australia (both accepted and published) and in the UK, the US, Brazil, Canada, China, Japan and Republic of Korea jurisdictions. We also
claim common law protections for other marks we use in our business. Competitors and other companies could adopt similar marks or try to prevent us from using our marks,
consequently impeding our ability to build brand identity and possibly leading to customer confusion.
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Manufacturing
Our laboratories are located in our headquarters in Modi’in, Israel, and are in part compliant with FDA regulations setting forth current good laboratory practices, or
GLP. While our bioanalytical laboratory complies with these regulations, the chemistry and formulation, as well as the analytical laboratories, are limited in manufacturing
scale and resources and are intended to support our projects for research and development activities only. These laboratories are not compliant with cGMP. Hence, we cannot
independently manufacture drug substances or drug products for our current clinical trials or for commercial distribution. The cGMP contract manufacturing organization of
the drug substances and drug products used for our current clinical trials do have these necessary cGMP approvals.
There can be no assurance that our therapeutic candidates, if approved, can be manufactured in sufficient commercial quantities, in compliance with regulatory
requirements, and at an acceptable cost. Our contract manufacturers, who we also plan to use as we execute our independent commercialization for montixafortide to begin
producing commercial scale product, are, and will be, subject to extensive governmental regulation in connection with the manufacture of any pharmaceutical products or
medical devices. Our contract manufacturers must ensure that all of the processes, methods and equipment are compliant with cGMP on an ongoing basis, mandated by the
FDA and other regulatory authorities, and conduct extensive audits of vendors, contract laboratories and suppliers.
Contract Research Organizations
We outsource certain preclinical and clinical development activities to CROs, which meet FDA or European Medicines Agency regulatory standards. We create and
implement the drug development plans and, during the preclinical and clinical Phases of development, manage the CROs according to the specific requirements of the
therapeutic candidate under development.
Competition
The pharmaceutical, medical device and biotechnology industries are intensely competitive. Our therapeutic candidates, if commercialized, would compete with
existing drugs and therapies. In addition, there are many pharmaceutical companies, biotechnology companies, medical device companies, public and private universities,
government agencies and research organizations actively engaged in research and development of products targeting the same markets as our therapeutic candidates. Many of
these organizations have substantially greater financial, technical, manufacturing and marketing resources than we do. In certain cases, our competitors may also be able to use
alternative technologies that do not infringe upon our patents to formulate the active materials in our therapeutic candidates. They may, therefore, bring to market products that
are able to compete with our candidates, or other products that we may develop in the future.
Motixafortide
There are a number of potentially competitive compounds under development that act as CXCR4 inhibitors, including, among others, Mozobil® (plerixafor), which is
being marketed by Sanofi Genzyme as a stem cell mobilizer for autologous stem cell transplantation; burixafor developed by GPCR Therapeutics; X4P-001 (mavorixafor)
developed by X4 Pharmaceuticals Inc for WHIM syndrome; GMI-1359 developed by Glyco-Mimetics Inc for Solid Tumors and AD-214 developed by AdAlta Ltd for
idiopathic pulmonary fibrosis (IPF).
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In the field of stem cell mobilization, in addition to the above-referenced Mozobil, Magenta’s MGTA-145 is a compound under development that could potentially be
approved for stem cell mobilization in patients with genetic and autoimmune diseases, however, this development status is unclear as Magenta recently announced the failure
of lead asset and their intention to seek strategic alternatives.
During 2023, Mozobil’s patent will expire. The following companies have developed and applied for FDA approval for Plerixafor generic drugs: Dr. Reddys Labs
LTD, TEVA Pharms USA, Zydus Pharms USA IND, MSN Laboratories Private Ltd, Auromedics Pharma LLC, Amneal EU Ltd and Kindos Pharma Co Ltd.
Immuno-oncology is an area of great interest in the pharmaceutical market, specifically, immuno-oncology combination therapies. Currently there are thousands of
immuno-oncology combination treatments being tested in clinical trials that aim to transform scientific innovation into practice-changing cancer drugs.
In the field of pancreatic cancer, motixafortide, if approved, will compete with the few, currently approved treatments for PDAC. In the first line setting, Gemcitabine
in combination with Abraxane® or FOLFIRINOX regimen are the current standard of care and there are a few targeted therapies including Tarceva and Lynparza. Oncologists
have limited options of existing therapies for second-line metastatic patients. The only FDA-approved second-line treatment is Onivyde® in combination with 5FU and LV for
gemcitabine-treated patients. In addition to chemotherapy, Merck’s KEYTRUDA® was approved for MSI-H cancers (approximately 1% of all cases) and Lynparza® was
recently approved for maintenance of BRCA mutated pancreatic cancer (approximately 7% of all cases).
In the last years we have seen a number of late-stage clinical failures of compounds for advanced PDAC, most notably Apexigen’s APX005, Erytech’s Eryspase and
Rafael Pharmaceuticals’s devimistat in the last year. Most of these failed trials have been based on a single promising endpoint. There are very few compounds in advanced
stages of development in PDAC, most notably TME Pharma’s (previously known as Noxxon) NOX-A12, which has announced initiation of a Phase 2 trial as a triple
combination study in PDAC.
The field of AML has seen quite a few approvals in recent years, most of them being for specific subpopulations in specific lines of therapy. If approved,
motixafortide will compete with many currently approved treatments for AML that include chemotherapy (doxorubicin, cytarabine, vincristine); radiation therapy; stem cell
transplantation; hypomethylating agents Dacogen® (decitabine, Eisai and Johnson & Johnson); Vidaza® (azacitidine, Celgene); FLT3 Inhibitors Xospata® (gilteritinib),
Vanflyta® (quizartinib); Rydapt® (midostaurin); IDH inhibitors Idhifa® (enasidenib) and Tibsovo® (ivosidenib). Other approved drugs for AML are Vyxeos® (liposomal
cytarabine); Venclexta/Venclyxto® (Venetoclax, AbbVie); Daunorubicin® (Jazz Pharmaceuticals); Revlimid® (lenalidomide, Celgene); Daurismo® (glasdegib, Pfizer);
Mylotarg® (gemtuzumab, Pfizer); and Rezlidhia® (olutasidenib, Rigel)
In addition there are a number of potentially competitive compounds in development to treat AML including, among others, crenolanib (Arog Phramaceuticals), oral
azacytidine (Celgene/Bristol Myers Squibb); guadecitabine (Astex Pharmaceuticals / Otsuka); uprolesan (Glycomimetics); pracinostat (MEI Pharma/Helsinn); devimistat
(Rafael Pharmaceuticals); ibrutinib (AbbVie); enasidenib (Bristol Myers Squibb); alvocidib (Tolero Pharmaceuticals); daratumumab (Johnson & Johnson); brentuximab
(Seattle Genetics); selinexor (Karyopharm Therapeutics and Ono Pharmaceutical Co Ltd.); Nexavar (sorafenib, Bayer) vosaroxim (Denovo Biopharma LLC).
AGI-134
The field of cancer immunotherapy is rapidly growing, targeting CTLA-4, PD1 or PDL1 via antibody blockade. In recent years, approval has been granted for use of
these agents for various oncology- related indications such as melanoma, non-small cell lung cancer, renal cell carcinoma, head and neck, gastric and colorectal cancer, liver
cancer and bladder cancer. As noted above, there are currently hundreds of immuno-oncology combination treatments being tested in clinical trials. Many of these
combinations could be competitive with AGI-134.
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In general, the competitive landscape is comprised of compounds that target tumor specific neoantigens and create adaptive, anti-tumor immune response. Examples
of such therapeutic approaches include oncolytic viruses, dendritic cell vaccines, personalized neoantigen-based cancer vaccines, pathogen-associated molecular patterns
(PAMPs), damage-associated molecular pattern (DAMPs) and cancer vaccines.
If approved, AGI-134 will compete with approved treatments such as the oncolytic viruses Imlygic® (T-VEC; Amgen) and dendritic cell cancer vaccine Provenge®
(sipuleucel-T; Dendreon Corp). In addition, there are several potentially-competitive compounds that are currently under development, including, among others, Pexa-Vec
(pexastimogene devacirepvec, SillaJen and Transgene); Reolysin (pelareorep, Adlai Nortye Pharmaceutical Co Ltd and Oncolytics Biotech Inc.); Cavatak (MSD/Viralytics);
NeoVax (BioNTech/Neon Therapeutics); IVAC Mutanome (BioNTech); TLR9 agonists such as lefitolimod (MGN-1703, Mologen Ag); tilsotolimod (IMO-2125, Idera
Pharmaceuticals Inc.); SD-101 (TriSalus Life Sciences); CMP-001 (Checkmate Pharmaceuticals); ADU-S100 (Aduro BioTech Inc./Novartis); imprime PGG® (HiberCell) and
MG1MA3 (Turnstone Biologics Inc/AbbVie). Most of these competitors have ongoing combination trials with the approved checkpoint inhibitors.
BL-5010
BL-5010 competes with a variety of approved destructive and non-destructive treatments for skin lesions. Both Endwarts® (Meda Health) and Eskata® (Aclaris
therapeutics) are medical device-based treatments marketed for removal of warts.
Insurance
We maintain insurance for our offices and laboratory in Israel. This insurance covers approximately NIS 15.8 million (approximately $4.5 million) of equipment,
consumables and lease improvements against risk of fire, lightning, natural perils and burglary (the latter coverage limited to NIS 790,500 (approximately $225,000)), and NIS
4.6 million (approximately $1.3 million) of consequential damages (covering fixed damages and extra expenses). For our clinical activities, we carry life science liability
insurance covering general liability with an annual coverage amount of $30.0 million per occurrence and product liability and clinical trials coverage with an annual coverage
amount of $30.0 million each claim and in the aggregate. The annual aggregate as well as the maximum indemnity for a single occurrence, claim or circumstances under this
insurance is $30.0 million. In addition, we maintain the following insurance: employer’s liability with coverage of NIS 31.0 million (approximately $8.8 million) for each
occurrence and in the aggregate; third-party liability with coverage of NIS 15.5 million (approximately $4.4 million) for each occurrence and in the aggregate; all risk
coverage of approximately NIS 8.0 million (approximately $2.3 million) for electronic and mechanical equipment; directors’ and officers’ liability with coverage of $15.0
million for each claim and in the aggregate; stock throughput insurance covering the API, clinical trials materials; and a global travel insurance policy.
We procure stock throughput insurance (cargo marine) coverage when we ship substances for our clinical studies. Such insurance is customized to the special
requirements of the applicable shipment, such as temperature and/or climate sensitivity. If required, we insure the substances to the extent they are stored in central depots and
at clinical sites.
We believe that the amounts of our insurance policies are adequate and customary for a business of our kind. However, because of the nature of our business, we
cannot assure you that we will be able to maintain insurance on a commercially reasonable basis or at all, or that any future claims will not exceed our insurance coverage.
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Environmental Matters
We are subject to various environmental, health and safety laws and regulations, including those governing air emissions, water and wastewater discharges, noise
emissions, the use, management and disposal of hazardous, radioactive and biological materials and wastes and the cleanup of contaminated sites. We believe that our
business, operations and facilities are being operated in compliance in all material respects with applicable environmental and health and safety laws and regulations. Based on
information currently available to us, we do not expect environmental costs and contingencies to have a material adverse effect on us. The operation of our facilities, however,
entails risks in these areas. Significant expenditures could be required in the future if we are required to comply with new or more stringent environmental or health and safety
laws, regulations or requirements. See “Business — Government Regulation and Funding — Israel Ministry of Environment — Toxin Permit.”
Government Regulation and Funding
We operate in a highly controlled regulatory environment. Stringent regulations establish requirements relating to analytical, toxicological and clinical standards and
protocols in respect of the testing of pharmaceuticals and medical devices. Regulations also cover research, development, manufacturing and reporting procedures, both pre-
and post-approval. In many markets, especially in Europe, marketing and pricing strategies are subject to national legislation or administrative practices that include
requirements to demonstrate not only the quality, safety and efficacy of a new product, but also its cost-effectiveness relating to other treatment options. Failure to comply with
regulations can result in stringent sanctions, including product recalls, withdrawal of approvals, seizure of products and criminal prosecution.
Before obtaining regulatory approvals for the commercial sale of our therapeutic candidates, we or our licensees must demonstrate through preclinical studies and
clinical trials that our therapeutic candidates are safe and effective. Historically, the results from nonclinical studies and early clinical trials often have not accurately predicted
results of later clinical trials. In addition, a number of pharmaceutical products have shown promising results in early clinical trials but subsequently failed to establish
sufficient safety and efficacy results to obtain necessary regulatory approvals. We have incurred and will continue to incur substantial expense for, and devote a significant
amount of time to, preclinical studies and clinical trials. Many factors can delay the commencement and rate of completion of clinical trials, including the inability to recruit
patients at the expected rate, the inability to follow patients adequately after treatment, the failure to manufacture sufficient quantities of materials used for clinical trials, and
the emergence of unforeseen safety issues and governmental and regulatory delays. If a therapeutic candidate fails to demonstrate safety and efficacy in clinical trials, this
failure may delay development of other therapeutic candidates and hinder our ability to conduct related preclinical studies and clinical trials. Additionally, as a result of these
failures, we may also be unable to find additional licensees or obtain additional financing.
Governmental authorities in all major markets require that a new pharmaceutical product or medical device be approved or exempted from approval before it is
marketed, and have established high standards for technical appraisal, which can result in an expensive and lengthy approval process. The time to obtain approval varies by
country. In the past, it generally took from six months to four years from the application date, depending upon the quality of the results produced, the degree of control
exercised by the regulatory authority, the efficiency of the review procedure and the nature of the product. Some products are never approved. In recent years, there has been a
trend towards shorter regulatory review times in the United States as well as certain European countries, despite increased regulation and higher quality, safety and efficacy
standards.
Historically, different requirements by different countries’ regulatory authorities have influenced the submission of applications. However, a trend toward
harmonization of drug and medical device approval standards, starting in individual countries in Europe and then in the EU as a whole, in Japan, the United Kingdom and in
the United States under the aegis of what is now known as the International Council on Harmonisation, or ICH (created as the International Conference on Harmonisation in
1990), is gradually narrowing these differences. In many cases, compliance with ICH standards can help avoid duplication of non-clinical and clinical trials and enable
companies to use the same basis for submissions to each of the respective regulatory authorities. The adoption of the Common Technical Document format by the ICH has
greatly facilitated use of a single regulatory submission for seeking approval in the ICH regions and many other countries worldwide.
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Summaries of the United States, EU, United Kingdom and Israeli regulatory processes follow below.
United States
In the United States, drugs are subject to rigorous regulation by the FDA. The U.S. Federal Food, Drug and Cosmetic Act, or FDCA, and other federal and state
statutes and regulations govern, among other things, the research, development, testing, manufacture, storage, record-keeping, packaging, labeling, adverse event reporting,
advertising, promotion, marketing, distribution and import and export of pharmaceutical products. Failure to comply with the applicable U.S. requirements may subject us to
stringent administrative or judicial sanctions, such as agency refusal to approve pending applications, warning letters, product recalls, product seizures, total or partial
suspension of production or distribution, injunctions or criminal prosecution.
Unless a drug is exempt from the NDA process or the Biologics License Application, or BLA, process or subject to another regulatory procedure, the steps required
before a drug may be marketed in the United States include:
•
•
•
•
•
•
preclinical laboratory tests, animal studies and formulation development;
submission to the FDA of an Investigational New Drug, or IND, application to conduct human clinical testing;
adequate and well controlled clinical trials to determine the safety and efficacy of the drug for each indication as well as to establish the exposure levels;
submission to the FDA of an application for marketing approval;
satisfactory completion of an FDA inspection of the manufacturing facility or facilities at which the drug is manufactured; and
FDA review and approval of the drug and drug labeling for marketing.
Preclinical studies include laboratory evaluation of product chemistry, toxicity, formulation and stability, as well as animal studies. For preclinical studies conducted
in the United States, and certain studies carried out outside the United States, we submit the results of the nonclinical studies, together with manufacturing information and
analytical results, to the FDA as part of an IND, which must become effective before we may commence human clinical trials.
Clinical Trials (INDs)
Clinical trials involve the administration of the investigational drug to people under the supervision of qualified investigators in accordance with the principles of
good clinical practice, or GCP. We conduct clinical trials under protocols detailing the trial objectives, the parameters to be used in monitoring safety, and the effectiveness
criteria to be evaluated. We must submit each U.S. study protocol to the FDA as part of an IND. An IND will automatically become effective 30 days after receipt by the FDA,
unless before that time the FDA raises concerns or questions about issues such as the conduct of the trials as outlined in the IND. In such a case, the IND sponsor and the FDA
must resolve any outstanding FDA concerns or questions before clinical trials can proceed. Submission of an IND does not always result in the FDA allowing clinical trials to
commence and the FDA may halt a clinical trial if unexpected safety issues surface or the study is not being conducted in compliance with applicable requirements.
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The FDA may refuse to accept an IND for review if applicable regulatory requirements are not met. Moreover, the FDA may delay or prevent the start of clinical
trials if the manufacturing of the study drug fails to meet cGMP requirements or the clinical trials are not adequately designed. Such government regulation may delay or
prevent the study and marketing of potential products for a considerable time period and may impose costly procedures upon a manufacturer’s activities. In addition, the FDA
may, at any time, impose a clinical hold on ongoing clinical trials. If the FDA imposes a clinical hold, clinical trials cannot continue without FDA authorization and then only
under terms authorized by the FDA.
Success in early-stage clinical trials does not assure success in later-stage clinical trials. Results obtained from clinical activities are not always conclusive and may be
susceptible to varying interpretations that could delay, limit or prevent regulatory approval. Even if a therapeutic candidate receives regulatory approval, later discovery of
previously unknown problems with a product may result in restrictions on the product or even withdrawal of marketing approval for the product.
Foreign clinical trials may or may not be conducted under an IND. However, their safety assessments should be submitted annually.
We conduct clinical trials typically in three sequential phases (1-3), but the phases may overlap or be combined. An institutional review board, or IRB, must review
and approve each trial before it can begin. Phase 1 includes the initial administration of a tested drug to a small number of humans. These trials are closely monitored and may
be conducted in patients but are usually conducted in healthy volunteer subjects. These trials are designed to determine the metabolic and pharmacologic actions of the drug in
humans and the side effects associated with increasing doses as well as, if possible, to gain early evidence on effectiveness. Phase 2 usually involves trials in a limited patient
population to evaluate dosage tolerance and appropriate dosage, identify possible adverse effects and safety risks and preliminarily evaluate the efficacy of the drug for
specific indications. Phase 3 trials are large trials used to further evaluate clinical efficacy and test further for safety by using the drug in its final form in an expanded patient
population. There can be no assurance that we or our licensees will successfully complete Phase 1, Phase 2 or Phase 3 testing with respect to any therapeutic candidate within
any specified period of time, if at all. Furthermore, clinical trials may be suspended at any time on various grounds, including a finding that the subjects or patients are being
exposed to an unacceptable health risk. We and our licensees perform some of our nonclinical and clinical testing outside of the United States. The acceptability of the results
of our preclinical and clinical testing by the FDA will be dependent upon adherence to applicable U.S. and foreign standards and requirements, including GLP, GCP and the
Declaration of Helsinki for protection of human subjects.
Marketing Applications (NDAs and BLAs)
After successful completion of the required clinical testing, an NDA, or in the case of certain biological products a BLA, is prepared and submitted to the FDA. FDA
approval of the NDA or BLA is required before product marketing may begin in the United States. The NDA/BLA must include the preclinical and clinical testing results and
a compilation of detailed information relating to the product’s pharmacology, toxicology, chemistry, manufacture and manufacturing controls. The cost of preparing and
submitting an NDA may be substantial. Under U.S. federal law, the submission of NDAs is generally subject to substantial application user fees, and the manufacturer and/or
sponsor under an NDA approved by the FDA is also subject to annual product and establishment user fees. These fees are typically increased annually.
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The FDA has 60 days from its receipt of an NDA/BLA to determine whether the application will be accepted for filing based on the FDA threshold determination
that the application is sufficiently complete to permit substantive review. Once the submission is accepted for filing, the FDA begins an in-depth review of the submitted
application. Under U.S. federal law, the FDA has agreed to certain performance goals in the review of NDAs/BLAs. Most such applications for non-priority drug products are
to be reviewed within 10 months. The review process may be significantly extended by FDA requests for additional information or clarification or if the applicant submits a
major amendment during the review. The FDA may also refer applications to an advisory committee, typically a panel that includes clinicians and other experts, for review,
evaluation and a recommendation as to whether the application should be approved. This often, but not exclusively, occurs for novel drug products or drug products that
present difficult questions of safety or efficacy. The FDA is not bound by the recommendation of an advisory committee.
Before approving an application, the FDA typically will inspect the facility or facilities where the product is manufactured. The FDA will not approve the application
unless the FDA determines that the product is manufactured in substantial compliance with cGMP. If the FDA determines that the NDA or BLA is supported by adequate data
and information, the FDA may issue an approval letter. During review, the FDA may request additional information via an information request, or IR letter, or state
deficiencies via a deficiency letter, or DR letter. Upon compliance with the conditions stated, the FDA will typically issue an approval letter. An approval letter authorizes
commercial marketing of the drug with specific prescribing information for specific indications. As a condition of approval, the FDA may require additional trials or post-
approval testing and surveillance to monitor the drug’s safety or efficacy, the adoption of risk evaluation and mitigation strategies, and may impose other conditions, including
labeling and marketing restrictions on the use of the drug, which can materially affect its potential market and profitability. Once granted, product approvals may be withdrawn
if compliance with regulatory standards for manufacturing and quality control are not maintained or if additional safety problems are identified following initial marketing.
If the FDA’s evaluation of the NDA or BLA submission or manufacturing processes and facilities is not favorable, the FDA may refuse to approve the NDA or BLA
and may issue a complete response letter. The complete response letter, or CRL, indicates that the review cycle for an application is complete and that the application is not
ready for approval. The complete response letter will describe specific deficiencies and, when possible, will outline recommended actions the applicant might take in order to
place the application in condition for approval. Following receipt of a CRL, the company may submit additional information and start a new review cycle, withdraw the
application or request a hearing. Failure to take any of the above actions may result in the FDA considering the application withdrawn following one year from issuance of the
CRL. In such cases, the FDA will notify the company and the company will have 30 days to respond and request an extension of time in which to resubmit the application.
The FDA may grant reasonable requests for extension. If the company does not respond within 30 days of the FDA’s notification, the application will be considered
withdrawn. Even with submission of additional information for a new review cycle, the FDA ultimately may decide that the application does not satisfy the regulatory criteria
for approval.
The Pediatric Research Equity Act, or PREA, requires NDAs and BLAs (or supplements) for a new active ingredient, new indication, new dosage form, new dosing
regimen or new route of administration to contain results assessing the safety and efficacy for the claimed indication in all relevant pediatric subpopulations. Data to support
dosing and administration also must be provided for each pediatric subpopulation for which the drug is safe and effective. The FDA may grant deferrals for the submission of
results or full or partial waivers from the PREA requirements (for example, if the product is ready for approval in adults before pediatric studies are complete, if additional
safety data is needed, among others). In addition, under the Best Pharmaceuticals for Children Act, or BPCA, the FDA may issue a written request to the company to conduct
clinical trials in the pediatric population that are related to the moiety and expand on the claimed indication. The studies are voluntary but may award the company with 6
months of marketing exclusivity if conducted according to good scientific principles and address the written request. Finally, a sponsor can request that a product that must be
studied under PREA to be studied also under the BPCA to allow the sponsor to be eligible for six-months of pediatric exclusivity. The pediatric studies requested under BPCA
are usually more extensive and would generally also fulfill the PREA requirement; however, even if the sponsor does not complete the studies outlined in the BPCA written
request, it is still required to complete any studies required under PREA.
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Post-Marketing Requirements
Once an NDA or BLA is approved, the drug sponsor will be subject to certain post-approval requirements, including requirements for adverse event reporting,
submission of periodic reports, manufacturing, labeling, packaging, advertising, promotion, distribution, record-keeping and other requirements. For example, the approval
may be subject to limitations on the uses for which the product may be marketed or conditions of approval, or contain requirements for costly post-marketing testing and
surveillance to monitor the safety or efficacy of the product or require the adoption of risk evaluation and mitigation strategies. In addition, the FDA requires the reporting of
any adverse effects observed after the approval or marketing of a therapeutic candidate and such events could result in limitations on the use of such approved product or its
withdrawal from the marketplace. Also, some types of changes to the approved product, such as manufacturing changes and labeling claims, are subject to further FDA review
and approval. Additionally, the FDA strictly regulates the promotional claims that may be made about prescription drug products. In particular, the FDA requires
substantiation of any claims of superiority of one product over another including, in many cases, requirements that such claims be proven by adequate and well controlled
head-to-head clinical trials. To the extent that market acceptance of our therapeutic candidates may depend on their superiority over existing products, any restriction on our
ability to advertise or otherwise promote claims of superiority, or any requirements to conduct additional expensive clinical trials to provide proof of such claims, could
negatively affect the sales of our therapeutic candidates and our costs.
Orphan Drug Designation
The Orphan Drug Act, or ODA, provides for granting special status to a drug or biological product to treat a rare disease or condition (i.e., a disease or condition that
affects fewer than 200,000 individuals in the United States) upon request of a sponsor. This status is referred to as orphan designation (or sometimes “orphan status”). For a
therapeutic candidate to qualify for orphan designation, both the candidate and the disease or condition must meet certain criteria specified in the ODA’s implementing
regulations (set forth at 21 CFR Part 316). Orphan designation qualifies the sponsor of the candidate for various development incentives of the ODA, including tax credits for
qualified clinical testing, waiver of NDA/BLA user fees and eligibility for seven-year marketing exclusivity, referred to as orphan exclusivity upon marketing approval. The
granting of an orphan designation request does not alter the standard regulatory requirements and process for obtaining marketing approval. Safety and effectiveness of a
candidate must still be established through adequate and well-controlled studies.
Expedited Programs for Serious Conditions
The FDA has put in place four programs intended to facilitate and expedite development and review of a new drug intended to address an unmet medical need in the
treatment of a serious or life-threatening condition: fast track designation, breakthrough therapy designation, accelerated approval and priority review designation. Each
program offers the sponsor a defined set of opportunities such as expedited development and review, intensive FDA guidance during development, marketing approval based
on an effect on a surrogate endpoint or an intermediate clinical endpoint that is reasonably likely to predict the drug’s clinical benefit, and a shorter time for review of
marketing application. Fast Track and Breakthrough Therapy designations may be requested during development, while Accelerated Approval and Priority Review relate to
the marketing approval stage.
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European Union/European Economic Area
Clinical Trials
Within the European Union (EU) and the European Economic Area (EEA), which is composed of the 27 member states of the EU plus Norway, Iceland and
Liechtenstein, the authorization of clinical trials occurs at member state level. The European Medicines Agency, or EMA, plays a key role in ensuring that GCP standards are
applied across the European Economic Area, or EEA in cooperation with the member states. It also manages a database of clinical trials carried out in the EU.
Clinical trials in the EU are now regulated under Regulation (EU) 536/2014, or the CTR. As opposed to the former law, Directive 2001/20/EC, or CTD, which as an
EU directive was not directly applicable in the member states, the CTR has immediate effect and does not have to be transposed into national law. While national law
transposing the CTD varied to a great extent, the CTR aims at significant further harmonization of the law governing clinical trials in the EU. After significant delay, the CTR
has now become applicable on January 31, 2022. The CTR further harmonizes the assessment and supervision processes for clinical trials throughout the EU via a Clinical
Trials Information System, or CTIS, which includes a centralized EU portal and database for clinical trials. The exact timing of the Regulation’s application depends on
confirmation of full functionality of CTIS through an independent audit. The CTR will become applicable six months after the European Commission publishes notice of this
confirmation. The CTR provides inter alia:
•
Consistent rules for conducting clinical trials throughout the EU;
• Making information on the authorization, conduct and results of each clinical trial carried out in the EU publicly available;
•
•
•
•
Harmonized electronic submission and assessment process for clinical trials conducted in multiple member states;
Improved collaboration, information sharing and decision-making between and within member states;
Increased transparency of information on clinical trials; and
Higher standards of safety for all participants in EU clinical trials.
The authorization of a clinical trial (Phase I-III) in an EU member state requires the submission of a clinical trial application (CTA) via the EU Portal. The application
will be reviewed by the competent authorities of the member states where the trial is supposed to take place. The application and approval process is conducted by the member
states under the cooperation system set forth in the CTR. Particularities under member states’ national law still apply to some extent. In general, the CTA should include,
among other documents, the study protocol, results of the nonclinical studies and manufacturing information and analytical results. Also, the sponsor has to suggest one of the
concerned member states as reporting member state. The CTR aims at speeding up the validation and review of clinical trial applications and therefore provides strict
deadlines.
Marketing Authorization Procedures
A medicinal product may only be placed on the market in the EEA if it has obtained a marketing authorization according to the applicable EU and/or member state
law. A marketing authorization may either be granted in a national procedure, or in a coordinated procedure of several member states pursuant to Directive 2001/83/EC, as
amended, or under the centralized EU procedure in accordance with Regulation (EC) No. 726/2004, as amended, or its predecessor, Regulation 2309/93. Depending on the
nature of the medicinal product, several different legal frameworks of the EU and the member states may be relevant for the market clearance.
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Centralized Procedure (CP)
The Centralized Procedure according to Regulation 726/2004/EC allows a marketing authorization holder to market the medicine and make it available to patients
and healthcare professionals throughout the entire EEA on the basis of a single marketing authorization, granted by the European Commission, acting in its capacity as the
European Licensing Authority on the advice of the EMA. The EMA is the administrative body responsible for coordinating the existing scientific resources available in the
member states for evaluation, supervision and pharmacovigilance of medicinal products. Certain medicinal products (e.g., products derived from biotechnology, orphan
medicinal products and medicinal products for human use, which contain an active substance authorized in the Union after 20 May 2004 and which are intended for the
treatment of AIDS, cancer, neurodegenerative disorders or diabetes) must be authorized centrally. For each application submitted to the EMA for scientific assessment, the
EMA is required to ensure that the opinion of the Committee for Medicinal Products for Human Use, or CHMP, is given within 210 days after receipt of a valid application or
within 150 days by means of an accelerated procedure (excluding clock stops); the review period can be extended. If the opinion is positive, the EMA is required to send the
opinion to the European Commission, which is responsible for preparing the decision granting a marketing authorization. If the initial opinion of the CHMP is negative, the
applicant is afforded an opportunity to seek a re-examination of the opinion. The CHMP is required to re-examine its opinion within 60 days following receipt of the request
by the applicant. A refusal of a centralized marketing authorization constitutes a prohibition on placing the given medicinal product on the market in the EU.
The EMA’s Committee for Advanced Therapies (CAT) is responsible for assessing the quality, safety and efficacy of advanced therapy medicinal products (ATMP).
ATMP include gene therapy medicinal products, somatic cell therapy medicinal products and tissue engineered products. The role of the CAT is to prepare a draft opinion on
an application for marketing authorization for an ATMP candidate that is submitted to the EMA. The EMA then provides a final opinion regarding the application for
marketing authorization. The European Commission grants or refuses marketing authorization after the EMA has delivered its opinion. ATMP are further regulated under
Regulation (EC) No 1394/2007 on advanced therapy medicinal products.
National Authorization Procedure
A National Authorization Procedure is used when applying for a marketing authorization in one individual EEA state. The national procedure can only be used if the
medicinal product does not already have a marketing authorization in another EEA state.
Mutual Recognition Procedure (MRP)
The mutual recognition procedure (Art. 28 et seq. Directive 2001/83/EC) should be used if a medicinal product already has a marketing authorization in one EEA
member state, and the authorization holder would like to extend the authorization to other member states. An application for mutual recognition may be addressed to one or
more EEA countries. The country in which the national marketing authorization has been granted acts as the Reference Member State, and the other countries concerned
(Concerned Member States) can, upon successful completion of the procedure, recognize the marketing authorization. The assessment time is 180 days plus 30 days.
Decentralized Procedure (DCP)
The decentralized procedure (introduced by Directive 2004/27/EU) is used in cases where the medicinal product has not received a marketing authorization in the EU
at the time of application. It allows the common assessment of an application submitted simultaneously to several member states. One of the member states will take the lead
in evaluating the application as Reference Member State. The Reference Member State should prepare an assessment report that is then used to facilitate agreement with the
Concerned Member States and the grant of a national marketing authorization in all of these member states. The assessment time is 210 days + 30 days.
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Manufacturing Requirements
Any medicinal product placed on the market in the EEA must be manufactured in accordance with the principles of good manufacturing practice as set out in
Directive EC2017/1572 supplementing Directive 2001/83/EC of the European Parliament and of the Council as regards the principles and guidelines of good manufacturing
practice for medicinal products for human use for human use and Volume 4 of the “Rules Governing Medicinal Products in the European Community”. Directive
2017/1572/EU has replaced Directive 2003/94/EC. Directive 2003/94/EC will still be applicable to clinical trials conducted in accordance with the former regime under
transitional provisions. Furthermore, distribution of medicinal products in the EU is subject to Directive 2001/83/EC, 92/25/EEC and current guidance on good distribution
practice, or GDP. Moreover, EU law requires the clinical results in support of clinical safety and efficacy to be based upon clinical trials conducted in the EU in compliance
with the requirements of the CTR and Directive 2005/28/EC, which implement good clinical practice in the conduct of clinical trials on medicinal products for human use.
Clinical trials conducted outside the EU and used to support applications for marketing within the EU must have been conducted in a way consistent with the principles set out
in the CTR or if conducted prior to 31 January 2022, its predecessor Directive 2001/20/EC. The conduct of a clinical trial in the EU requires, pursuant to the CTR,
authorization by the relevant national competent authority where a trial takes place, and an ethics committee to have issued a favorable opinion in relation to the arrangements
for the trial. It also requires that the sponsor of the trial, or a person authorized to act on his behalf in relation to the trial, be established in the EU.
Law Relating to Pediatric Research
Regulation (EC) 1901/2006 (as amended by Regulation (EC) 1902/2006 and Regulation (EU) 2019/5), or the Pediatric Regulation, was adopted on December 12,
2006. This Regulation governs the development of medicinal products for human use in order to meet the specific therapeutic needs of the pediatric population (children aged
0 to 17 years). It requires any application for marketing authorization made after July 26, 2008 in respect of a medicinal product not authorized in the EU on January 26, 2007,
the time the Regulation entered into force, to include studies in children conducted in accordance with a pediatric investigation plan agreed to by the relevant European
authorities. This does not apply if the product is subject to an agreed waiver or deferral or if the product is excluded from the scope of Regulation 1901/2006, which is the case
for inter alia generics, homeopathic and traditional (herbal) medicinal products. Waivers can be granted in certain circumstances where pediatric studies are not required or
desirable. Deferrals can be granted in certain circumstances where the initiation or completion of pediatric studies should be deferred until appropriate studies in adults have
been performed. Moreover, this regulation imposes the same obligation from January 26, 2009 on an applicant seeking approval of a new indication, pharmaceutical form or
route of administration for a product already authorized and still protected by a supplementary protection certificate granted under Regulation (EC) no. 469/2009 or its
precursor Regulation (EEC) 1768/92 by a patent that qualifies for the granting of such a supplementary protection certificate. The pediatric Regulation 1901/2006 also
provides, subject to certain conditions, a reward for performing such pediatric studies, regardless of whether the pediatric results provided resulted in the grant of a pediatric
indication. This reward comes in the form of an extension of six months to the supplementary protection certificate granted in respect of the product, unless the product is
subject to Orphan Drug designation, in which case the 10-year market exclusivity period for such orphan products is extended to 12 years. If any of the non-centralized
procedures for marketing authorization have been used, the six-month extension of the supplementary protection certificate is only granted if the medicinal product is
authorized in all member states. Where the product is no longer covered by a patent or supplementary protection certificate, the applicant may make a separate application for
a Pediatric Use Marketing Authorization, or PUMA, which, on approval, will provide eight years’ protection for data and 10 years’ marketing protection for the pediatric
results.
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Post-authorization Obligations
An authorization to market a medicinal product in the EU carries with it an obligation to comply with many post-authorization regulations relating to the marketing
and other activities of authorization holders. These include requirements relating to provision of a risk management plan and provision of annual periodic safety update
reports, carrying out of post-authorization efficacy studies and/or post-authorization safety studies, maintenance of a pharmacovigilance system master file, adverse event
reporting, signal detection and management and other pharmacovigilance activities conducted under an established quality system, advertising, packaging and labelling,
patient package leaflets, and distribution. The regulations frequently operate within a criminal law framework, and failure to comply with the requirements may not only affect
the authorization, but also can lead to financial and other sanctions levied on the company in question and responsible officers. EU pharmacovigilance legislation has been
significantly modified by the Pharmacovigilance Directive, Directive 2010/84/EU which amended the legal framework of pharmacovigilance for medicines marketed within
the EU provided in Regulation (EC) No 726/2004 with respect to EU authorized medicinal products and in Directive 2001/83/EC with respect to nationally authorized
medicinal products (including those authorized through the mutual recognition and decentralized systems). Furthermore, EU good pharmacovigilance practice (GVP) rules
apply. With the amended pharmacovigilance requirements, the financial and organizational burden on market authorization holders increased significantly, such as the
obligation to maintain a pharmacovigilance system master file that applies to all holders of marketing authorizations granted in accordance with Directive 2001/83/EC or
Regulation (EC) No 726/2004. Marketing authorization holders must furthermore collect data on adverse events associated with use of the authorized product outside the
scope of the authorization. Pharmacovigilance for biological products and medicines with a new active substance is strengthened by subjecting their authorization to additional
monitoring activities.
Another relevant aspect in the EU regulatory framework is the “sunset clause”: a provision leading to the cessation of the validity of any marketing authorization if it
is not followed by marketing within three years or, if marketing is interrupted for a period of three consecutive years.
Data Privacy in the EU
The EU has a strict regime on data privacy under the General Regulation on Data Protection, Regulation 2016/679 (GDPR) that has become applicable on May 25,
2018. The GDPR as an EU regulation does not have to be implemented into member states’ national law but applies directly in all member states. It applies to companies with
an establishment in the European Economic Area (EEA) that includes the 27 member states of the EU and Norway, Iceland and Liechtenstein. Furthermore, the GDPR applies
to companies not located in the EEA but processing personal data of individuals located in the EEA (e.g., through online business). The GDPR implements stringent
operational requirements for controllers of personal data, including, for example, obligations to justify the collection, use and other processing of personal data (e.g., based on
the individual’s consent), to notify the individuals concerned about data processing activities, to protect all processed personal data through appropriate technical and
organizational measures, and to implement a data protection compliance management. Furthermore, the GDPR defines high data security and compliance standards for the
transfer of personal data to third countries, including the U.S. The operational requirements under the GDPR are even stricter in case of sensitive personal data, such as health
or genetic data, that typically have to be stored in a pseudonymized (i.e., key-coded) manner. The GDPR provides that EU member states may in certain areas deviate from
GDPR standards which results in varying laws and regulations at member states level. The applicable data protection laws in the EEA may limit our ability to share and
otherwise process personal data. If our business falls below the GDPR standards, we may be subject to severe administrative fines (under the GDPR, in the amount of up to
4 % of the total worldwide annual turnover of our preceding financial year) and suffer significant loss of reputation.
