Table of Contents
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
Form 10-K
(Mark one)
☒
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT
OF 1934
For the fiscal year ended December 31, 2021
or
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT
OF 1934
For the transition period from to
Commission file number 001-37558
Nabriva Therapeutics plc
(Exact name of registrant as specified in its charter)
Ireland
(State or other jurisdiction of incorporation or organization)
25-28 North Wall Quay
IFSC, Dublin 1, Ireland
(Address of principal executive offices)
Not applicable
(I.R.S. Employer Identification No.)
Not applicable
(Zip Code)
+353 1 649 2000
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
Title of each class
Ordinary Shares, nominal value $0.01 per share
Trading Symbol
NBRV
Name of each exchange on which registered
The Nasdaq Stock Market LLC
Securities registered pursuant to Section 12(g) of the Act: None
Indicate by check mark if the registrant is a well-known seasoned issuer, as defined in Rule 405 of the Securities Act. Yes ☐ No ⌧
Indicate by check mark if the registrant is not required to file reports pursuant to Section 13 or Section 15(d) of the Act. Yes ☐ No ⌧
Indicate by check mark whether the registrant (1) has filed all reports required to be filed by Section 13 or 15(d) of the Securities Exchange Act of 1934 during the
preceding 12 months (or for such shorter period that the registrant was required to file such reports), and (2) has been subject to such filing requirements for the past 90 days. Yes
⌧ No ☐
Indicate by check mark whether the registrant has submitted electronically every Interactive Data File required to be submitted pursuant to Rule 405 of Regulation S-
T (§232.405 of this chapter) during the preceding 12 months (or for such shorter period that the registrant was required to submit such files). Yes ⌧ No ☐
Indicate by check mark whether the registrant is a large accelerated filer, an accelerated filer, a non-accelerated filer, a smaller reporting company or an emerging
growth company. See the definitions of “large accelerated filer,” “accelerated filer,” “smaller reporting company” and “emerging growth company” in Rule 12b-2 of the
Exchange Act.
Large accelerated filer ☐ Accelerated filer ☐
Non-accelerated filer ⌧
Smaller reporting company ☒ Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised
financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Indicate by check mark whether the registrant has filed a report on and attestation to its management’s assessment of the effectiveness of its internal control over
financial reporting under Section 404(b) of the Sarbanes Oxley Act (15 U.S.C. 7262(b)) by the registered public accounting firm that prepared or issued its audit report. ☐
Indicate by check mark whether the registrant is a shell company (as defined in Rule12b-2 of the Act). Yes ☐ No ⌧
As of June 30, 2021 (the last business day of the registrant’s most recently completed second fiscal quarter), the aggregate market value of the registrant’s voting
securities held by non-affiliates was approximately $67.5 million based on the last reported sale price of the registrant’s ordinary shares on June 30, 2021. As of February 28,
2022, the registrant had 60,525,366 ordinary shares outstanding.
Table of Contents
NABRIVA THERAPEUTICS plc
INDEX TO REPORT ON FORM 10-K
Item 1:
Item 1A:
Item 1B
Item 2:
Item 3:
Item 4:
Item 5:
Item 6:
Item 7:
Item 7A:
Item 8:
Item 9:
Item 9A:
Item 9B:
Item 9C:
Item 10:
Item 11:
Item 12:
Item 13:
Item 14:
Item 15:
Item 16:
PART I
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
PART II
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity
Securities
[Reserved]
Management’s Discussion and Analysis of Financial Condition and Results of Operations
Quantitative and Qualitative Disclosures About Market Risk
Financial Statements and Supplementary Data
Changes in and Disagreements With Accountants on Accounting and Financial Disclosure
Controls and Procedures
Other Information
Disclosure Regarding Foreign Jurisdictions That Prevent Inspections
PART III
Directors, Executive Officers and Corporate Governance
Executive Compensation
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
Certain Relationships and Related Transactions, and Director Independence
Principal Accountant Fees and Services
PART IV
Exhibits and Financial Statement Schedules
Form 10-K Summary
Page
1
65
129
130
130
130
131
131
132
146
147
148
148
149
149
150
155
169
173
175
176
176
Table of Contents
CAUTIONARY NOTE REGARDING FORWARD-LOOKING STATEMENTS
This Annual Report on Form 10-K contains forward-looking statements that involve important risks and
uncertainties. All statements contained in this Annual Report, other than statements of historical fact, including statements
regarding our strategy, future operations, future financial position, future revenues, projected costs, prospects, plans and
objectives of management, are forward-looking statements. The words “anticipate, “around” “believe,” “estimate,”
“expect,” “intend,” “may,” “plan,” “predict,” “project,” “target,” “potential,” “will,” “would,” “could,” “should,”
“continue,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking
statements contain these identifying words. The forward-looking statements in this report include, among other things,
statements about:
● our ability to successfully commercialize SIVEXTRO and realize value from our agreement with Merck &
Co., Inc.;
● our ability to successfully commercialize XENLETA (lefamulin) for the treatment of community-acquired
bacterial pneumonia, or CABP, including the availability of and ease of access to XENLETA through
hospital formularies, managed care plans and major U.S. specialty distributors;
● our expectations regarding how far into the future our cash on hand and anticipated revenues from product
sales will fund our ongoing operations and the continued availability and cost of capital to sustain our
operations on a longer term basis;
● our sales, marketing and distribution capabilities and strategy;
● the potential extent of revenues from future sales of SIVEXTRO, XENLETA and/or CONTEPO, if
approved;
● our ability to build, manage and maintain a sales force for the commercialization of SIVEXTRO, XENLETA
and CONTEPO, if approved;
● our ability to resolve the matters set forth in the Complete Response Letter we received from the U.S. Food
and Drug Administration, or FDA, in connection with our New Drug Application, or NDA, for CONTEPO
for the treatment of complicated urinary tract infections, or cUTIs, including acute pyelonephritis;
● the timing of the resubmission of the NDA for CONTEPO for the treatment of cUTIs and potential
marketing approval of CONTEPO and other product candidates, including the completion of any post
marketing requirements with respect to XENLETA for CABP and any other product candidates we may
develop or obtain;
● our plans to pursue development of other product candidates including XENLETA for the treatment of
infections in patients with cystic fibrosis;
● our expectations regarding our strategy to expand our product pipeline through opportunistically in-licensing
or acquiring the rights to complementary products, product candidates and technologies for the treatment of a
range of infectious diseases or other products, including additional community products;
● our ability to comply with the restrictive covenants under our debt facility with Hercules Capital, Inc., or
Hercules, including but not limited to the ability to maintain minimum cash balance requirements;
● our ability to satisfy interest and principal payments under our debt facility with Hercules;
● our ability to successfully maintain inventory levels to satisfy product demand, as well as limit the
unrealizable value of inventory based on historical usage, known trends, inventory age and market
conditions;
Table of Contents
● our expectations about the impact of the COVID-19 pandemic on our business operations, ongoing clinical
trials and regulatory matters, including the ability of regulatory authorities to operate;
● the uncertainties inherent in the initiation and conduct of clinical trials, availability and timing of data from
clinical trials, and whether results of early clinical trials or clinical trials in different disease indications will
be indicative of the results of ongoing or future trials;
● our plans and the related cost expectations to pursue development of XENLETA for additional indications
other than CABP, and of CONTEPO for additional indications other than cUTI;
● the future development and commercialization of XENLETA in the greater China region and Canada;
● our expectations with respect to milestone payments pursuant to the Agreement and Plan of Merger, dated
July 23, 2018, and expectations with respect to potential advantages of CONTEPO or any other product
candidate that we acquired in connection with the acquisition of Zavante Therapeutics, Inc., or the
Acquisition;
● our ability to establish and maintain arrangements for manufacture of our product candidates;
● the potential advantages of SIVEXTRO, XENLETA, CONTEPO, and our other product candidates;
● our estimates regarding the market opportunities for SIVEXTRO, XENLETA, CONTEPO, and our other
product candidates;
● the rate and degree of market acceptance and clinical benefit of SIVEXTRO for acute bacterial skin and skin
structure infections, XENLETA for CABP, CONTEPO for cUTI and our other product candidates, if
approved;
● our ability to establish and maintain collaborations including additional licensing agreements for XENLETA
outside the United States, Canada and the greater China region;
● the potential benefits under our license agreements with Sumitomo Pharmaceuticals (Suzhou), or the China
Region License Agreement, and with Sunovion Pharmaceuticals Canada Inc., or the Sunovion License
Agreement;
● our future intellectual property position;
● our ability to maintain the level of our expenses consistent with our internal budgets and forecasts;
● the demand for securities of pharmaceutical and biotechnology companies in general and our ordinary shares
in particular;
● competitive factors;
● risks of relying on external parties such as contract manufacturing and sales organizations;
● compliance with current or prospective governmental regulation;
● general economic and market conditions;
● our ability to attract and retain qualified employees and key personnel;
● our business and business relationships, including with our employees and suppliers;
Table of Contents
● our ability to satisfy milestone, royalty and transaction revenue payments pursuant to the Stock Purchase
Agreement between our wholly owned subsidiary Zavante Therapeutics, Inc. and SG Pharmaceuticals, Inc.;
and
● other risks and uncertainties, including those described in ‘‘Risk Factors’’ in Part I, Item 1A of this Annual
Report on Form 10-K.