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United Kingdom
Effect of Brexit and Changed Legislation
The withdrawal of the United Kingdom (UK) from the EU took effect on January 1, 2021 (Brexit), and there are 27 member states remaining in the EU. As of
January 1, 2021, the UK is a “third country” with regard to the EU (subject to the terms of the EU UK Trade Agreement) and EU law ceased to apply directly in the UK.
However, the UK has retained the EU regulatory regime as standalone UK legislation with some amendments to reflect procedural and other requirements with respect to
marketing authorizations and other regulatory provisions. Therefore, the UK regulatory regime with respect to medicines and medical devices is currently similar to EU
regulations, but under new legislation, the Medicines and Medical Devices Act 2021, the UK may adopt changed regulations that may diverge from the EU legislative regime
for medicines and their research, development and commercialization, medical devices and clinical trials. The separate UK regulatory system for these areas, albeit with
transitional recognition procedures in the UK, may lead to additional regulatory costs.
In order to market a medicinal product in the United Kingdom, a license or marketing authorization must be obtained from the United Kingdom Medicines and
Healthcare Products Regulatory Agency, or MHRA. The United Kingdom legislation includes multiple assessment routes for applications for medicinal products, including a
150-day national assessment or a rolling review application. Further, and for a transitional period until 31 December 2022, the MHRA may rely on a decision taken by the
European Commission on the approval of a new marketing authorization in the centralized procedure. In addition, the MHRA has the power to have regard to marketing
authorizations approved in EU member states.
The MHRA reviews applications for orphan designation at the time of a marketing authorization application or as part of a subsequent variation to that authorization.
To qualify for orphan designation, a medicine must meet certain criteria in the United Kingdom including that the medicine for the treatment, prevention or diagnosis of a
disease that is life-threatening or chronically debilitating, the prevalence of the condition must not be more than 5 in 10,000 or it must be unlikely that the marketing would
generate sufficient returns to justify investment and no satisfactory method of diagnosis, prevention or treatment must exist in Great Britain or, if such a method exists the
medicine must be of significant benefit to those affected by the condition. On grant of a marketing authorization with orphan status, the medicinal product will benefit from up
to 10 years of market exclusivity from similar products in the approved orphan indication starting from the date of first approval of the product in Great Britain.
The United Kingdom has adopted new legislation, the Medicines and Medical Devices Act 2021 and may make changes to the licensing or authorization of
medicines in the future.
Clinical Trials
As a consequence of Brexit, the United Kingdom has not adopted the new EU Regulation on Clinical Trials (Reg. EU No. 536/2014), or CTR, that became applicable
on 31 January 2022. The rules with respect to clinical trials in the United Kingdom are therefore different from those in the EU and are based on previous EU legislation. In
January 2022, the United Kingdom issued a consultation with respect to changes to clinical trial legislation.
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Data Privacy in the EU
The UK’s data protection regime is currently based on the GDPR which continues to form part of law in the United Kingdom with some amendments following
Brexit although there is a risk of divergence in the future which may increase our overall data protection compliance cost.
Israel
Israel Ministry of the Environment — Toxin Permit
In accordance with the Israeli Dangerous Substances Law - 1993, the Israeli Ministry of the Environment is required to grant a permit in order to use toxic materials.
Because we utilize toxic materials in the course of operation of our laboratories, we were required to apply for a permit to use these materials. Our current toxin permit will
remain in effect until February 2025.
Clinical Testing in Israel
In order to conduct clinical testing on humans in Israel, special authorization must first be obtained from the ethics committee and the head of the medical center in
which the clinical studies are planned to be conducted, as required under the Guidelines for Clinical Trials in Human Subjects implemented pursuant to the Israeli Public
Health Regulations (Clinical Trials in Human Subjects), as amended from time to time, and other applicable legislation. These regulations require authorization by the
institutional ethics committee and the head of the medical center. Israeli Ministry of Health, except for certain circumstances, is required to approve each trial as well. . The
institutional ethics committee must, among other things, evaluate the anticipated benefits that are likely to be derived from the project to determine if it justifies the risks and
inconvenience to be inflicted on the human subjects, and the committee must ensure that adequate protection exists for the rights and safety of the participants as well as the
accuracy of the information gathered in the course of the clinical testing. Since we intend to perform a portion of the clinical studies on certain of our therapeutic candidates in
Israel, we will be required to obtain authorization from the ethics committee and head of medical center of each institution in which we intend to conduct our clinical trials,
and in most cases, from the Israeli Ministry of Health.
Other Countries
In addition to regulations in the United States, the EU and Israel, we are subject to a variety of other regulations governing clinical trials and commercial sales and
distribution of drugs in other countries. Whether or not our products receive approval from the FDA, approval of such products must be obtained by the comparable regulatory
authorities of countries other than the United States before we can commence clinical trials or marketing of the product in those countries. The approval process varies from
country to country, and the time may be longer or shorter than that required for FDA approval. The requirements governing the conduct of clinical trials and product licensing
vary greatly from country to country.
Related Matters
From time to time, legislation is drafted, introduced and passed in governmental bodies that could significantly change the statutory provisions governing the
approval, manufacturing and marketing of products regulated by the FDA or EMA and other applicable regulatory bodies to which we are subject. In addition, regulations and
guidance are often revised or reinterpreted by the national agency in ways that may significantly affect our business and our therapeutic candidates. It is impossible to predict
whether such legislative changes will be enacted, whether FDA or EMA regulations, guidance or interpretations will change, or what the impact of such changes, if any, may
be. We may need to adapt our business and therapeutic candidates and products to changes that occur in the future.
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Israeli Government Programs
Israel Innovation Authority
Research and Development Grants. A number of our therapeutic products have been financed, in part, through funding from the IIA in accordance with Research
Law. Through December 31, 2022 we have received approximately $22.0 million in aggregate funding from the IIA and have paid the IIA approximately $7.0 million in
royalties under our approved programs. As of December 31, 2022, we have no contingent obligation to the IIA other than for motixafortide. In connection with the in-licensing
of motixafortide from Biokine, and as a condition to IIA consent to the transaction, we agreed to abide by any obligations resulting from funds previously received by Biokine
from the IIA. The contingent liability to the IIA assumed by us relating to this transaction (which liability has no relation to the funding actually received by us) amounts to
$3.7 million as of December 31, 2022. We have a full right of offset for amounts payable to the IIA from payments that we may owe to Biokine in the future.
Under the Research Law and the terms of the grants, royalties on the revenues derived from sales of products developed with the support of the IIA were payable to
the Israeli government, generally at the rate of 3% although these terms would be different if we were to receive IIA approval to manufacture or to transfer the rights to
manufacture our products developed with IIA grants outside of Israel. The obligation to make these payments terminates upon repayment of the amount of the received grants
as adjusted for fluctuation in the dollar/shekel exchange rate, plus interest and any additional amounts as described below.
Pursuant to the Research Law and the tracks published by the IIA, recipients of funding from the IIA are prohibited from manufacturing products developed using
IIA grants or derived from technology developed with IIA grants outside of Israel and from transferring rights to manufacture such products outside of Israel. However, the
IIA could, in special cases, approve the transfer of manufacture or of manufacturing rights of a product developed in an approved program or which resulted therefrom,
outside of Israel. If we were to receive approval to manufacture or to transfer the rights to manufacture our products developed with IIA grants outside of Israel, we would be
required to pay an increased total amount of royalties (possibly up to 300% of the grant amounts plus interest), depending on the portion of total manufacturing that was
performed outside of Israel. In addition, the royalty rate applicable to us could possibly increase. Such increased royalties constituted the total repayment amount required in
connection with the transfer of manufacturing rights of IIA-funded products outside Israel. The tracks published by the IIA do enable companies to seek prior approval for
conducting manufacturing activities outside of Israel without being subject to increased royalties (but resulting in a lower grant amount).
Under the Research Law and the tracks published by the IIA, we are prohibited from transferring or licensing our IIA-financed technologies, technologies derived
therefrom and related intellectual property rights and know-how outside of Israel except under limited circumstances and only with the approval of the IIA and generally upon
making a payment to the IIA. The required approvals may not be received for any proposed transfer and, if received, we could be required to pay the IIA an amount calculated
in accordance with the applicable formula set out in the tracks published by the IIA. The scope of the support received, the royalties that we already paid to the IIA, the
amount of time that elapsed between the date on which the technology was transferred and the date on which the applicable project performance period for the IIA grants was
completed, and the sale price and the form of transaction are to be taken into account in order to calculate the amount of the payment to the IIA. The repayment amount is
subject to a maximum limit calculated in accordance with a formula set forth in guidelines published by the IIA. In addition, any decrease in the percentage of manufacture
performed in Israel of any product or technology, as originally declared in the application to the IIA with respect to the product or technology, could require us to notify, or to
obtain the approval of, the IIA, and could result in increased royalty payments to the IIA of up to 300% of the total grant amounts received in connection with the product or
technology, plus interest, depending on the portion of total manufacturing that was performed outside of Israel.
Approval of the transfer or license of technology to residents of Israel is required and could be granted in specific circumstances, but only if the recipient agrees to
abide by the provisions of applicable laws, including the restrictions on the transfer of know-how and the obligation to pay royalties. Additionally, a royalty payment is
generally required to be made from the consideration paid for such transfer.
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The State of Israel does not own intellectual property rights in technology developed with IIA funding and there is no restriction on the export of products
manufactured using technology and know-how developed with IIA funding. The technology and know-how are, however, subject to transfer of technology and manufacturing
rights restrictions as described above.
Israel Ministry of Health
Israel’s Ministry of Health, which regulates medical testing, has adopted protocols that correspond, generally, to those of the FDA and the EMA, making it
comparatively straightforward for studies conducted in Israel to satisfy FDA and the EMA requirements, thereby enabling medical technologies subjected to clinical trials in
Israel to reach U.S. and EU commercial markets in an expedited fashion. Many members of Israel’s medical community have earned international prestige in their chosen
fields of expertise and routinely collaborate, teach and lecture at leading medical centers throughout the world. Israel also has free trade agreements with the United States and
the EU.
C. Organizational Structure
Our corporate structure consists of BioLineRx Ltd., one wholly owned subsidiary, BioLineRx USA, Inc., and a substantially wholly owned U.K. subsidiary,
Agalimmune Ltd.
D. Property, Plant and Equipment
We are headquartered in Modi’in, Israel. We entered into a lease agreement in August 2014, for an aggregate of 1,663 square meters (approximately 17,900 square
feet) of space. Monthly rent is NIS 120,300 (approximately $34,000), including maintenance fees and parking. The initial term of the lease expired in June 2020, and we
exercised our option to extend the lease through June 30, 2025. We have the option to extend the lease for two additional lease periods totaling up to an additional 5 years,
each option at a 5% increase to the preceding lease payment amount.
This facility houses both our administrative and research operations and our central laboratory. The central laboratory consists of approximately 380 square meters
(approximately 4,200 square feet) and includes a bioanalytical laboratory, a formulation laboratory and a tissue culture laboratory. Our bioanalytical laboratory has received
GLP certification.
In addition, in October, 2022, we entered into a lease agreement for our office in Waltham, Massachusetts for an aggregate of 4,880 square feet of space. Monthly rent
is $23,600. The term of the lease expires in December 2024.
ITEM 4A. UNRESOLVED STAFF COMMENTS
None.
ITEM 5. OPERATING AND FINANCIAL REVIEW AND PROSPECTS
You should read the following discussion of our financial condition and results of operations in conjunction with the financial statements and the notes thereto
included elsewhere in this Annual Report on Form 20-F. The following discussion contains forward-looking statements that reflect our plans, estimates and beliefs. Our actual
results could differ materially from those discussed in the forward-looking statements. Factors that could cause or contribute to these differences include those discussed below
and elsewhere in this Annual Report on Form 20-F, particularly those in “Item 3. Key Information — Risk Factors.” Our discussion and analysis for the year ended December
31, 2021 can be found in our Annual Report on Form 20-F for the fiscal year ended December 31, 2021, filed with the SEC on March 16, 2022, as amended by Amendment
No. 1 to our Annual Report on Form 20-F for the fiscal year ended December 31, 2021, filed with the SEC on September 9, 2022. (File No. 001-35223).
73
We are a pre-commercial-stage biopharmaceutical company focused on oncology. Our current development and commercialization pipeline consists of two clinical-
stage therapeutic candidates – motixafortide (BL-8040), a novel peptide for the treatment of stem-cell mobilization and solid tumors, and AGI-134, an immuno-oncology
agent in development for solid tumors. In addition, we have an off-strategy, legacy therapeutic product called BL-5010 for the treatment of skin lesions. We have generated our
pipeline by systematically identifying, rigorously validating and in-licensing therapeutic candidates that we believe exhibit a high probability of therapeutic and commercial
success. To date, except for BL-5010, none of our therapeutic candidates have been approved for marketing or sold commercially. Our strategy includes commercializing our
therapeutic candidates through out-licensing arrangements with biotechnology and pharmaceutical companies and evaluating, on a case-by-case basis, the commercialization
of our therapeutic candidates independently. In this regard, we are currently executing on an independent commercialization plan for motixafortide in stem cell mobilization
for autologous bone marrow transplantation in multiple myeloma patients.
A. Operating Results
History of Losses
Since our inception in 2003, we have generated significant losses in connection with our research and development. As of December 31, 2022, we had an
accumulated deficit of $330.0 million. We may continue to generate losses in connection with the research and development activities relating to our pipeline of therapeutic
candidates. Such research and development activities are budgeted to expand over time and will require further resources if we are to be successful. As a result, we expect to
continue to incur operating losses, which may be substantial over the next several years, and we expect to need to obtain additional funds to further pursue our research and
development programs.
We have funded our operations primarily through the sale of equity securities (both in public and private offerings), funding received from the IIA, payments received
under out-licensing arrangements, and interest earned on investments. We expect to continue to fund our operations over the next several years through our existing cash
resources, the commercialization of our lead therapeutic candidate, motixafortide, if approved, potential future milestone and royalty payments that we may receive from our
existing out-licensing agreement, potential future upfront, milestone or royalty payments that we may receive from out-licensing transactions for our other therapeutic
candidates, potential revenues that we may receive from the direct commercialization of our other therapeutic candidates, interest earned on our investments, and additional
capital to be raised through public or private equity offerings or debt financings. As of December 31, 2022, we held $51.1 million of cash, cash equivalents and short-term
bank deposits.
Revenues
Our revenues to date have been generated primarily from milestone payments under previously existing out-licensing agreements.
We expect our revenues, if any, for the next several years to be derived primarily from the independent commercialization of motixafortide in stem cell mobilization,
if approved by the FDA, as well as payments from any future out- licensing agreement and other potential collaboration arrangements, including future royalties on product
sales.
74
Research and Development
Our research and development expenses consist primarily of salaries and related personnel expenses, fees paid to external service providers, up-front and milestone
payments under our license agreements, patent-related legal fees, costs of preclinical studies and clinical trials, drug and laboratory supplies and costs for facilities and
equipment. We primarily use external service providers to manufacture our product candidates for clinical trials and for the majority of our preclinical and clinical
development work. We charge all research and development expenses to operations as they are incurred. We expect our research and development expense to remain our
primary expense in the near future as we continue to develop our therapeutic candidates.
The following table identifies our current major research and development projects:
Project
Status
1.
motixafortide
Phase 3 registration study in autologous stem cell mobilization
(GENESIS) completed; top-line results announced May 2021 showed
highly statistically significant evidence across all primary and secondary
endpoints favoring motixafortide in combination with G-CSF
(p<0.0001). In addition, the combination was found to be safe and well
tolerated. Pharmaco-economic studies showed positive results regarding
the cost-effectiveness of using motixafortide versus both G-CSF alone
and plerixafor in combination with G-CSF. NDA submission made in
September 2022, and in November 2022 the FDA accepted for review
the NDA with a PDUFA target action date of September 9, 2023.
Expected Near Term Milestones
1.
FDA decision on NDA filing expected in third quarter of
2023
2.
3.
4.
5.
Phase 2 investigator-initiated study in first-line metastatic PDAC patients 2. Data from the study is anticipated in 2023*
Phase 1b study in patients with ARDS secondary to COVID-19 and other
respiratory viral infections
Phase 2b randomized clinical trial in first-line metastatic PDAC patients
under collaboration with GenFleet
3. Data from the study is anticipated in 2023*
4.
Initiation of the study is expected in 2023
Phase 1 study for gene therapies in SCD
5.
Initiation of the study is expected in 2023
AGI-134
Phase 1/2a study completed. Results announced December 2022. The study met
its primary endpoint of safety and tolerability. Generation of an immune
response and markers of clinical efficacy were assessed as secondary endpoints.
Determination of next steps for the program in the first half of
2023
*These studies are investigator-initiated studies; therefore, the timelines are ultimately controlled by the independent investigators and are subject to change.
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We expect that a large percentage of our research and development expenses in the future will be incurred in support of our current and future preclinical and clinical
development projects. Due to the inherently unpredictable nature of preclinical and clinical development processes, we are unable to estimate with any certainty the costs we
will incur in the continued development of the therapeutic candidates in our pipeline for commercialization. Clinical development timelines, the probability of success and
development costs can differ materially from expectations. We expect to continue to test our product candidates in preclinical studies for toxicology, safety and efficacy, and to
conduct additional clinical trials for each product candidate. If we are not able to enter into an out-licensing arrangement with respect to any therapeutic candidate prior to the
commencement of later stage clinical trials, we may fund the trials for the therapeutic candidate ourselves.
While we are currently focused on advancing each of our product development projects as well as the U.S. commercialization of motixafortide, our future research
and development expenses will depend on the clinical success of each therapeutic candidate, as well as ongoing assessments of each therapeutic candidate’s commercial
potential. In addition, we cannot forecast with any degree of certainty which therapeutic candidates may be subject to future out-licensing arrangements, when such out-
licensing arrangements will be secured, if at all, and to what degree such arrangements would affect our development plans and capital requirements.
As we obtain results from clinical trials, we may elect to discontinue or delay clinical trials for certain therapeutic candidates or projects in order to focus our
resources on more promising therapeutic candidates or projects. Completion of clinical trials by us or our licensees may take several years or more, but the length of time
generally varies according to the type, complexity, novelty and intended use of a therapeutic candidate.
The cost of clinical trials may vary significantly over the life of a project as a result of differences arising during clinical development, including, among others:
•
•
•
•
•
•
•
the number of sites included in the clinical trials;
the length of time required to enroll suitable patients;
the number of patients that participate in the clinical trials;
the duration of patient follow-up;
whether the patients require hospitalization or can be treated on an out-patient basis;
the development stage of the therapeutic candidate; and
the efficacy and safety profile of the therapeutic candidate.
The lengthy process of completing clinical trials and seeking regulatory approval for our product candidates requires expenditure of substantial resources. Any failure
or delay in completing clinical trials, or in obtaining regulatory approvals, could cause a delay in generating product revenue and cause our research and development
expenses to increase and, in turn, have a material adverse effect on our operations. Due to the factors set forth above, we are not able to estimate with any certainty when we
would recognize any net cash inflows from our projects.
We expect our sales and marketing expenses to become our most significant cost as we advance our U.S. commercialization plan for motixafortide in stem cell
mobilization for autologous bone marrow transplantation for multiple myeloma patients.
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Sales and Marketing Expenses
Sales and marketing expenses consist primarily of commercialization activities and compensation for employees in commercialization, business development and
marketing functions. Other signicant sales and marketing costs include costs for marketing and communication materials, professional fees for outside market research and
consulting, legal services related to partnering transactions and travel costs.
General and Administrative Expenses
General and administrative expenses consist primarily of compensation for employees in executive and operational functions, including accounting, finance, legal,
investor relations, information technology and human resources. Other significant general and administration costs include facilities costs, professional fees for outside
accounting and legal services, travel costs, insurance premiums and depreciation.
Non-Operating Expense and Income
Non-operating expense and income includes fair-value adjustments of liabilities on account of the warrants issued in equity financings we carried out in February
2019, May-June 2020 and September 2022. These fair-value adjustments are highly influenced by our share price at each period end (revaluation date). Non-operating expense
and income also includes issuance expenses of the ATM sales agreements between us and H.C. Wainwright & Co., LLC, or HCW, entered into in September 2020 and
September 2021, and the pro-rata share of issuance expenses from the placements related to the warrants. Sales-based royalties and other revenue from the license agreement
with Perrigo have also been included as part of non-operating income, as the out-licensed product is not an integral part of our strategy, and the amounts are not material.
Financial Expense and Income
Financial expense and income consist of interest earned on our cash, cash equivalents and short-term bank deposits; interest expense related to our loans from Kreos
Capital; bank fees and other transactional costs. In addition, it may also include gains/losses on foreign exchange hedging transactions, which we carry out from time to time
to protect against a portion of our NIS-denominated expenses (primarily compensation) in relation to the dollar.
Critical Accounting Policies and Estimates
Our consolidated financial statements are prepared in conformity with International Financial Reporting Standards, or IFRS, as issued by the International
Accounting Standards Board, or IASB. In preparing our consolidated financial statements, we make judgements, estimates and assumptions about the application of our
accounting policies which affect the reported amounts of assets, liabilities, revenue and expenses. Our critical accounting judgements and sources of estimation uncertainty are
described in Note 4 to our consolidated financial statements, which are included elsewhere in this Annual Report.
Revenue Recognition
We recognize revenues in accordance with International Financial Reporting Standards No. 15, or IFRS 15. IFRS 15, “Revenue from Contracts with Customers,”
which was issued in May 2014, amends revenue recognition requirements and establishes principles for reporting information about the nature, amount, timing and uncertainty
of revenue and cash flows arising from contracts with customers. The standard replaces International Auditing Standard, or IAS, 18, “Revenue” and IAS 11, “Construction
Contracts” and related interpretations. The standard is effective for annual periods beginning on or after January 1, 2018, and we have adopted it as of that date.
77
IFRS 15 introduces a five-step model for recognizing revenue from contracts with customers, as follows:
•
•
•
•
•
identify the contract with a customer;
identify the performance obligations in the contract;
determine the transaction price;
allocate the transaction price to the performance obligations in the contract; and
recognize revenue when (or as) the entity satisfies a performance obligation.
Accrued Expenses
We are required to estimate accrued expenses as part of our process of preparing financial statements. This process involves estimating the level of service performed
on our behalf and the associated cost incurred in instances where we have not been invoiced or otherwise notified of actual costs. Examples of areas in which subjective
judgments may be required include costs associated with services provided by contract organizations for preclinical development, clinical trials and manufacturing of clinical
materials. We account for expenses associated with these external services by determining the total cost of a given study based on the terms of the related contract. We accrue
for costs incurred as the services are being provided by monitoring the status of the trials and the invoices received from our external service providers. In the case of clinical
trials, the estimated cost normally relates to the projected costs of treating the patients in our trials, which we recognize over the estimated term of the trial according to the
number of patients enrolled in the trial on an ongoing basis, beginning with patient enrollment. As actual costs become known to us, we adjust our accruals.
Investments in Financial Assets
The primary objective of our investment activities is to preserve principal while maximizing the income that we receive from our investments without significantly
increasing risk and loss. Our investments are exposed to market risk due to fluctuations in interest rates, which may affect our interest income and the fair market value of our
investments. We manage this exposure by performing ongoing evaluations of our investments. Due to the short-term maturities of our investments to date, their carrying value
has always approximated their fair value.
A financial asset is classified in this category if our management has designated it as a financial asset upon initial recognition, because it is managed, and its
performance is evaluated, on a fair-value basis in accordance with a documented risk management or investment strategy. Our investment policy with regard to excess cash, as
adopted by our Board of Directors, is composed of the following objectives: (i) preserving investment principal; (ii) providing liquidity; and (iii) providing optimum yields
pursuant to the policy guidelines and market conditions. The policy provides detailed guidelines as to the securities and other financial instruments in which we are allowed to
invest. In addition, in order to maintain liquidity, investments are structured to provide flexibility to liquidate at least 50% of all investments within 15 business days.
Information about these assets, including details of the portfolio and income earned, is provided internally on a quarterly basis to our key management personnel and on a
semi-annual basis to the Investment Monitoring Committee of our Board of Directors. Any divergence from this investment policy requires approval from our Board of
Directors.
78
Stock-based Compensation
We account for stock-based compensation arrangements in accordance with the provisions of IFRS 2. IFRS 2 requires companies to recognize stock compensation
expense for awards of equity instruments based on the grant-date fair value of those awards (with limited exceptions). The cost is recognized as compensation expense over
the life of the instruments, based upon the grant-date fair value of the equity or liability instruments issued. The fair value of our stock-based compensation grants is computed
as of the grant date based on the Black-Scholes model, using the standard parameters established in that model including estimates relating to volatility of our stock, risk-free
interest rates, estimated life of the equity instruments issued and the market price of our stock. As our ordinary shares are publicly traded on the TASE, we do not need to
estimate their fair market value. Rather, we use the actual closing market price of our ordinary shares on the date of grant, as reported by the TASE.
Warrants
In connection with a loan transaction entered into with Kreos Capital in October 2018, we issued a warrant to purchase 63,837 ADSs at an exercise price of $14.10
per ADS. The warrant is exercisable for a period of ten years from the date of issuance. Since the exercise price was not deemed to be fixed, the warrant is not qualified for
classification as an equity instrument and has therefore been classified as a non-current financial liability.
In connection with a public offering we completed in February 2019, we issued warrants to purchase 1,866,667 ADSs at an exercise price of $11.25 per ADS. The
warrants are exercisable for a period of five years from the date of issuance. Since the exercise price was not deemed to be fixed, the warrant is not qualified for classification
as an equity instrument and has therefore been classified as a non-current financial liability.
In connection with a registered direct offering we completed in May 2020, we issued warrants to purchase 5,142,859 ADSs at an exercise price of $2.25 per ADS and
also issued warrants to purchase 257,143 ADSs at an exercise price of $2.1875 per ADS. The warrants are exercisable for a period of two and one-half years from the date of
issuance. Since the exercise price was not deemed to be fixed, the warrant is not qualified for classification as an equity instrument and has therefore been classified as a non-
current financial liability. The warrants expired in November 2022.
In connection with a registered direct offering we completed in June 2020, we issued warrants to purchase 2,510,286 ADSs at an exercise price of $2.25 per ADS and
also issued warrants to purchase 125,514 ADSs at an exercise price of $2.1875 per ADS. The warrants are exercisable for a period of two and one-half years from the date of
issuance. Since the exercise price was not deemed to be fixed, the warrant is not qualified for classification as an equity instrument and has therefore been classified as a non-
current financial liability. The warrants expired in November 2022.
In connection with an underwritten public offering we completed in January 2021, we issued warrants to purchase 718,750 ADSs at an exercise price of $3.00 per
ADS. The warrants are exercisable for a period of five years from the date of issuance. The warrants have been classified as shareholder’s equity.
In connection with a registered direct offering we completed in September 2022, we issued warrants to purchase 13,636,365 ADSs at an exercise price of $1.15 per
ADS. The warrants are exercisable for a period of five years from the date of issuance. Since the exercise price of those warrants were not deemed to be fixed, the warrants are
not qualified for classification as an equity instrument and have therefore been classified as a non-current financial liability. We also issued warrants to purchase 681,818
ADSs at an exercise price of $1.375 per ADS. The warrants are exercisable for a period of five years from the date of issuance and have been classified as shareholder’s
equity.
79
Results of Operations -- Overview
Revenues
We did not record any revenues for the years ended December 31, 2020, 2021 and 2022.
Cost of revenues
We did not record any cost of revenues for the years ended December 31, 2020, 2021 and 2022.
Comparison of the Year Ended December 31, 2022 to the Year Ended December 31, 2021
Research and development expenses
Research and development expenses for the year ended December 31, 2022 were $17.6 million, a decrease of $1.9 million, or 9.7% compared to $19.5 million for the
year ended December 31, 2021. The decrease resulted primarily from lower expenses related to NDA supporting activities related to motixafortide, as well as lower expenses
associated with the completed motixafortide GENESIS clinical trial, offset by an increase in expenses associated with the AGI-134 study and increase in payroll and related
expenses.
Sales and marketing expenses
Sales and marketing expenses for the year ended December 31, 2022 were $6.5 million, an increase of $5.5 million, or 550% compared to $1.0 million for the year
ended December 31, 2021. The increase resulted primarily from initiation of pre-commercialization activities related to motixafortide, as well as an increase in market
research.
General and administrative expenses
General and administrative expenses for the year ended December 31, 2022 were $5.1 million, an increase of $0.8 million, or 18.6% compared to $4.3 million for the
year ended December 31, 2021. The increase resulted primarily from an increase in share-based compensation and small increases in a number of G&A expenses.
Non-operating income (expense), net
We recognized net non-operating income of $5.7 million for the year ended December 31, 2022 compared to net non-operating expenses of $1.8 million for the year
ended December 31, 2021. Non-operating income for the year ended December 31, 2022 primarily relates to fair-value adjustments of warrant liabilities on our balance sheet,
offset by warrant offering expenses. Non-operating expenses for the year ended December 31, 2021 primarily relate to fair-value adjustments of warrant liabilities on our
balance sheet and issuance expenses of the ATM.
Financial income (expense), net
We recognized net financial expenses of $1.5 million for the year ended December 31, 2022 compared to net financial expenses of $0.4 million for the year ended
December 31, 2021. Net financial expenses for the year ended December 31, 2022 period primarily relate to interest paid on loan and losses recorded on foreign currency
(primarily NIS) cash balances due to the strengthening of the US dollar during the period, offset by investment income earned on our bank deposits. Net financial expenses for
the 2021 period primarily relate to interest paid on loans, offset by investment income earned on our bank deposits.
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B. Liquidity and Capital Resources
Since our inception, we have funded our operations primarily through public and private offerings of our equity securities, payments received under our strategic
licensing and collaboration arrangements, interest earned on investments and funding from the IIA. As of December 31, 2022, we held $51.1 million of cash, cash equivalents
and short-term bank deposits. We have invested substantially all of our available cash funds in short-term bank deposits.
In September 2021, we entered into an “at-the-market” offering agreement, or ATM, with H.C. Wainwright, or HCW, pursuant to which we may offer and sell, at our
option, up to $25.0 million of our ADSs through an at-the-market equity program under which HCW agreed to act as sales agent. This agreement replaced a substantially
identical ATM program that we previously had with HCW. As of the issuance date of this report, we have sold 608,651 of our ADSs for total gross proceeds of approximately
$1.4 million under the ATM.
In September 2022, we entered into a loan agreement with Kreos Capital. Under the Loan Agreement, Kreos Capital will provide the Company with access to term
loans in an aggregate principal amount of up to $40 million in three tranches as follows: (a) a loan in the aggregate principal amount of up to $10 million, available for
drawdown upon closing of the Loan Agreement and until April 1, 2023, (b) a loan in the aggregate principal amount of up to $20 million, available for drawdown upon
achievement of certain milestones and until April 1, 2024, and (c) a loan in the aggregate principal amount of up to $10 million, available for drawdown upon achievement of
certain milestones and until October 1, 2024. We drew down the initial tranche of $10 million following execution of the agreement in September 2022.
In September 2022, we entered into definitive agreements with certain institutional investors providing for the issuance and sale in a registered direct offering of
13,636,365 of our ADSs and warrants to purchase up to an aggregate of 13,636,365 ADSs at a combined purchase price of $1.10 per ADS and associated investor warrant, for
aggregate gross proceeds of approximately $15 million. The transaction closed in September 2022.
Net cash used in operating activities was $26.2 million for the year ended December 31, 2022, compared with net cash used in operating activities of $23.6 million
for the year ended December 31, 2021. The $2.6 million increase in net cash used in operating activities in 2022 was primarily the result of an increase in sales and marketing
expenses.
Net cash provided by investing activities was $4.0 million for the year ended December 31, 2022, compared to net cash used in investing activities of $38.2 million
for the year ended December 31, 2021. The changes in cash flows from investing activities relate primarily to investments in, and maturities of, short-term bank deposits.
Net cash provided by financing activities was $20.4 million for the year ended December 31, 2022, compared to net cash provided by financing activities of $57.7
million for the year ended December 31, 2021. The cash flows in 2022 primarily reflect the underwritten public offering of our ADSs in September 2022 and the net proceeds
of a loan from Kreos Capital, offset by repayments of a previous loan from Kreos Capital. The cash flows in 2021 primarily reflect the underwritten public offering of our
ADSs in January 2021, warrant exercises, and net proceeds from the ATM Facility, offset by repayments of a loan from Kreos Capital.
We have incurred accumulated losses in the amount of $330 million through December 31, 2022, and we expect to continue incurring losses and negative cash flows
from operations until our product or products reach commercial profitability. Management monitors rolling forecasts of our liquidity reserves on the basis of anticipated cash
flows and maintains liquidity balances at levels that are sufficient to meet its needs. The execution of an independent commercialization plan for motixafortide in the United
States implies an increased level of expenses prior to and following launch of the product. However, as is common with FDA approvals of innovative pharmaceutical
products, there is significant uncertainty regarding the receipt of approval, as well as the timing and scope of any potential approval ultimately received in order to launch
commercialization of the product. Therefore, our cash flow projections are subject to various risks and uncertainties concerning their fulfilment, and these factors and the risk
inherent in our operations may cast significant doubt on our ability to continue as a going concern. Our independent registered public accounting firm has included a “going
concern” explanatory paragraph in its report on our financial statements for the year ended December 31, 2022.
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Developing drugs, conducting clinical trials and commercializing products is expensive and we will need to raise substantial additional funds to achieve our strategic
objectives. Although we believe our existing cash and other resources will be sufficient to fund our current projected cash requirements into the first half of 2024, we will
require additional financing in the future to fund our operations. Additional financing may not be available on acceptable terms, if at all. We expect to also continue to seek to
finance our operations through other sources, including commercialization, if approved, in the United States for motixafortide, our lead therapeutic candidate, out-licensing
arrangements for the development and commercialization of our therapeutic candidates or other partnerships or joint ventures, as well as grants from government agencies and
foundations. Our future capital requirements will depend on many factors, including:
•
•
•
•
•
•
•
•
•
•
•
•
•
the progress and costs of our preclinical studies, clinical trials and other research and development activities;
the scope, prioritization and number of our clinical trials and other research and development programs;
the amount of revenues we receive under our collaboration or licensing arrangements;
the costs of the development and expansion of our operational infrastructure;
the costs and timing of obtaining regulatory approval of our therapeutic candidates;
the ability of our collaborators to achieve development milestones, marketing approval and other events or developments under our collaboration agreements;
the costs of filing, prosecuting, enforcing and defending patent claims and other intellectual property rights;
the costs and timing of securing manufacturing arrangements for clinical or commercial production;
the costs of establishing sales and marketing capabilities or contracting with third parties to provide these capabilities for us;
the costs of acquiring or undertaking development and commercialization efforts for any future product candidates;
the magnitude of our general and administrative expenses;
interest and principal payments on the loan from Kreos Capital;
any cost that we may incur under current and future licensing arrangements relating to our therapeutic candidates;
82
• market conditions;
•
•
payments to the IIA; and
the impact of the COVID-19 pandemic and the Russian invasion of Ukraine, which may exacerbate the magnitude of the factors discussed above.
Until we can generate significant continuing revenues, we expect to satisfy our future cash needs through payments received under our collaborations, debt or equity
financings, or by out-licensing other product candidates. We cannot be certain that additional funding will be available to us on acceptable terms, or at all.
If funds are not available, we may be required to delay, reduce the scope of, or eliminate one or more of our research or development programs or our
commercialization efforts.
Contractual Obligations
The following table summarizes our significant contractual obligations at December 31, 2022:
Car leasing obligations
Premises leasing obligations
Purchase commitments
Total
Total
Less than
1 year
1-3 years
(in thousands of U.S. dollars)
4-5 years
More than
5 years
242
2,860
5,908
9,010
0
569
4,692
5,261
242
884
1,196
2,322
-
617
20
637
-
790
-
790
The premises leasing obligations in the foregoing table include our commitments under the lease agreement for our facility in Modi’in, Israel and our facility in
Waltham, Massachusetts. See “Item 4. Information on the Company — Property, Plant and Equipment.” As for our facility in Israel, the initial term of the lease began on June
15, 2015 and expired June 2020. We have exercised an option to extend the lease through June 30, 2025 and have the option to extend the lease for two additional lease
periods totaling up to an additional 5 years, each option at a 5% increase to the preceding lease payment amount. The monthly lease fee is $25,500. In addition, we pay
building maintenance charges of $8,700 per month. As for our facility in the US, we entered into a lease agreement in October 2022. The monthly leased fee is $23,600. The
term of the lease expires in December 2024.
The foregoing table does not include our in-licensing agreements. Under our in-licensing agreements, we are obligated to make certain payments to our licensors
upon the achievement of agreed-upon milestones. We are unable at this time to estimate the actual amount or timing of the costs we will incur in the future under these
agreements; however, we do not expect any material financial milestone obligations to be achieved within the next 12 months. Some of the in-licensing agreements are
accompanied by consulting, support and cooperation agreements, pursuant to which we are required to pay the licensors a fixed monthly amount, over a period stipulated in
the applicable agreement, for their assistance in the continued research and development under the applicable license. All of our in-licensing agreements are terminable at-will
by us upon prior written notice of 30 to 90 days. We are unable at this time to estimate the actual amount or timing of the costs we will incur in the future under these
agreements. See “Item 4. Information on the Company — Business Overview — In-Licensing Agreements.”
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C. Research and Development, Patents and Licenses
For our research and development policies, see “Item 4 — Information on the Company — Business Overview — Our Strategy.” For information regarding patents,
see Item 4 — Information on the Company — Intellectual Property.” For information regarding licenses, see “Item 4 — Information on the Company — Collaboration and
Out-Licensing Arrangements” and Item 4 — Information on the Company — In-Licensing Agreements.”
D. Trend Information
We are a pre-commercial stage company and it is not possible for us to predict with any degree of accuracy the outcome of our research, development or
commercialization efforts. As such, it is not possible for us to predict with any degree of accuracy any known trends, uncertainties, demands, commitments or events that are
reasonably likely to have a material effect on our net sales or revenues, income from continuing operations, profitability, liquidity or capital resources, or that would cause
reported financial information to not necessarily be indicative of future operating results or financial conditions. However, to the extent possible, certain trends, uncertainties,
demands, commitments and events are in this “Operating and Financial Review and Prospects.”
E. Critical Accounting Estimates
Our consolidated financial statements are prepared in conformity with IFRS, as issued by the IASB. In preparing our consolidated financial statements, we make
judgements, estimates and assumptions about the application of our accounting policies which affect the reported amounts of assets, liabilities, revenue and expenses. Our
critical accounting judgements and sources of estimation uncertainty are described in Note 4 to our consolidated financial statements, which are included elsewhere in this
Annual Report.