We may not actually achieve the plans, intentions or expectations disclosed in our forward-looking statements,
and you should not place undue reliance on our forward-looking statements. Actual results or events could differ materially
from the plans, intentions and expectations disclosed in the forward-looking statements we make.
You should refer to “Risk Factor Summary” and “Risk Factors” in Part I, Item 1A of this Annual Report for a
discussion of important factors that we believe could cause actual results or events to differ materially from the forward-
looking statements that we make. Our forward-looking statements do not reflect the potential impact of any future
acquisitions, mergers, dispositions, joint ventures or investments we may make. We do not assume any obligation to update
any forward-looking statements, except as required by applicable law.
Throughout this Annual Report on Form 10-K, unless the context requires otherwise, all references to “Nabriva,”
“the Company,” we,” “our,” “us” or similar terms refer to Nabriva Therapeutics plc, together with its consolidated
subsidiaries.
SPECIAL NOTE
On December 2, 2020, our board of directors effected a one-for-ten reverse stock split of our ordinary shares, or
the Reverse Stock Split. As a result of the Reverse Stock Split, every ten ordinary shares of $0.01 each (nominal value) in
the authorized and unissued and authorized and issued share capital of the company were consolidated into one ordinary
Share of $0.10 each (nominal value), and the nominal value of each ordinary share was subsequently immediately reduced
from $0.10 to $0.01 nominal value per share. All outstanding stock options, restricted stock units and warrants entitling
their holders to purchase or acquire ordinary shares were adjusted as a result of the Reverse Stock Split. Accordingly, all
ordinary share, common share, equity award, warrant and per share amounts in this Annual Report on Form 10-K have
been adjusted to reflect the Reverse Stock Split.
Table of Contents
RISK FACTOR SUMMARY
Our business is subject to a number of risks of which you should be aware before making an investment decision.
Below we summarize what we believe are the principal risk factors but these risks are not the only ones we face, and you
should carefully review and consider the full discussion of our risk factors in the “Risk Factors” in Part I, Item 1A, together
with the other information in this Annual Report.
● We depend heavily on the success of SIVEXTRO, XENLETA and CONTEPO. The U.S. Food and Drug
Administration, or FDA, has approved SIVEXTRO for oral and intravenous use by adults and adolescents for the
treatment of acute bacterial skin and skin structure infections, or ABSSSI, and XENLETA for oral and
intravenous use for the treatment of community-acquired bacterial pneumonia, or CABP. CONTEPO is being
developed for complicated urinary tract infections, or cUTI. If we are unable to obtain marketing approval for
CONTEPO, or if we fail in our commercialization efforts for SIVEXTRO and/or XENLETA, or experience
significant delays in doing so, our business will be materially harmed.
● We have incurred significant losses since our inception and anticipate that we will incur losses for at least the next
several years and may never generate profits from operations or maintain profitability.
● We will need substantial additional funding. If we are unable to raise capital when needed or on acceptable terms,
we could be forced to delay, reduce or eliminate our product development programs or commercialization efforts.
● If we fail to meet the requirements for continued listing on The Nasdaq Global Select Market, our ordinary shares
could be delisted from trading, which would decrease the liquidity of our ordinary shares and our ability to raise
additional capital.
● Our level of indebtedness and debt service obligations could adversely affect our financial condition and may
make it more difficult for us to fund our operations. We may not have cash available to us in an amount sufficient
to enable us to make interest or principal payments on our indebtedness when due or to comply with minimum
cash balance requirements.
● The number of ordinary shares underlying our outstanding warrants is significant in relation to our currently
outstanding ordinary shares, which could have a negative effect on the market price of our ordinary shares and
make it more difficult for us to raise funds through future equity offerings.
● SIVEXTRO, XENLETA and any other product candidate that receives marketing approval may fail to achieve
the degree of market acceptance by physicians, patients, third-party payors and others in the medical community
necessary for commercial success and the market opportunity for such products and product candidates, if
approved, may be smaller than we estimate.
● We have entered into a Sales Promotion and Distribution Agreement with Merck & Co. related to the promotion,
distribution and sale of SIVEXTRO. If our collaboration with Merck is not successful, we may incur significant
expenses related to the distribution of SIVEXTRO without realizing adequate value from the agreement.