ITEM 6. DIRECTORS, SENIOR MANAGEMENT AND EMPLOYEES
A. Executive Officers and Directors
The following table sets forth information for our executive officers and directors as of March 21, 2023. Unless otherwise stated, the address for our directors and
officers is c/o BioLineRx Ltd., 2 HaMa’ayan Street, Modi’in 7177871, Israel.
Name
Age
Position(s)
Philip A. Serlin, CPA, MBA
Mali Zeevi, CPA
Ella Sorani, Ph.D.
Tami Rachmilewitz, M.D.
Holly W. May
Aharon Schwartz, Ph.D. (1)
Michael J. Anghel, Ph.D. (1)(4)
Rami Dar, MBA (1)(2)(3)(4)
B.J. Bormann, Ph.D. (1)(3)
Raphael Hofstein, Ph.D. (1)(2)(3)
Avraham Molcho, M.D. (1)(2)(3)
Sandra Panem, Ph.D. (1)
62
47
55
53
61
80
84
66
64
73
65
76
Chief Executive Officer
Chief Financial Officer
Chief Development Officer
Chief Medical Officer
US President
Chairman of the Board
Director
External Director
Director
Director
External Director
Director
(1)
Independent director under applicable Nasdaq Capital Market and SEC rules, as affirmatively determined by our Board.
(2) A member of our audit committee.
(3) A member of our compensation committee.
(4) A member of our investment committee
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Philip A. Serlin, CPA, MBA, has served as our Chief Executive Officer since October 2016. From May 2009 to October 2016, Mr. Serlin served as our Chief Financial
and Operating Officer. From January 2008 to August 2008, Mr. Serlin served as the Chief Financial Officer and Chief Operating Officer of Kayote Networks Inc. From
January 2006 to December 2007, he served as the Chief Financial Officer of Tescom Software Systems Testing Ltd., an IT services company publicly traded in both Tel Aviv
and London. His background also includes senior positions at Chiaro Networks Ltd. and at Deloitte, where he was head of the SEC and U.S. Accounting Department at the
National Office in Tel Aviv, as well as seven years at the SEC at its Washington, D.C., headquarters. Mr. Serlin is a CPA and holds a B.Sc. in accounting from Yeshiva
University and a Master’s degree in economics and public policy from The George Washington University.
Mali Zeevi, CPA, has served as our Chief Financial Officer since October 2016. Prior to becoming Chief Financial Officer, Ms. Zeevi served as our Senior Director of
Finance and Reporting beginning in 2011 and as our Director of Finance and Reporting beginning in 2009. Before joining BioLineRx, Ms. Zeevi was employed by Tescom
Software Systems Testing Ltd., her last position there being Vice President Finance. Ms. Zeevi also served as a CPA at Kesselman&Kesselman, a member firm of
PricewaterhouseCoopers International Limited. She holds a B.A. in business and accountancy from the College of Management Academic Studies in Israel.
Ella Sorani, Ph.D., has served as our Chief Development Officer since January 2021. From February 2017 to December 2020, Dr. Sorani served as our Vice President
Research and Development. Before joining BioLineRx, from 2000 through 2016, Dr. Sorani served in a number of management positions in the global R&D division at Teva
Pharmaceutical Industries Ltd. In her most recent position as Senior Director and Global Project Leader, Dr. Sorani led the development of one of Teva’s leading innovative
late stage compounds. Dr. Sorani holds a B.Sc. in chemistry and an M.Sc. and Ph.D. in pharmacology, all from Tel Aviv University.
Tami Rachmilewitz, M.D., has served as our Chief Medical Officer since January 2023. Dr. Rachmilewitz brings over 15 years of clinical development industry
experience to the Company, including overseeing clinical development programs in oncology, immunology, and neurodegeneration. Previously, she was Senior Vice President
of Clinical Development at VBL Therapeutics, where she led all aspects of the company’s immuno-oncology clinical trial programs and oversaw its clinical operations and
medical affairs teams. Her prior experience also includes clinical development leadership positions at NeuroDerm Ltd., Teva Pharmaceutical Industries Ltd., and Novartis.
During her career, Dr. Rachmilewitz has led early to late phase clinical development programs, including large multinational pivotal trials. Dr. Rachmilewitz received her
Bachelor of Medical Sciences degree from The Hebrew University of Jerusalem, and her Doctor of Medicine degree from the Hadassah Medical School at the Hebrew
University of Jerusalem, where she also performed her internship and residency in psychiatry. .
Holly W. May, has served as our US president since September 2022. From June 2022 to August 2022, Ms. May served as our Chief Commercial Officer. Prior to
joining BioLineRx, Ms. May served as Chief Commercial Officer at AVROBIO since September 2019, where she was responsible for building the company’s global
commercial organization and over-arching commercial capabilities, inclusive of driving the development and execution of commercial strategy. Prior to that, she served as
Vice President and Head of Commercial at SOBI, Inc., where she led all aspects of commercial strategy, operations and performance. Prior to joining SOBI, Ms. May held
leadership roles of increasing strategic importance across marketing, operations, sales, and planning at Sanofi and Genzyme, with her last roles encompassing Vice President
in the Genzyme rare disease unit, and Head of Marketing, Operations and Strategic Planning for Sanofi’s global oncology division. She holds a BA in Zoology from Miami
University of Ohio, and an MBA with a concentration in marketing from the University of Akron.
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Aharon Schwartz, Ph.D., has served as the Chairman of our Board of Directors since 2004. He served in a number of positions in Teva from 1975 through 2011, the
most recent being Vice President, Head of Teva Innovative Ventures from 2008. Dr. Schwartz is currently a member of the board of directors of Protalix Ltd. (NYSE
American:PLX) and Barcode Ltd. He also works as an independent consultant. Dr. Schwartz received his Ph.D. in organic chemistry from the Weizmann Institute, his M.Sc. in
organic chemistry from the Technion and a B.Sc. in chemistry and physics from the Hebrew University of Jerusalem. In addition, Dr. Schwartz holds a Ph.D. from the Hebrew
University of Jerusalem in the history and philosophy of science.
Michael J. Anghel, Ph.D., has served on our Board of Directors since 2010 and on our Investment Monitoring Committee since 2010. From 1977 to 1999, he led the
Discount Investment Corporation Ltd. (of the IDB Group) activities in the fields of technology and communications. Dr. Anghel was instrumental in founding Tevel, one of
the first Israeli cable television operators and later in founding Cellcom Israel Ltd. (NYSE:CEL), the second Israeli cellular operator. In 1999, he founded CAP Ventures, an
advanced technology investment company. From 2004 to 2005, Dr. Anghel served as CEO of DCM, the investment banking arm of the Israel Discount Bank (TASE:DSCT).
Over the years, Dr. Anghel has been involved in founding and managing various technology enterprises and has served on the Boards of Directors of various major Israeli
corporations and financial institutions, many of them publicly traded in the U.S. and Israel. During the past two years, he completed long term tenures as director on the boards
of: Partner Communications Company, Ltd. (Nasdaq:PTNR, TASE:PTNR), Strauss Group Ltd. (TASE:STRS), and Orbotech Ltd. (Nasdaq:ORBK), He currently serves as
director on the boards of InMode Ltd. (Nasdaq:INMD) and Ellomay Capital Ltd. (NYSE American: ELLO). Prior to launching his business career, Dr. Anghel served as a full-
time member of the faculty of the Recanati Graduate School of Business Administration of the Tel Aviv University, where he taught finance and corporate strategy. He
currently serves as Chairman of the Tel Aviv University’s Executive Program. Dr. Anghel holds a B.A. (Economics) from the Hebrew University in Jerusalem and an MBA
and Ph.D. (Finance) from Columbia University, New York.
Rami Dar, MBA, has served as an external director on our Board of Directors since July 2022. Mr. Dar has served since March 2020 as a board member of Nordia
Springs, and since January 2018 as chairman of Novolog Ltd. (TLV: NVLG). From 2002 to 2019, Mr. Dar served as Chief Executive Officer of Hazera Seeds Ltd. (formerly
Hazera Genetics), a leading global seed company, and prior to that, from 1998 to 2002, served in various management positions in Teva Pharmaceuticals Ltd., including as
Business Development Executive from 2001 to 2002, Chief Executive Officer of Teva Medical Ltd., from 1998 to 2001, and Chief Executive Officer of Teva Pharmaceuticals
Ltd. Israel from 1995 to 1998. Mr. Dar holds a B.A. in economics and philosophy and an M.A. in economics, both from the Hebrew University of Jerusalem, Israel, and an
Executive M.B.A. from Columbia University, New York, USA.
BJ Bormann, Ph.D., has served on our Board of Directors since August 2013 and on our Compensation Committee since 2022. Dr. Bormann currently serves as the
Vice President of Translational Science and Network Alliances at The Jackson Laboratory, a non-profit organization focused on the genetic basis of disease. Dr. Bormann was
previously the Chief Executive Officer of Supportive Therapeutics, LLC, a Boston based company that is developing two molecules for use in the supportive care of oncology
patients. In the past several years Dr. Bormann has held executive positions in several biotechnology companies including NanoMedical Systems (Austin, Texas), Harbour
Antibodies (Rotterdam, The Netherlands) and Pivot Pharmaceuticals (PVTF: OTC listed). Prior to these engagements, Dr. Bormann was Senior Vice President responsible for
world-wide alliances, licensing and business development at Boehringer Ingelheim Pharmaceuticals, Inc. from 2007 to 2013. From 1996 to 2007, she served in a number of
positions at Pfizer, Inc., the last one being Vice President of Pfizer Global Research and Development and world-wide Head of Strategic Alliances. Dr. Bormann serves on the
board of directors of various companies, including Xeris BioPharma, Inc (Nasdaq:XERS) and NanoMedical Systems (private). Dr. Bormann received her Ph.D. in biomedical
science from the University of Connecticut Health Center and her B.Sc. from Fairfield University in biology. Dr. Bormann completed postdoctoral training at Yale Medical
School in the department of pathology.
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Raphael Hofstein, Ph.D., has served on our Board of Directors since 2003, our Audit Committee since 2007 and our Compensation Committee since 2012. Dr.
Hofstein has served as the President and Chief Executive Officer of MaRS Innovation (a commercialization company for 15 of Toronto’s universities, institutions and research
institutes plus the MaRS Discovery District) from June 2009 to March 2020. From 2000 through June 2009, Dr. Hofstein was the President and Chief Executive Officer of
Hadasit Medical Research Services and Development Ltd., or Hadasit, the technology transfer company of Hadassah University Hospitals. He has served as chairman of the
board of directors of Hadasit since 2006. Prior to joining Hadasit, Dr. Hofstein was the President of Mindsense Biosystems Ltd. and the Business Unit Director of Ecogen Inc.
and has held a variety of other positions, including manager of R&D and chief of immunochemistry at the International Genetic Science Partnership. Dr. Hofstein serves on
the board of directors of numerous companies. Dr. Hofstein received his Ph.D. and M.Sc. from the Weizmann Institute of Science, and his B.Sc. in chemistry and physics from
the Hebrew University in Jerusalem. Dr. Hofstein completed postdoctoral training at Harvard Medical School in both the departments of biological chemistry and
neurobiology.
Avraham Molcho, M.D., has served as an external director on our Board of Directors and on our Audit Committee since 2010. In addition, Dr. Molcho has served on
our Compensation Committee since 2012. Dr. Molcho is the co-founder of Biolojic Design Ltd., a technology platform that encourages human antibody discovery. In 2012,
he became the co-founder of Ayana Pharma Ltd. (formerly DoxoCure), a privately-held company engaged in the manufacturing of liposome-based therapeutics. He served as
Ayana’s Chief Executive Officer and director until 2019. From 2006 through 2008, Dr. Molcho served as the Chief Executive Officer and Chairman of Neovasc Medical, a
privately-held Israeli medical device company. From 2006 until 2019, Dr. Molcho was a venture partner at Forbion Capital Partners, a Dutch life sciences venture capital firm.
From 2001 through 2006, Dr. Molcho was a managing director and the head of life sciences of Giza Venture Capital and, in that capacity, was involved in the founding of our
company. He was also the Deputy Director General of Abarbanel Mental Health Center, the largest acute psychiatric hospital in Israel, from 1999 to 2001. Dr. Molcho holds
an M.D. from Tel-Aviv University School of Medicine and an MBA from Tel-Aviv University Recanati Business School.
Sandra Panem, Ph.D., has served on our Board of Directors since February 2014. She is currently a managing partner at Cross Atlantic Partners, which she joined in
2000. She is also co-founder and President of NeuroNetworks Fund, a not-for-profit venture capital fund focusing on epilepsy, schizophrenia and autism. From 1994 to 1999,
Dr. Panem was President of Vector Fund Management, the then asset management affiliate of Vector Securities International. Prior thereto, Dr. Panem served as Vice President
and Portfolio Manager for the Oppenheimer Global BioTech Fund, a mutual fund that invested in public and private biotechnology companies. Previously, she was Vice
President at Salomon Brothers Venture Capital, a fund focused on early and later-stage life sciences and technology investments. Dr. Panem was also a Science and Public
Policy Fellow in economic studies at the Brookings Institution, and an Assistant Professor of Pathology at the University of Chicago. Dr. Panem currently serves on the board
of directors of Acorda Therapeutics, Inc. (Nasdaq:ACOR). Previously, Dr. Panem served on numerous boards of public and private companies, including Martek Biosciences
(Nasdaq:MATK), IBAH Pharmaceuticals (Nasdaq:IBAH), Confluent Surgical, Molecular Informatics and Labcyte, Inc. She received a B.S. in biochemistry and a Ph.D. in
microbiology from the University of Chicago.
87
B. Compensation
Employment Agreements
We have entered into written employment agreements with each of our executive officers, the terms of which are consistent with the provisions of our Compensation
Policy for Executives and Directors, or Compensation Policy, which was approved by our shareholders in July 2022. All of these agreements contain customary provisions
regarding noncompetition, confidentiality of information and assignment of inventions. However, the enforceability of the noncompetition provisions may be limited under
applicable law.
In addition, we have entered into agreements with each executive officer and director pursuant to which we have agreed to indemnify each of them to the fullest
extent permitted by law to the extent that these liabilities are not covered by directors’ and officers’ insurance. The terms of these agreements and of our directors’ and
officers’ insurance are consistent with the provisions of the Compensation Policy.
Compensation of Directors and Senior Management
The following table presents in the aggregate all compensation we paid to all of our directors and senior management as a group for the year ended December 31,
2022. The table does not include any amounts we paid to reimburse any of such persons for costs incurred in providing us with services during this period.
All directors and senior management as a group, consisting of 12 persons
Pension,
retirement,
options and
other similar
benefits
(in thousands of U.S. dollars)
Salaries, fees,
commissions
and bonuses
2,165
1,310
In accordance with the Companies Law, the following table presents information regarding compensation actually received or accrued by our five executive officers
during the year ended December 31, 2022.
Name and Position
Salary
Social
Benefits(1)
Value of
Options
Granted(2)
Bonuses
(in thousands of U.S. dollars)
All Other
Compensation(3)
Total
Philip A. Serlin
Chief Executive Officer
Mali Zeevi
Chief Financial Officer
Abi Vainstein-Haras
Chief Medical Officer (4)
Ella Sorani
Chief Development Officer
Holly W. May
President BioLineRx USA, Inc.
297
193
211
218
224
80
47
43
52
-
238
122
105
167
104
401
102
102
102
83
20
18
19
20
-
1,036
482
480
559
411
(1)
“Social Benefits” include payments to the National Insurance Institute, advanced education funds, managers’ insurance and pension funds, vacation pay and recuperation
pay as mandated by Israeli law.
(2) Consists of amounts recognized as share-based compensation expense on the Company’s statement of comprehensive loss for the year ended December 31, 2022.
(3)
“All Other Compensation” includes automobile-related expenses pursuant to the Company’s automobile leasing program, telephone, basic health insurance and holiday
presents.
(4) Dr. Vainstein-Haras resigned as of December 31, 2022.
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For additional information concerning our equity compensation plan, see “— Beneficial Ownership of Executive Officers and Directors — Equity Compensation
Plan.”
C. Board Practices
Board of Directors
According to the Companies Law, the management of our business is vested in our Board of Directors. However, certain of our committees are required to have a
majority of independent directors. Our Board of Directors may exercise all powers and may take all actions that are not specifically granted to our shareholders. Our executive
officers are responsible for our day-to-day management and have individual responsibilities established by our Board of Directors. Executive officers are appointed by and
serve at the discretion of our Board of Directors, subject to any applicable employment agreements we have entered into with the executive officers.
Under the Companies Law, we are not required to have a majority of independent directors. We are required to appoint at least two external directors, unless we
qualify as an Eligible Company (as defined below) and opt to follow an exemption provided under the Relief Regulations (as defined below). See “— External Directors.”
According to our Articles of Association, our Board of Directors must consist of at least five and not more than 10 directors, including external directors. Currently,
our Board of Directors consists of seven directors, including two external directors as required by the Companies Law. Pursuant to our Articles of Association, other than the
external directors, for whom special election requirements apply under the Companies Law as detailed below, our directors are elected at a general or extraordinary meeting of
our shareholders and serve on the Board of Directors until they are removed by the majority of our shareholders at a general or extraordinary meeting of our shareholders or
upon the occurrence of certain events, in accordance with the Companies Law and our Articles of Association. In addition, our Articles of Association allow our Board of
Directors to appoint directors, other than external directors, to fill vacancies on the Board of Directors to serve until the next general meeting or extraordinary meeting, or
earlier if required by our Articles of Association or applicable law. We have held elections for each of our non-external directors at each annual meeting of our shareholders
since our initial public offering in Israel. External directors are elected for an initial term of three years and may be elected, under certain conditions, to two additional terms,
although the term of office for external directors for Israeli companies traded on certain foreign stock exchanges, including Nasdaq, may be further extended under certain
conditions. External directors may be removed from office only pursuant to the terms of the Companies Law. Our last annual meeting of shareholders was held in July 2022.
For additional information concerning external directors, see “— External Directors.”
The Companies Law provides that an Israeli company may, under certain circumstances, exculpate an office holder from liability with respect to a breach of his duty
of care toward the company if appropriate provisions allowing such exculpation are included in its articles of association. See “— Exculpation, insurance and indemnification
of office holders.” Our Articles of Association contain such provisions, and we have entered into agreements with each of our office holders undertaking to indemnify them to
the fullest extent permitted by law, to the extent that these liabilities are not covered by insurance.
89
In accordance with the exemption available to foreign private issuers under applicable Nasdaq rules, we do not follow the requirements of the Nasdaq Rules with
regard to the process of nominating directors, and instead follow Israeli law and practice, in accordance with which our Board of Directors is authorized to recommend to our
shareholders director nominees for election, and, in some circumstances, our shareholders may nominate candidates for election as directors by the shareholders’ general
meeting.
In addition, under the Companies Law, our Board of Directors must determine the minimum number of directors who are required to have financial and accounting
expertise. Under applicable regulations, a director with financial and accounting expertise is a director who, by reason of his or her education, professional experience and
skill, has a high level of proficiency in and understanding of business accounting matters and financial statements. He or she must be able to thoroughly comprehend the
financial statements of the listed company and initiate debate regarding the manner in which financial information is presented. In determining the number of directors
required to have such expertise, a company’s board of directors must consider, among other things, the type and size of the company and the scope and complexity of its
operations. Our Board of Directors has determined that we require at least one director with the requisite financial and accounting expertise. Mr. Rami Dar and Dr. Michael J.
Anghel have such financial and accounting expertise.
The term office holder is defined in the Companies Law as a general manager, chief business manager, deputy general manager, vice general manager, executive vice
president, vice president, or any other person assuming the responsibilities of any of the foregoing positions, without regard to such person’s title, or a director or any other
manager directly subordinate to the general manager. Each person listed above under “Executive Officers and Directors” is an office holder under the Companies Law.
Chairman of the Board. Under the Companies Law, a person cannot hold the role of both chairman of the board of directors and chief executive officer of a company,
without shareholder approval by special majority and for periods of time not exceeding three years each. Furthermore, a person who is directly or indirectly subordinate to a
chief executive officer of a company may not serve as the chairman of the board of directors of that company and the chairman of the board of directors may not otherwise
serve in any other capacity in a company or in a subsidiary of that company other than as a director or the chairman of the board of directors of such a subsidiary.
DIVERSITY OF THE BOARD OF DIRECTORS
Board Diversity Matrix (As of March 21, 2023)
Country of Principal Executive Offices
Foreign Private Issuer
Disclosure Prohibited under Home Country Law
Total Number of Directors
Part I: Gender Identity
Directors
Part II: Demographic Background
Underrepresented Individual in Home Country Jurisdiction
LGBTQ+
Did Not Disclose Demographic Background
Israel
Yes
No
7
90
Female
2
Male
5
Non-Binary
0
Did Not
Disclose
Gender
0
0
0
0
External Directors
Under Israeli law, the boards of directors of companies whose shares are publicly traded are, subject to certain exceptions, required to include at least two members
who qualify as external directors. Our external directors are Dr. Avraham Molcho, who was re-elected as an external director by our shareholders in July 2022 for an additional
three-year term and Mr. Rami Dar, who was elected as an external director by our shareholders in July 2022 for a three-year term.
External directors must be elected by majority vote of the shares present and voting at a shareholders meeting, provided that either:
•
•
the majority of the shares that are voted at the meeting, including at least a majority of the shares held by non-controlling shareholders or shareholders who do
not have a personal interest in the election of the external director (other than a personal interest not deriving from a relationship with a controlling shareholder)
who voted at the meeting, excluding abstentions, vote in favor of the election of the external director; or
the total number of shares held by non-controlling, disinterested shareholders (as described in the preceding bullet point) that are voted against the election of the
external director does not exceed 2% of the aggregate voting rights in the company.
After an initial term of three years, external directors may be re-elected to serve in that capacity for up to two additional terms of three years provided that either (a)
the board of directors has recommended such re-election and such re-election is approved by a majority vote at a shareholders’ meeting, subject to the conditions described
above for election of external directors, (b) (1) the re-election has been recommended by one or more shareholders holding at least 1% of the company’s voting rights and is
approved by a majority of non-controlling, disinterested shareholders who hold among them at least 2% of the company’s voting rights; and (2) the external director who has
been nominated in such fashion by the shareholders is not a linked or competing shareholder, and does not have or has not had, on or within the two years preceding the date
of such person’s appointment to serve as another term as external director, any affiliation with a linked or competing shareholder, or (c) the external director has proposed
himself for reappointment and the reappointment was approved by the majority described in (b)(1) above. The term “linked or competing shareholder” means the
shareholder(s) who nominated the external director for reappointment or a material shareholder of the company holding more than 5% of the shares in the company, provided
that at the time of the reappointment, such shareholder(s) of the company, the controlling shareholder of such shareholder(s) of the company, or a company under such
shareholder(s) of the company’s control, has a business relationship with the company or are competitors of the company; the Israeli Minister of Justice, in consultation with
the Israeli Securities Authority, or ISA, may determine that certain matters will not constitute a business relationship or competition with the company. The term of office for
external directors for Israeli companies traded on certain foreign stock exchanges, including Nasdaq, may be extended beyond the initial three terms permitted under the
Companies Law indefinitely in increments of additional three-year terms, provided in each case that the following conditions are met: (a) the audit committee and the board of
directors confirm that, in light of the external director’s expertise and special contribution to the work of the board of directors and its committees, the re-election for such
additional period(s) is beneficial to the company; (b) the re-election is approved by the shareholders by a special majority required for the re-election of external directors; and
(c) the term of office of the external director, and the considerations of the audit committee and the board of directors in deciding to recommend re-election of the external
director for such additional term of office, are presented to the shareholders prior to the vote on re-election. External directors may be removed from office by the same
percentage of shareholders required for their election or by a court, in each case, only under limited circumstances, including ceasing to meet the statutory qualification for
appointment or violating the duty of loyalty to the company. If an external directorship becomes vacant and there are less than two external directors on the board of directors
at the time, then the board of directors is required under the Companies Law to call a shareholders’ meeting immediately to appoint a replacement external director. Each
committee of the board of directors that exercises the powers of the board of directors must include at least one external director (unless the company is an Eligible Company
and opted to follow the exemption provided under the Relief Regulations regarding appointment of external directors and composition of the audit and compensation
committees). Under the Companies Law external directors of a company are prohibited from receiving, directly or indirectly, any compensation from the company other than
for their services as external directors pursuant to the provisions and limitations set forth in regulations promulgated under the Companies Law.
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A person may not serve as an external director if (a) the person is a relative of a controlling shareholder of a company or (b) at the date of the person’s appointment or
within the prior two years, the person, the person’s relatives, entities under the person’s control, the person’s partner, the person’s employer, or anyone to whom that person is
subordinate, whether directly or indirectly, have or have had any affiliation with (1) a company, (2) a company’s controlling shareholder at the time of such person’s
appointment or (3) any entity that is either controlled by the company or under common control with the company at the time of such appointment or during the prior two
years. If a company does not have a controlling shareholder or a shareholder who holds company shares entitling him to vote at least 25% of the votes in a shareholders
meeting, then a person may not serve as an external director if, such person or such person’s relative, partner, employer or any entity under the person’s control, has or had, on
or within the two years preceding the date of the person’s appointment to serve as external director, any affiliation with the chairman of the company’s board, chief executive
officer, a substantial shareholder who holds at least 5% of the issued and outstanding shares of the company or voting rights which entitle him to vote at least 5% of the votes
in a shareholders meeting, or the chief financial officer of the company.
The term “affiliation” includes:
•
•
•
•
an employment relationship;
a business or professional relationship even if not maintained on a regular basis (excluding insignificant relationships);
control; and
service as an office holder, excluding service as a director in a private company prior to the first offering of its shares to the public if such director was appointed
as a director of the private company in order to serve as an external director following the public offering.
The term “relative” is defined as a spouse, sibling, parent, grandparent or descendant; a spouse’s sibling, parent or descendant; and the spouse of each of such
persons.
In addition, no person may serve as an external director if that person’s professional activities create, or may create, a conflict of interest with that person’s
responsibilities as a director or otherwise interfere with that person’s ability to serve as an external director or if the person is an employee of the ISA or of an Israeli stock
exchange. Furthermore, a person may not continue to serve as an external director if he or she received direct or indirect compensation from us for his or her role as a director.
This prohibition does not apply to compensation paid or given for service as an external director in accordance with regulations promulgated under the Companies Law or
amounts paid pursuant to indemnification and/or exculpation contracts or commitments and insurance coverage.
Following the termination of an external director’s service on a board of directors, such former external director and his or her spouse and children may not be
provided a direct or indirect benefit by the company, its controlling shareholder or any entity under its controlling shareholder’s control. This includes engagement to serve as
an executive officer or director of the company or a company controlled by its controlling shareholder or employment by, or providing services to, any such company for
consideration, either directly or indirectly, including through a corporation controlled by the former external director, for a period of two years (and for a period of one year
with respect to relatives of the former external director).
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If at the time an external director is appointed all members of the board of directors are of the same gender, the external director must be of the other gender. A
director of one company may not be appointed as an external director of another company if a director of the other company is acting as an external director of the first
company at such time.
The Companies Law provides that an external director must meet certain professional qualifications or have financial and accounting expertise and that at least one
external director must have financial and accounting expertise. However, if at least one of our other directors (1) meets the independence requirements of the Exchange Act,
(2) meets the standards of the Nasdaq Rules for membership on the audit committee and (3) has financial and accounting expertise as defined in the Companies Law and
applicable regulations, then neither of our external directors is required to possess financial and accounting expertise as long as both possess other requisite professional
qualifications. Our Board of Directors is required to determine whether a director possesses financial and accounting expertise by examining whether, due to the director’s
education, experience and qualifications, the director is highly proficient and knowledgeable with regard to business-accounting issues and financial statements, to the extent
that the director is able to engage in a discussion concerning the presentation of financial information in the company’s financial statements, among others. Furthermore, our
Board of Directors is also required to take into consideration a director’s education, experience and knowledge in any of the following: (1) accounting issues and accounting
control issues characteristic to the segment in which the company operates and to companies of the size and complexity of the company, (2) the functions of the external
auditor and the obligations imposed on such auditor, and (3) preparation of financial reports and their approval in accordance with the Companies Law and the Israeli
Securities Law, 5728-1968, or the Israeli Securities Law. The regulations define a director with the requisite professional qualifications as a director who satisfies one of the
following requirements: (1) the director holds an academic degree in either economics, business administration, accounting, law or public administration; (2) the director
either holds an academic degree in any other field or has completed another form of higher education in the company’s primary field of business or in an area which is relevant
to the office of an external director; or (3) the director has at least five years of experience serving in any one of the following, or at least five years of cumulative experience
serving in two or more of the following capacities: (1) a senior business management position in a corporation with a substantial scope of business; (2) a senior position in the
company’s primary field of business; or (3) a senior position in public administration. Our Board of Directors has determined that Mr. Rami Dar possesses “accounting and
financial” expertise, and that both of our external directors possess the requisite professional qualifications.
In addition, the Companies Regulations (Relief for Companies the Shares of which are Registered for Trading Outside of Israel) – 2000, or the Relief Regulations,
provide an exemption for companies the shares of which are listed for trading on specified exchanges outside of Israel, including Nasdaq, provided that: (i) such company does
not have a controlling shareholder; and (ii) the company complies with the requirements of the foreign securities laws and stock exchange regulations applicable to companies
which are incorporated under the laws of such foreign countries with regard to appointing independent directors and composition of the audit and compensation committees,
or collectively, Eligible Companies. Any Eligible Company which opts to comply with the applicable foreign securities laws and stock exchange regulations shall be exempt
from the following rules under the Companies Law: (i) the requirement to have at least two external directors appointed to serve in a public company; (ii) that at least one of
the external directors is required to have financial and accounting expertise and the rest are required to have professional expertise; and (iii) that all of the board committees
which are empowered and authorized to exercise any of the board’s authorities must consist of at least one external director. The exemption from these rules under the Relief
Regulations requires that the board be composed of both male and female directors.
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Audit Committee
Under the Companies Law, the board of directors of a public company must appoint an audit committee. The audit committee must be comprised of at least three
directors, including all of the external directors, and one of the external directors must serve as chairperson of the committee. Additionally, a majority of the members of the
committee must be independent directors. The audit committee of a company may not include:
•
•
•
the chairman of the company’s board of directors;
a controlling shareholder or a relative of a controlling shareholder of the company (as each such term is defined in the Companies Law); or
any director employed by the company, by a controlling shareholder of the company or by any other entity controlled by a controlling shareholder of the
company, or any director who provides services to the company, to a controlling shareholder of the company or to any other entity controlled by a controlling
shareholder of the company on a regular basis (other than as a member of the board of directors), or any other director whose main source of income derives
from a controlling shareholder of the company.
The term “controlling shareholder” is defined in the Companies Law as a shareholder with the ability to direct the activities of the company, other than by virtue of
being an office holder. A shareholder is presumed to be a controlling shareholder if the shareholder holds 50% or more of the voting rights in a company or has the right to
appoint the majority of the directors of the company or its general manager.
A majority of the total number of then-serving members of an audit committee shall constitute a quorum for the transaction of business at the audit committee
meetings, provided, that the majority of the members present at such meeting are unaffiliated directors and at least one of such members is an external director.
The audit committee of a publicly traded company must consist of a majority of independent directors. An “independent director” is defined as either an external
director or as a director who meets the following criteria:
•
•
he or she meets the qualifications for being appointed as an external director, except for (i) the requirement that the director be an Israeli resident (which does not
apply to companies such as ours whose securities have been offered outside of Israel or are listed outside of Israel) and (ii) the requirement for accounting and
financial expertise or professional qualifications; and
he or she has not served as a director of the company for a period exceeding nine consecutive years. For this purpose, a break of less than two years in the service
shall not be deemed to interrupt the continuation of the service.
Any person who is not eligible to serve on the audit committee is further restricted from participating in its meetings and votes, unless the chairman of the audit
committee determines that such person’s presence is necessary in order to present a certain matter, provided however, that company employees who are not controlling
shareholders or relatives of such shareholders may be present in the meetings but not for the actual votes, and likewise, company counsel or company secretary who are not
controlling shareholders or relatives of such shareholders may be present in the meetings and for the decisions if such presence is requested by the audit committee.
Pursuant to Nasdaq Rules, our Board of Directors may appoint one director to our Audit Committee who (1) is not an Independent Director as defined in Nasdaq
Marketplace Rule 5605(a)(2), (2) meets the criteria set forth in Section 10A(m)(3) under the Exchange Act, and (3) is not one of our current officers or employees or “family
member,” as defined in Nasdaq Marketplace Rule 5605(a)(2), of an officer or employee, if our Board of Directors, under exceptional and limited circumstances, determines
that the appointment is in our best interests and the best interest of our shareholders, and our Board of Directors discloses, in our next annual report subsequent to the
determination, the nature of the relationship and the reasons for that determination.
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The members of our Audit Committee are Mr. Rami Dar (Chairperson), Dr. Avraham Molcho and Dr. Raphael Hofstein.
Our Board of Directors has determined that Mr. Rami Dar (Chairperson) qualifies as an audit committee financial expert as defined by rules of the SEC.
In November 2012, our Board of Directors adopted an audit committee charter that added to the responsibilities of our Audit Committee under the Companies Law,
setting forth the responsibilities of the audit committee consistent with the rules of the SEC and the Nasdaq Rules, including the following:
•
•
•
oversight of the company’s independent registered public accounting firm and recommending the engagement, compensation or termination of engagement of
our independent registered public accounting firm to our Board of Directors in accordance with Israeli law;
recommending the engagement or termination of the office of our internal auditor; and
reviewing and pre-approving the terms of audit and non-audit services provided by our independent auditors.
Our Audit Committee provides assistance to our Board of Directors in fulfilling its legal and fiduciary obligations in matters involving our accounting, auditing,
financial reporting, internal control and legal compliance functions by pre-approving the services performed by our independent accountants and reviewing their reports
regarding our accounting practices and systems of internal control over financial reporting. Our Audit Committee also oversees the audit efforts of our independent
accountants and takes those actions it deems necessary to satisfy itself that the accountants are independent of management. Pursuant to the Companies Law, the audit
committee of a company shall be responsible for: (i) determining whether there are delinquencies in the business management practices of a company, including in
consultation with an internal auditor or independent auditor, and making recommendations to the company’s board of directors to improve such practices; (ii) determining
whether to approve certain related party transactions (including compensation of office holders or transactions in which an office holder has a personal interest and whether
such transaction is material or otherwise an extraordinary transaction); (iii) where the company’s board of directors approves the working plan of the internal auditor,
examining such working plan before its submission to the board and proposing amendments thereto; (iv) examining internal control and the internal auditor’s performance,
including whether the internal auditor has sufficient resources and tools to dispose of his responsibilities (taking into consideration the special needs and size of a company);
(v) examining the scope of the auditor’s work and compensation and submitting its recommendation with respect thereto to the corporate body considering the appointment
thereof (either the board or the general meeting of shareholders); and (vi) establishing procedures for the handling of employees’ complaints as to the management of the
business and the protection to be provided to such employees. The responsibilities of the audit committee under the Companies Law also include the following matters: (i) the
establishment of procedures to be followed in respect of related party transactions with a controlling shareholder (where such are not extraordinary transactions), which may
include, where applicable, the establishment of a competitive process for such transaction, under the supervision of the audit committee, or individual, or other committee or
body selected by the audit committee, in accordance with criteria determined by the audit committee; and (ii) to determine procedures for approving certain related party
transactions with a controlling shareholder, which having been determined by the audit committee not to be extraordinary transactions, were also determined by the audit
committee not to be negligible transactions. Under the Companies Law, the approval of the audit committee is required for specified actions and transactions with office
holders and controlling shareholders. See “— Approval of Related Party Transactions under Israeli Law.”
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Pursuant to the Relief Regulations, companies the shares of which are listed for trading on specified exchanges outside of Israel, including Nasdaq, and which qualify
as Eligible Companies, are exempt from the following rules regarding the audit committee under the Companies Law: (i) the committee shall be comprised of at least three
members, who shall include all of the external directors, and the majority of the members shall be independent; (ii) certain persons may not be members of the audit
committee; (iii) the controlling shareholder or his relatives shall not be members of the audit committee; (iv) the chairman of the audit committee shall be an external director;
(v) a person who is prohibited from being a member of the audit committee shall not be present at the committee’s meetings; (vi) if the committee also serves as a financial
reports committee, the rules applicable to the financial reports committee shall apply; and (vii) the legal quorum shall be the majority of the committee members, provided that
the majority of directors present are independent, at least one of whom is an external director.
Compensation Committee
Pursuant to the Companies Law, the board of directors of an Israeli publicly-traded company is required to appoint a compensation committee comprised of at least
three members, including all of the external directors of a company, and one of the external directors must serve as chairman of the committee. A majority of the members of
the Compensation Committee are required to be external directors and the rest of the members shall be members whose terms of service are as required under the Companies
Law. Such compensation committee may not include:
•
•
•
the chairman of the company’s board of directors;
a controlling shareholder or a relative of a controlling shareholder of the company (as each such term is defined in the Companies Law); or
any director employed by the company, by a controlling shareholder of the company or by any other entity controlled by a controlling shareholder of the
company, or any director who provides services to the company on a permanent basis, to a controlling shareholder of the company or to any other entity
controlled by a controlling shareholder of the company on a regular basis (other than as a member of the board of directors), or any other director whose main
source of income derives from a controlling shareholder of the company.
A majority of the total number of then-serving members of a compensation committee shall constitute a quorum for the transaction of business at the compensation
committee meetings. The compensation committee of a publicly-traded company must consist of a majority of external directors.
Pursuant to the Relief Regulations, companies the shares of which are listed for trading on specified exchanges outside of Israel, including Nasdaq and qualify as
Eligible Companies are exempt from the following rules regarding the compensation committee under the Companies Law: (i) the board of a public company is required to
appoint a compensation committee; and (ii) the compensation committee shall be comprised of at least three members, all of the external directors shall be members and shall
constitute the majority of its members and the rest of the members shall be members whose terms of service are as required under the Companies Law.
Any person who is not eligible to serve on the compensation committee is further restricted from participating in its meetings and votes, unless the chairman of the
compensation committee determines that such person’s presence is necessary in order to present a certain matter, provided however, that company employees who are not
controlling shareholders or relatives of such shareholders may be present in the meetings but not for the actual votes, and likewise, company counsel and secretary who are not
controlling shareholders or relatives of such shareholders may be present in the meetings and for the decisions if such presence is requested by the compensation committee.
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The responsibilities of the compensation committee include the following:
•
•
•
•
•
to make recommendations to the board of directors as to a compensation policy for officers, as well as to recommend once every three years to extend the
compensation policy, subject to receipt of the required corporate approvals;
to make recommendations to the board of directors as to any updates to the compensation policy which may be required;
to review the implementation of the compensation policy by the company;
to approve transactions relating to terms of office and employment of certain company office holders, that require the approval of the compensation committee
pursuant to the Companies Law; and
to exempt, under certain circumstances, a transaction relating to terms of office and employment from the requirement of approval of the shareholders meeting.
Our Compensation Committee is comprised of Dr. Raphael Hofstein, Dr. B.J Bormann and our two external directors Mr. Rami Dar, who was elected by our
shareholders as an external director, in July 2022 and Dr. Avraham Molcho who serves as the Chairperson of our Compensation Committee.
Under the Companies Law, a board of directors of an Israeli publicly-traded company, following the recommendation of the compensation committee, is required to
establish a compensation policy, to be approved by the shareholders of the company, and pursuant to which the terms of office and compensation of the company’s officer
holders will be decided.
A company’s compensation policy shall be determined based on, and take into account, certain parameters set forth in Section 267B(a) and Parts A and B of Annex
1A of the Companies Law, which were legislated as part of Amendment 20.
Under the Companies Law, the board of directors of a publicly traded company is obligated, after considering the recommendations of the compensation committee,
to adopt a compensation policy according to which the compensation of the company’s office holders will be determined. The final adoption of the compensation policy is
subject to the approval of the shareholders of the company, and such approval is subject to certain special majority requirements, as set forth in the Companies Law, pursuant
to which one of the following must be met:
(i)
the majority of the votes includes at least a majority of all the votes of shareholders who are not controlling shareholders of the company or who do not have a
personal interest in the compensation policy and participating in the vote; abstentions shall not be included in the total of the votes of the aforesaid shareholders;
or
(ii) the total of opposing votes from among the shareholders described in subsection (i) above does not exceed 2% of all the voting rights in the company.
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For this purpose, under the Companies Law “personal interest” is defined as: (1) a shareholder’s personal interest in the approval of an act or a transaction of the
company, including (i) the personal interest of his or her relative (which includes for these purposes any members of his/her (or his/her spouse’s) immediate family or the
spouses of any such members of his or her (or his/her spouse’s) immediate family); and (ii) a personal interest of a body corporate in which a shareholder or any of his/her
aforementioned relatives serves as a director or the chief executive officer, owns at least 5% of its issued share capital or its voting rights or has the right to appoint a director
or chief executive officer, but (2) excluding a personal interest arising solely from the fact of holding shares in the company or in a body corporate.
Nonetheless, even if the shareholders of the company do not approve the compensation policy, the board of directors of a company may approve the compensation
policy, provided that the compensation committee and, thereafter, the board of directors resolved, based on detailed, documented, reasons and after a second review of the
compensation policy, that the approval of the compensation policy is for the benefit of the company.
In December 2013, a general meeting of our shareholders approved our first Executive Compensation Policy which had been recommended by our Compensation
Committee and approved by our Board of Directors. At the annual general meeting of our shareholders in 2022, our shareholders approved our current Compensation Policy.
Below is a summary discussion of the main provisions of the Compensation Policy:
The Compensation Policy includes, among other issues prescribed by the Companies Law, a framework for establishing the terms of office and employment of our
office holders, a recoupment policy and guidelines with respect to the structure of the variable pay of our office holders.
Compensation is considered performance-based to the extent that a direct link is maintained between compensation and performance and that rewards are consistent
with long-term stakeholder value creation. At the company level, we analyze the overall compensation trends of the market in order to make informed decisions about our
compensation approach.
According to the Compensation Policy, the fixed components of our office holder compensation will be examined at least every two years and compared to the
market. Our Board of Directors may change the amount of the fixed components for one or more of our office holders after receiving a recommendation for such from our
Compensation Committee, provided such change is within the limits determined by the Compensation Policy. The change may be made if our Board of Directors concludes
that such a change would promote our goals, operating plans and objectives and after taking into account the business and legal implications of the proposed change and its
impact on our internal labor relations. Any such changes are subject to formal approval by the relevant parties. Our Board of Directors will has the authority to approve a
change in the incentive structure of all executive officers, including but not limited to the chief executive officer, up to an immaterial amount in any one year (immaterial being
defined as a change of up to 5% of an officer’s total compensation). The fixed component of compensation remunerates the specific role covered and scope of responsibilities.
It also reflects the experience and skills required for each position, as well as the level of excellence demonstrated and the overall quality of the office holder’s contribution to
our business. The weighting of fixed compensation within the overall package is designed to reduce the risk of excessively risk-oriented behavior, to discourage initiatives
focused on short-term results which might jeopardize our mid and long-term business sustainability and value creation, and to allow us a flexible compensation approach. We
offer our employees benefit plans based on common practice in the local labor market of the office holder.
As for the variable components of compensation, the types and amounts of such components will be determined with an aim at creating maximum matching between
the Compensation Policy and our operating plan and objectives. Variable components of compensation will be primarily based on measurable long-term criteria. Nevertheless,
we are allowed to base a non-material part of variable compensation on qualitative non-measurable criteria which focus on the office holder’s contribution to the Company.
Our variable compensation aims to remunerate for achievements by directly linking pay to performance outcomes in the short and long term. To strengthen the alignment of
shareholder interests and the interests of management and employees, performance measurements reflect our actual results overall, as well as of the individual office holder.
To support the aforementioned principles, we provide two types of variable compensation: short-term - annual bonus; and long-term - stock option plans.
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Annual bonuses will be based on achievement of the business goals set out in our annual operating plan approved by the board of directors at the beginning of each
year. The operating plan encompasses all aspects of our activities and as such sets the business targets for each member of the management team. Consequently, our
Compensation Committee and Board of Directors should be able to judge the suitability of a bonus payment by deliberating retrospectively at year end and comparing actual
performance and target achievements against the forecasted operating plan. The annual bonus mechanism will be directly tied to meeting objectives - both our business
objectives and the office holder’s personal objectives. The Board of Directors’ satisfaction with the officer’s performance will also affect the bonus amount. Annual bonus
payments are subject to the limitations set out in the Compensation Policy and also subject to the discretion of our Compensation Committee and approval by the Board of
Directors. In order to maintain some measure of flexibility, after calculating the compensation amount, the Board of Directors may exercise discretion about the final amount
of the bonus.
Equity-based compensation may be granted in any form permitted under our share incentive plan in effect from time to time and shall be made in accordance with the
terms of such share incentive plan. Equity-based compensation to office holders shall be granted from time to time and be individually determined and awarded according to
the performance, educational background, prior business experience, qualifications, role and the personal responsibilities of each officer. The vesting period will generally be
four years, with the vesting schedule to be determined in accordance with market compensation trends. Our policy is to grant equity-based compensation with exercise prices
at market value. Furthermore, in order to create a ceiling for the variable compensation: (1) the aggregate value of annual grants to any one office holder (based on the Black
Scholes calculation as of the date of grant) will be no more than the higher of 2% of our market capitalization at the end of the measurement period or $1.5 million; and (2) it
is our intention that the maximum outstanding equity awards under its share incentive plan will not exceed 12% of our total fully-diluted share capital. Our Board of Directors
may, following approval by our Compensation Committee, make provisions with respect to the acceleration of the vesting period of any office holder’s awards, including,
without limitation, in connection with a corporate transaction involving a change of control.
We have also established a defined ratio between the variable and the fixed components of compensation, as well as a maximum amount for all variable components
as of the date on which they are paid (or as of the grant date for non-cash variable equity components), and subject to the limitations on variable compensation components
which are set out in the Compensation Policy. In all events, the weight of all the variable components (out of the total compensation amount which is to be granted for any
year will not be greater than 80% for each office holder and may vary from one office holder to the other).
In the event of an accounting restatement, we shall be entitled to recover from office holders’ bonus compensation granted, earned or vested based on a pre-
accounting restatement of our financial results in the amount of the excess over what would have been paid under the accounting restatement, with a three-year look-back
period. However, the compensation recovery will not be triggered in the event of a financial restatement required due to changes in applicable financial reporting standards.
All compensation arrangements of office holders are to be approved in the manner prescribed by applicable law. Our Compensation Committee will review the
Compensation Policy on an annual basis, and monitor its implementation, and recommend to our Board of Directors and shareholders to amend the Compensation Policy as it
deems necessary from time to time. The term of the Compensation Policy is three years from the date of its adoption, or July 2, 2022. Following such three-year term, the
Compensation Policy, including any revisions recommended by our Compensation Committee and approved by our Board of Directors, as applicable, will be brought once
again to the shareholders for approval.
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Nominating Committee
Our Board of Directors does not currently have a nominating committee, having availed BioLineRx of the exemption available to foreign private issuers under the
Nasdaq Rules. See “Item 16G. Corporate Governance.”
Investment Monitoring Committee
Our Board of Directors has established an Investment Monitoring Committee which consists of the following four members: Directors Dr. Michael Anghel
(Chairperson) and Mr. Rami Dar; Ms. Mali Zeevi, our Chief Financial Officer; and Mr. Raziel Fried, our Treasurer and Budgetary Control Director. The function of the
Investment Monitoring Committee includes providing recommendations to our Board of Directors regarding investment guidelines and performing an on-going review of the
fulfillment of established investment guidelines. The Investment Monitoring Committee convenes for a meeting in accordance with our needs, but in any event at least twice
per year.
Internal Auditor
Under the Companies Law, the board of directors of an Israeli public company must appoint an internal auditor recommended by the audit committee and nominated
by the board of directors. An internal auditor may not be:
•
•
•
•
a person (or a relative of a person) who holds more than 5% of the company’s shares;
a person (or a relative of a person) who has the power to appoint a director or the general manager of the company;
an executive officer or director of the company; or
a member of the company’s independent accounting firm.
The role of the internal auditor is to examine, among other things, our compliance with applicable law and orderly business procedures. Our internal auditor is Tali
Yaron Adv. (LLB, LLM), a director at Deloitte Israel.
Approval of Related Party Transactions under Israeli Law
Fiduciary duties of office holders
The Companies Law imposes a duty of care and a duty of loyalty on all office holders of a company. The duty of care of an office holder is based on the duty of care
set forth in connection with the tort of negligence under the Israeli Torts Ordinance (New Version) 5728-1968. This duty of care requires an office holder to act with the degree
of proficiency with which a reasonable office holder in the same position would have acted under the same circumstances.
The duty of care includes a duty to use reasonable means, in light of the circumstances, to obtain:
•
information on the advisability of a given action brought for his or her approval or performed by virtue of his or her position; and
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•
all other important information pertaining to these actions.
The duty of loyalty requires an office holder to act in good faith and for the benefit of the company, and includes the duty to:
•
•
•
•
refrain from any act involving a conflict of interest between the performance of his or her duties in the company and his or her other duties or personal affairs;
refrain from any activity that is competitive with the business of the company;
refrain from exploiting any business opportunity of the company for the purpose of gaining a personal advantage for himself or herself or others; and
disclose to the company any information or documents relating to the company’s affairs which the office holder received as a result of his or her position as an
office holder.
We may approve an act performed in breach of the duty of loyalty of an office holder provided that the office holder acted in good faith, the act or its approval does
not harm the company, and the office holder discloses his or her personal interest, as described below.
Disclosure of personal interests of an office holder and approval of acts and transactions
The Companies Law requires that an office holder promptly disclose to the company any personal interest that he or she may have and all related material
information or documents relating to any existing or proposed transaction by the company. An interested office holder’s disclosure must be made promptly and in any event no
later than the first meeting of the board of directors at which the transaction is considered. An office holder is not obliged to disclose such information if the personal interest
of the office holder derives solely from the personal interest of his or her relative in a transaction that is not considered as an extraordinary transaction.
The term personal interest is defined under the Companies Law to include the personal interest of a person in an action or in the business of a company, including the
personal interest of such person’s relative or the interest of any corporation in which the person or any of his/her relatives serves as a director or the chief executive officer,
owns at least 5% of its issued share capital or its voting rights or has the right to appoint a director or chief executive officer, but excluding a personal interest stemming solely
from the fact of holding shares in such corporation. A personal interest furthermore includes the personal interest of a person for whom the office holder holds a voting proxy
or the interest of the office holder with respect to his or her vote on behalf of the shareholder for whom he or she holds a proxy even if such shareholder itself has no personal
interest in the approval of the matter. An office holder is not, however, obliged to disclose a personal interest if it derives solely from the personal interest of his or her relative
in a transaction that is not considered an extraordinary transaction.
Under the Companies Law, an extraordinary transaction which requires approval is defined as any of the following:
•
•
•
a transaction other than in the ordinary course of business;
a transaction that is not on market terms; or
a transaction that may have a material impact on the company’s profitability, assets or liabilities.
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Under the Companies Law, once an office holder has complied with the disclosure requirement described above, a company may approve a transaction between the
company and the office holder or a third party in which the office holder has a personal interest, or approve an action by the office holder that would otherwise be deemed a
breach of duty of loyalty. However, a company may not approve a transaction or action that is adverse to the company’s interest or that is not performed by the office holder in
good faith.
Under the Companies Law, unless the articles of association of a company provide otherwise, a transaction with an office holder, a transaction with a third party in
which the office holder has a personal interest, and an action of an office holder that would otherwise be deemed a breach of duty of loyalty requires approval by the board of
directors. Our Articles of Association do not provide otherwise. If the transaction or action considered is (i) an extraordinary transaction or (ii) an action of an office holder
that would otherwise be deemed a breach of duty of loyalty and may have a material impact on a company’s profitability, assets or liabilities, then audit committee approval is
required prior to approval by the board of directors.
Under the Companies Law, a transaction with an office holder in a public company regarding his or her terms of office and employment should be determined in
accordance with the company’s compensation policy. Nonetheless, provisions were established that allow a company, under special circumstances, to approve terms of office
and employment that are not in line with the approved compensation policy. The following are required for the approval of the terms of office or employment of the officers
of a public company:
•
•
A transaction with an office holder in a public company that is neither a director nor the chief executive officer regarding his or her terms of office and
employment requires approval by the (i) compensation committee; and (ii) the board of directors. Approval of terms of office and employment for such officers
which do not comply with the compensation policy may nonetheless be approved subject to two cumulative conditions: (i) the compensation committee and
thereafter the board of directors, approved the terms after having taken into account the various considerations and mandatory requirements set forth in the
Companies Law with respect to office holder compensation, and (ii) the shareholders of the company have approved the terms by means of the following special
majority requirements, or the Special Majority Requirements, as set forth in the Companies Law, pursuant to which the shareholder approval must either include
at least one-half of the shares held by non-controlling and disinterested shareholders who actively participate in the voting process (without taking abstaining
votes into account), or, alternatively, the total shareholdings of the non-controlling and disinterested shareholders who vote against the transaction must not
represent more than 2% of the voting rights in the company. However, the transaction may still be approved despite shareholder rejection, provided that a
company’s compensation committee and thereafter the board of directors have determined to approve the proposal, based on detailed reasoning, after having re-
examined the terms of office and employment, and taken the shareholder rejection into consideration.
A transaction with the chief executive officer in a public company regarding his or her terms of office and employment requires approval by the (i) compensation
committee; (ii) the board of directors; and (iii) the shareholders of the company by the Special Majority Requirements. Approval of terms of office and
employment for the chief executive officer which do not comply with the compensation policy may nonetheless be approved subject to two cumulative
conditions: (i) the compensation committee and thereafter the board of directors, approved the terms after having taken into account the various considerations
and mandatory requirements set forth in the Companies Law with respect to office holder compensation and (ii) the shareholders of the company have approved
the terms by means of the Special Majority Requirements, as detailed above. However, a transaction with a chief executive officer that is not approved by
shareholders may still be approved despite shareholder rejection, provided that a company’s compensation committee and thereafter the board of directors have
determined to approve the proposal, based on detailed reasoning, after having re-examined the terms of office and employment, and taken the shareholder
rejection into consideration. In addition, the compensation committee may exempt the transaction from shareholder approval of terms of office and employment
with a candidate for the office of chief executive officer where such officer has no relationship with the controlling shareholder or the company, if it has found,
based on detailed reasons, that bringing the transaction to the approval of the shareholders meeting shall prevent the employment of such candidate by the
company. Such approval may be given only in respect of terms of office and employment which are in accordance with the company’s compensation policy.
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In July 2022, our shareholders voted against a proposal to grant Mr. Philip Serlin, our Chief Executive Officer, equity compensation that had been determined by
our Board of Directors to be reasonable and to comply with the requirements of our Compensation Policy. In August 2022, our Board of Directors, on
recommendation of our Compensation Committee, determined to approve the proposal based on the criteria set forth above, i.e., the determination was based on
detailed reasoning after having re-examined Mr. Serlin’s terms of employment and having taken into account the rejection by the shareholders.
•
A transaction with a director who is not the chief executive officer of a public company regarding his or her terms of office and engagement requires approval by
the (i) compensation committee; (ii) the board of directors; and (iii) the shareholders of the company. Approval of terms of office and employment for directors
of a company which do not comply with the compensation policy may nonetheless be approved subject to two cumulative conditions: (i) the compensation
committee and thereafter the board of directors, approved the terms after having taken into account the various considerations and mandatory requirements set
forth in the Companies Law with respect to office holder compensation and (ii) the shareholders of the company have approved the terms by means of the
Special Majority Requirements, as detailed above. In addition, pursuant to a relief provided under the Companies Regulations (Relief in Interested Party
Transactions), 2000, the compensation committee may exempt the transaction from shareholder approval of the terms of office and engagement with a non-
executive director, if the compensation committee and board of directors determined that such terms of office are only for the benefit of the company, or if the
compensation terms of the director do not exceed the maximum compensation paid to external directors pursuant to the applicable regulations.
A director who has a personal interest in a matter that is considered at a meeting of the board of directors or the audit committee may generally not be present at the
meeting or vote on the matter unless a majority of the directors or members of the audit committee have a personal interest in the matter, or, unless the chairman of the audit
committee or board of directors (as applicable) determines that he or she should be present to present the transaction that is subject to approval. If a majority of the directors
have a personal interest in the matter, such matter also requires approval of the shareholders of the company by the Special Majority Requirements.
Disclosure of personal interests of a controlling shareholder and approval of transactions
Under the Companies Law, the disclosure requirements that apply to an office holder also apply to a controlling shareholder of a public company. See “— Audit
Committee” for the general definition of “controlling shareholder” under the Companies Law. In connection with matters governing: (i) extraordinary transactions with a
controlling shareholder or in which a controlling shareholder has a personal interest, (ii) certain private placements in which the controlling shareholder has a personal interest,
(iii) certain transactions with a controlling shareholder or relative with respect to services provided to or employment by the company, (iv) the terms of employment and
compensation of the general manager, and (v) the terms of employment and compensation of office holders of the company when such terms deviate from the compensation
policy previously approved by the company’s shareholders, the definition of “controlling shareholder” also includes shareholders that hold 25% or more of the voting rights if
no other shareholder owns more than 50% of the voting rights in the company (and the holdings of two or more shareholders which each have a personal interest in such
matter will be aggregated for the purposes of determining such threshold).
103
Under the Companies Law, extraordinary transactions with a controlling shareholder or in which a controlling shareholder has a personal interest, including a private
placement in which a controlling shareholder has a personal interest, as well as transactions for the provision of services whether directly or indirectly by a controlling
shareholder or his or her relative, or a company such controlling shareholder controls, require the approval of the audit committee, the board of directors and the shareholders,
in that order. Transactions concerning the terms of engagement of a controlling shareholder or a controlling shareholder’s relative, whether as an office holder or an employee,
require the approval of the compensation committee, the board of directors and the shareholders, in that order. In addition, the approval of such extraordinary transactions by
the shareholders require at least a majority of the shares voted by the shareholders of the company participating and voting in a shareholders’ meeting, provided that one of the
following requirements is fulfilled:
•
•
at least a majority of the shares held by shareholders who have no personal interest in the transaction and are voting at the meeting must be voted in favor of
approving the transaction, excluding abstentions; or
the shares voted by shareholders who have no personal interest in the transaction who vote against the transaction represent no more than 2% of the voting rights
in the company.
If such transaction concerns the terms of office and employment of such controlling shareholder, in his capacity as an office holder or an employee of the company,
such terms of office and employment approved by the compensation committee and board of directors shall be in accordance with the compensation policy of the company.
Nonetheless, the compensation committee and the board of directors may approve terms of office and compensation of a controlling shareholder which do not comply with the
company’s compensation policy, provided that the compensation committee and, thereafter, the board of directors approve such terms, based on, among other things, the
considerations and mandatory requirements set forth in the Companies Law. Following such approval by the compensation committee and board of directors, shareholder
approval would be required.
To the extent that any such transaction with a controlling shareholder is for a period extending beyond three years, approval, in the same manner described above, is
required once every three years, unless, with respect to extraordinary transactions with a controlling shareholder or in which a controlling shareholder has a personal interest,
the audit committee determines that the duration of the transaction is reasonable given the circumstances related thereto.
Duties of shareholders
Under the Companies Law, a shareholder has a duty to refrain from abusing its power in the company and to act in good faith and in an acceptable manner in
exercising its rights and performing its obligations to the company and other shareholders, including, among other things, voting at general meetings of shareholders on the
following matters:
•
•
•
an amendment to the articles of association;
an increase in the company’s authorized share capital;
a merger; and
104
•
the approval of related party transactions and acts of office holders that require shareholder approval.
A shareholder also has a general duty to refrain from discriminating against other shareholders.
The remedies generally available upon a breach of contract will also apply to a breach of the above-mentioned duties, and in the event of discrimination against other
shareholders, additional remedies are available to the injured shareholder.
In addition, any controlling shareholder, any shareholder that knows that its vote can determine the outcome of a shareholder vote and any shareholder that, under a
company’s articles of association, has the power to appoint or prevent the appointment of an office holder, or has another power with respect to a company, is under a duty to
act with fairness towards the company. The Companies Law does not describe the substance of this duty except to state that the remedies generally available upon a breach of
contract will also apply in the event of a breach of the duty to act with fairness, taking the shareholder’s position in the company into account.
Exculpation, insurance and indemnification of office holders
Under the Companies Law, a company may not exculpate an office holder from liability for a breach of the duty of loyalty. An Israeli company may exculpate an
office holder in advance from liability to the company, in whole or in part, for damages caused to the company as a result of a breach of duty of care but only if a provision
authorizing such exculpation is included in its articles of association. Our Articles of Association include such a provision. An Israeli company may not exculpate a director
from liability arising out of a prohibited dividend or distribution to shareholders.
An Israeli company may indemnify an office holder in respect of the following liabilities and expenses incurred for acts performed as an office holder, either in
advance of an event or following an event, provided a provision authorizing such indemnification is contained in its articles of association:
•
•
•
financial liability imposed on him or her in favor of another person pursuant to a judgment, settlement or arbitrator’s award approved by a court. However, if an
undertaking to indemnify an office holder with respect to such liability is provided in advance, then such an undertaking must be limited to events which, in the
opinion of the board of directors, can be foreseen based on the company’s activities when the undertaking to indemnify is given, and to an amount or according
to criteria determined by the board of directors as reasonable under the circumstances, and such undertaking shall detail the abovementioned events and amount
or criteria;
reasonable litigation expenses, including attorneys’ fees, incurred by the office holder as a result of an investigation or proceeding instituted against him or her by
an authority authorized to conduct such investigation or proceeding, provided that (1) no indictment was filed against such office holder as a result of such
investigation or proceeding; and (2) no financial liability, such as a criminal penalty, was imposed upon him or her as a substitute for the criminal proceeding as a
result of such investigation or proceeding or, if such financial liability was imposed, it was imposed with respect to an offense that does not require proof of
criminal intent;
a monetary liability imposed on an office holder in favor of an injured party at an Administrative Procedure (as defined below) pursuant to Section 52(54)(a)(1)
(a) of the Securities Law;
105
•
•
expenses incurred by an office holder or certain compensation payments made to an injured party that were instituted against an office holder in connection with
an Administrative Procedure under the Securities Law, including reasonable litigation expenses and reasonable attorneys’ fees; and
reasonable litigation expenses, including attorneys’ fees, incurred by the office holder or imposed by a court in proceedings instituted against him or her by the
company, on its behalf or by a third party or in connection with criminal proceedings in which the office holder was acquitted or as a result of a conviction for an
offense that does not require proof of criminal intent.
An “Administrative Procedure” is defined as a procedure pursuant to chapters H3 (Monetary Sanction by the Israeli Securities Authority), H4 (Administrative Enforcement
Procedures of the Administrative Enforcement Committee) or I1 (Arrangement to prevent Procedures or Interruption of procedures subject to conditions) to the Securities
Law, which may result in sanctions, including monetary sanctions and certain restrictions on serving as a director or senior officer of a public company for certain periods of
time.
An Israeli company may insure an office holder against the following liabilities incurred for acts performed as an office holder if and to the extent provided in the
company’s articles of association:
•
•
•
•
•
a breach of duty of loyalty to the company, to the extent that the office holder acted in good faith and had a reasonable basis to believe that the act would not
prejudice the company;
a breach of duty of care to the company or to a third party, including a breach arising out of the negligent (but not grossly negligent) conduct of the office holder;
a financial liability imposed on the office holder in favor of a third party;
a monetary liability imposed on the office holder in favor of an injured party at an Administrative Procedure pursuant to Section 52(54)(a)(1)(a) of the Securities
Law; and
expenses incurred by an office holder in connection with an Administrative Procedure instituted against him or her, including reasonable litigation expenses and
reasonable attorneys’ fees.
An Israeli company may not indemnify or insure an office holder against any of the following, and any provision in a company’s articles of association which allows
for any of the following is invalid:
•
•
•
a breach of duty of loyalty, except to the extent that the office holder acted in good faith and had a reasonable basis to believe that the act would not prejudice the
company;
a breach of duty of care committed intentionally or recklessly, excluding a breach arising out of the negligent conduct of the office holder;
an act or omission committed with intent to derive illegal personal benefit; or
106
•
a fine or forfeit levied against the office holder.
Under the Companies Law and the regulations promulgated thereunder, exculpation, indemnification and insurance of office holders must be approved by the
compensation committee and the board of directors and must be provided in accordance with the Company’s Compensation Policy duly adopted by the shareholders.
Our Articles of Association allow us to indemnify and insure our office holders for any liability imposed on them as a consequence of an act (including any omission)
which was performed by virtue of being an office holder. In November 2011, our shareholders approved (i) the amendment of our Articles of Association to authorize
indemnification and insurance in connection with administrative enforcement proceedings, including without limitation, the specific amendments to the Israeli Securities Law
and the Companies Law described above and (ii) a new form of indemnification letter for our directors and officers so as to reflect the amendment to our Articles of
Association, which new form of letter was also approved in October 2011 by our Audit Committee and Board of Directors, and in November 2011 by our shareholders. The
terms of such agreements are consistent with the provisions of the Compensation Policy which was approved by our shareholders in July 2022.
Our office holders are currently covered by a directors’ and officers’ liability insurance policy. The terms of such directors’ and officers’ insurance are consistent with
the provisions of the Compensation Policy which was approved by our shareholders in July 2022. The Compensation Policy authorizes us to purchase insurance policies
(including run-off policies) to cover the liability of directors and office holders that are in office at such time and that shall be in office from time to time, including directors
and office holders that may have a controlling interest in the Company. Such insurance policies are authorized within the following limits: the Compensation Committee has
determined that the premium for each policy, the maximum deductible and the terms of the policy are consistent with market conditions and not materially affect our profits,
property or liabilities. In addition, the Compensation Committee is authorized to increase the coverage purchased and/or the premium paid for such policies by up to 20% in
any year, as compared to the previous year, or cumulatively for a number of years, without an additional shareholders’ approval to the extent permitted under the Companies
Law. See also “Related Party Transactions — Indemnification Agreements.”
As of the date of this Annual Report on Form 20-F, except as disclosed in Item 8.A below no claims have been filed under our directors’ and officers’ liability
insurance policy, there is no pending litigation or proceeding against any of our directors or officers as to which indemnification is being sought, nor are we aware of any
pending or threatened litigation that may result in claims for indemnification by any director or officer.
For significant ways in which our corporate governance practices differ from those required by the Nasdaq Rules, see “Item 16G. Corporate Governance.”
D. Employees
As of December 31, 2022, we had 49 employees, 42 of whom are employed in Israel and 7 of whom in the US. Of our employees, 17 hold M.D. or Ph.D. degrees.
Management and administration
Research and development
Sales and marketing
Total
107
2020
December 31,
2021
2022
9
27
2
38
9
27
2
38
12
29
8
49
While none of our employees are party to any collective bargaining agreements, in Israel we are subject to certain labor statutes and national labor court precedent
rulings, as well as to certain provisions of the collective bargaining agreements between the Histadrut (General Federation of Labor in Israel) and the Coordination Bureau of
Economic Organizations (including the Industrialists’ Associations) which are applicable to our employees by virtue of expansion orders issued in accordance with relevant
labor laws by the Israel Ministry of Labor and Welfare, and which apply such agreement provisions to our employees even though they are not directly part of a union that has
signed a collective bargaining agreement. The laws and labor court rulings that apply to our employees principally concern the minimum wage laws, procedures for dismissing
employees, determination of severance pay, leaves of absence (such as annual vacation or maternity leave), sick pay and other conditions for employment. The expansion
orders which apply to our employees principally concern the requirement for length of the workday and work week, mandatory contributions to a pension fund, annual
recreation allowance, travel expenses payment and other conditions of employment. We generally provide our employees with benefits and working conditions beyond the
required minimums.
We have never experienced any employment-related work stoppages and believe our relationship with our employees is good.
E. Share Ownership
The following table sets forth information regarding the beneficial ownership of our outstanding ordinary shares as of March 21, 2023 of each of our directors and
executive officers individually and as a group.
Directors
Aharon Schwartz(1)
Michael J. Anghel(2)
B.J. Bormann(3)
Rami Dar(4)
Raphael Hofstein(5)
Avraham Molcho(6)
Sandra Panem(7)
Executive officers
Philip A. Serlin(8)
Mali Zeevi(9)
Ella Sorani(10)
Tami Rachmilewitz, M.D.(11)
Holly May (12)
Number of
Ordinary
Shares
Beneficially
Held
Percent of
Class
4,425,000
720,000
720,000
270,000
720,000
720,000
720,000
7,960,321
2,421,471
2,171,580
-
-
*
*
*
*
*
*
*
*
*
*
*
All directors and executive officers as a group (12 persons)(13)
20,848,372
1.6%
108
* Less than 1.0%.
(1)
(2)
(3)
(4)
(5)
(6)
(7)
(8)
(9)
Includes 4,425,000 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 810,000 ordinary shares issuable
upon exercise of outstanding options that are not exercisable within 60 days of March 21, 2023.
Includes 720,000 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 810,000 ordinary shares issuable
upon exercise of outstanding options that are not exercisable within 60 days of March 21, 2023.
Includes 720,000 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 810,000 ordinary shares issuable
upon exercise of outstanding options that are not exercisable within 60 days of March 21, 2023.
Includes 270,000 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 810,000 ordinary shares issuable
upon exercise of outstanding options that are not exercisable within 60 days of March 21, 2023.
Includes 720,000 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 810,000 ordinary shares issuable
upon exercise of outstanding options that are not exercisable within 60 days of March 21, 2023.
Includes 720,000 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 810,000 ordinary shares issuable
upon exercise of outstanding options that are not exercisable within 60 days of March 21, 2023.
Includes 720,000 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 810,000 ordinary shares issuable
upon exercise of outstanding options that are not exercisable within 60 days of March 21, 2023.
Includes 7,960,321 issued ordinary shares upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 8,517,853 ordinary shares issuable
upon exercise of outstanding equity instruments that are not exercisable within 60 days of March 21, 2023.
Includes 2,421,471 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 1,942,713 ordinary shares issuable
upon exercise of outstanding equity instruments that are not exercisable within 60 days of March 21, 2023.
(10) Includes 2,171,580 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 2,018,479 ordinary shares issuable
upon exercise of outstanding equity instruments that are not exercisable within 60 days of March 21, 2023.
(11) Does not include 1,740,000 ordinary shares issuable upon exercise of outstanding equity instruments that are not exercisable within 60 days of March 21, 2023.
(12) Does not include 8,566,005 ordinary shares issuable upon exercise of outstanding equity instruments that are not exercisable within 60 days of March 21, 2023.
(13) Includes 20,848,372 ordinary shares issuable upon exercise of outstanding options within 60 days of March 21, 2023. Does not include 28,455,050 ordinary shares
issuable upon exercise of outstanding equity instruments that are not exercisable within 60 days of March 21, 2023.
109
Change in Control
To our knowledge, (i) we are not directly or indirectly owned or controlled by another corporation, by any foreign government or by any other natural or legal person
severally or jointly, except as disclosed in the above table regarding our major shareholders, and (ii) there are no arrangements which would result in our change in control at a
subsequent date.
Significant Changes in the Ownership of Major Shareholders
To our knowledge, other than as disclosed in the table above, our other filings with the SEC and this Annual Report, there has been no significant change in the
percentage ownership held by any major shareholder since January 1, 2019.
Major Shareholders Voting Rights
Our major shareholders do not have different voting rights.
Record Holders
Bank of New York Mellon, or BNY, is the holder of record for the Company’s American Depositary Receipt program, pursuant to which each ADS represents 15
ordinary shares. As of December 31, 2022, BNY held 815,854,571 ordinary shares representing 88.4% of our issued share capital held at that date. Certain of these ordinary
shares were held by brokers or other nominees. As a result, the number of holders of record or registered holders in the United States is not representative of the number of
beneficial holders or of the residence of beneficial holders.
Equity Compensation Plan
2003 Share Incentive Plan
In 2003, we adopted the BioLineRx Ltd. 2003 Share Incentive Plan, or the Plan. The Plan provides for the granting of options, ordinary shares, restricted stock units
and performance stock units to our directors, employees, consultants and service providers, and to the directors, employees, consultants and service providers of our
subsidiaries and affiliates. The Plan provides for equity grants to be made at the determination of our Board of Directors in accordance with applicable law. As of March 15,
2022, there were 43.7 million ordinary shares issuable upon the exercise of outstanding equity grants under the Plan.
In August 2013, our Board of Directors approved amendments to the Plan to take into account changes in laws and regulations that had occurred since its adoption
and to extend the term of the plan until November 2023. In January 2016, our Board of Directors approved amendments to the Plan in order to permit the granting of restricted
stock units, or RSUs, and performance stock units, or PSUs, to eligible grantees.
110
From time to time, our Board of Directors has approved an increase in the number of shares reserved for the purpose of equity grants pursuant to the Plan. As of
March 21, 2023, the number of shares so reserved was 72.4 million.
Administration of Our Plan
Our Plan is administered by our Board of Directors for the purposes of making equity grants and approving the terms of those grants, including, in the case of
options, exercise price, method of payment, vesting schedule, acceleration of vesting and the other matters necessary in the administration of these plans. Equity grants made
under the Plan to eligible employees and office holders are made under Section 102 of the Israel Income Tax Ordinance pursuant to which the securities granted must be
allocated or issued to a trustee and be held in trust for two years from the date upon which such grant was made, provided that securities granted prior to January 1, 2006, or
the ordinary shares issued upon exercise of options, are subject to being held in trust for two years from the end of the year in which the securities are granted. Under Section
102, any tax payable by an employee from the grant of securities or the exercise of options is deferred until the transfer of the securities (or ordinary shares issued upon the
exercise of options) by the trustee to the employee or upon the sale of the securities or ordinary shares, as the case may be, and gains may qualify to be taxed as capital gains at
a rate equal to 25%, subject to compliance with specified conditions.
Options granted under the Plan generally vest over four years, and they expire 10 years from the grant date. If we terminate an employee for cause, all of the
employee’s vested and unvested options expire immediately from the time of delivery of the notice of discharge, unless determined otherwise by the Audit Committee or the
Board of Directors. Upon termination of employment for any other reason, including due to death or disability of the employee, vested options may be exercised within three
months of the termination date, unless otherwise determined by the Compensation Committee or the Board of Directors. Vested options which are not exercised and unvested
options return to the pool of reserved ordinary shares under the Plan for reissuance. The right to receive ordinary shares pursuant to PSUs granted under the Plan will vest
upon the achievement by BioLineRx of certain performance goals to be established by the Board of Directors.
In the event of a merger, consolidation, reorganization or similar transaction or our voluntary liquidation or dissolution, all of our unexercised vested equity grants
and any unvested equity grants will be automatically terminated. However, in the event of a change of control, or merger, consolidation, reorganization or similar transaction
resulting in the acquisition of at least 50% of our voting power, or the sale or transfer of all or substantially all of our outstanding shares assets, the equity grants then
outstanding may be assumed or substituted for an appropriate number of shares of each class of shares or other securities and/or assets of the successor company in such
transaction (or a parent or subsidiary or another affiliate of such successor company) as were distributed to our shareholders in respect of the transaction. In addition to the
foregoing, our Board of Directors has approved the inclusion in the option agreements of the Company’s officers of a provision for accelerated vesting of options if both a
change of control of the Company occurs and, following such change of control, the officer’s employment is terminated or there is a significant demotion in the officer’s new
job or position.
To our knowledge the significant changes in the percentage of ownership held by our major shareholders reported in our Annual Reports on Form 20-F during the
past three year have been the decrease in 2020 below 5% in the percentage ownership held by BVF Partners L.P. and Senvest Management, LLC.
F. Disclosure of a registrant’s action to recover erroneously awarded compensation.
Not applicable.
111
ITEM 7. MAJOR SHAREHOLDERS AND RELATED PARTY TRANSACTIONS
A. Major Shareholders
Except as set forth in “Item 6. Directors, Senior Management and Employees—E. Share Ownership,” to the best of our knowledge, no other person who we know
beneficially owns 5.0% or more of the Company’s ordinary shares outstanding as of March 21, 2023.
B. Related Party Transactions
Agreements with Directors and Officers
Employment Agreements
We have entered into employment agreements with each of our executive officers. See “Item 6. Directors, Senior Management and Employees — Compensation of
Directors and Senior Management.”
Indemnification Agreements
Our Articles of Association and Compensation Policy approved by our shareholders permit us to exculpate, indemnify and insure our directors and office holders to
the fullest extent permitted by the Companies Law. We have entered into agreements with each of our office holders undertaking to indemnify them to the fullest extent
permitted by law, including with respect to liabilities resulting from this offering to the extent that these liabilities are not covered by insurance. We have obtained directors’
and officers’ insurance for each of our officers and directors. See “Item 6. Directors, Senior Management and Employees — Board Practices — Exculpation, insurance and
indemnification of office holders.”
GSAP Agreement
On February 9, 2023, we entered into an agreement with GSAP Biomed Ltd., or GSAP, pursuant to which GSAP will provide ongoing quality assurance support
services to us. Rami Dar, one of the external directors of our board of directors who also serves as the chairman of our audit committee and as a member of our compensation
committee and investment committee, is a non-executive chairman of Novolog Ltd., which is the parent company of GSAP. Under the agreement, we agreed to pay GSAP NIS
46,000/month (approximately $12,667 per month) as compensation for the services provided thereunder.
C. Interests of Experts and Counsel
Not applicable.
ITEM 8. FINANCIAL INFORMATION
A. Consolidated Statements and other Financial Information
See “Item 18. Financial Statements.”