● We have entered into and may enter into additional collaborations with third parties for the development or
commercialization of XENLETA, CONTEPO and our other product candidates. If those collaborations are not
successful, we may not be able to capitalize on the market potential of these products and product candidates.
● If we are unable to obtain and maintain patent protection for our technology, products and product candidates, or
if the scope of the patent protection is not sufficiently broad, our competitors could develop and commercialize
technology, products and product candidates similar or identical to ours, and our ability to successfully
commercialize our technology, products and product candidates may be adversely affected.
Table of Contents
● Business interruptions resulting from the SARS-CoV-2 infection causing COVID-19 outbreak or similar public
health crises have caused and could continue to cause a disruption of the commercialization of our products and
the development of our product candidates and adversely impact our business.
● If clinical trials of XENLETA, CONTEPO or any of our other product candidates fail to demonstrate safety and
efficacy to the satisfaction of the FDA, regulatory authorities in the European Union, or other regulatory
authorities or do not otherwise produce favorable results, we may incur additional costs or experience delays in
completing, or ultimately be unable to complete, the development and commercialization of XENLETA,
CONTEPO or any other product candidate.
● If we experience delays or difficulties in the enrollment of patients in our clinical trials, our receipt of necessary
marketing approvals could be delayed or prevented.
● If serious adverse or undesirable side effects are identified in SIVEXTRO, XENLETA, or CONTEPO or any
other product candidate that we develop or following their approval and commercialization, we may need to
modify, abandon or limit our development or marketing of that product or product candidate.
● We are a “smaller reporting company”, and the reduced disclosure requirements applicable to smaller reporting
companies may make our ordinary shares less attractive to investors.
● The rights of our shareholders may differ from the rights typically offered to shareholders of a U.S. corporation.
We are incorporated as a public limited company under Irish law.
● The intended efficiency of our corporate structure depends on the application of the tax laws and regulations in
the countries where we operate, and we may have exposure to additional tax liabilities or our effective tax rate
could change, which could have a material impact on our results of operations and financial position.
● U.S. persons who own 10 percent or more of our shares may be subject to U.S. federal income taxation on certain
of our foreign subsidiaries’ income even if such income is not distributed to such U.S. persons.
● A transfer of our ordinary shares, other than a transfer effected by means of the transfer of book-entry interests in
the Depository Trust Company, may be subject to Irish stamp duty.
● We may be classified as a passive foreign investment company for one or more of our taxable years, which may
result in adverse U.S. federal income tax consequence to U.S. holders.
Table of Contents
ITEM 1. BUSINESS
Overview
PART I
We are a biopharmaceutical company engaged in the commercialization and research and development of novel
anti-infective agents to treat serious infections. We have the commercial rights to two approved products, SIVEXTRO and
XENLETA, as well as one development product candidate, CONTEPO. We may potentially develop XENLETA and
CONTEPO for additional indications. Both the oral and intravenous, or IV, formulations of XENLETA formulations and
CONTEPO were granted Qualified Infectious Disease Product, or QIDP, and Fast Track designation by the FDA.
Incentives for QIDP status include an additional five years of exclusivity, in addition to any other exclusivity periods, as
well as fast track and priority review status, for which both XENLETA formulations and CONTEPO are eligible.
SIVEXTRO
SIVEXTRO is a novel oxazolidinone class antibiotic to treat susceptible Gram-positive pathogens including
MRSA, one of the serious public health threats identified by the CDC. Available in both IV and oral formulations,
SIVEXTRO was approved by the FDA for the treatment of adults with ABSSSI, such as cellulitis, wound infections, and
Erysipelas and in 2020 the label was expanded to include adolescents 12 years of age and older.
On July 15, 2020, we announced that we entered into a Sales Promotion and Distribution Agreement, the
Distribution Agreement, with MSD International GmbH, or MSD, and Merck Sharp & Dohme Corp., or the Supplier, each
a subsidiary of Merck & Co. Under the Distribution Agreement, MSD appointed us as its sole and exclusive distributor of
certain products containing tedizolid phosphate as the active ingredient previously marketed and sold by Supplier and MSD
under the trademark SIVEXTRO® for injection, intravenous and oral use in the United States and its territories.
SIVEXTRO is an oxazolidinone-class antibacterial indicated in adults and patients 12 years of age and older for the
treatment of ABSSSI caused by susceptible isolates of the following Gram-positive microorganisms: Staphylococcus
aureus, including MRSA and methicillin-susceptible, or MSSA, isolates, Streptococcus pyogenes, Streptococcus
agalactiae, Streptococcus anginosus group (including Streptococcus anginosus, Streptococcus intermedius and
Streptococcus constellatus), and Enterococcus faecalis.