Legal Proceedings
On January 5, 2023, a putative securities class action complaint captioned Winston Peete v. BioLineRx Ltd. and Philip A. Serlin (Case no: Case 2:23-cv-00041 was
filed in the U.S. District Court for the District of New Jersey by purported shareholder Winston Peete, naming us and our chief executive officer, Mr. Serlin, as defendants.
The complaint asserts violations of Sections 10(b) and 20(a) of the Securities Exchange Act of 1934 and Rule 10b-5 promulgated thereunder, claiming that the defendants
made false and materially misleading statements and failed to disclose material adverse facts pertaining to our financial position with regard to the development of
motixafortide and that we would require a loan and a securities offering to commercialize motixafortide. The complaint asserts a putative class period of February 23, 2021 to
September 19, 2022, inclusive and seeks certification as a class action and an unspecified amount of damages. In addition, on February 5, 2023, we received a lawsuit and
motion to approve the lawsuit as a class action lawsuit pursuant to the Class Action Lawsuits Law 5766-2006 which was filed against us and Mr. Serlin in the Tel Aviv District
Court (Economic Division). The motion asserts substantially similar allegations as the U.S. action described above. The motion asserts to define the class as all shareholders
who held the company's securities traded on the Tel Aviv Stock Exchange, on September 19, 2022 and the class period relates to the company's statements between February
23, 2021, and September 19, 2022. The total amount claimed, if the lawsuit is certified as a class action, as set forth in the motion is approximately NIS 113.5 million
(approximately $32 million). The outcome of both legal proceedings is uncertain at this point. Based on an initial evaluation of the lawsuits, we believe that they are without
merit and intend to vigorously defend ourselves against such actions.
112
Dividend Distributions
We have never declared or paid cash dividends to our shareholders. Currently we do not intend to pay cash dividends. We currently intend to reinvest any future
earnings in developing and expanding our business. Any future determination relating to our dividend policy will be at the discretion of our Board of Directors and will
depend on a number of factors, including future earnings, our financial condition, operating results, contractual restrictions, capital requirements, business prospects,
applicable Israeli law and other factors our Board of Directors may deem relevant.
B. Significant Changes
None.
ITEM 9. THE OFFER AND LISTING
A. Offer and Listing Details
Our ADSs have been trading on Nasdaq under the symbol “BLRX” since July 2011. Our ordinary shares have been trading on the TASE under the symbol “BLRX”
since February 2007.
B. Plan of Distribution
Not applicable.
C. Markets
Our ADSs trade on Nasdaq under the symbol “BLRX.” Our ordinary shares trade on the TASE under the symbol “BLRX.”
D. Selling Shareholders
Not applicable.
E. Dilution
Not applicable.
F. Expenses of the Issue
Not applicable.
113
ITEM 10. ADDITIONAL INFORMATION
A. Share Capital
Not applicable.
B. Articles of Association
A copy of our Articles of Association is attached as Exhibit 2.1 to this Annual Report. Other than as disclosed below, the information called for by this Item is set
forth in Exhibit 2.2 to this Annual Report and is incorporated by reference into this Annual Report.
C. Material Contracts
For a discussion of our out-licensing and in-licensing agreements, see “Item 4. Information on the Company.” The following are summary descriptions of certain
other material contracts to which we are a party. The descriptions provided below do not purport to be complete and are qualified in their entirety by the complete agreements,
which are attached as exhibits to this Annual Report on Form 20-F.
Loan Agreements with Kreos Capital
In October 2018, we entered into a loan agreement with Kreos Capital. The purpose of the loan was to finance the $10 million payment made by the Company to
Biokine as part of the consideration for amending the license agreement for motixafortide. See “Item 4. Information on the Company — Business Overview — In-Licensing
Agreements — motixafortide.” The loan had a 12-month interest-only period, which concluded in September 2019, followed by a 36-month repayment period beginning in
October 2019. Borrowings under the loan bore interest at a fixed rate of 9.5% per annum. As security for the loan, Kreos Capital received a first-priority, secured interest in all
Company assets, including intellectual property. In connection with providing the loan, Kreos Capital received a warrant to purchase 63,837 ADSs at an exercise price of
$14.10 per ADS. The warrant is exercisable for a period of ten years from the date of issuance. In September 2022, this loan was repaid in full.
In September 2022, we entered into a new loan agreement with Kreos Capital, or the Loan Agreement. Under the Loan Agreement, Kreos Capital will provide us
with access to term loans in an aggregate principal amount of up to $40 million in three tranches as follows: (a) a loan in the aggregate principal amount of up to $10 million,
available for drawdown upon closing of the Loan Agreement and until April 1, 2023, or Tranche A, (b) a loan in the aggregate principal amount of up to $20 million, available
for drawdown upon achievement of certain milestones and until April 1, 2024, or Tranche B, and (c) a loan in the aggregate principal amount of up to $10 million, available
for drawdown upon achievement of certain milestones and until October 1, 2024, or Tranche C and together with Tranche A and Tranche B, the Loans. We drew down the
initial tranche of $10 million following execution of the agreement in September 2022.
We intend to use the proceeds of the Loans, together with cash on-hand, to facilitate the commercial launch of motixafortide in autologous stem cell mobilization for
multiple myeloma patients, as well as for general corporate purposes.
Until July 1, 2023, Tranche A is payable on an interest-only basis, and thereafter in up to 36 equal monthly payments of principal and interest accrued thereon,
subject to extension of the interest-only payment period if certain milestones are met, with a corresponding reduction in the principal and interest payment period through July
1, 2026. Until July 1, 2024, Tranche B is payable on an interest-only basis, and thereafter in up to 36 equal monthly payments of principal and interest accrued thereon, subject
to extension of the interest-only payment period if certain milestones are met, with a corresponding reduction in the principal and interest payment period through July 1,
2027. Until January 1, 2025, Tranche C is payable on an interest-only basis, and thereafter in up to 30 equal monthly payments of principal and interest accrued thereon,
subject to extension of the interest-only payment period if certain milestones are met, with a corresponding reduction in the principal and interest payment period through July
1, 2027.
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Interest on each tranche of the Loans accrues at a fixed rate of 9.5% per annum from the drawdown date until repayment in full of the tranche. In addition, the Lender
will be entitled to mid-to-high single-digit royalties on motixafortide sales for stem cell mobilization, up to $13.5 million.
We may prepay all, but not less than all, of the outstanding balance of any of the Loans. In case of prepayment within 12 months of a drawdown, we will pay a sum
equal to (i) the principal balance then outstanding, and (ii) an aggregate of all remaining interest payments that would have been paid on the Loans throughout the remainder
of the term of the Loan, discounted back at the secured overnight financing rate administered by the Federal Reserve Bank of New York. In case of prepayment within 13-24
months of the effective date of the Loan Agreement, we will pay a sum equal to 102% of principal balance then outstanding. In case of prepayment within 25-36 months of the
effective date of the Loan Agreement, we will pay a sum equal to 101% of the principal balance then outstanding. In connection with any prepayment, we will also pay an end
of loan payment equal to 5% of the amount of each tranche drawn down upon the final repayment of each such tranche, or the End of Loan Payment, and any other unpaid
fees or costs, if any. In addition, if we prepay the Loans in the first 24 months from the first drawdown and, in the event that the combined cash return to Kreos Capital from
the drawn down Loans under the Loan Agreement, including prepayment amounts and any revenue based payments, or the Combined Loan Cash Economics, do not reach 1.3
times the aggregate amount of drawn down Loans, or the Minimum Cash Return Amount, we shall pay Kreos Capital an additional cash amount equal to the difference
between the Combined Loan Cash Economics paid or payable and the Minimum Cash Return Amount.
The Loans are subject to mandatory accelerated repayment provisions that require repayment of the outstanding principal amount of the Loans, and all accrued and
unpaid interest thereon, upon the occurrence of an event of default, subject to certain limitations and cure rights. In addition, in the event of acceleration upon an event of
default (a) we will be required to pay the aggregate of the monthly interest payments scheduled to be paid by the Company for the period from the date of acceleration to the
expiry of the applicable Loan, in each case discounted from the applicable monthly repayment date to the date of prepayment at the rate of 2% per annum and (b) the End of
Loan Payment.
In connection with entering into the Loan Agreement, we agreed to pay the Lender a fee of up to $30,000 plus value-added-tax for legal and other ancillary fees.
Pursuant to the Loan Agreement, upon the execution of the agreement, we agreed to pay Kreos Capital a transaction fee equal to $500,000, and, upon the drawdown of each
tranche of the Loans, we shall pay Kreos Capital an advance payment of the last month’s payment of principal and interest for such tranche. Additionally, we will be required
to pay an End of Loan Payment.
Outstanding borrowings under the Loan Agreement are secured by (a) a first priority fixed charge over certain assets and intellectual property of the Company as well
as all shares held by the Company in BioLineRx USA, Inc, or the Fixed Charge, (b) a first priority floating charge over all our assets as of the date of the Loan Agreement or
thereafter acquired, other than the assets charged under the Fixed Charge or as otherwise specifically excluded pursuant to the terms of the floating charge, and (c) subject to
the provisions of the Fixed Charge, a security interest in our intellectual property.
The Loan Agreement contains customary representations and warranties, indemnification provisions in favor of the Lender, events of default and affirmative and
negative covenants, including, among others, covenants that limit or restrict the Company’s ability to, among other things, incur additional indebtedness, merge or consolidate,
make acquisitions, pay dividends or other distributions or repurchase equity, and dispose of assets, in each case subject to certain exceptions. In addition, the Company is
required to maintain a cash balance of at least $10 million. The Company has also granted Kreos Capital certain information rights.
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Collaboration Agreement with GenFleet
In June 2022, we entered into a collaboration agreement with GenFleet, an immuno-oncology focused biopharmaceutical company based in China, to advance
motixafortide through a randomized Phase 2b clinical trial in PDAC. Under the terms of the agreement, GenFleet will fully fund, design and execute a randomized Phase 2b
clinical trial that will enroll approximately 200 first-line metastatic PDAC patients in China. This randomized controlled study will aim to evaluate the superiority of
motixafortide in combination with an anti-PD-1 and chemotherapy compared to chemotherapy alone, the current standard of care and is expected to commence in 2023
(although timelines are ultimately controlled by the independent investigator and are therefore subject to change). As part of the collaboration, we will supply motixafortide,
while GenFleet will supply the other study drugs for the trial. Trial oversight will be administered by a Joint Development Committee. GenFleet will be eligible to receive
low-to-mid-single digit tiered percentage royalties on future motixafortide sales, if approved.
D. Exchange Controls
There are no Israeli government laws, decrees or regulations that restrict or that affect our export or import of capital or the remittance of dividends, interest or other
payments to non-resident holders of our securities, including the availability of cash and cash equivalents for use by us and our wholly owned subsidiaries, except or otherwise
as set forth under “Item 10E. Additional Information — Taxation.”
E. Taxation
The following description is not intended to constitute a complete analysis of all tax consequences relating to the ownership or disposition of our ordinary shares or
ADSs, both referred to in this Item 10E as the ordinary shares. You should consult your own tax advisor concerning the tax consequences of your particular situation, as well
as any tax consequences that may arise under the laws of any state, local, non-U.S., including Israeli, or other taxing jurisdiction.
Israeli Tax Considerations
The following is a summary of the material Israeli tax laws applicable to us. This section also contains a discussion of material Israeli tax consequences concerning
the ownership and disposition of our shares. This summary does not discuss all the aspects of Israeli tax law that may be relevant to a particular investor in light of his or her
personal investment circumstances or to some types of investors subject to special treatment under Israeli law. Examples of this kind of investor include residents of Israel or
traders in securities who are subject to special tax regimes not covered in this discussion. Because certain parts of this discussion are based on new tax legislation that has not
yet been subject to judicial or administrative interpretation, we cannot assure you that the appropriate tax authorities or the courts will accept the views expressed in this
discussion.
General Corporate Tax Structure in Israel
Israeli companies are generally subject to corporate tax on their taxable income. The regular corporate tax rate in Israel is 23% for the year 2018 and thereafter.
Capital gains derived by an Israeli company are now generally subject to tax at the same rate as the corporate tax rate.
As of December 31, 2022, the tax loss carryforwards of BioLineRx were approximately $330 million. The tax loss carryforwards have no expiration date.
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Taxation of Israeli Individual Shareholders on Receipt of Dividends. Israeli residents who are individuals are generally subject to Israeli income tax for dividends paid
on our ordinary shares (other than bonus shares or share dividends) at a rate of either 25% or 30%, if the recipient of such dividend is a substantial shareholder (as defined
below) at the time of distribution or at any time during the preceding 12-month period.
Taxation of Israeli Resident Corporations on Receipt of Dividends. Israeli resident corporations are generally exempt from Israeli corporate tax for dividends paid on
our ordinary shares.
Taxation of Non-Israeli Shareholders on Receipt of Dividends. Non-residents of Israel (individuals or corporations) are generally subject to Israeli income tax on the
receipt of dividends paid on our ordinary shares at the rate of 25% (or 30% if such person is a “substantial shareholder” at the time receiving the dividend or on any date in the
12 months preceding such date), which tax will be withheld at the source, unless a lower rate is provided in the Ordinance or under a tax treaty between Israel and the
shareholder’s country of residence and subject to the receipt in advance of a valid certificate from the Israeli Tax Authorities.
Under the U.S.-Israel Tax Treaty (the “Treaty”), Israeli withholding tax on dividends paid to a U.S. resident for treaty purposes may not, in general, exceed 25%.
Where the recipient is a U.S. corporation owning 10% or more of the voting stock of the paying corporation during the part of the paying corporation’s taxable year which
precedes the date of payment of the dividend and during the whole of its prior taxable year (if any) and the dividend is not paid from the profits of a Benefited Enterprise, the
Israeli tax withheld may not exceed 12.5%, subject to certain conditions.
A “substantial shareholder” is generally a person who alone, or together with his relative or another person who collaborates with him on a regular basis, holds,
directly or indirectly, at least 10% of any of the “means of control” of the corporation. “Means of control” generally include the right to vote, receive profits, nominate a
director, a general manager of the company or holders of similar offices in other bodies of persons, receive assets upon liquidation, or instruct someone who holds any of the
aforesaid rights regarding the manner in which he or she is to exercise such right(s), and all regardless of the source of such right.
A non-resident of Israel who receives dividends from which tax was withheld is generally exempt from the duty to file returns in Israel in respect of such income,
provided that: (1) such income was not derived from a business conducted in Israel by the taxpayer (2) the taxpayer has no other taxable sources of income in Israel with
respect to which a tax return is required to be filed and (3) the taxpayer is not obliged to pay excess tax.
Payers of dividends on our shares, including the Israeli stockbroker effectuating the transaction or the financial institution through which the securities are held, are
required, subject to any of the foregoing exemptions, reduced tax rates and the demonstration of a shareholder of his, her or its foreign residency, to withhold taxes upon the
distribution of dividends at a rate of 25%, provided that the shares are registered with a nominee company.
Taxation of Capital Gains. Israeli law imposes a capital gains tax on the sale of any capital assets by residents of Israel, as defined for Israeli tax purposes, and on the
sale of assets located in Israel, including shares in Israeli companies, by non-residents of Israel, unless a specific exemption is available or unless a tax treaty between Israel
and the shareholder’s country of residence provides otherwise and subject to the receipt in advance of a valid certificate from the Israeli Tax Authorities. The law distinguishes
between real capital gain and inflationary surplus. The inflationary surplus is a portion of the total capital gain that is equivalent to the increase of the relevant asset’s purchase
price which is attributable to the increase in the Israeli consumer price index or, in certain circumstances, a foreign currency exchange rate, between the date of purchase and
the date of sale. The real capital gain is the excess of the total capital gain over the inflationary surplus.
Capital Gains Taxes Applicable to Israeli Resident Shareholders. An individual is subject to a tax at a rate of 25% on real capital gains derived from the sale of
shares, as long as the individual is not a substantial shareholder at the time of sale or at any time during the 12-month period preceding the company’s issuance of the shares.
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An individual who is a substantial shareholder at the time of sale or at any time during the preceding 12-month period is subject to tax at a rate of 30% in respect of
real capital gains derived from the sale of shares issued by the company in which he or she is a substantial shareholder.
Capital Gains Taxes Applicable to Non-Israeli Resident Shareholders. Shareholders that are not Israeli residents are generally exempt from Israeli capital gains tax on
any gains derived from the sale, exchange or disposition of our ordinary shares, provided that such shareholders did not acquire their ordinary shares prior to our initial public
offering on the TASE and such gains were not derived from a permanent establishment or business activity of such shareholders in Israel. However, non-Israeli corporations
will not be entitled to the foregoing exemptions if one or more Israeli residents (a) have a controlling interest of more than 25% in such non-Israeli corporation or (b) are the
beneficiaries of or are entitled to 25% or more of the revenues or profits of such non-Israeli corporation, whether directly or indirectly.
In addition, under the Treaty, the sale, exchange or disposition of our ordinary shares by a shareholder who is a U.S. resident (for purposes of the Treaty) holding the
ordinary shares as a capital asset is exempt from Israeli capital gains tax unless (1) the shareholder holds, directly or indirectly, shares representing 10% or more of our voting
capital during any part of the 12-month period preceding such sale, exchange or disposition; (2) the capital gains arising from such sale are attributable to a permanent
establishment of the shareholder located in Israel; (3) a shareholder who is an individual is present in Israel for a period or periods aggregating 183 days or more during a
taxable year. In either case, the sale, exchange or disposition of ordinary shares would be subject to Israeli tax, to the extent applicable (subject to the receipt in advance of a
valid certificate from the Israeli tax authorities); however, under the Treaty, the U.S. resident would be permitted to claim a credit for the tax against the U.S. federal income
tax imposed with respect to the sale, exchange or disposition, subject to the limitations in U.S. laws applicable to foreign tax credits. The Treaty does not relate to U.S. state or
local taxes.
Shareholders may be required to demonstrate that they are exempt from tax on their capital gains in order to avoid withholding at source at the time of sale.
The purchaser, the Israeli stockbrokers or financial institution through which the shares are held are obliged, subject to the above mentioned exemptions, to withhold
tax upon the sale of securities on the amount of the consideration paid upon the sale of the securities (or on the Real Capital Gain realized on the sale, if known), at the rate of
25% in respect of an individual or at a corporate rate in respect of a corporation (23%).
Upon the sale of securities traded on a stock exchange, a detailed return, including a computation of the tax due, must be filed and an advance payment must be paid
on January 31 and July 31 of every tax year in respect of sales of securities made within the previous six months. However, if all tax due was withheld at source according to
applicable provisions of the Israel Income Tax Ordinance and regulations promulgated thereunder, the aforementioned return need not be filed and no advance payment must
be paid. Capital gain is also reportable on the annual income tax returns.
Excess Tax. Individuals who are subject to tax in Israel (whether such individual is an Israeli resident or non-Israeli resident) are also subject to an additional tax at a
rate of 3% on annual income exceeding NIS 698,280 for 2023 and thereafter, (which amount is linked to the annual change in the Israeli consumer price index), including, but
not limited to, dividends, interest and capital gains.
U.S. Federal Income Tax Considerations
The following is a general summary of certain material U.S. federal income tax considerations relating to the purchase, ownership and disposition of our ordinary
shares and ADSs by U.S. Investors (as defined below) that are initial purchasers of such ordinary shares or ADSs and that hold such ordinary shares or ADSs as capital assets
for U.S. federal income tax purposes (generally, property held for investment). This summary is based on the Internal Revenue Code of 1986, as amended, or the Code, the
regulations of the U.S. Department of the Treasury issued pursuant to the Code, or the Treasury Regulations, the Treaty, and administrative and judicial interpretations thereof,
all as in effect on the date hereof and all of which are subject to change, possibly with retroactive effect, or to different interpretation. No ruling has been sought from the IRS
with respect to any U.S. federal income tax consequences described below, and there can be no assurance that the IRS or a court will not take a contrary position. This
summary is for general information only and does not address all of the tax considerations that may be relevant to specific U.S. Investors in light of their particular
circumstances or to U.S. Investors subject to special treatment under U.S. federal income tax law (such as, without limitation, banks, insurance companies, tax-exempt entities,
retirement plans, regulated investment companies, partnerships, dealers in securities, brokers, real estate investment trusts, grantor trusts, persons who acquire our ordinary
shares through the exercise or cancellation of employee stock options or otherwise as compensation for their services, certain former citizens or residents of the United States,
persons who acquire our ordinary shares or ADSs as part of a straddle, hedge, conversion transaction or other integrated investment, persons that have a “functional currency”
other than the Dollar, persons that own (or are deemed to own, indirectly or by attribution) 10% or more of our ordinary shares or ADSs (by vote or value), persons subject to
special tax accounting rules under section 451(b), or persons that generally mark their securities to market for U.S. federal income tax purposes). This summary does not
address any U.S. state or local or non-U.S. tax considerations, any U.S. federal estate, gift or alternative minimum tax considerations or any additional U.S. federal tax
consequences other than U.S. federal income tax consequences.
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As used in this summary, the term “U.S. Investor” means a beneficial owner of our ordinary shares or ADSs that is, for U.S. federal income tax purposes, (i) an
individual citizen or resident of the United States, (ii) a corporation, or other entity taxable as a corporation for U.S. federal income tax purposes, created or organized in or
under the laws of the United States, any state thereof, or the District of Columbia, (iii) an estate the income of which is subject to U.S. federal income tax regardless of its
source or (iv) a trust with respect to which 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 its substantial decisions, or a trust that has validly elected to be treated as a U.S. person for U.S. federal income tax purposes, whose status as a
U.S. person is not overwritten by an applicable tax treaty.
If an entity treated as a partnership for U.S. federal income tax purposes holds our ordinary shares or ADSs, the tax treatment of such entity and each person treated
as a partner thereof will generally depend upon the status and activities of the entity and such person. An investor that is treated as a partnership for U.S. federal income tax
purposes should consult its own tax advisor regarding the U.S. federal income tax considerations applicable to it and its partners of the purchase, ownership and disposition of
its ordinary shares or ADSs.
Prospective investors should be aware that this summary does not address the tax consequences to investors who are not U.S. Investors. Prospective investors should
consult their own tax advisors as to the particular tax considerations applicable to them relating to the purchase, ownership and disposition of their ordinary shares or ADSs,
including the applicability of U.S. federal, state and local tax laws and non-U.S. tax laws.
Taxation of U.S. Investors
The discussions under “— Distributions,” and under “— Sale, Exchange or Other Disposition of Ordinary Shares or ADSs” below assumes that we will not be treated
as a passive foreign investment company, or PFIC, for U.S. federal income tax purposes. However, we have not determined whether we will be a PFIC for the taxable year
ending December 31, 2023, and it is possible that we will be a PFIC for the taxable year ending December 31, 2023 or in any subsequent year. For a discussion of the rules
that would apply if we are treated as a PFIC, see the discussion under “— Passive Foreign Investment Company.”
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Distributions. We have no current plans to pay dividends. To the extent we pay any dividends, a U.S. Investor will be required to include in gross income as a taxable
dividend the amount of any distributions made on the ordinary shares or ADSs, including the amount of any Israeli taxes withheld, when actually or constructively received, to
the extent that those distributions are paid out of our current or accumulated earnings and profits as determined for U.S. federal income tax purposes. Any distributions in
excess of our earnings and profits will be applied against and will reduce the U.S. Investor’s tax basis in its ordinary shares or ADSs and to the extent they exceed that tax
basis, will be treated as gain from the sale or exchange of those ordinary shares or ADSs. We do not intend to calculate our earnings and profits under U.S. federal income tax
principles. Therefore, a U.S. Investor should expect that a distribution will be treated 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. If we were to pay dividends to holders of our ordinary shares, we expect to pay such dividends in NIS; however,
dividends paid to holders of our ADSs will be paid in dollars. A dividend paid in NIS, including the amount of any Israeli taxes withheld, will be includible in a U.S.
Investor’s income as a dollar amount calculated by reference to the exchange rate in effect on the date such dividend is received, regardless of whether the payment is in fact
converted into dollars. If the dividend is converted to dollars on the date of receipt, a U.S. Investor generally will not recognize a foreign currency gain or loss. However, if the
U.S. Investor converts the NIS into dollars on a later date, the U.S. Investor must include, in computing its income, any gain or loss resulting from any exchange rate
fluctuations. The gain or loss will be equal to the difference between (i) the dollar value of the amount included in income when the dividend was received and (ii) the amount
received on the conversion of the NIS into dollars. Such gain or loss will generally be ordinary income or loss and United States source for U.S. foreign tax credit purposes.
U.S. Investors should consult their own tax advisors regarding the tax consequences to them if we pay dividends in NIS or any other non-U.S. currency.
Subject to certain significant conditions and limitations, including potential limitations under the Treaty, any Israeli taxes paid on or withheld from distributions from
us and not refundable to a U.S. Investor may be credited against the investor’s U.S. federal income tax liability or, alternatively, may be deducted from the investor’s taxable
income. This election is made on a year-by-year basis and applies to all foreign taxes paid by a U.S. Investor or withheld from amounts paid to a U.S. Investor that year.
Dividends paid on the ordinary shares or ADSs generally will constitute income from sources outside the United States and be categorized as “passive category income” or, in
the case of some U.S. Investors, as “general category income” for U.S. foreign tax credit purposes.
As a result of recent changes to the U.S. foreign tax credit rules, a withholding tax generally will need to satisfy certain additional requirements in orders to be
considered a creditable tax for a U.S. investor. We have not determined whether these requirements have been met and, accordingly, no assurance can be given that any
withholding tax on dividends paid by us will be creditable. Since the rules governing foreign tax credits are complex, U.S. Investors should consult their own tax advisor
regarding the availability of foreign tax credits in their particular circumstances.
Dividends paid on the ordinary shares and ADSs will not be eligible for the “dividends-received” deduction generally allowed to corporate U.S. Investors with
respect to dividends received from U.S. corporations.
Distributions treated as dividends that are received by an individual U.S. Investor from “qualified foreign corporations” generally qualify for a reduced maximum tax
rate so long as certain holding period and other requirements are met. A non-U.S. corporation (other than 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 (i) 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 program,
or (ii) with respect to any dividend it pays on stock which is readily tradable on an established securities market in the United States. Any dividend paid by us in a taxable year
in which we are a PFIC (or with respect to which we were a PFIC in the preceding taxable year) will be subject to tax at regular ordinary income rates. As mentioned above,
we believe we were not a PFIC for our 2022 taxable year and have not determined whether we will be a PFIC for our 2023 taxable year. U.S. Investors should consult their
own tax advisors regarding the availability of the lower rate for dividends paid with respect to our ordinary shares and ADSs.
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The additional 3.8% Medicare tax (described below) may apply to dividends received by certain U.S. Investors who meet certain modified adjusted gross income
thresholds.
Sale, Exchange or Other Disposition of Ordinary Shares and ADSs. Subject to the discussion under “— Passive Foreign Investment Company” below, a U.S. Investor
generally will recognize capital gain or loss upon the sale, exchange or other taxable disposition of ordinary shares or ADSs in an amount equal to the difference between the
amount realized on the sale, exchange or other taxable disposition and the U.S. Investor’s adjusted tax basis in such ordinary shares or ADSs. This capital gain or loss will be
long-term capital gain or loss if the U.S. Investor’s holding period in the ordinary shares or ADSs exceeds one year. Preferential tax rates for long-term capital gain will apply
to individual U.S. Investors. The deductibility of capital losses is subject to limitations. The gain or loss will generally be income or loss from sources within the United States
for U.S. foreign tax credit purposes, subject to certain possible exceptions under the Treaty. The additional 3.8% Medicare tax (described below) may apply to gains
recognized upon the sale, exchange, or other taxable disposition of our ordinary shares or ADSs by certain U.S. Investors who meet certain modified adjusted gross income
thresholds.
U.S. Investors should consult their own tax advisors regarding the U.S. federal income tax consequences of receiving currency other than Dollars upon the disposition
of ordinary shares or ADSs.
Medicare Tax. In addition, certain U.S. persons, including individuals, estates and trusts, will be subject to an additional 3.8% Medicare tax, or net investment income
tax, on unearned income. For individuals, the additional Medicare tax applies to the lesser of (i) “net investment income” or (ii) the excess of “modified adjusted gross
income” over $200,000 ($250,000 if married and filing jointly or $125,000 if married and filing separately). “Net investment income” generally equals the taxpayer’s gross
investment income reduced by the deductions that are allocable to such income. Investment income generally includes passive income such as interest, dividends, annuities,
royalties, rents, and capital gains. U.S. Investors are urged to consult their own tax advisors regarding the implications of the additional Medicare tax resulting from their
ownership and disposition of ordinary shares or ADSs.
Passive Foreign Investment Company
In general, a corporation organized outside the United States will be treated as a PFIC for U.S. federal income tax purposes in any taxable year in which either (i) at
least 75% of its gross income is “passive income” or (ii) on average at least 50% of its assets by value produce passive income or are held for the production of passive
income. Passive income for this purpose generally includes, among other things, certain dividends, interest, royalties, rents and gains from commodities and securities
transactions and from the sale or exchange of property that gives rise to passive income. Passive income also includes amounts derived by reason of the temporary investment
of funds, including those raised in the public offering. Assets that produce or are held for the production of passive income may include cash, even if held as working capital
or raised in a public offering, as well as marketable debt securities and other assets that may produce passive income. In determining whether a non-U.S. corporation is a
PFIC, a proportionate share of the income and assets of each corporation in which it owns, directly or indirectly, at least a 25% interest (by value) is taken into account.
Under the tests described above, whether or not we are a PFIC will be determined annually based upon the composition of our income and the composition and
valuation of our assets, all of which are subject to change.
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We believe that we were a PFIC for U.S. federal income tax purposes for taxable years ended prior to December 31, 2009 and for taxable years ended December 31,
2011, 2012 and 2014 through 2019. We believe we were not a PFIC for taxable years ended 2009, 2010, 2013, 2020, 2021 and 2022, and we have not determined whether we
will be a PFIC for the taxable year ending December 31, 2023. Because the PFIC determination is highly fact intensive and made at the end of each taxable year, there can be
no assurance that we will not be a PFIC for taxable year ending December 31, 2023 or in any subsequent year. Upon request, we intend to annually inform U.S. Investors if we
and any of our subsidiaries were a PFIC with respect to the preceding year.
U.S. Investors should be aware of certain tax consequences of investing directly or indirectly in us if we are a PFIC. A U.S. Investor is subject to different rules
depending on whether the U.S. Investor makes an election to treat us as a “qualified electing fund,” known as a QEF election, for the first taxable year that the U.S. Investor
holds ordinary shares or ADSs, which is referred to in this disclosure as a “timely QEF election,” makes a “mark-to-market” election with respect to the ordinary shares or
ADSs (if such election is available) or makes neither election.
QEF Election. A U.S. Investor who makes a timely QEF election, referred to in this disclosure as an “Electing U.S. Investor,” with respect to us must report for U.S.
federal income tax purposes his pro rata share of our ordinary earnings and net capital gain, if any, for our taxable year that ends with or within the taxable year of the Electing
U.S. Investor. The “net capital gain” of a PFIC is the excess, if any, of the PFIC’s net long-term capital gains over its net short-term capital losses. The amount so included in
income generally will be treated as ordinary income to the extent of such Electing U.S. Investor’s allocable share of the PFIC’s ordinary earnings and as long-term capital gain
to the extent of such Electing U.S. Investor’s allocable share of the PFIC’s net capital gains. Such Electing U.S. Investor generally will be required to translate such income
into Dollars based on the average exchange rate for the PFIC’s taxable year with respect to the PFIC’s functional currency. Such income generally will be treated as income
from sources outside the United States for U.S. foreign tax credit purposes. Amounts previously included in income by such Electing U.S. Investor under the QEF rules
generally will not be subject to tax when they are distributed to such Electing U.S. Investor. The Electing U.S. Investor’s tax basis in ordinary shares or ADSs generally will
increase by any amounts so included under the QEF rules and decrease by any amounts not included in income when distributed.
An Electing U.S. Investor will be subject to U.S. federal income tax on such amounts for each taxable year in which we are a PFIC, regardless of whether such
amounts are actually distributed to such Electing U.S. Investor. However, an Electing U.S. Investor may, subject to certain limitations, elect to defer payment of current U.S.
federal income tax on such amounts, subject to an interest charge. If an Electing U.S. Investor is an individual, any such interest will be treated as non-deductible “personal
interest.”
Any net operating losses or net capital losses of a PFIC will not pass through to the Electing U.S. Investor and will not offset any ordinary earnings or net capital gain
of a PFIC recognized by Electing U.S. Investors in subsequent years.
So long as an Electing U.S. Investor’s QEF election with respect to us is in effect with respect to the entire holding period for ordinary shares or ADSs, any gain or
loss recognized by such Electing U.S. Investor on the sale, exchange or other disposition of such ordinary shares or ADSs generally will be long-term capital gain or loss if
such Electing U.S. Investor has held such ordinary shares or ADSs for more than one year at the time of such sale, exchange or other disposition. Preferential tax rates for
long-term capital gain will apply to individual U.S. Investors. The deductibility of capital losses is subject to limitations.
A U.S. Investor makes a QEF election by completing the relevant portions of and filing IRS Form 8621 in accordance with the instructions thereto. A QEF election
generally may not be revoked without the consent of the IRS. Upon request, we intend to annually furnish U.S. Investors with information needed in order to complete IRS
Form 8621 (which form would be required to be filed with the IRS on an annual basis by the U.S. Investor) and to make and maintain a valid QEF election for any year in
which we or any of our subsidiaries are a PFIC. A QEF election will not apply to any taxable year during which we are not a PFIC but will remain in effect with respect to any
subsequent taxable year in which we become a PFIC. Each U.S. Investor is encouraged to consult its own tax advisor with respect to tax consequences of a QEF election with
respect to us.
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Mark-to-Market Election. Alternatively, if our ordinary shares or ADSs are treated as “marketable stock,” a U.S. Investor would be allowed to make a “mark-to-
market” election with respect to our ordinary shares or ADSs, provided the U.S. Investor completes and files IRS Form 8621 in accordance with the relevant instructions and
related Treasury Regulations. If that election is made, the U.S. Investor generally would include as ordinary income in each taxable year the excess, if any, of the fair market
value of the ordinary shares or ADSs at the end of the taxable year over such investor’s adjusted tax basis in the ordinary shares or ADSs. Thus, the U.S. Investor may
recognize taxable income without receiving any cash to pay its tax liability with respect to such income. The U.S. Investor would also be permitted an ordinary loss in respect
of the excess, if any, of the U.S. Investor’s adjusted tax basis in 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 previously included in income as a result of the mark-to-market election. A U.S. Investor’s tax basis in the ordinary shares or ADSs would be adjusted to
reflect any such income or loss amount. Gain realized on the sale, exchange or other disposition of the ordinary shares or ADSs would be treated as ordinary income, and any
loss realized on the sale, exchange or other disposition of the ordinary shares or ADSs would be treated as ordinary loss to the extent that such loss does not exceed the net
mark-to-market gains previously included in income by the U.S. Investor, and any loss in excess of such amount will be treated as capital loss. Amounts treated as ordinary
income will not be eligible for the favorable tax rates applicable to qualified dividend income or long-term capital gains.
Generally, stock will be considered marketable stock if it is “regularly traded” on a “qualified exchange” within the meaning of applicable Treasury Regulations. A
class of stock is regularly traded on an exchange during any calendar year during which such class of stock is traded, other than in de minimis quantities, on at least 15 days
during each calendar quarter. To be marketable stock, our ordinary shares or ADSs must be regularly traded on a qualifying exchange (i) in the United States that is registered
with the SEC or a national market system established pursuant to the Exchange Act or (ii) outside the United States that is properly regulated and meets certain trading, listing,
financial disclosure and other requirements. A mark-to-market election will not apply to our ordinary shares or ADSs held by a U.S. Investor for any taxable year during
which we are not a PFIC, but will remain in effect with respect to any subsequent taxable year in which we become a PFIC unless our ordinary shares or ADSs cease to be
marketable. A mark-to-market election generally may not be revoked without the consent of the IRS. Such election will not apply to any PFIC subsidiary that we own. Each
U.S. Investor is encouraged to consult its own tax advisor with respect to the availability and tax consequences of a mark-to-market election with respect to our ordinary
shares or ADSs.
Default PFIC Rules. A U.S. Investor who does not make a timely QEF election or a mark-to-market election, referred to in this disclosure as a “Non-Electing U.S.
Investor,” will be subject to special rules with respect to (a) any “excess distribution” (generally, the portion of any distributions received by the Non-Electing U.S. Investor on
the ordinary shares or ADSs in a taxable year in excess of 125% of the average annual distributions received by the Non-Electing U.S. Investor in the three preceding taxable
years, or, if shorter, the Non-Electing U.S. Investor’s holding period for the ordinary shares or ADSs), and (b) any gain realized on the sale or other disposition of such
ordinary shares or ADSs. Under these rules:
•
•
the excess distribution or gain would be allocated ratably over the Non-Electing U.S. Investor’s holding period for the ordinary shares or ADSs;
the amount allocated to the current taxable year and any year prior to us becoming a PFIC would be taxed as ordinary income; and
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•
the amount allocated to each of the other taxable years would be subject to tax at the highest rate of tax in effect for the applicable class of taxpayer for that year,
and an interest charge for the deemed deferral benefit would be imposed with respect to the resulting tax attributable to each such other taxable year.
If a Non-Electing U.S. Investor who is an individual dies while owning our ordinary shares or ADSs, the Non-Electing U.S. Investor’s successor would be ineligible
to receive a step-up in tax basis of the ordinary shares or ADSs. Non-Electing U.S. Investors are encouraged to consult their tax advisors regarding the application of the PFIC
rules to their specific situation.
A Non-Electing U.S. Investor who wishes to make a QEF election for a subsequent year may be able to make a special “purging election” pursuant to Section
1291(d) of the Code. Pursuant to this election, a Non-Electing U.S. Investor would be treated as selling his or her ordinary shares or ADSs for fair market value on the first day
of the taxable year for which the QEF election is made. Any gain on such deemed sale would be subject to tax under the rules for Non-Electing U.S. Investors as discussed
above. Non-Electing U.S. Investors are encouraged to consult their tax advisors regarding the availability of a “purging election” as well as other available elections.
To the extent a distribution on our ordinary shares or ADSs does not constitute an excess distribution to a Non-Electing U.S. Investor, such Non-Electing U.S.
Investor generally will be required to include the amount of such distribution in gross income as a dividend to the extent of our current or accumulated earnings and profits (as
determined for U.S. federal income tax purposes) that are not allocated to excess distributions. The tax consequences of such distributions are discussed above under “—
Taxation of U.S. Investors — Distributions.” Each U.S. Investor is encouraged to consult its own tax advisor with respect to the appropriate U.S. federal income tax treatment
of any distribution on our ordinary shares or ADSs.
If we are treated as a PFIC for any taxable year during the holding period of a Non-Electing U.S. Investor, we will continue to be treated as a PFIC for all succeeding
years during which the Non-Electing U.S. Investor is treated as a direct or indirect Non-Electing U.S. Investor even if we are not a PFIC for such years. A U.S. Investor is
encouraged to consult its tax advisor with respect to any available elections that may be applicable in such a situation, including the “deemed sale” election of Section 1298(b)
(1) of the Code. In addition, U.S. Investors should consult their tax advisors regarding the IRS information reporting and filing obligations that may arise as a result of the
ownership of shares in a PFIC, including IRS Form 8621.
We may invest in the equity of foreign corporations that are PFICs or may own subsidiaries that own PFICs. U.S. Investors will be subject to the PFIC rules with
respect to their indirect ownership interests in such PFICs, such that a disposition of the shares of the PFIC or receipt by us of a distribution from the PFIC generally will be
treated as a deemed disposition of such shares or the deemed receipt of such distribution by the U.S. Investor, subject to taxation under the PFIC rules. There can be no
assurance that a U.S. Investor will be able to make a QEF election or a mark-to-market election with respect to PFICs in which we invest. Each U.S. Investor is encouraged to
consult its own tax advisor with respect to tax consequences of an investment by us in a corporation that is a PFIC.
The U.S. federal income tax rules relating to PFICs are complex. U.S. Investors are urged to consult their own tax advisors with respect to the purchase, ownership
and disposition of ordinary shares or ADSs, any elections available with respect to such ordinary shares or ADSs and the IRS information reporting obligations with
respect to the purchase, ownership and disposition of ordinary shares or ADSs.
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Certain Reporting Requirements
Certain U.S. Investors may be required to file IRS Form 926, Return by U.S. Transferor of Property to a Foreign Corporation and IRS Form 5471, Information Return
of U.S. Persons With Respect to Certain Foreign Corporations, reporting transfers of cash or other property to us and information relating to the U.S. Investor and us.
Substantial penalties may be imposed upon a U.S. Investor that fails to comply.
Certain U.S. Investors owning “specified foreign financial assets” with an aggregate value in excess of $50,000 on the last day of the taxable year or $75,000 at any
time during the taxable year (or such higher dollar amount as may be prescribed by applicable IRS guidance) may be required to file IRS Form 8938, Statement of Specified
Foreign Financial Assets, with respect to such assets with their tax returns. “Specified foreign financial assets” generally include any financial accounts maintained by foreign
financial institutions, as well as any of the following held for investment and not held in accounts maintained by financial institutions: (i) stocks and securities issued by non-
U.S. persons, which may include the ordinary shares or ADSs, (ii) financial instruments and contracts held for investment that have non-U.S. issuers or counterparties and (iii)
interests in foreign entities. The IRS has issued guidance exempting “specified foreign financial assets” held in a financial account from reporting under this provision
(although the financial account itself, if maintained by a foreign financial institution, may remain subject to this reporting requirement). U.S. Investors are urged to consult
their tax advisors regarding the application of these requirements to their ownership of the ordinary shares or ADSs.
If we are treated as a PFIC, U.S. Investors generally are required to file annual tax returns (including on IRS Form 8621) containing such information as the U.S.
Treasury requires (whether or not a mark-to-market election is or has been made). A U.S. Investor that is not otherwise required to file a U.S. tax return must still file IRS
Form 8621 in accordance with the instructions for the Form. Failure to file IRS Form 8621 for each applicable taxable year may result in substantial penalties and the statute
of limitations on the assessment and collection of U.S. federal income taxes of such U.S. Investor for the related taxable year may not close until three years after the date on
which the required information is filed. U.S. Investors should consult their tax advisors regarding the IRS information reporting and filing obligations that may arise as a result
of the ownership of shares in a PFIC, including IRS Form 8621.
Backup Withholding Tax and Information Reporting Requirements
Generally, information reporting requirements will apply to distributions on our ordinary shares or ADSs or proceeds on the disposition of our ordinary shares or
ADSs paid within the United States (and, in certain cases, outside the United States) to U.S. Investors other than certain exempt recipients, such as corporations. Furthermore,
backup withholding may apply to such amounts if the U.S. Investor fails to (i) provide a correct taxpayer identification number, (ii) report interest and dividends required to be
shown on its U.S. federal income tax return, or (iii) make other appropriate certifications in the required manner. U.S. Investors who are required to establish their exempt
status generally must provide such certification on IRS Form W-9.
Backup withholding is not an additional tax. Amounts withheld as backup withholding from a payment may be credited against a U.S. Investor’s U.S. federal income
tax liability and such U.S. Investor may obtain a refund of any excess amounts withheld by timely filing the appropriate claim for refund with the IRS and furnishing any
required information in a timely manner.
U.S. Investors should consult their own tax advisors concerning the tax consequences relating to the purchase, ownership and disposition of the ordinary shares or
ADSs.
F. Dividends and Paying Agents
Not applicable.
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G. Statement by Experts
Not applicable.
H. Documents on Display
We are currently subject to the information and periodic reporting requirements of the Exchange Act, and file periodic reports and other information with the SEC
through its electronic data gathering, analysis and retrieval (EDGAR) system. As a foreign private issuer, all documents which were filed after September 24, 2010 on the
SEC’s EDGAR system are available for retrieval on the SEC’s website at www.sec.gov.
As a foreign private issuer, we are exempt from the rules under the Exchange Act related to the furnishing and content of proxy statements, and our 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, we are not
required under the Exchange Act to file annual, quarterly and current reports and financial statements with the SEC as frequently or as promptly as United States companies
whose securities are registered under the Exchange Act.
In addition, since our ordinary shares are traded on the TASE, we also file periodic and immediate reports with, and furnish information to, the TASE and the ISA, or
the ISA, as required under Chapter Six of the Israel Securities Law, 1968 and the regulations enacted pursuant thereof, as applicable to a public company which also trades on
Nasdaq. Copies of our filings with the ISA can be retrieved electronically through the MAGNA distribution site of the ISA (www.magna.isa.gov.il) and the TASE website
(www.maya.tase.co.il).
We maintain a corporate website at www.biolinerx.com. Information contained on, or that can be accessed through, our website does not constitute a part of this
Annual Report on Form 20-F. We have included our website address in this Annual Report on Form 20-F solely as an inactive textual reference.
I. Subsidiary Information
Not applicable.
J. Annual Report to Security Holders
Not applicable.
ITEM 11. QUANTITATIVE AND QUALITATIVE DISCLOSURE ON MARKET RISK
We are exposed to a variety of risks in the ordinary course of our business, including, but not limited to, interest rate risk, foreign exchange risk, liquidity risk and
credit risk, as discussed below. We regularly assess each of these risks to minimize any adverse effects on our business as a result of those factors. See Note 3 to our
consolidated financial statements, which are included elsewhere in this Annual Report, for further discussion of our exposure to these risks.
Risk of Interest Rate Fluctuation
Our investments consist primarily of cash, cash equivalents and short-term bank deposits. We may also invest in investment-grade marketable securities with
maturities of up to three years, including commercial paper, money market funds, and government/non-government debt securities. The primary objective of our investment
activities is to preserve principal while maximizing the income that we receive from our investments without significantly increasing risk and loss. Our investments are
exposed to market risk due to fluctuation in interest rates, which may affect our interest income and the fair market value of our investments. We manage this exposure by
performing ongoing evaluations of our investments. Due to the short-term maturities of our investments to date, their carrying value has always approximated their fair value.
It will be our policy to hold investments to maturity in order to limit our exposure to interest rate fluctuations.
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Foreign Currency Exchange Risk
Our reporting and functional currency is the dollar. However, we pay a significant portion of our expenses in NIS and in euro, and we expect this to continue. If the
dollar weakens against the NIS or the euro in the future, there may be a negative impact on our results of operations. The revenues from our current out-licensing and co-
development arrangements are payable in dollars and euros. Although we expect our revenues from future licensing arrangements to be denominated primarily in dollars, we
are exposed to the currency fluctuation risks relating to the recording of our revenues in currencies other than dollars. For example, if the euro strengthens against the dollar,
our reported revenues in dollars may be lower than anticipated. To date, fluctuations in the exchange rates have not materially affected our results of operations or financial
condition for the periods under review.
From time to time, we have engaged in currency hedging transactions to decrease the risk of financial exposure from fluctuations in the exchange rates of our
principal operating currencies, and we may continue to do so in the future. These measures, however, may not adequately protect us from the material adverse effects of such
fluctuations.
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
Set forth below is a summary of some of the material terms of the deposit agreement among BioLineRx, The Bank of New York Mellon as depositary, or the
Depositary, and the owners and holders from time to time of our ADSs.
Description of the ADSs
Each of our ADSs represents 15 of our ordinary shares deposited with the principal Tel Aviv office of Bank Leumi Le-Israel, as Custodian for the Depositary. Our
ADSs trade on Nasdaq.
The form of the deposit agreement for the ADS and the form of American Depositary Receipt (ADR) that represents an ADS have been incorporated by reference as
exhibits to this Annual Report on Form 20-F. Copies of the deposit agreement are available for inspection at the principal office of The Bank of New York Mellon, located at
101 Barclay Street, New York, New York 10286.
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Charges of Depositary
We will pay the fees, reasonable expenses and out-of-pocket charges of the Depositary and those of any registrar only in accordance with agreements in writing
entered into between us and the Depositary from time to time. The following charges shall be incurred by any party depositing or withdrawing ordinary shares or by any party
surrendering ADRs or to whom ADRs are issued (including, without limitation, issuance pursuant to a stock dividend or stock split declared by us or an exchange of stock
regarding the ADRs or deposited ordinary shares or a distribution of ADRs pursuant to the terms of the deposit agreement):
•
•
•
•
•
•
•
•
•
•
taxes and other governmental charges;
any applicable transfer or registration fees;
certain cable, telex and facsimile transmission charges as provided in the deposit agreement;
any expenses incurred in the conversion of foreign currency;
a fee of $5.00 or less per 100 ADSs (or a portion thereof) for the execution and delivery of ADRs and the surrender of ADRs, including if the deposit agreement
terminates;
a fee of $.05 or less per ADS (or portion thereof) for any cash distribution made pursuant to the deposit agreement;
a fee for the distribution of securities pursuant to the deposit agreement;
in addition to any fee charged for a cash distribution, a fee of $.05 or less per ADS (or portion thereof) per annum for depositary services;
a fee for the distribution of proceeds of rights that the Depositary sells pursuant to the deposit agreement; and
any other charges payable by the Depositary, any of the Depositary’s agents, or the agents of the Depositary’s agents in connection with the servicing of ordinary
shares or other Deposited Securities.
The Depositary may own and deal in our securities and in ADSs.
The Depositary collects its fees for delivery and surrender of ADSs directly from investors depositing shares or surrendering ADSs for the purpose of withdrawal or
from intermediaries acting for them. The Depositary collects fees for making distributions to investors by deducting those fees from the amounts distributed or by selling a
portion of distributable property to pay the fees. The Depositary may collect its annual fee for depositary services by deduction from cash distributions or by directly billing
investors or by charging the book-entry system accounts of participants acting for them. The Depositary may collect any of its fees by deduction from any cash distribution
payable (or by selling a portion of securities or other property distributable) to ADS holders that are obligated to pay those fees. The Depositary may generally refuse to
provide fee-attracting services until its fees for those services are paid.
From time to time, the Depositary may make payments to us to reimburse us for costs and expenses generally arising out of establishment and maintenance of the
ADS program, waive fees and expenses for services provided to us by the Depositary or share revenue from the fees collected from ADS holders. In performing its duties
under the deposit agreement, the Depositary may use brokers, dealers, foreign currency dealers or other service providers that are owned by or affiliated with the Depositary
and that may earn or share fees, spreads or commissions.
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The Depositary may convert currency itself or through any of its affiliates and, in those cases, acts as principal for its own account and not as agent, advisor, broker or
fiduciary on behalf of any other person and earns revenue, including, without limitation, transaction spreads, that it will retain for its own account. The revenue is based on,
among other things, the difference between the exchange rate assigned to the currency conversion made under the deposit agreement and the rate that the Depositary or its
affiliate receives when buying or selling foreign currency for its own account. The Depositary makes no representation that the exchange rate used or obtained in any currency
conversion under the deposit agreement will be the most favorable rate that could be obtained at the time or that the method by which that rate will be determined will be the
most favorable to ADS holders, subject to the Depositary’s obligations under the deposit agreement. The methodology used to determine exchange rates used in currency
conversions is available upon request.
Liability of Holders for Taxes, Duties or Other Charges
Any tax or other governmental charge with respect to ADSs or any deposited ordinary shares represented by any ADS shall be payable by the holder of such ADS to
the Depositary. The Depositary may refuse to effect transfer of such ADS or any withdrawal of deposited ordinary shares represented by such ADS until such payment is
made, and may withhold any dividends or other distributions or may sell for the account of the holder any part or all of the deposited ordinary shares represented by such ADS
and may apply such dividends or distributions or the proceeds of any such sale in payment of any such tax or other governmental charge and the holder of such ADS shall
remain liable for any deficiency.
ITEM 13. DEFAULTS, DIVIDENDS ARREARAGES AND DELINQUENCIES
Not applicable.
ITEM 14. MATERIAL MODIFICATIONS TO THE RIGHTS OF SECURITY HOLDERS AND USE OF PROCEEDS
Not applicable.
ITEM 15. CONTROLS AND PROCEDURES
a.
Disclosure Controls and Procedures
We have performed an evaluation of the effectiveness of our disclosure controls and procedures that are designed to ensure that the material financial and non-
financial information required to be disclosed to the SEC is recorded, processed, summarized and reported timely. Based on our evaluation, our Chief Executive Officer, or the
CEO, and the Chief Financial Officer, or the CFO, have concluded that our disclosure controls and procedures (as defined in Rules 13a-15(e) and 15d-15(e) of the Exchange
Act) as of the end of the period covered by this report are effective. Notwithstanding the foregoing, there can be no assurance that our disclosure controls and procedures will
detect or uncover all failures of persons within the Company to disclose material information otherwise required to be set forth in our reports.
b. Management’s Annual Report on Internal Control over Financial Reporting
Our management is responsible for establishing and maintaining adequate internal control over financial reporting, as such term is defined in Rule 13a-15(f)
promulgated under the Exchange Act. Our internal control system was designed to provide reasonable assurance to our management and board of directors regarding the
reliability of financial reporting and the preparation and fair presentation of published financial statements for external purposes in accordance with generally accepted
accounting principles. All internal control systems, no matter how well designed, have inherent limitations. Therefore, even those systems determined to be effective can
provide only reasonable assurance with respect to financial statement preparation and presentation and 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 policies or procedures may deteriorate.
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Our management, including the CEO and CFO, conducted an evaluation, pursuant to Rule 13a-15(c) promulgated under the Exchange Act, of the effectiveness, as of
the end of the period covered by this Annual Report, of its internal control over financial reporting based on the framework in Internal Control—Integrated Framework issued
by the Committee of Sponsoring Organizations of the Treadway Commission (2013). Based on the results of this evaluation, management concluded that our internal control
over financial reporting was effective as of December 31, 2022.
c.
Attestation Report of Registered Public Accounting Firm
Kesselman & Kesselman, a member firm of PricewaterhouseCoopers International Ltd., our independent registered public accounting firm, has issued an attestation
report on the effectiveness of our internal control over financial reporting, appearing under “Item 18. Financial Statements” on page F-2.
d.
Changes in Internal Control over Financial Reporting
There were no changes in our internal control over financial reporting that occurred 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]
ITEM 16A. AUDIT COMMITTEE FINANCIAL EXPERTS
Our Board of Directors has determined that Mr. Rami Dar is the audit committee financial expert. Mr. Dar is one of our independent directors for the purposes of the
Nasdaq Rules.
ITEM 16B. CODE OF ETHICS
In July 2011, our Board of Directors adopted a Code of Business Conduct and Ethics, or the Code of Conduct, that applies to all our employees, including without
limitation our CEO, CFO and controller. Our Code of Conduct may be viewed on our website at www.biolinerx.com . A copy of our Code of Conduct may be obtained,
without charge, upon a written request addressed to our investor relations department, 2 HaMa’ayan Street, Modi’in 7177871, Israel (Telephone no. +972-8-642-9100) (e-
mail: info@BioLineRx.com).
ITEM 16C. PRINCIPAL ACCOUNTANT FEES AND SERVICES
Fees Paid to Independent Registered Public Accounting Firm
The following table sets forth, for each of the years indicated, the fees billed by Kesselman & Kesselman, a member firm of PricewaterhouseCoopers International
Ltd., our independent registered public accounting firm.
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Services Rendered
Audit Fees(1)
Audit-Related Fees(2)
Tax Fees(3)
All Other Fees
Total
Year Ended December 31,
2022
2021
(in thousands of U.S. dollars)
130
25
20
-
175
130
4
18
-
152
(1) Audit fees consist of services that would normally be provided in connection with statutory and regulatory filings or engagements, including services that generally only
the independent accountant can reasonably provide.
(2) Audit-related services relate to reports to the IIA and work regarding a public listing or offering.
(3) Tax fees relate to tax compliance, planning and advice.
Our Audit Committee, in accordance with its charter, reviews and pre-approves all audit services and permitted non-audit services (including the fees and other
terms) to be provided by our independent auditors.
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.
ITEM 16G. CORPORATE GOVERNANCE
Nasdaq Listing Rules and Home Country Practices
The Sarbanes-Oxley Act, as well as related rules subsequently implemented by the SEC, requires foreign private issuers, such as us, to comply with various corporate
governance practices. In complying with the Nasdaq Rules, we have elected to follow certain corporate governance practices permitted under the Companies Law and the
rules of the TASE in lieu of compliance with certain corporate governance requirements otherwise required by the Nasdaq Rules.
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In accordance with Israeli law and practice and subject to the exemption set forth in Rule 5615 of the Nasdaq Rules, we follow the provisions of the Companies Law,
rather than the Nasdaq Rules, with respect to the following requirements:
•
•
•
•
•
Distribution of annual and quarterly reports to shareholders. Under Israeli law, as a public company whose shares are traded on the TASE, we are not required to
distribute annual and quarterly reports directly to shareholders and the generally accepted business practice in Israel is not to distribute such reports to
shareholders but to make such reports publicly available through the website of the ISA and the TASE. In addition, we make our audited financial statements
available to our shareholders at our offices. As a foreign private issuer, we are generally exempt from the SEC’s proxy solicitation rules.
Quorum. While the Nasdaq Rules require that the quorum for purposes of any meeting of the holders of a listed company’s common voting stock, as specified in
the company’s bylaws, be no less than 33 1/3% of the company’s outstanding common voting stock, under Israeli law, a company is entitled to determine in its
articles of association the number of shareholders and percentage of holdings required for a quorum at a shareholders meeting. Our Articles of Association
provide that a quorum of two or more shareholders holding at least 25% of the voting rights in person or by proxy is required for commencement of business at a
general meeting. However, the quorum set forth in our Articles of Association with respect to an adjourned meeting consists of any number of shareholders
present in person or by proxy.
Independent Directors. Our Board of Directors includes two external directors in accordance with the provisions contained in Sections 239-249 of the Companies
Law and Rule 10A-3 of the general rules and regulations promulgated under the Securities Act, rather than a majority of independent directors. Israeli law does
not require, nor do our independent directors conduct, regularly scheduled meetings at which only they are present. We are required, however, to ensure that all
members of our Audit Committee are “independent” under the applicable Nasdaq and SEC criteria for independence (as a foreign private issuer we are not
exempt from the SEC independence requirement), and we must also ensure that a majority of the members of our Audit Committee are independent directors as
defined in the Companies Law. Furthermore, Israeli law does not require, nor do our independent directors conduct, regularly scheduled meetings at which only
they are present, which the Nasdaq Rules otherwise require.
Audit Committee. Our Audit Committee complies with all of the requirements under Israeli law, and is composed of two external directors, which are all of our
external directors, and only one other director, who cannot be the chairman of our Board of Directors. Consistent with Israeli law, the independent auditors are
elected at a meeting of shareholders instead of being appointed by the Audit Committee.
Nomination of our Directors. With the exception of our external directors and directors elected by our Board of Directors due to vacancy, our directors are
elected by a general or extraordinary meeting of our shareholders, to hold office until they are removed from office by the majority of our shareholders at a
general or extraordinary meeting of our shareholders. See “Item 6. Directors, Senior Management and Employees — Board Practices — Board of Directors.”
The nominations for directors, which are presented to our shareholders, are generally made by our directors, but nominations may be made by one or more of our
shareholders as provided under the Companies Law or in an agreement between us and our shareholders. Currently, there is no agreement between us and any
shareholder regarding the nomination of directors. In accordance with our Articles of Association, under the Companies Law, any one or more shareholders
holding, in the aggregate, either (1) at least 5% of our outstanding shares and at least 1% of our outstanding voting power or (2) at least 5% of our outstanding
voting power, may nominate one or more persons for election as directors at a general or special meeting by delivering a written notice of such shareholder’s
intent to make such nomination or nominations to our registered office. Each such notice must set forth all of the details and information as required to be
provided in the Companies Law.
132
•
•
•
•
Compensation Committee and Compensation of Officers. Israeli law, and our Articles of Association, do not require that a compensation committee composed
solely of independent members of our Board of Directors determine (or recommend to the board of directors for determination) an executive officer’s
compensation, as required under Nasdaq’s listing standards related to compensation committee independence and responsibilities; nor do they require that the
Company adopt and file a compensation committee charter. Instead, our Compensation Committee has been established and conducts itself in accordance with
provisions governing the composition of and the responsibilities of a compensation committee as set forth in the Companies Law, and is comprised of all of our
external directors (who must comprise the majority of the members of the Compensation Committee), and at least one additional director who is entitled to the
same compensation payable to our external directors, and who is not the chairman of our Board of Directors or otherwise employed by or a provider of services
to, the Company. Additionally, we comply with the requirements set forth under the Companies Law, pursuant to which transactions with office holders
regarding their terms of office and employment, and a transaction with a controlling shareholder in a company regarding his or her employment and/or his or her
terms of office with the company, may require the approval of the compensation committee, the board of directors and under certain circumstances the
shareholders, either in accordance with our compensation policy or, in special circumstances in deviation therefrom, taking into account certain considerations set
forth in the Companies Law. See “Item 6. Directors, Senior Management and Employees — Board Practices — Compensation Committee” for information
regarding the Compensation Committee, and “Item 6. Directors, Senior Management and Employees — Approval of Related Party Transactions under Israeli
Law” for information regarding the special approvals required with respect to approval of terms of office and employment of office holders, pursuant to the
Companies Law. The requirements for shareholder approval of any office holder compensation, and the relevant majority or special majority for such approval,
are all as set forth in the Companies Law. Thus, we will seek shareholder approval for all corporate actions with respect to office holder compensation requiring
such approval under the requirements of the Companies Law, including seeking prior approval of the shareholders for the compensation policy and for certain
office holder compensation, rather than seeking approval for such corporate actions in accordance with Nasdaq Listing Rules.
Approval of Related Party Transactions. All related party transactions are approved in accordance with the requirements and procedures for approval of
interested party acts and transactions, set forth in sections 268 to 275 of the Companies Law, and the regulations promulgated thereunder, which require the
approval of the audit committee, the compensation committee, the board of directors and shareholders, as may be applicable, for specified transactions, rather
than approval by the audit committee or other independent body of our Board of Directors as required under the Nasdaq Rules.
Shareholder Approval. We seek shareholder approval for all corporate actions requiring such approval in accordance with the requirements of the Companies
Law, which are different or in addition to the requirements for seeking shareholder approval under Nasdaq Listing Rule 5635, rather than seeking approval for
corporation actions in accordance with such listing rules.
Equity Compensation Plans. We do not necessarily seek shareholder approval for the establishment of, and amendments to, stock option or equity compensation
plans (as set forth in Nasdaq Listing Rule 5635(c)), as such matters are not subject to shareholder approval under Israeli law. Our equity compensation plan is
available to our employees, none of whom are currently U.S. employees, and provides features necessary to comply with applicable non-U.S. tax laws.
133
ITEM 16H. MINE SAFETY DISCLOSURE
Not applicable.
ITEM 16I. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS
Not applicable.
ITEM 17. FINANCIAL STATEMENTS
The Registrant has responded to Item 18 in lieu of responding to this Item.
ITEM 18. FINANCIAL STATEMENTS
See the financial statements beginning on page F-1. The following financial statements are filed as part of this Annual Report on Form 20-F together with the report
of the independent registered public accounting firm.
ITEM 19. EXHIBITS
Exhibit
Number
2.1(1)
2.2(1)
2.3(2)
2.4(2)
4.1(3)
4.2(1)
4.3(3)
4.4(1)
4.5(2)
4.6(1)
4.7†(4)
4.8(5)
4.9(6)
4.10(7)†
Exhibit Description
Articles of Association, as amended September 24, 2020
Description of Securities Registered under Section 12
Deposit Agreement dated as of July 21, 2011 among the Registrant, The Bank of New York Mellon, as Depositary, and all Owners and Holders from time to
time of American Depositary Shares issued thereunder
Form of American Depositary Receipt; the Form is Exhibit A of the deposit agreement which is Exhibit 2.2 above.
Employment Agreement with Philip Serlin, dated May 24, 2009
Amendment to Employment Agreement between BioLineRx Ltd. and Philip Serlin, dated September 24, 2020
Employment Agreement with Mali Zeevi, dated September 16, 2009
Amendment to Employment Agreement between BioLineRx Ltd and Mali Zeevi, dated September 24, 2020
Employment Agreement with Ella Sorani, dated January 11, 2017
Amendment to Employment Agreement between BioLineRx Ltd and Ella Sorani, dated September 24, 2020
License Agreement entered into as of November 25, 2007 between BioLine Innovations Jerusalem L.P. and Innovative Pharmaceutical Concepts, Inc.
BioLineRx Ltd. Amended and Restated 2003 Share Incentive Plan
License Agreement entered into as of September 2, 2012 by and between the Registrant and Biokine Therapeutics Ltd.
Amendment Agreement entered into as of October 2, 2018 by and between the Registrant and Biokine Therapeutics Ltd.
134
4.11(7)
4.12(8)
4.13(10)
4.14(11)†
4.15†
4.16(3)†
4.17†
4.18†
4.19†
4.20(9)
4.21(12)
4.22(13)
4.23(14)
4.24(15)
4.25(16)
4.26(16)
4.27(16)
8.1(17)
12.1
12.2
13.1
13.2
15.1
101
Warrant issued to Kreos Capital V dated October 2, 2018
Compensation Policy for Executives and Directors, as amended
Lease Agreement entered into as of August 7, 2014 between S.M.L. Solomon Industrial Buildings Ltd. and Infrastructure Management and Development
Established by C.P.M. Ltd. as Lessor and the Registrant as Lessee, as amended (English summary of the Hebrew original)
License Agreement entered into as of December 22, 2014 between the Registrant and Wartner Europe BV
Amendment No. 2 to Clinical Trial Collaboration and Supply Agreement entered into as of July 24, 2018 between the Registrant and Merck Sharp & Dohme
B.V.
Amended and Restated Exclusive License Agreement entered into as of April 30, 2013 between the University of Massachusetts and Agalimmune Ltd.
Patent and Know-how License Agreement entered into as of September 19, 2017 between Kode Biotech Limited and Agalimmune Ltd.
Second Amendment Agreement entered into as of October 16, 2018 between the University of Massachusetts and Agalimmune Ltd.
Amendment No. 1 to License Agreement entered into as of June 18, 2018 between the Registrant and Wartner Europe BV
First Addendum to License Agreement entered into as of October 16, 2019 by and between the Registrant and Biokine Therapeutics Ltd., as amended.
Form of Warrant issued February 7, 2019
Form of Underwriter Warrant to be issued by BioLineRx Ltd. on January 22, 2021
At-the-Market Sales Agreement, dated September 3, 2021, between BioLineRx Ltd. and H.C. Wainwright & Co., LLC
Agreement for the Provision of a Loan Facility entered into as of September 14, 2022, by and between the Registrant and Kreos Capital VII Aggregator
SCSP
Form of Securities Purchase Agreement dated as of September 18, 2022 between the Registrant and the investors listed therein
Form of Warrant issued by the Registrant on September 21, 2022
Form of Placement Agent Warrant issued by the Registrant on September 21, 2022
List of Subsidiaries of BioLineRx Ltd.
Certification by Chief Executive Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002
Certification by Chief Financial Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002
Certification by Chief Executive Officer pursuant to 18 U.S.C. Section 1350, as adopted pursuant to Section 906 of the Sarbanes-Oxley Act of 2002
Certification by Chief 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 Kesselman & Kesselman, Certified Public Accountant (Isr.), a member of PricewaterhouseCoopers International Limited, independent registered
public accounting firm for the Registrant
The following financial information from BioLineRx Ltd.’s Annual Report on Form 20-F for the fiscal year ended December 31, 2022 formatted in Inline
XBRL (Extensible Business Reporting Language): (i) Consolidated Statements of Financial Position at December 31, 2022 and 2021; (ii) Consolidated
Statements of Comprehensive Loss for the years ended December 31, 2022, 2021 and 2020; (iii) Statements of Changes in Equity for the years ended
December 31, 2022, 2021 and 2020; (iv) Consolidated Cash Flow Statements for the years ended December 31, 2022, 2021 and 2020; and (v) Notes to the
Consolidated Financial Statements.
135
Portions of this exhibit have been omitted and filed separately with the Securities and Exchange Commission pursuant to a confidential treatment request.
(1)
Incorporated by reference to the Registrant’s Annual Report on Form 20-F filed on February 23, 2021.
(2)
Incorporated by reference to Exhibit 1 of the Registration Statement on Form F-6EF (No. 333-218969) filed by the Bank of New York Mellon on June 26, 2017 with
respect to the Registrant’s American Depositary Shares.
(3)
Incorporated by reference to the Registrant’s Annual Report on Form 20-F filed on March 23, 2017.
(4)
Incorporated by reference to the Registrant’s Registration Statement on Form 20-F (No. 001-35223) filed on July 1, 2011.
(5)
Incorporated by reference to the Registrant’s Annual Report on Form 20-F filed on March 10, 2016.
(6)
Incorporated by reference to the Registrant’s Annual Report on Form 20-F/A filed on May 31, 2016.
(7)
Incorporated by reference to the Registrant’s Form 6-K filed on October 3, 2018.
(8)
Incorporated by reference to the Registrant’s Form 6-K filed on May 27, 2022.
(9)
Incorporated by reference to the Registrant’s Annual Report on Form 20-F filed on March 12, 2020.
(10) Incorporated by reference to the Registrant’s Annual Report on Form 20-F filed on March 23, 2015.
(11) Incorporated by reference to the Registrant’s Annual Report on Form 20-F/A filed on September 22, 2015.
(12) Incorporated by reference to the Registrant’s Form 6-K filed on February 7, 2019.
(13) Incorporated by reference to the Registrant’s Form 6-K filed on January 21, 2021.
(14) Incorporated by reference to the Registrant’s Form 6-K filed on September 3, 2021.
(15) Incorporated by reference to the Registrant’s Form 6-K filed on September 15, 2022.
(16) Incorporated by reference to the Registrant’s Form 6-K filed on September 21, 2022.
(17)
Incorporated by reference to the Registrant’s Annual Report on Form 20-F filed on March 16, 2022.
136
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
Date: March 22, 2023
BIOLINERX LTD.
By:
/s/ Philip A. Serlin
Philip A. Serlin
Chief Executive Officer
137
BioLineRx Ltd.
INDEX TO FINANCIAL STATEMENTS:
REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM (PCAOB name: Kesselman & Kesselman C.P.A.s and PCAOB ID No. 1309)
CONSOLIDATED FINANCIAL STATEMENTS:
CONSOLIDATED STATEMENTS OF FINANCIAL POSITION
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS
CONSOLIDATED STATEMENTS OF CHANGES IN EQUITY
CONSOLIDATED STATEMENTS OF CASH FLOWS
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
Page
F-2
F-4
F-5
F-6
F-7
F-9
Report of Independent Registered Public Accounting Firm
To the Board of Directors and Shareholders of BioLineRx Ltd.
Opinions on the Financial Statements and Internal Control over Financial Reporting
We have audited the accompanying consolidated statements of financial position of BioLineRx Ltd. and its subsidiaries (the “Company”) as of December 31, 2022 and 2021,
the related consolidated statements of comprehensive loss, changes in equity and cash flows, for each of the three years in the period ended December 31, 2022, including the
related notes (collectively referred to as the “consolidated financial statements”). We also have audited the Company's internal control over financial reporting as of December
31, 2022, based on criteria established in Internal Control - Integrated Framework (2013) issued by the Committee of Sponsoring Organizations of the Treadway Commission
(COSO).
In our opinion, the consolidated financial statements referred to above present fairly, in all material respects, the financial position of the Company as of December 31, 2022,
and 2021, 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. Also in our opinion, the Company maintained, in all material respects, effective internal
control over financial reporting as of December 31, 2022, based on criteria established in Internal Control - Integrated Framework (2013) issued by the COSO.
Substantial Doubt about the Company’s Ability to Continue as a Going Concern
The accompanying consolidated financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 1(b) to the
consolidated financial statements, the Company has suffered recurring losses from operations and has cash outflows from operating activities that indicate that a material
uncertainty exists that may cast significant doubt (or raise substantial doubt as contemplated by PCAOB standards) about its ability to continue as a going concern.
Management’s plans in regard to these matters are also described in Note 1(b). The consolidated financial statements do not include any adjustments that might result from the
outcome of this uncertainty.
Basis for Opinions
The Company's management is responsible for these consolidated financial statements, for maintaining effective internal control over financial reporting, and for its
assessment of the effectiveness of internal control over financial reporting, included in Management's Annual Report on Internal Control over Financial Reporting appearing
under Item 15. Our responsibility is to express opinions on the Company’s consolidated financial statements and on the Company's internal control over financial reporting
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 audits to obtain reasonable assurance about
whether the consolidated financial statements are free of material misstatement, whether due to error or fraud, and whether effective internal control over financial reporting
was maintained in all material respects.
Our audits of the consolidated financial statements included performing procedures to assess the risks of material misstatement of the consolidated 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 consolidated 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 consolidated financial statements. Our audit of internal control over financial reporting included obtaining an understanding of
internal control over financial reporting, assessing the risk that a material weakness exists, and testing and evaluating the design and operating effectiveness of internal control
based on the assessed risk. Our audits also included performing such other procedures as we considered necessary in the circumstances. We believe that our audits provide a
reasonable basis for our opinions.
Kesselman & Kesselman, 146 Derech Menachem Begin St. Tel-Aviv 6492103, Israel,
P.O Box 7187 Tel-Aviv 6107120, Telephone: +972 -3- 7954555, Fax:+972 -3- 7954556, www.pwc.com/il
F - 2
Definition and Limitations of Internal Control over Financial Reporting
A company’s internal control over financial reporting is a process designed to provide reasonable assurance regarding the reliability of financial reporting and the preparation
of financial statements for external purposes in accordance with generally accepted accounting principles. A company’s internal control over financial reporting includes those
policies and procedures that (i) pertain to the maintenance of records that, in reasonable detail, accurately and fairly reflect the transactions and dispositions of the assets of the
company; (ii) provide reasonable assurance that transactions are recorded as necessary to permit preparation of financial statements in accordance with generally accepted
accounting principles, and that receipts and expenditures of the company are being made only in accordance with authorizations of management and directors of the company;
and (iii) provide reasonable assurance regarding prevention or timely detection of unauthorized acquisition, use, or disposition of the company’s assets that could have a
material effect on the financial statements.
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.
Critical Audit Matters
The critical audit matter communicated below is a matter arising from the current period audit of the consolidated financial statements that was communicated or required to
be communicated to the audit committee and that (i) relates to accounts or disclosures that are material to the consolidated financial statements and (ii) involved our especially
challenging, subjective, or complex judgments. The communication of critical audit matters does not alter in any way our opinion on the consolidated financial statements,
taken as a whole, and we are not, by communicating the critical audit matter below, providing a separate opinion on the critical audit matter or on the accounts or disclosures
to which it relates.
Intellectual Property Impairment Assessment
As described in Notes 4 and 8 to the consolidated financial statements, the Company's intangible assets relating to its intellectual property was $21.7 million as of December
31, 2022. Management conducts an impairment test as of December 31 of each year, or more frequently if events or circumstances indicate that the carrying value of the
intellectual property may be impaired. Potential impairment is identified by comparing the recoverable amount of the intellectual property to its carrying value. Value in use to
the Company is estimated by management using a discounted cash flow model. Management's cash flow projections included significant judgments and assumptions relating
to the weighted average cost of capital and the amount and timing of projected future cash flows.
The principal considerations for our determination that performing procedures relating to the intellectual property impairment assessment is a critical audit matter are the
significant judgment by management in developing the weighted average cost of capital and the amount and timing of projected future cash flows. This in turn led to a high
degree of auditor judgment, subjectivity, and effort in performing procedures to evaluate these assumptions. In addition, the audit effort involved the use of professionals with
specialized skill and knowledge to assist in performing these procedures and evaluating the audit evidence obtained.
Addressing the matter involved performing procedures and evaluating audit evidence in connection with forming our overall opinion on the consolidated financial statements.
These procedures included testing the effectiveness of controls relating to management's intangible asset impairment assessment, including controls over the determination of
the cash flow projections and the significant assumptions used. These procedures also included, among others, testing management’s process for developing the value
estimate; evaluating the appropriateness of the discounted cash flow model; testing the completeness, accuracy, and relevance of underlying data used in the model; and
evaluating the significant assumptions used by management, including the weighted average cost of capital and the amount and timing of projected future cash flows.
Evaluating management’s assumptions related to the weighted average cost of capital and the amount and timing of projected future cash flows involved evaluating whether
the assumptions used by management were reasonable considering the consistency with external market and industry data. Professionals with specialized skill and knowledge
were used to assist in the evaluation of management’s valuation model and certain significant assumptions.
/s/ Kesselman & Kesselman
Certified Public Accountants (Isr.)
A member firm of PricewaterhouseCoopers International Ltd.
Tel Aviv, Israel
March 22, 2023
We have served as the Company’s auditor since 2003.
F - 3
BioLineRx Ltd.
CONSOLIDATED STATEMENTS OF FINANCIAL POSITION
Note
December 31,
2021
2022
in USD thousands
Assets
CURRENT ASSETS
Cash and cash equivalents
Short-term bank deposits
Prepaid expenses
Other receivables
Total current assets
NON-CURRENT ASSETS
Property and equipment, net
Right-of-use assets, net
Intangible assets, net
Total non-current assets
Total assets
Liabilities and equity
CURRENT LIABILITIES
Current maturities of long-term loans
Accounts payable and accruals:
Trade
Other
Current maturities of lease liabilities
Total current liabilities
NON-CURRENT LIABILITIES
Warrants
Long-term loans, net of current maturities
Lease liabilities
Total non-current liabilities
COMMITMENTS AND CONTINGENT LIABILITIES
Total liabilities
EQUITY
Ordinary shares
Share premium
Warrants
Capital reserve
Other comprehensive loss
Accumulated deficit
Total equity
Total liabilities and equity
5
6
16a
7
9
8
10
16b
16b
9
11c
10
9
14
11
12,990
44,145
127
142
57,404
952
1,331
21,704
23,987
81,391
10,587
40,495
198
721
52,001
726
1,772
21,885
24,383
76,384
2,757
1,542
5,567
1,227
168
9,719
1,859
-
1,726
3,585
6,966
1,744
427
10,679
4,509
8,626
1,729
14,864
13,304
25,543
21,066
339,346
975
13,157
(1,416)
(305,041)
68,087
81,391
27,100
338,976
1,408
14,765
(1,416)
(329,992)
50,841
76,384
The accompanying notes are an integral part of the consolidated financial statements.
F - 4
BioLineRx Ltd.
CONSOLIDATED STATEMENTS OF COMPREHENSIVE LOSS
RESEARCH AND DEVELOPMENT EXPENSES
SALES AND MARKETING EXPENSES
GENERAL AND ADMINISTRATIVE EXPENSES
OPERATING LOSS
NON-OPERATING INCOME (EXPENSES), NET
FINANCIAL INCOME
FINANCIAL EXPENSES
LOSS AND COMPREHENSIVE LOSS
LOSS PER ORDINARY SHARE – BASIC AND DILUTED
WEIGHTED AVERAGE NUMBER OF SHARES USED IN CALCULATION OF
LOSS PER ORDINARY SHARE
Note
16c
16d
16e
16f
16g
16h
13
13
2020
Year ended December 31,
2021
in USD thousands
2022
(18,173)
(840)
(3,914)
(22,927)
(5,701)
236
(1,629)
(30,021)
(19,466)
(1,003)
(4,308)
(24,777)
(1,830)
559
(1,006)
(27,054)
(17,629)
(6,462)
(5,066)
(29,157)
5,670
694
(2,158)
(24,951)
in USD
(0.12)
(0.04)
(0.03)
252,844,394
662,933,695
773,956,973
The accompanying notes are an integral part of the consolidated financial statements.
F - 5
BioLineRx Ltd.
STATEMENTS OF CHANGES IN EQUITY
Ordinary
shares
Share
premium Warrants
Capital
reserve
in USD thousands
Other
comprehensive
loss
Accumulated
deficit
Total
BALANCE AT JANUARY 1, 2020
4,692
265,938
-
12,132
(1,416)
(247,966)
33,380
CHANGES IN 2020:
Issuance of share capital and warrants,
net
Warrants exercised
Employee stock options exercised
Employee stock options expired
Share-based compensation
Comprehensive loss for the year
BALANCE AT DECEMBER 31, 2020
CHANGES IN 2021:
Issuance of share capital and warrants,
net
Warrants exercised
Employee stock options exercised
Employee stock options expired
Share-based compensation
Comprehensive loss for the year
4,777
393
8
-
-
-
9,870
8,956
2,235
5
-
-
-
9,395
2,826
228
854
-
-
279,241
40,476
18,967
41
621
-
-
BALANCE AT DECEMBER 31, 2021
21,066
339,346
CHANGES IN 2022:
Issuance of share capital and warrants,
net
Employee stock options exercised
Employee stock options expired
Share-based compensation
Comprehensive loss for the year
BALANCE AT DECEMBER 31, 2022
6,029
5
-
-
-
27,100
(1,007)
14
623
-
-
338,976
-
-
-
-
-
-
-
975
-
-
-
-
-
975
433
-
-
-
-
1,408
-
-
(228)
(854)
1,272
-
-
-
-
-
-
-
12,322
(1,416)
-
-
(39)
(621)
1,495
-
-
-
-
-
-
13,157
(1,416)
-
(14)
(623)
2,245
-
-
-
-
-
14,765
(1,416)
-
-
-
-
-
(30,021)
(277,987)
-
-
-
-
-
(27,054
(305,041)
-
-
-
-
(24,951)
(329,992)
14,172
3,219
8
-
1,272
(30,021)
22,030
50,407
21,202
7
-
1,495
(27,054)
68,087
5,455
5
-
2,245
(24,951)
50,841
The accompanying notes are an integral part of the consolidated financial statements.
F - 6
BioLineRx Ltd.
CONSOLIDATED STATEMENTS OF CASH FLOWS
CASH FLOWS - OPERATING ACTIVITIES
Loss
Adjustments required to reflect net cash used in operating activities (see appendix below)
Net cash used in operating activities
CASH FLOWS - INVESTING ACTIVITIES
Investments in short-term deposits
Maturities of short-term deposits
Purchase of property and equipment
Purchase of intangible assets
Net cash provided by (used in) investing activities
CASH FLOWS - FINANCING ACTIVITIES
Issuance of share capital and warrants, net of issuance costs
Exercise of warrants
Employee stock options exercised
Proceeds from long-term loan, net of issuance costs
Repayments of loans
Repayments of lease liabilities
Net cash provided by financing activities
INCREASE (DECREASE) IN CASH AND CASH EQUIVALENTS
CASH AND CASH EQUIVALENTS - BEGINNING OF YEAR
EXCHANGE DIFFERENCES ON CASH AND CASH EQUIVALENTS
CASH AND CASH EQUIVALENTS - END OF YEAR
2020
Year ended December 31,
2021
in USD thousands
2022
(30,021)
6,815
(23,206)
(33,500)
50,168
-
-
16,668
19,246
1,969
8
-
(3,133)
(224)
17,866
11,328
5,297
206
16,831
(27,054)
3,481
(23,573)
(78,000)
39,873
(97)
-
(38,224)
50,407
10,907
7
-
(3,376)
(196)
57,749
(4,048)
16,831
207
12,990
(24,951)
(1,289)
(26,240)
(44,000)
48,322
(131)
(185)
4,006
14,359
-
5
9,126
(2,832)
(220)
20,438
(1,796)
12,990
(607)
10,587
The accompanying notes are an integral part of the consolidated financial statements.
F - 7
BioLineRx Ltd.
CONSOLIDATED STATEMENTS OF CASH FLOWS
2020
Year ended December 31,
2021
in USD thousands
2022
APPENDIX
Adjustments required to reflect net cash used in operating activities:
Income and expenses not involving cash flows:
Depreciation and amortization
Exchange differences on cash and cash equivalents
Fair value adjustments of warrants
Share-based compensation
Interest and exchange differences on short-term deposits
Interest accrued
Warrant issuance costs
Exchange differences on lease liabilities
Changes in operating asset and liability items:
Decrease (increase) in prepaid expenses and other receivables
Increase (decrease) in accounts payable and accruals
Supplemental information on interest received in cash
Supplemental information on interest paid in cash
Supplemental information on non-cash transactions:
Changes in right-of-use asset and lease liabilities
Warrant issuance costs
Purchase of property and equipment
934
(206)
5,142
1,272
(232)
474
594
125
8,103
428
(1,716)
(1,288)
6,815
381
994
13
-
-
703
(207)
1,936
1,495
(262)
301
-
55
4,021
24
(564)
(540)
3,481
138
682
183
-
-
Fair value of exercised warrants (portion related to accumulated fair value adjustments)
1,251
10,295
The accompanying notes are an integral part of the consolidated financial statements.
F - 8
654
607
(6,425)
2,245
(672)
1,117
171
(224)
(2,527)
(650)
1,888
1,238
(1,289)
342
593
706
262
28
-
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 1 – GENERAL INFORMATION
a. General
BioLineRx Ltd. (“BioLineRx”), headquartered in Modi’in, Israel, was incorporated and commenced operations in April 2003. BioLineRx and its subsidiaries
(collectively, the “Company”) are engaged in the development of therapeutics, primarily in pre-commercialization and clinical stages, with a focus on the
field of oncology.
The Company’s American Depositary Shares (“ADSs”) are traded on the NASDAQ Capital Market, and its ordinary shares are traded on the Tel Aviv Stock
Exchange (“TASE”). Each ADS represents 15 ordinary shares.
In March 2017, the Company acquired Agalimmune Ltd. (“Agalimmune”), a privately held company incorporated in the United Kingdom, with a focus on
the field of immuno-oncology.
In April 2022, the Company re-activated BioLineRx USA, Inc., a previously inactive subsidiary incorporated in the US, to engage in pre-commercialization
and commercialization activities associated with the potential launch of motixafortide for stem-cell mobilization in the US. In this regard, the US Food and
Drug Administration (FDA) has accepted for review and filed the Company’s New Drug Application (NDA) for motixafortide in stem cell mobilization for
autologous transplantation for multiple myeloma patients, and has assigned the NDA a Prescription Drug User Fee Act (PDUFA) target action date of
September 9, 2023.
b. Going concern
The Company has incurred accumulated losses in the amount of $330 million through December 31, 2022, and it expects to continue incurring losses and
negative cash flows from operations until its product or products reach commercial profitability.
As mentioned in Note 3, Company management monitors rolling forecasts of the Company’s liquidity reserves on the basis of anticipated cash flows and
maintains liquidity balances at levels that are sufficient to meet its needs. Management believes that the Company’s current cash and other resources will be
sufficient to fund its projected cash requirements into the first half of 2024. The execution of an independent commercialization plan for motixafortide in the
US implies an increased level of expenses prior to and following launch of the product. However, as is common with FDA approvals of innovative
pharmaceutical products, there is significant uncertainty regarding the receipt of approval, as well as the timing and scope of any potential approval
ultimately received in order to launch commercialization of the product. Therefore, the Company’s cash flow projections are subject to various risks and
uncertainties concerning their fulfilment, and these factors and the risk inherent in the Company’s operations may cast significant doubt on the Company’s
ability to continue as a going concern. These consolidated financial statements have been prepared assuming that the Company will continue as a going
concern and do not include any adjustments that might result from the outcome of this uncertainty.
As a US SEC registrant, the Company is required to have its financial statements audited in accordance with Public Company Oversight Board (“PCAOB”)
standards. References in these IFRS financial statements to matters that may cast significant doubt about the Company’s ability to continue as a going
concern also raise substantial doubt as contemplated by the PCAOB standards.
Management’s plans include the independent commercialization of the Company’s product and, if and when required, raising capital through the issuance of
debt or equity securities, or capital inflows from strategic partnerships. There are no assurances, however, that the Company will be successful in obtaining
the level of financing needed for its operations. If the Company is unsuccessful in commercializing its products and/or raising capital, it may need to reduce
activities, or curtail or cease operations.
c. Approval of consolidated financial statements
The consolidated financial statements of the Company for the year ended December 31, 2022 were approved by the Board of Directors on March 21, 2023,
and signed on its behalf by the Chairman of the Board, the Chief Executive Officer and the Chief Financial Officer.
F - 9
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES
a.
Basis of presentation
The Company’s consolidated financial statements as of December 31, 2021 and 2022, and for each of the three years in the period ended December 31, 2022,
have been prepared in accordance with International Financial Reporting Standards (“IFRS”), as issued by the International Accounting Standards Board
(“IASB”). The significant accounting policies described below have been applied on a consistent basis for all years presented, unless noted otherwise.
The consolidated financial statements have been prepared on the basis of historical cost, subject to adjustment of warrant liabilities to their fair value through
profit or loss.
The preparation of financial statements in conformity with IFRS requires management to make estimates, judgments and assumptions that may affect the
reported amounts of assets, liabilities, equity and expenses, as well as the related disclosures of contingent assets and liabilities, in the process of applying the
Company’s accounting policies. Actual results could differ from those estimates.
Areas involving a higher degree of judgment or complexity, or areas where assumptions and estimates are significant to the consolidated financial statements,
are disclosed in Note 4. Actual results may differ materially from estimates and assumptions used by the Company’s management.
b.
Principles of consolidation
Consolidated entities are all entities over which BioLineRx has control. BioLineRx controls an entity when it is exposed to, or has rights to, variable returns
from its involvement with the entity and has the ability to affect those returns through its power over the entity. Consolidated entities are fully consolidated
from the date on which control of such entities is transferred to BioLineRx and they are de-consolidated from the date that control ceases.
c.
Functional and reporting currency
The functional and reporting currency in these financial statements is the U.S. dollar (“dollar”, “USD” or “$”), which is the primary currency of the
economic environment in which the Company operates. Foreign currency transactions are translated into the functional currency using the exchange rates at
the dates of the transactions. Foreign exchange gains and losses resulting from the settlement of such transactions and from the translation of monetary assets
and liabilities denominated in foreign currencies at year-end exchange rates are generally recognized in profit or loss.
F - 10
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
d. Cash equivalents and short-term bank deposits
Cash and cash equivalents include cash on hand and short-term bank deposits (up to three months from date of deposit) that are not restricted as to
withdrawal or use. Bank deposits with original maturity dates of more than three months and with a current maturity date of less than one year from the
balance sheet date are included in short-term bank deposits. The fair value of cash equivalents and short-term bank deposits approximates their carrying
value, since they bear interest at rates close to the prevailing market rates.
e.
Property and equipment
Property and equipment are stated at historical cost less depreciation. Historical cost includes expenditures that are directly attributable to acquisition of the
items. Assets are depreciated by the straight-line method over the estimated useful lives of the assets, provided that Company management believes the
residual values of the assets to be negligible, as follows:
Computers and communications equipment
Office furniture and equipment
Laboratory equipment
%
20-33
6-15
15-20
Asset residual values, methods of depreciation and useful lives are reviewed and adjusted, if appropriate, at each balance sheet date. An asset’s carrying
amount is written down immediately to its recoverable amount if the asset’s carrying amount is greater than its estimated recoverable amount. See g. below.
Leasehold improvements are amortized by the straight-line method over the shorter of the lease term or the estimated useful life of the improvements.
f.
Intangible assets
The Company applies the cost method of accounting for initial and subsequent measurements of intangible assets. Under this method of accounting,
intangible assets are carried at cost less any accumulated amortization and any accumulated impairment losses.
Intellectual property
The Company recognizes in its financial statements intellectual property developed by the Company to the extent that the conditions stipulated in paragraph
o. below are met. Intellectual property acquired by the Company is initially measured at cost. Intellectual property used by the Company for development
purposes and not yet generating revenues is not amortized and is tested annually for impairment. See g. below.
Computer software
Acquired computer software licenses are capitalized based on the costs incurred to acquire and bring to use the specific software. These costs are amortized
over the estimated useful lives of the software (3-5 years).
F - 11
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
g.
Impairment of non-financial assets
Impairment of intellectual property is required when the Company decides to terminate or suspend the development of a project based on such intellectual
property. In addition, the Company performs impairment reviews on an annual basis, or more frequently if events or changes in circumstances indicate a
potential impairment. Property and equipment, as well as computer software, are tested for impairment whenever events or changes in circumstances indicate
that the carrying amount may not be recoverable. An impairment loss is recognized equal to the amount by which the asset’s carrying amount exceeds its
recoverable amount. The recoverable amount is the higher of an asset’s fair value less costs to sell and the asset’s value in use to the Company.
h. Financial assets
The Company accounts for financial assets in accordance with IFRS 9 “Financial Instruments.”
1) Classification
The financial assets of the Company are classified as financial assets at amortized cost. The classification is done on the basis of the Company’s
business model for managing the financial assets and the contractual cash flow characteristics of the financial assets.
Financial assets at amortized cost
Financial assets at amortized cost are assets held pursuant to a business model whose objective is to hold assets in order to collect contractual cash
flows and the contractual terms of the financial assets give rise on specified dates to cash flows that are solely payments of principal and interest on the
principal amount outstanding.
Financial assets at amortized cost are included in current assets, except for those with maturities greater than 12 months after the balance sheet date (in
which case they are classified as non-current assets).
The Company’s financial assets at amortized cost are included in other receivables and bank deposits in the consolidated statements of financial
position.
F - 12
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
h. Financial assets (cont.)
2) Recognition and measurement
Regular purchases and sales of financial assets are recognized on the settlement date, which is the date on which the asset is delivered to the Company
or delivered by the Company. Investments are initially recognized at fair value plus transaction costs, except for trade receivables, which are recognized
initially at the amount of consideration that is unconditional unless they contain significant financing components.
Financial assets are derecognized when the rights to receive cash flows from the investments have expired or have been transferred and the Company
has transferred substantially all risks and rewards of ownership. Financial assets at amortized cost are measured in subsequent periods at amortized cost
using the effective interest method.
3)
Impairment
The Company recognizes a loss allowance for expected credit losses on financial assets at amortized cost. At each reporting date, the Company assesses
whether the credit risk on a financial instrument has increased significantly since initial recognition. If the financial instrument is determined to have
low credit risk at the reporting date, the Company assumes that the credit risk on a financial instrument has not increased significantly since initial
recognition. The Company had no material credit losses in 2021 and 2022.
i. Warrants
Receipts in respect of warrants are classified as equity to the extent that they confer the right to purchase a fixed number of shares for a fixed exercise price.
In the event that the exercise price or the numbers of shares to be issued are not deemed to be fixed, the warrants are classified as a non-current derivative
financial liability. This liability is initially recognized at its fair value on the date the contract is entered into and subsequently accounted for at fair value at
each reporting date. The fair value changes are charged to non-operating income and expense on the statement of comprehensive loss. Issuance costs
allocable to warrants classified as a liability are also recorded as non-operating expense on the statement of comprehensive loss.
F - 13
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
j.
Share capital
The Company’s ordinary shares are classified as equity. Incremental costs directly attributable to the issuance of new shares are presented in equity as a
deduction from the issuance proceeds.
k. Trade payables
Trade payables are obligations to pay for goods or services that have been acquired in the ordinary course of business from suppliers. These payables are
classified as current liabilities if payment is due within one year or less. If not, they are presented as non-current liabilities. Trade payables are recognized
initially at fair value and subsequently measured at amortized cost using the effective interest method.
l.
Deferred taxes
Deferred taxes are recognized using the liability method, on temporary differences arising between the tax bases of assets and liabilities and their carrying
amounts in the consolidated financial statements. Deferred income tax assets are recognized only to the extent that it is probable that future taxable income
will be available against which the temporary differences can be utilized.
As the Company is currently engaged primarily in development and regulatory activities, no deferred tax assets are included in the financial statements.
m. Borrowings
Borrowings are initially recognized at fair value, net of transaction costs incurred. Borrowings are subsequently measured at amortized cost. Any difference
between the proceeds (net of transaction costs) and the redemption amount is recognized in profit or loss over the period of the borrowings using the
effective interest method.
With respect to long-term loans (see Note 10), a financial liability is recognized for each tranche upon drawdown. Upon initial recognition, the effective
interest rate is calculated by estimating the future cash flows, including loan principal repayments, interest and royalties.
The royalty feature does not meet the definition of a derivative, is not classified separately, and is not measured separately, since it is an integral part of the
loan terms and conditions and cannot be transferred or settled separately from the loan.
Determining the weighted effective interest rate requires certain judgments and estimations regarding the timing and amount of the Company’s future
revenues. The loans are subsequently measured at amortized cost. Furthermore, revisions to the estimated amounts or timing of future cash flows, if
necessary, may result in an adjustment of the amortized cost of the loan to reflect the present value of actual and revised estimated contractual cash flows,
discounted using the original effective interest rate. This adjustment will be recognized in profit or loss as financial income or expense.
Borrowings are classified as current liabilities unless the Company has an unconditional right to defer settlement of the liability for at least 12 months
subsequent to the reporting period.
F - 14
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
n. Revenue from contracts with customers
The Company accounts for revenue in accordance with IFRS 15, “Revenue from Contracts with Customers.”
IFRS 15 introduces a five-step model for recognizing revenue from contracts with customers, as follows:
•
•
•
•
•
identify the contract with a customer;
identify the performance obligations in the contract;
determine the transaction price;
allocate the transaction price to the performance obligations in the contract; and
recognize revenue when (or as) the entity satisfies a performance obligation.
During the years included in these financial statements, the Company did not generate revenues, other than immaterial amounts received from an out-
licensing agreement signed in 2014 with Perrigo Company plc., which have been included in non-operating income.
o. Research and development expenses
Research expenses are charged to profit or loss as incurred.
An intangible asset arising from development (or from the development phase of an internal project) is recognized if all of the following conditions are
fulfilled:
•
•
•
•
•
•
technological feasibility exists for completing development of the intangible asset so that it will be available for use or sale.
it is management’s intention to complete development of the intangible asset for use or sale.
the Company has the ability to use or sell the intangible asset.
it is probable that the intangible asset will generate future economic benefits, including existence of a market for the output of the intangible asset or
the intangible asset itself or, if the intangible asset is to be used internally, the usefulness of the intangible asset.
adequate technical, financial and other resources are available to complete development of the intangible asset, as well as the use or sale thereof.
the Company has the ability to reliably measure the expenditure attributable to the intangible asset during its development.
Other development costs that do not meet the foregoing conditions are charged to profit or loss as incurred. Development costs previously expensed are not
recognized as an asset in subsequent periods. As of December 31, 2022, the Company has not yet capitalized development expenses.
F - 15
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
p. Employee benefits
1)
Pension and severance pay obligations
Israeli labor laws and the Company’s employment agreements require the Company to pay retirement benefits to employees terminated or leaving
their employment in certain other circumstances. Substantially all of the Company’s employees are covered by a defined contribution plan under
Section 14 of the Israel Severance Pay Law. In the US, the Company provides defined contribution benefits in the framework of a 401(k) plan, up to
certain pre-defined limits, in accordance with industry standards for such benefits.
The amounts recorded as an employee benefit expense in respect of pension and severance pay obligations for the years 2020, 2021 and 2022 were
$668,000, $744,000 and $792,000 respectively.
2)
Vacation and recreation pay
Labor laws in Israel entitle every employee to vacation and recreation pay, both of which are computed annually. The entitlement with respect to
each employee is based on the employee’s length of service at the Company. The Company recognizes a liability and an expense in respect of
vacation and recreation pay based on the individual entitlement of each employee. In the US, the Company allows unlimited paid time off. This
policy allows employees to take vacation days as needed, and the Company does not recognize a liability in respect of vacation.
3)
Share-based payments
The Company operates an equity-settled, share-based compensation plan, under which it grants equity instruments (options, restricted stock units
and performance stock units) of the Company as additional consideration for services from employees and service providers. The fair value of the
employee services received in exchange for grant of the equity instruments is recognized as an expense. The total amount to be expensed is
determined by reference to the fair value of the equity instruments granted:
•
•
including any market performance conditions (for example, the Company’s share price); and
excluding the impact of any service and non-market performance vesting conditions (for example, profitability, sales growth targets and the
employee remaining with the entity over a specified time period).
Non-market performance and service conditions are included in assumptions about the number of equity instruments that are expected to vest. The
total expense is recognized over the vesting period, which is the period over which all of the specified vesting conditions are to be satisfied.
Performance stock unit expenses are recognized only if it is probable that the performance condition will be achieved.
When the equity instruments are exercised, the Company issues new shares. The proceeds received, net of any directly attributable transaction costs,
are credited to share capital (at par value) and share premium when the equity instruments are exercised.
F - 16
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
q. Loss per share
1) Basic
The basic loss per share is calculated by dividing the loss attributable to the holders of ordinary shares by the weighted average number of ordinary
shares outstanding during the year.
2) Diluted
The diluted loss per share is calculated by adjusting the weighted average number of outstanding ordinary shares, assuming conversion of all dilutive
potential shares. The Company’s dilutive potential shares consist of warrants issued to investors, as well as equity instruments granted to employees and
service providers. The dilutive potential shares were not taken into account in computing loss per share in 2020, 2021 and 2022, as their effect would
have been anti-dilutive.
r.
Leases
The Company’s leases include property and motor vehicle leases. At the inception of a contract, the Company assesses whether a contract is, or contains, a
lease. A contract is, or contains, a lease if the contract conveys the right to control the use of an identified asset for a period of time in exchange for
consideration. The Company reassesses whether a contract is, or contains, a lease only if the terms and conditions of the contract are changed.
At the commencement date, the Company measures the lease liability at the present value of the lease payments that are not paid at that date. Simultaneously,
the Company recognizes a right-of-use asset in the amount of the lease liability.
Since the interest rate implicit in the lease cannot be readily determined, the Company uses the Company’s incremental borrowing rate. This rate is the rate
of interest that the Company would have to pay to borrow over a similar term, and with a similar security, the funds necessary to obtain an asset of a similar
value to the right-of-use asset in a similar economic environment.
The lease term is the non-cancellable period for which the Company has the right to use an underlying asset, together with both the periods covered by an
option to extend the lease, if the Company is reasonably certain to exercise that option, and periods covered by an option to terminate the lease, if the
Company is reasonably certain not to exercise that option.
F - 17
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
r.
Leases (cont.)
After the commencement date, the Company measures the right-of-use asset applying the cost model, less any accumulated depreciation and any
accumulated impairment losses and adjusted for any remeasurement of the lease liability.
Assets are depreciated by the straight-line method over the estimated useful lives of the right of use assets or the lease period, whichever is shorter, as
follows:
Property
Motor vehicles
Years
11
3
Interest on the lease liability is recognized in profit or loss in each period during the lease term, in an amount that produces a constant periodic rate of interest
on the remaining balance of the lease liability.
F - 18
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 2 – SIGNIFICANT ACCOUNTING POLICIES (cont.)
s. New standards and interpretations not yet adopted
Classification of Liabilities as Current or Non-current (Amendment to IAS 1)
The narrow-scope amendments to IAS 1, "Presentation of Financial Statements," clarify that liabilities are classified as either current or noncurrent,
depending on the rights that exist at the end of the reporting period. Classification is unaffected by the entity’s expectations or events after the reporting date
(e.g., the receipt of a waiver or a breach of covenant). The amendments also clarify what IAS 1 means when it refers to the ‘settlement’ of a liability. The
amendments could affect the classification of liabilities, particularly for entities that previously considered management’s intentions to determine
classification and for some liabilities that can be converted into equity. They must be applied retrospectively in accordance with the normal requirements in
IAS 8, "Accounting Policies, Changes in Accounting Estimates and Errors." The amendment should be applied retrospectively for annual periods beginning
on or after January 1, 2024. Earlier application is permitted. The adoption of the amendment is not expected to have a material impact on the Company’s
financial statements.
Significant Accounting Policies (Amendment to IAS 1)
The IASB has amended IAS 1 to require entities to disclose their material, rather than their significant, accounting policies. The amendments provide a
definition of “material accounting policy information” and explain how to identify when accounting policy information is material. They further clarify that
immaterial accounting policy information does not need to be disclosed and, if disclosed, should not obscure material accounting information. The
amendments apply from January 1, 2023, but may be adopted earlier.
Changes in Accounting Estimates and Errors (Amendment to IAS 8)
The amendments to IAS 8 clarify how entities should distinguish changes in accounting policies from changes in accounting estimates. Such distinction is
important because changes in accounting estimates are applied prospectively only to future transactions and other future events, but changes in accounting
policies are generally also applied retrospectively to past transactions and other past events, and also to present events and present transactions.
The Amendments to IAS 8 will be applied retrospectively for annual periods beginning on or after January 1, 2023. Early adoption is permitted. Initial
application of Amendments to IAS 8 is not expected to have material impact on the Company's financial statements.
F - 19
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 3 – FINANCIAL INSTRUMENTS AND FINANCIAL RISK MANAGEMENT
Based on assessments by Company management, the Company’s exposure to credit risk as of December 31, 2022, is immaterial (see Note 3b). The activities of
the Company expose it to market risk, primarily as a result of currency risk.
The Company’s Finance Department is responsible for carrying out risk management activities in accordance with policies approved by its Board of Directors. In
this regard, the Finance Department identifies, defines and assesses financial risk in close cooperation with other Company departments. The Board of Directors
provides written guidelines for overall risk management, as well as written policies dealing with specific areas, such as exchange rate risk, interest rate risk, credit
risk, use of financial instruments and investment of excess cash.
a. Market risk
1) Concentration of currency risk
The Company’s activities are partly denominated in non-dollar currencies (primarily the New Israeli Shekel, or “NIS,” and the Euro), which exposes
the Company to risks resulting from changes in exchange rates.
The effect of fluctuations in various exchange rates on the Company’s income and equity is as follows:
Sensitive instrument
NIS-linked balances:
Cash and cash equivalents
Other receivables
Trade payables
Other payables
Total NIS-linked balances
Euro-linked trade payables
Total
Sensitive instrument
NIS-linked balances:
Cash and cash equivalents
Other receivables
Trade payables
Other payables
Total NIS-linked balances
Euro-linked trade payables
Total
Income (loss)
December 31, 2022
Value on
10% increase 5% increase balance sheet 5% decrease 10% decrease
in USD thousands
Income (loss)
(416)
(66)
38
114
(330)
(144)
(474)
(218)
(34)
20
60
(172)
(76)
(248)
4,573
721
(416)
(1,257)
3,621
(1,590)
2,031
241
38
(22)
(66)
191
84
275
508
80
(46)
(140)
402
177
579
Income (loss)
December 31, 2021
Value on
10% increase 5% increase balance sheet 5% decrease 10% decrease
in USD thousands
Income (loss)
(427)
(13)
40
102
(298)
(158)
(456)
(224)
(7)
21
53
(157)
(83)
(240)
4,699
142
(442)
(1,119)
3,280
(1,230)
2,050
522
16
(49)
(124)
365
193
558
247
7
(23)
(59)
172
92
264
The Company also maintains cash and cash equivalent balances in other currencies in amounts that are not material.
F - 20
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 3 – FINANCIAL INSTRUMENTS AND FINANCIAL RISK MANAGEMENT (cont.)
a. Market risk (cont.)
1) Concentration of currency risk (cont.)
Set forth below is certain data regarding dollar exchange rates:
As of December 31:
2020
2021
2022
Percentage increase (decrease) in the exchange rate:
2021
2022
Set forth below is information on the linkage of monetary items:
Exchange rate
of NIS
per $1
Exchange rate
of Euro
per $1
3.215
3.110
3.519
0.815
0.884
0.938
(3.3)%
13.2%
8.5%
6.1%
December 31, 2021
December 31, 2022
Dollar
NIS
Other currencies Dollar
NIS
Other Currencies
USD in thousands
USD in thousands
Assets:
Current assets:
Cash and cash equivalents
Short term bank deposits
Other receivables
Liabilities:
Current liabilities:
Current maturities of long-
term loans
Accounts payable and
accruals:
Trade
Other
Non-current liabilities
Long-term loans, net of
current maturities
Net balance
7,223
44,145
-
51,368
4,699
-
142
4,841
1,068
-
-
1,068
5,685
40,495
-
46,180
4,573
-
721
5,294
329
-
-
329
2,757
-
-
1,542
-
-
2,700
108
442
1,119
2,425
4,359
487
416
1,257
-
5,565
45,803
-
1,561
3,280
-
2,425
(1,357)
8,626
15,014
31,166
-
1,673
3,621
2,191
-
-
2,191
(1,862)
F - 21
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 3 – FINANCIAL INSTRUMENTS AND FINANCIAL RISK MANAGEMENT (cont.)
a. Market risk (cont.)
2)
Fair value of financial instruments
As of December 31, 2022, the financial instruments of the Company consist of non-derivative assets and liabilities (primarily working capital items,
deposits, and current and long-term loans), as well as warrants classified as a liability.
With regard to non-derivative assets and liabilities, given their nature, the fair value of the financial instruments included in working capital is generally
close or identical to their carrying amount.
With regard to the warrants classified as a non-current financial liability, see Note 11c. With regard to long-term loans, see Note 10.
3)
Exposure to market risk and management thereof
In the opinion of Company management, the market risk to which the Company is exposed is primarily related to currency risk exposure, as mentioned
above. Additionally, Company management does not consider the interest rate risk mentioned in paragraph 4 below to be material.
4)
Interest rate risk
Company management does not consider interest rate risk to be material, as the Company holds deposits whose fair value and/or cash flows are not
materially affected by changes in interest rates.
b. Credit risk
Credit risk is managed at the Company level. These risks relate to cash and cash equivalents, bank deposits and other receivables.
The Company’s cash, cash equivalents and short-term bank deposits at December 31, 2021, and 2022 were deposited with highly rated major Israeli and U.S.
banks. In the Company’s opinion, the credit risk associated with these balances is remote.
The Company considers its maximum exposure to credit risk to be as follows:
Assets:
Cash and cash equivalents
Short-term bank deposits
Other receivables
Total
F - 22
December 31,
2021
2022
in USD thousands
12,990
44,145
142
57,277
10,587
40,495
721
51,803
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 3 – FINANCIAL INSTRUMENTS AND FINANCIAL RISK MANAGEMENT (cont.)
c. Liquidity risk
Company management monitors rolling forecasts of the Company’s liquidity reserves on the basis of anticipated cash flows and maintains the liquidity
balances at a level that is sufficient to meet its needs.
Although the Company has succeeded in generating revenues from a number of out-licensing transactions in the past, and is currently gearing up for the
potential launch of its lead program, motixafortide, in 2023, it cannot determine with reasonable certainty if and when it will become profitable on a current
basis. Management believes that the Company’s current cash and other resources will be sufficient to fund its projected cash requirements into the first half
of 2024. However, in the event that the Company does not begin to generate sustainable cash flows from its operating activities in the future, the Company
will need to carry out significant cost reductions or raise additional funding. See also Note 1b regarding the significant doubt about the Company's ability to
continue as a going concern.
d. Fair value of financial instruments
The different levels of valuation of financial instruments are defined as follows:
Level 1
Quoted prices (unadjusted) in active markets for identical assets or liabilities.
Level 2
Inputs, other than quoted prices included within level 1 that are observable for the asset or liability, either directly (as prices) or indirectly
(derived from prices).
Level 3
Inputs for the asset or liability that are not based on observable market data (unobservable inputs).
The Company utilizes valuation techniques that maximize the use of observable inputs and minimize the use of unobservable inputs to the extent possible,
and also considers counterparty credit risk, in its assessment of fair value. The fair value of the financial instruments included in the working capital of the
Company, as well as the long-term loan, is usually identical or close to their carrying value. The fair value of the warrants is based on Level 3 measurements.
The fair value of the warrants, calculated based on the Black-Scholes model, was $4,509,000 as of December 31, 2022.
For more information on the parameters used to value the warrants, see Note 11c.
F - 23
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 3 – FINANCIAL INSTRUMENTS AND FINANCIAL RISK MANAGEMENT (cont.)
e. Changes in financial liabilities with cash flows included in financing activities
Long-term
loans
Balance as of January 1, 2021
Changes during the year 2021:
Principal and interest payments
Share premium resulting from exercise of warrants
Amounts recognized through profit and loss
Balance as of December 31, 2021
Changes during the year 2022:
Net proceeds of loan
Principal and interest payments
Amounts recognized through profit and loss
Balance as of December 31, 2022
Warrants
in USD thousands
10,218
5,832
(3,814)
739
2,757
9,126
(3,177)
1,462
10,168
-
(10,295)
1,936
1,859
9,075
-
(6,425)
4,509
Total
16,050
(3,376)
(10,295)
2,237
4,616
18,201
(2,832)
(5,308)
14,677
f. Fair value measurement of warrants using significant unobservable inputs (level 3)
The following table presents the changes in level 3 instruments for the years ended December 31, 2020, 2021 and 2022:
Balance as of January 1, 2020
Changes during 2020:
Issuances
Exercises
Changes in fair value through profit and loss
Balance as of December 31, 2020
Changes during 2021:
Issuances
Exercises
Changes in fair value through profit and loss
Balance as of December 31, 2021
Changes during 2022:
Issuances
Exercises
Changes in fair value through profit and loss
Balance as of December 31, 2022
F - 24
Warrants
in USD
thousands
658
5,669
(1,251)
5,142
10,218
-
(10,295)
1,936
1,859
9,075
-
(6,425)
4,509
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 4 – CRITICAL ACCOUNTING ESTIMATES AND JUDGMENTS
As part of the financial reporting process, Company management is required to make estimates that affect the value of assets, liabilities, income, expenses and
certain disclosures included in the Company’s consolidated financial statements. By their very nature, such accounting estimates are subjective and complex and
consequently may differ from actual results. The estimates are continually evaluated and adjusted based on historical experience and other factors, including
expectation of future events that are believed to be reasonable under the circumstances.
Below are the critical accounting estimates used in the preparation of the financial statements that required Company management to make assumptions involving
significant uncertainty.
Impairment of indefinite-lived intangible assets
As mentioned in Notes 2f and 2g, the Company performs impairment reviews of intangible assets not subject to amortization on an annual basis, or more
frequently if events or changes in circumstances indicate a potential impairment.
The recoverable amount is determined using discounted cash flow calculations as detailed in Note 8. The analysis estimates the future cash flows the Company
expects to derive from the asset, incorporates expectations about possible variations in the amount or timing of those future cash flows, as well as the uncertainty
inherent in the asset, and the risk-adjusted cash flows are then discounted using the Company’s estimated post-tax weighted average cost of capital (“WACC”).
The main estimates used in calculating the recoverable amount include the WACC estimation and the amounts and of timing of projected future cash flows. Such
amounts and timing are influenced by the expected outcome of development activities, the probability of success and timing in gaining regulatory approval, size
of the potential market and the Company’s specific market share, either via direct sales or a potential out-licensing deal.
In light of the significant clinical and regulatory progress, the continued investments in the program made by the Company, and following the valuation analysis
performed as detailed in Note 8, the Company concluded that the value of intangible assets related to motixafortide and AGI-134 were higher than their carrying
value as of December 31, 2021 and 2022.
Fair value estimations of warrants
As described in Notes 3d and 11, the Company completed financing transactions in which it issued ADSs and warrants to purchase additional ADSs. The fair
value of the warrants, which are not traded on an active market, is determined by using valuation techniques. These valuation techniques maximize the use of
observable market data where it is available and rely as little as possible on entity specific estimates.
F - 25
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 5 – CASH AND CASH EQUIVALENTS
Cash on hand and in bank
Short-term bank deposits
December 31,
2021
2022
in USD thousands
8,461
4,529
12,990
3,623
6,964
10,587
The short-term bank deposits included in cash and cash equivalents bear interest at annual rates of between 0.15% and 3.15%.
NOTE 6 – SHORT-TERM BANK DEPOSITS
The short-term bank deposits are in dollars and bear interest at annual rates of between 0.53% and 6.00%.
F - 26
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 7 – PROPERTY AND EQUIPMENT
Set forth below are the composition of property and equipment and the related accumulated depreciation, grouped by major classifications:
Cost
Accumulated depreciation
Balance
at
Additions Deletions
Balance
at
Balance
at
Additions Deletions
Balance
at
beginning during during end of beginning during during end of
of year
of year
year
year
year
year
in USD thousands
year
year
in USD thousands
Net book value
December 31,
2021
2022
in USD thousands
Composition in 2022
Office furniture and
equipment
Computers and
communications
equipment
Laboratory equipment
Leasehold improvements
NOTE 8 – INTANGIBLE ASSETS
207
37
-
244
124
14
-
138
83
106
863
1,590
2,028
4,688
98
16
8
159
-
-
-
-
961
1,606
2,036
4,847
678
1,509
1,425
3,736
34
69
268
385
-
-
-
-
712
1,578
1,693
4,121
185
81
603
952
249
28
343
726
The value in use of intellectual property has been calculated with the assistance of an external appraiser, based on assumptions and estimates of the Company. The
value in use of the assets was estimated by using the decision-tree approach to valuing research products. This approach incorporates the option of abandonment at
each development stage. The traditional Discounted Cash Flows (DCF) model is implemented at the final node of the decision tree. The DCF analysis estimates
the future cash flows the Company expects to derive from the asset, and incorporates expectations about possible variations in the amount or timing of those
future cash flows, and the uncertainty inherent in the assets. As of December 31, 2022, the value in use of the intangible assets according to the impairment testing
exceeded its book value. Therefore, no impairment was recognized.
Intellectual property includes the following intangible assets acquired by the Company:
-
-
$6.7 million recorded as a result of the acquisition of Agalimmune, primarily related to its main drug candidate, AGI-134 (see Note 1a).
$15.0 million recorded as a result of an amendment to the in-licensing agreement with Biokine Therapeutics Ltd. ("Biokine") that reduced, for that
consideration, future payments to be made by the Company on sublicense receipts (as defined in the license agreement) from 40% to 20%.
These assets are used for the Company's research and development activities and are not amortized.
F - 27
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 8 – INTANGIBLE ASSETS (cont.)
Set forth below are the composition of intangible assets and the related accumulated depreciation, grouped by major classifications:
Cost
Accumulated depreciation and impairment
Balance
at
Additions Deletions
Balance
at
Balance
at
Additions Deletions
Balance
at
beginning during during end of beginning during during end of
of year
of year
year
year
year
year
in USD thousands
year
year
in USD thousands
Net book value
December 31,
2021
2022
in USD thousands
Composition in 2022
Intellectual property
Computer software
NOTE 9 – LEASES
A. Right-of-use assets
21,792
616
22,408
-
185
185
- 21,792
801
-
- 22,593
96
608
704
-
4
4
-
-
-
96 21,696 21,696
189
612
708 21,704 21,885
8
Cost
Accumulated depreciation
Balance
at
Additions Deletions
Balance
at
Balance
at
Additions Deletions
Balance
at
beginning during during end of beginning during during end of
year
of year
year of year
year
year
in USD thousands
year
year
in USD thousands
Net book value
December 31,
2021
2022
in USD thousands
Composition in 2022
Property
Motor vehicles
1,552
579
2,131
545
177
722
-
420
420
2,097
336
2,433
405
395
800
177
88
265
-
404
404
582 1,147
79
184
661 1,331
1,515
257
1,772
F - 28
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 9 – LEASES (cont.)
B. Lease liabilities
Balance at
Additions
beginning
of year
during
year
Deletions
during
year
Interest
expense
during
year
in USD thousands
Exchange
differences
during
year
Payments
during
year
Balance at
end of
year
Composition in 2022
Property
Motor vehicles
1,708
186
1,894
545
177
722
-
16
16
223
25
248
(202)
(22)
(224)
(354)
(114)
(468)
1,920
236
2,156
F - 29
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 9 – LEASES (cont.)
C. Additional disclosures
1)
The Company leases two premises – its corporate headquarters and development facilities in Modi’in, Israel, and its US commercial headquarters in
Waltham, Massachusetts.
a.
The Company leases its premises in Israel under a lease agreement entered into in August 2014. Payments under the lease commenced in June
2015, and the initial term of the lease expired in June 2020. The Company exercised its option to extend the lease through June 30, 2025, and has
the option to extend the lease for two additional lease periods totaling up to five additional years, each option at a 5% increase to the preceding
lease payment amount. The monthly lease payment is approximately $26,000. In addition, the Company pays building maintenance charges
of approximately $9,000 per month.
b.
The Company leases its premises in Boston under a lease agreement entered into and commenced in October 2022. The term of the lease will
expire in December 2024. The monthly lease fee is approximately $24,000.
2)
The Company has entered into lease agreements in connection with a number of vehicles. The lease periods are generally for three years. The annual
lease fees, linked to the CPI, are approximately $122,000. To secure the terms of the lease agreements, the Company has prepaid two months of lease
payments to the leasing companies.
3) As of December 31, 2022, minimum future rental payments (taking into consideration the aforementioned extension periods) under the leases are as
follows:
Year
2023
2024
2025
2026
2027-2030
Property
Motor
vehicles
in USD thousands
Total
569
584
301
301
1,105
2,860
122
89
31
-
-
242
691
673
332
301
1,105
3,102
Extension and termination options are included in most of the property leases. These are used to maximize operational flexibility in terms of managing
the assets used in the Company’s operations. The substantial majority of extension and termination options are exercisable solely by the Company and
not by the lessors.
F - 30
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 10 – LONG-TERM LOAN
In October 2018, the Company entered into a $10 million loan agreement with Kreos Capital. This loan was repaid in full in September 2022.
In September 2022, the Company entered into a new $40 million loan agreement with Kreos Capital (via Kreos Capital VII Aggregator SCSp). Pursuant to the
new agreement, the first tranche of $10 million was drawn down by the Company upon closing. The remaining $30 million will be made available in two
additional tranches subject to the achievement of pre-specified milestones. The tranches are available for drawdown at the Company’s discretion at various time
points through October 1, 2024.
Each tranche carries a pre-defined interest-only payment period, followed by a loan principal amortization period of up to 36 months subsequent to the interest-
only period. The interest-only periods are subject to possible extension based on certain pre-defined milestones. Borrowings under the financing will bear interest
at a fixed annual rate of 9.5% (~11.0%, including associated cash fees). As security for the loan, Kreos Capital received a first-priority secured interest in all
Company assets, including intellectual property, and the Company undertook to maintain a minimum cash balance. In addition, Kreos Capital will be entitled to
mid-to-high single-digit royalties on motixafortide sales, up to a pre-defined cap.
The loan's current value includes the accrual of effective interest, including estimated future royalties.
NOTE 11 – EQUITY
a.
Share capital
The Company’s share capital is composed of ordinary shares, as follows:
Authorized share capital
Issued and paid-up share capital
Authorized share capital (in NIS)
Issued and paid-up share capital (in NIS)
Issued and paid-up share capital (in USD)
F - 31
Number of Ordinary Shares
December 31,
2021
2022
1,500,000,000 2,500,000,000
715,156,008
922,958,942
In USD and NIS Amounts
December 31,
2021
2022
150,000,000 250,000,000
71,515,600 92,295,894
21,066,368 27,100,201
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 11 – EQUITY (cont.)
b. Rights related to shares
The ordinary shares confer upon their holders voting and dividend rights and the right to receive assets of the Company upon its liquidation. As of December
31, 2021 and 2022, all outstanding share capital consisted of ordinary shares.
c. Changes in the Company’s equity
1)
In connection with the loan agreement with Kreos Capital signed in October 2018 (see Note 10), Kreos Capital received warrants to purchase 63,837
ADSs at an exercise price of $14.10 per ADS. The warrants issued have been classified as a non-current financial liability due to a net settlement
provision. The warrant is exercisable for a period of ten years from the date of issuance.
The fair value of the warrants at the date of issuance, computed using the Black-Scholes option pricing model, amounted to $861,000. The fair value of
the warrants as of December 31, 2022 was $6,000 (December 31, 2021 - $42,000) and was based on the then current price of an ADS, a risk-free interest
rate of 3.99%, an average standard deviation of 79.68%, and on the remaining contractual life of the warrants.
The change in fair value for the years ended December 31, 2021 and 2022, of $13,000 and $36,000, respectively, has been recorded as non-operating
income on the statement of comprehensive loss. As of December 31, 2022, none of these warrants had been exercised.
2)
In February 2019, the Company completed an underwritten public offering of 1,866,667 of its ADSs and warrants to purchase 1,866,667 ADSs, at a
public offering price of $8.25 per ADS and accompanying warrant. The warrants are exercisable immediately, expire five years from the date of
issuance and have an exercise price of $11.25 per ADS. The offering raised a total of $15.4 million, with net proceeds of $14.1 million, after deducting
fees and expenses. The amount of the offering consideration initially allocated to the warrants was $5.0 million. Total issuance costs initially allocated
to the warrants were $0.4 million.
The warrants have been classified as a non-current financial liability due to a net settlement provision. This liability was initially recognized at its fair
value on the date the contract was entered into and is subsequently accounted for at fair value at each balance sheet date. The fair value changes are
charged to non-operating income and expense in the statement of comprehensive loss.
The fair value of the warrants as of December 31, 2022 was $1,000 (December 31, 2021 -$564,000), and was based on the then current price of an
ADS, a risk-free interest rate of 4.73%, an average standard deviation of 82.14%, and on the remaining contractual life of the warrants.
The changes in fair value for the years ended December 31, 2021 and 2022 of $405,000 and $563,000, respectively, have been recorded as non-
operating income on the statement of comprehensive loss. As of December 31, 2022, none of these warrants had been exercised.
F - 32
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 11 – EQUITY (cont.)
c. Changes in the Company’s equity (cont.)
3)
In May and June 2020, the Company sold in registered direct offerings an aggregate of 7,653,145 ADSs at a price of $1.75 per ADS. The Company also
issued to investors in the offerings unregistered warrants to purchase 7,653,145 ADSs. The warrants were exercisable immediately, were to expire two
and half years from the date of issuance and had an exercise price of $2.25 per ADS. In addition, the Company granted to the placement agent’s
designees, as part of the placement fees, warrants to purchase 382,657 ADSs. These warrants were exercisable immediately, were set to expire two and
half years from the date of issuance and had an exercise price of $2.1875 per ADS. The offerings raised a total of $13.4 million, with net proceeds of
$12.0 million, after deducting fees and expenses. The amount of the offering consideration initially allocated to the warrants was $5.7 million. Total
issuance costs initially allocated to the warrants were $0.6 million.
The warrants issued were classified as a non-current financial liability due to a net settlement provision. This liability was initially recognized at its fair
value on the date the contract was entered into and is subsequently accounted for at fair value at each balance sheet date. The fair value changes were
charged to non-operating income and expense in the statement of comprehensive loss.
As of December 31, 2021 and 2022, 5,739,741 of these warrants had been exercised. The fair value of the unexercised warrants as of December 31,
2021 was $1,253,000. In November 2022, the warrants expired.
The changes in fair value for the years ended December 31, 2021 and 2022 of $2,354,000 and $1,253,000 have been recorded as non-operating
expenses and non-operating income respectively, on the statement of comprehensive loss.
4)
In January 2021, the Company completed an underwritten public offering of 14,375,000 of its ADSs at a public offering price of $2.40 per ADS. The
offering raised total gross proceeds of $34.5 million, with net proceeds of $31.4 million after deducting fees and expenses. In addition, warrants to
purchase 718,750 ADSs were granted to the underwriters. These warrants are exercisable immediately, expire five years from the date of issuance and
have an exercise price of $3.00 per ADS.
The warrants have been classified as shareholders’ equity, with initial recognition at fair value on the date issued. The total issuance costs initially
allocated to the warrants were recorded as an offset to share premium.
The fair value of the warrants on the issuance date was approximately $1.0 million, which was recorded as issuance costs, and computed using the
Black and Scholes option pricing model, based upon the then current price of an ADS, a risk-free interest rate of approximately 0.45% and an average
standard deviation of approximately 73.8%.
As of December 31, 2022, none of these warrants had been exercised.
F - 33
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 11 – EQUITY (cont.)
c. Changes in the Company’s equity (cont.)
5)
In September 2022, the Company completed a registered direct offering of 13,636,365 ADSs at a price of $1.10 per ADS. The Company also issued to
investors in the offering unregistered warrants to purchase 13,636,365 ADSs. The warrants are exercisable immediately, expire five years from the date
of issuance and have an exercise price of $1.15 per ADS. In addition, the Company granted to the placement agent in the offering, as part of the
placement fee, warrants to purchase 681,818 ADSs. These warrants are exercisable immediately, expire five years from the date of issuance and have an
exercise price of $1.375 per ADS. Gross proceeds from the offering totaled $15.0 million, with net proceeds of $13.5 million, after deducting fees and
expenses. The offering consideration allocated to the placement agent warrants amounted to $0.4 million.
The warrants issued to the investors have been classified as a non-current financial liability due to a net settlement provision. This liability was initially
recognized at its fair value on the issuance date and is subsequently accounted for at fair value at each balance sheet date. The fair value changes are
charged to non-operating income and expense in the statement of comprehensive loss.
The fair value of the warrants is computed using the Black-Scholes option pricing model. The fair value of the warrants upon issuance was computed
based on the then-current price of an ADS, a risk-free interest rate of 3.62%, and an average standard deviation of 82.5%. The gross consideration
initially allocated to the investor warrants amounted to $9.1 million, with total issuance costs initially allocated to the warrants amounting to $0.8
million.
The fair value of the warrants amounted to $4,502,000 as of December 31, 2022, and was based on the then current price of an ADS, a risk-free interest
rate of 4.1%, an average standard deviation of 85.5%, and on the remaining contractual life of the warrants.
The changes in fair value from the issuance date through December 31, 2022 of $4,573,000 have been recorded as non-operating income in the
statement of comprehensive loss.
As of December 31, 2022, none of these warrants had been exercised.
The placement agent warrants have been classified in shareholders’ equity, with initial recognition at fair value on the date issued, using the same
assumptions as the investor warrants.
F - 34
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 11 – EQUITY (cont.)
d.
Share purchase agreements
1)
2)
In September 2020, the Company entered into an ATM sales agreement with H.C. Wainwright & Co., LLC (“HCW”), pursuant to which the Company
was entitled, at its sole discretion, to offer and sell through HCW, acting as sales agent, ADSs having an aggregate offering price of up to $25.0 million
throughout the period during which the ATM facility remained in effect. The Company agreed to pay HCW a commission of 3.0% of the gross proceeds
from the sale of ADSs under the facility. Expenses associated with establishment of the ATM facility with HCW, amounting to $0.2 million, were
recorded in 2020 as non-operating expenses. In September 2021, the Company terminated the agreement. During 2021, the Company issued a total of
4,745,368 ADSs under the agreement for total gross proceeds of $18.5 million. From the effective date of the agreement through its termination,
7,381,101 ADSs were sold under the program for total gross proceeds of approximately $24.5 million.
In September 2021, the Company entered into a new $25.0 million ATM sales agreement with HCW under substantially identical terms to the previous
agreement. Expenses associated with establishment of the ATM facility with HCW, amounting to $0.1 million, were recorded in non-operating expenses
during the period. During 2022, the Company issued a total of 206,324 ADSs under the program for total gross proceeds of approximately $0.3 million.
From the effective date of the agreement through the issuance date of this report, 608,651 ADSs have been sold under the program for total gross
proceeds of approximately $1.4 million.
e.
Share-based payments
1) Share Incentive plan – general
In 2003, the Company adopted the 2003 Share Incentive Plan (the “Plan”). The Plan provides for the granting of stock options and ordinary shares to
the Company’s employees, directors, consultants and other service providers. Options are issued at the determination of the Board of Directors in
accordance with applicable law. The options are generally exercisable for a ten-year period and the grants generally vest over a four-year period. In
2013, the Company’s Board of Directors approved amendments to the Plan to take into account changes in laws and regulations that had occurred since
its adoption and to extend the term of the plan until November 2023. In 2016, the Board of Directors approved amendments to the Plan to allow for the
grant of restricted stock units (“RSUs”) and performance stock units (“PSUs”). In 2022, the Board approved certain amendments to the Plan in order to
conform the Plan to U.S. tax regulations for the benefit BioLineRx USA, Inc. employees.
PSUs are RSUs that are linked to any one or more performance goals (in addition to, or in lieu of, time-based vesting terms) determined appropriate by
the Board of Directors. The specific performance goals, as well as the time period associated with achieving such goals, are approved by the Board and
are set forth in the grantee’s grant agreement. To date, each PSU grant has had between three to five performance goals on which vesting is based, each
such goal being either a specified Company milestone and or the success of a specific project, with vesting of 20-40% on the achievement of each goal.
The tranche of PSUs associated with a given milestone expires 12 months after the target date established for that milestone. As of December 31, 2022,
2,786,608 PSUs were vested in accordance with their original terms.
F - 35
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 11 – EQUITY (cont.)
e.
Share-based payments (cont.)
1) Share Incentive plan – general (cont.)
As of December 31, 2022, there were 92,601,858 ordinary shares issuable upon the exercise of outstanding equity instruments under the Plan.
Company employees and directors are granted options under Section 102 of the Israeli Income Tax Ordinance (the “Ordinance”), primarily under the
“capital gains” track. Non-employees of the Company (consultants and other service providers) are granted options under Section 3(i) of the Ordinance.
As of December 31, 2022, there were 21.3 million remaining authorized but unissued ordinary shares in the pool reserved for future share-based
incentive grants.
2)
Employee share incentive plan:
The following table contains additional information concerning equity instruments granted to employees and directors under the existing share
incentive plans.
2020
Year ended December 31,
2021
2022
Outstanding at beginning of year
Granted
Forfeited and expired
Exercised
Outstanding at end of year*
Exercisable at end of year
Number
of options
19,358,913
18,689,300
(1,776,037)
(290,597)
35,981,579
11,535,679
Weighted
average
exercise
price
(in NIS)
Number
of options
2.6 35,981,579
6,588,200
0.5
(1,438,642)
2.2
0.1
(174,923)
1.5 40,956,214
3.2 18,663,353
Weighted
average
exercise
price
(in NIS)
Number
of options
1.5 40,956,214
0.4 53,696,305
(4,618,062)
3.0
0.1
(162,599)
0.7 89,871,858
1.7 26,663,961
Weighted
average
exercise
price
(in NIS)
0.7
0.3
0.8
0.1
0.4
0.8
* As of December 31, 2020, 2021 and 2022, includes 2,421,799, 4,084,748, and 10,482,277 PSUs at an exercise price of 0.10 NIS (par value of
ordinary shares), for which performance obligations have not been met.
F - 36
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 11 – EQUITY (cont.)
e.
Share-based payments (cont.)
2)
Employee share incentive plan (cont.):
The total consideration received from the exercise of equity instruments during 2020, 2021 and 2022 was not material.
Set forth below is data regarding the range of exercise prices and weighted-average remaining contractual life (in years) for the equity instruments
outstanding at the end of each of the years indicated.
Range of
exercise prices
(in NIS)
Up to 0.99
1.00-2.00
2.01-10.00
As of December 31,
2021
2022
Number
of options
outstanding
25,752,128
14,524,086
680,000
40,956,214
Weighted average
remaining
contractual life
(in yrs.)
8.8
6.6
4.8
8.0
Number
of options
outstanding
75,663,492
13,668,366
540,000
89,871,858
Weighted average
remaining
contractual life
(in yrs.)
9.0
5.5
4.2
8.4
The fair value of equity instruments granted to employees through December 31, 2022 has been determined using the Black-Scholes option-pricing
model. These values are based on the following assumptions as of the applicable grant dates:
Expected dividend yield
Expected volatility
Risk-free interest rate
Expected life of options (in years)
2020
2021
2022
0%
63%
1%
6
0%
67%
1%
6
0%
67%
4%
6
The remaining unrecognized deferred compensation expense as of December 31, 2022 was $4.8 million. This amount will be expensed over the
remaining vesting period of the equity instruments.
F - 37
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 11 – EQUITY (cont.)
e.
Share-based payments (cont.)
3) Stock options to consultants
From inception through December 31, 2020, the Company issued to consultants options for the purchase of 596,523 ordinary shares at a weighted
average exercise price of NIS 5.23 per share.
In 2021, the Company issued additional options to consultants for the purchase of 2,700,000 ordinary shares at a weighted average price of NIS 0.66
per share.
In 2022, the Company did not issue additional options to consultants.
The options to consultants generally vest over four years and may be exercised for periods of between five and ten years. As of December 31, 2022,
2,730,000 options to consultants were outstanding with a weighted average exercise price of NIS 1.02 per share and a weighted average contractual life
of 7.9 years.
Company management estimates the fair value of the options granted to consultants based on the value of services received over the vesting period of
the applicable options. The value of such services (primarily in respect of clinical advisory services) is estimated based on the additional cash
compensation the Company would need to pay if such options were not granted. The value of services recorded in each of the years 2020, 2021 and
2022 was not material.
F - 38
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 12 – TAXES ON INCOME
a. Corporate taxation
The taxable income of BioLineRx, not subject to benefits as detailed below, is taxed at the standard Israeli corporate tax rate, which was 23% for all years
included in these financial statements. The taxable income of BioLineRx USA, Inc. is subject to a federal tax rate of 21%.
b. Tax loss carryforwards
As of December 31, 2022, the tax loss carryforwards of BioLineRx were approximately $326 million. The tax loss carryforwards have no expiration date.
The Company has not created deferred tax assets in respect of these tax loss carryforwards. See Note 2, paragraph l.
c.
Tax assessments
In accordance with Israeli tax regulations, the tax returns filed by BioLineRx through the 2020 tax year are considered final.
d. Theoretical taxes
As described in Note 2, paragraph 1, the Company has not recognized any deferred tax assets in the financial statements, as it does not expect to generate
taxable income in the foreseeable future. The reported tax on the Company’s income before taxes differs from the theoretical amount that would arise using
the weighted average tax rate applicable to income of the consolidated entities as follows:
Loss before taxes
Theoretical tax benefit
Disallowed deductions (tax exempt
income):
Loss (gain) on adjustment of
warrants to fair value
Share-based compensation
Other
Increase in taxes for tax losses and
timing differences incurred in the
reporting year for which deferred
taxes were not created
Taxes on income for the reported year
Year ended December 31,
2020
2021
2022
in USD
thousands
(30,021)
23.0%
in USD
thousands
(27,045)
23.0%
in USD
thousands
(24,951)
23.0%
(6,905)
(6,220)
1,280
292
11
5,322
-
F - 39
480
343
11
5,386
-
(5,739)
(1,478)
516
11
6,690
-
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 13 – LOSS PER SHARE
The following table contains the data used in the computation of the basic loss per share:
Loss attributed to ordinary shares
Number of shares used in basic calculation
Basic and diluted loss per ordinary share
2020
Year ended December 31,
2021
in USD thousands
2022
(30,021)
(27,054)
(24,951)
in thousands
252,844
662,934
773,957
in USD
(0.12)
(0.04)
(0.03)
All outstanding options and warrants have been excluded from the calculation of the diluted loss per share for all years presented, since their effect was anti-
dilutive.
NOTE 14 – COMMITMENTS AND CONTINGENT LIABILITIES
a. Commitments
1) Obligation to pay royalties to the State of Israel
The Company is required to pay royalties to the State of Israel (represented by the Israel Innovation Authority, or IIA), computed on the basis of
proceeds from the sale or license of products whose development was supported by grants from the predecessor of the IIA, the Office of the Chief
Scientist. This obligation relates solely to financial participation in the development of products by the Company.
In accordance with the terms of grants provided by the IIA, the State is entitled to royalties on the sale or license of any product whose development
was supported with State participation. These royalties are generally 3% in the first three years from initial repayment, 4% of sales in the three
subsequent years and 5% of sales in the seventh year until repayment of 100% of the grants (linked to the dollar) received by the Company, plus annual
interest at the LIBOR rate. Under certain circumstances, the royalty rate is calculated according to a formula based on the ratio of participation by the
IIA in the project to the total project costs incurred by the Company.
In connection with the in-licensing of motixafortide from Biokine Therapeutics Ltd. (“Biokine”), and as a condition to IIA consent to the transaction,
the Company agreed to abide by any obligations resulting from funds previously received by Biokine from the IIA. The contingent liability to the IIA
assumed by the Company relating to this transaction amounts to $3.7 million as of December 31, 2022. The Company has a full right of offset for
amounts payable to the IIA from payments due to Biokine in the future.
F - 40
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 14 – COMMITMENTS AND CONTINGENT LIABILITIES (cont.)
a. Commitments (cont.)
2)
Licensing agreements
From time to time, the Company enters into in-licensing agreements with academic institutions, research institutions and companies (the “licensors”) in
connection with the development of therapeutic compounds. Pursuant to these licensing agreements, the Company generally obtains the rights for one
or more therapeutic compounds in pre-clinical and early clinical stages of development, in order to continue development of the compounds through
more advanced stages of development and, subsequently, to manufacture, distribute and market the drugs or to out-license the development,
manufacturing and commercialization rights to third parties. Such development activities are carried out by either the Company and/or by companies or
institutions to which the Company has entered into an out-license agreement, subject to certain restrictions stipulated in the various agreements.
The licenses that have been granted to the Company are broad and comprehensive, and generally include various provisions and usage rights as
follows: (i) territorial scope of the license (global); (ii) term of the license (unrestricted but not shorter than the life of the patent); and (iii) development
of the therapeutic compound (allowing the Company to perform all development activities on its own, or by outsourcing under Company supervision,
as well as out-licensing development under the license to other companies, subject to the provisions of the licensing agreements).
According to the provisions of the licensing agreements, the intellectual property rights in the development of any licensed technology, through the date
the applicable license agreement is effective, remain with the licensor, while the rights in products and/or other deliverables developed by the Company
after the license is granted belong to the Company. In cases where the licensor has a claim to an invention that was jointly developed with the Company,
the licensor also co-owns the related intellectual property. In any event, the scope of the license also covers these intellectual property rights.
In addition, the Company generally undertakes in the licensing agreements to protect registered patents resulting from developments under the various
licenses, to promote the registration of patents covering new developments in cooperation with the licensor, and to bear responsibility for all related
costs. Pursuant to the various agreements, the Company generally works to register the various patents on a broad basis worldwide, and if the Company
decides not to initiate or continue a patent registration proceeding in a given country, the Company is required to notify the applicable licensor to this
effect and the licensor is entitled to take action for registration of the patent in such country.
F - 41
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 14 – COMMITMENTS AND CONTINGENT LIABILITIES (cont.)
a. Commitments (cont.)
2)
Licensing agreements (cont.)
The consideration paid pursuant to the licensing agreements generally includes several components that may be payable over the license period and that
relate, inter alia, to the progress made in research and development activities, as well as commercial success, as follows: (a) one-time, up-front payment
and/or periodic payments; (b) payments through the early stages of development (i.e., through the end of phase 2); (c) payments upon the achievement
of milestones necessary for advancing to phase 3; (d) payments from the end of a successful phase 3 trial through approval of the therapeutic
compound; and e) royalties on sales of the final product resulting from development under the license or including any component thereof, generally
less than 5% of the Company’s net sales of the product, although in specific instances (for example, with regard to Motixafortide, where the royalty rate
on net sales directly commercialized by the Company payable to Biokine is 10%) the royalty rate has been higher or lower than this range. In instances
where the Company has out-licensed the product for further development, the Company pays a percentage of the net consideration received from the
licensee (“Sublicense Receipts”) to the upstream licensor that generally range from 20% to 29.5% of such consideration, although in specific instances
the percentage paid has been higher or lower than this range. These Sublicense Receipts generally take the place of most or all of the milestone and
royalty payments set forth in (b) through (e) above.
The license agreements may be cancelled by the licensor only in specific circumstances, generally upon the occurrence of one of the following events:
(a) the Company’s failure to meet certain milestones stipulated in the applicable license agreement and appended timetables; (b) default, insolvency,
receivership, liquidation, etc. of the Company that is not imposed and/or lifted within the timeframe stipulated in the license agreement; and (c)
fundamental breach of the license agreement that is not corrected within the stipulated timeframe. The Company may generally cancel a license
agreement with prior notice of 30 to 90 days, due to unsuccessful development or any other cause.
The Company has undertaken to indemnify certain licensors, their employees, officers, representatives or anyone acting on their behalf for any damage
and/or expense that they may incur in connection with the Company’s use of a license granted to it, all in accordance with the terms stipulated in the
applicable license agreements.
Some of the license agreements are accompanied by consulting, support and cooperation agreements, pursuant to which the Company is committed to
pay the various licensers a fixed monthly amount over the period stipulated in the agreement for their assistance in the continued research and
development under the license.
F - 42
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 14 – COMMITMENTS AND CONTINGENT LIABILITIES (cont.)
a. Commitments (cont.)
3) Commitments in respect of Agalimmune and Biokine
The consideration due to Agalimmune shareholders is based on certain development and commercial milestones, including future sales of Agalimmune
products. In addition, the selling shareholders of Agalimmune have certain reversionary rights in the event of a breach of the transaction agreement and
certain other limited triggering events.
In accordance with the license agreement of motixafortide with Biokine (as amended), the Company is required to pay Biokine a payment of 20% of
amounts received as consideration in connection with any sublicensing or sale of the licensed technology. Biokine is also eligible to receive up to a total
of $5 million in future milestone payments. Subject to certain limitations, if the Company independently sell products related to Motixafortide, the
Company will pay Biokine a royalty payment of 10% of net sales.
4)
Purchase orders
The Company’s outstanding open purchase order commitments as of December 31, 2022 amounted to $5.9 million.
b. Guarantees
To secure the Company’s lease obligation on its Israeli premises, the Company has provided a bank guarantee in the amount of $100,000 for the benefit of
the lessor, which remains outstanding as of December 31, 2022.
c. Contingent liabilities
On January 5, 2023, a putative securities class action complaint was filed in the U.S. against the Company and its Chief Executive Officer. The complaint
claims that the Company made false and materially misleading statements and failed to disclose material adverse facts pertaining to its financial position with
regard to the development of motixafortide and that the Company would require a loan and a securities offering to commercialize motixafortide. The
Company also received, on February 5, 2023, a substantially similar lawsuit and motion to approve the lawsuit as a class action in the Tel Aviv District
Court. The total amount claimed in Tel Aviv, if the lawsuit is certified as a class action, is approximately NIS 113.5 million (approximately $32 million).
The outcome of both legal proceedings is uncertain at this point. Based on an initial evaluation, management of the Company believes that they are without
merit and intends to vigorously defend the Company and its Chief Executive Officer against such actions.
F - 43
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 15 – TRANSACTIONS AND BALANCES WITH RELATED PARTIES
Transactions with related parties
Expenses:
Benefits to related parties:
Compensation and benefits to senior management, including benefit component of
equity instrument grants
Compensation and benefits to directors, including benefit component of equity
instrument grants
Key management compensation
Year ended December 31,
2020
2021
2022
in USD thousands
2,391
2,302
2,968
373
300
507
Key management includes directors and executive officers. The compensation paid or payable to key management for services during each of the years
indicated is presented below.
Salaries and other short-term employee benefits
Post-employment benefits
Other long-term benefits
Share-based compensation
F - 44
2020
Year ended December 31,
2021
in USD thousands
1,883
136
35
548
2,602
1,656
126
33
949
2,764
2022
2,298
131
35
1,011
3,475
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 16 – SUPPLEMENTARY FINANCIAL STATEMENT INFORMATION
a. Other receivables
Government institutions
Other
b. Accounts payable and accruals
1) Trade:
Accounts payable:
Overseas
In Israel
2) Other:
Accrued expenses
Accrual for vacation and recreation pay
Payroll and related expenses
Other
December 31,
2021
2022
in USD thousands
140
2
142
687
34
721
December 31,
2021
2022
in USD thousands
4,504
1,063
5,567
521
397
307
2
1,227
6,061
905
6,966
976
377
307
84
1,744
The carrying amounts of accounts payable and accruals approximate their fair value, as the effect of discounting is not material.
F - 45
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 16 – SUPPLEMENTARY FINANCIAL STATEMENT INFORMATION (cont.)
c. Research and development expenses
Research and development services
Payroll and related expenses
Share based compensation
Lab, occupancy and telephone
Professional fees
Depreciation and amortization
Other
d.
Sales and marketing expenses
Marketing
Payroll and related expenses
Overseas travel
e. General and administrative expenses
Payroll and related expenses
Share based compensation
Professional fees
Insurance
Depreciation
Other
F - 46
2020
Year ended December 31,
2021
in USD thousands
12,088
4,074
971
882
595
660
196
19,466
11,696
3,501
623
771
643
864
75
18,173
2022
9,296
4,495
1,198
902
954
615
169
17,629
2020
Year ended December 31,
2021
in USD thousands
729
249
25
1,003
585
234
21
840
2022
5,365
1,059
38
6,462
2020
Year ended December 31,
2021
in USD thousands
1,408
583
1,103
1,064
42
108
4,308
1,369
729
1,044
603
70
99
3,914
2022
1,706
895
1,248
1,046
39
132
5,066
BioLineRx Ltd.
NOTES TO THE CONSOLIDATED FINANCIAL STATEMENTS
NOTE 16 – SUPPLEMENTARY FINANCIAL STATEMENT INFORMATION (cont.)
f.
Non-operating income (expenses), net
Issuance costs
Changes in fair value of warrants
Other
g.
Financial income
Interest income
Exchange differences, net
h.
Financial expenses
Interest expense
Exchange differences, net
Bank commissions
F - 47
2020
Year ended December 31,
2021
in USD thousands
-
(1,936)
106
(1,830)
(784)
(5,142)
225
(5,701)
2022
(762)
6,425
7
5,670
2020
Year ended December 31,
2021
in USD thousands
277
282
559
236
-
236
2022
694
-
694
2020
Year ended December 31,
2021
in USD thousands
984
-
22
1,006
1,470
137
22
1,629
2022
1,786
346
26
2,158
CERTIFICATION OF THE CHIEF EXECUTIVE OFFICER UNDER SECTION 302 OF
THE SARBANES-OXLEY ACT
I, Philip A. Serlin, certify that:
Exhibit 12.1
1.
2.
3.
4.
I have reviewed this annual report on Form 20-F of BioLineRx Ltd.;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made,
in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial
condition, results of operations and cash flows of the company as of, and for, the periods presented in this report;
The company’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act
Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the company and
have:
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our
supervision, to ensure that material information relating to the company, including its consolidated subsidiaries, is made known to us by
others within those entities, particularly during the period in which this report is being prepared;
Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under
our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial
statements for external purposes in accordance with generally accepted accounting principles;
Evaluated the effectiveness of the company’s disclosure controls and procedures and presented in this report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
Disclosed in this report any change in the company’s internal control over financial reporting that occurred during the period covered
by the annual report that has materially affected, or is reasonably likely to materially affect, the company’s internal control over
financial reporting; and
5.
The company’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the company’s
auditors and the audit committee of the company’s board of directors (or persons performing the equivalent functions):
All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are
reasonably likely to adversely affect the company’s ability to record, process, summarize and report financial information; and
Any fraud, whether or not material, that involves management or other employees who have a significant role in the company’s internal
control over financial reporting.
Date: March 22, 2023
/s/ Philip A. Serlin
Philip A. Serlin
Chief Executive Officer
CERTIFICATION OF THE CHIEF FINANCIAL OFFICER UNDER SECTION 302 OF
THE SARBANES-OXLEY ACT
I, Mali Zeevi, certify that:
Exhibit 12.2
1.
2.
3.
4.
I have reviewed this annual report on Form 20-F of BioLineRx Ltd.;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made,
in light of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial
condition, results of operations and cash flows of the company as of, and for, the periods presented in this report;
The company’s other certifying officer(s) and I are responsible for establishing and maintaining disclosure controls and procedures (as defined in Exchange Act
Rules 13a-15(e) and 15d-15(e)) and internal control over financial reporting (as defined in Exchange Act Rules 13a-15(f) and 15d-15(f)) for the company and
have:
Designed such disclosure controls and procedures, or caused such disclosure controls and procedures to be designed under our
supervision, to ensure that material information relating to the company, including its consolidated subsidiaries, is made known to us by
others within those entities, particularly during the period in which this report is being prepared;
Designed such internal control over financial reporting, or caused such internal control over financial reporting to be designed under
our supervision, to provide reasonable assurance regarding the reliability of financial reporting and the preparation of financial
statements for external purposes in accordance with generally accepted accounting principles;
Evaluated the effectiveness of the company’s disclosure controls and procedures and presented in this report our conclusions about the
effectiveness of the disclosure controls and procedures, as of the end of the period covered by this report based on such evaluation; and
Disclosed in this report any change in the company’s internal control over financial reporting that occurred during the period covered
by the annual report that has materially affected, or is reasonably likely to materially affect, the company’s internal control over
financial reporting; and
5.
The company’s other certifying officer(s) and I have disclosed, based on our most recent evaluation of internal control over financial reporting, to the company’s
auditors and the audit committee of the company’s board of directors (or persons performing the equivalent functions):
All significant deficiencies and material weaknesses in the design or operation of internal control over financial reporting which are
reasonably likely to adversely affect the company’s ability to record, process, summarize and report financial information; and
Any fraud, whether or not material, that involves management or other employees who have a significant role in the company’s internal
control over financial reporting.
Date: March 22, 2023
/s/ Mali Zeevi
Mali Zeevi
Chief Financial Officer
CERTIFICATION OF CHIEF EXECUTIVE OFFICER UNDER SECTION 906 OF
THE SARBANES-OXLEY ACT
Exhibit 13.1
Pursuant to 18 U.S.C. Section 1350, as created by Section 906 of the Sarbanes-Oxley Act of 2002, the undersigned officer of BioLineRx
Ltd. (the “Company”) hereby certifies to such officer’s knowledge that:
(i)
the accompanying Annual Report on Form 20-F of the Company for the year ended December 31, 2022 (the “Report”) fully complies with the requirements of
Section 13(a) or Section 15(d), as applicable, of the Securities Exchange Act of 1934, as amended; and
(ii)
the information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
Date: March 22, 2023
/s/ Philip A. Serlin
Philip A. Serlin
Chief Executive Officer
The foregoing certification is being furnished solely to accompany the Report pursuant to 18 U.S.C. Section 1350, and is not being filed for the
purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and is not to be incorporated by reference to any filing of the
Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
CERTIFICATION OF CHIEF FINANCIAL OFFICER UNDER SECTION 906 OF
THE SARBANES-OXLEY ACT
Exhibit 13.2
Pursuant to 18 U.S.C. Section 1350, as created by Section 906 of the Sarbanes-Oxley Act of 2002, the undersigned officer of BioLineRx
Ltd. (the “Company”) hereby certifies to such officer’s knowledge that:
(i)
the accompanying Annual Report on Form 20-F of the Company for the year ended December 31, 2022 (the “Report”) fully complies with the requirements of
Section 13(a) or Section 15(d), as applicable, of the Securities Exchange Act of 1934, as amended; and
(ii)
the information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
Date: March 22, 2023
/s/ Mali Zeevi
Mali Zeevi
Chief Financial Officer
The foregoing certification is being furnished solely to accompany the Report pursuant to 18 U.S.C. Section 1350, and is not being filed for the
purposes of Section 18 of the Securities Exchange Act of 1934, as amended, and is not to be incorporated by reference to any filing of the
Company, whether made before or after the date hereof, regardless of any general incorporation language in such filing.
CONSENT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
We hereby consent to the incorporation by reference in the Registration Statements on Form S-8 (No. 333-176419, 333-183976, 333-201326,
333-208865 and 333-269334) and Form F-3 (No. 333-222332, 333-251857 and 333-229021) of BioLineRx Ltd. of our report dated March 22,
2023 relating to the financial statements and the effectiveness of internal control over financial reporting, which appears in this Form 20-F.
Tel-Aviv, Israel
March 22, 2023
/s/ Kesselman & Kesselman
Certified Public Accountants (Isr.)
A member firm of PricewaterhouseCoopers International Limited
Exhibit 15.1