Under the Distribution Agreement and subject to the fulfillment of certain conditions, including our engaging
sufficient sales representatives, restrictions relating to travel and physician office access in the United States and its
territories, or SIVEXTRO Territory, due to COVID-19 having continued to decrease in a sufficient portion of the
SIVEXTRO Territory so as not to hinder the successful detailing of SIVEXTRO, we have been granted the right to initially
promote SIVEXTRO in the SIVEXTRO Territory and, upon satisfaction of additional conditions, including an increase in
the number of our sales representatives, the right to exclusively distribute SIVEXTRO in the SIVEXTRO Territory,
including the sole right and responsibility to fill orders with respect to SIVEXTRO in the SIVEXTRO Territory. In April
2021, we satisfied those conditions, including the requirement to increase the number of sales representatives, and began
filling orders of SIVEXTRO with our own Nabriva National Drug Code, or NDC.
SIVEXTRO was the primary driver of our topline revenues in 2021, and we believe that will continue in the near
term. We believe SIVEXTRO will serve as the foundation of our portfolio in the near-term, and serve as the primary source
of our revenue as we continue to raise awareness around and establish other products in our portfolio. We plan to maximize
our resource allocation in the near-term to drive SIVEXTRO sales back to historical prescription trends in order to
effectively and efficiently drive our operating cash flow.
XENLETA
Discovered and developed by our team, XENLETA is a semi-synthetic pleuromutilin antibiotic that is the first in
its class for intraveneous, or IV, and oral administration in humans. XENLETA is designed to inhibit the synthesis of a
specific protein on the bacterial ribosome, which is required for bacteria to grow, by binding with high affinity and
specificity at molecular targets that are different than other currently available antibiotic classes causing cell death.
1
Table of Contents
Based on results from two global, Phase 3 clinical trials, we believe XENLETA is well-positioned for use as first-line
monotherapy for the treatment of CABP due to its novel mechanism of action, short five-day course of therapy for oral
XENLETA, targeted spectrum of activity, resistance profile, achievement of substantial drug concentrations in lung tissue
and fluid, availability of oral and IV formulations and a generally well-tolerated profile. We believe XENLETA represents
a potentially important new treatment option for the five to six million adults in the United States diagnosed with CABP
each year.
We believe that pleuromutilin antibiotics can help address the major public health threat posed by bacterial
resistance, which the World Health Organization, or WHO, characterized in 2017 as one of the biggest threats to human
health. Increasing resistance to antibiotics currently used to treat CABP is a growing concern and has become an important
issue for clinicians selecting the appropriate initial antibiotic treatment for patients prior to determining the specific
microbiological cause of the infection, referred to as empiric treatment. For example, the U.S. Centers for Disease Control
and Prevention, or CDC, has classified Streptococcus pneumoniae, currently the most common respiratory pathogen, as a
serious threat to human health as a result of increasing resistance to currently available antibiotics. In a recent retrospective
cohort study of Streptococcus pneumoniae blood and pulmonary isolates from U.S. sites, resistance to macrolide class
antibiotics was observed in 47.3% of Streptococcus pneumoniae colonies obtained from respiratory cultures, and 29.6%
from blood cultures. As resistance to macrolide class antibiotics in respiratory isolates was greater than 25% in all regions
of the U.S, we believe clinicians should consider alternatives to macrolide monotherapy for community acquired
pneumonia in the U.S. based on current treatment guidelines.
In addition, the CDC recently reported on the growing evidence of widespread resistance to macrolide class
antibiotics, which are designed to disrupt bacterial protein synthesis, in Mycoplasma pneumoniae, a common cause of
CABP that is associated with significant morbidity and mortality. Furthermore, Staphylococcus aureus, including
methicillin-resistant Staphylococcus aureus, or MRSA, which has also been designated as a serious threat to human health
by the CDC, has emerged as a more common cause of CABP in some regions of the world, and a possible pathogen to be
covered with empiric therapy.
As a result of increasing resistance to antibiotics and the wide array of potential pathogens that cause CABP, the
current standard of care for hospitalized patients with CABP whose treatment is initiated in the hospital usually involves
first-line empiric treatment with a combination of antibiotics (cephalosporins and macrolides) or monotherapy with a
respiratory fluoroquinolone. In patients where MRSA is suspected, fluoroquinolones are also typically administered in
combination with other antibiotics. Combination therapy presents the logistical challenge of administering multiple drugs
with different dosing regimens, with some drugs available only through IV administration, which may increase the risk of
drug-drug interactions and the potential for serious side effects. Fluoroquinolones are associated with safety and tolerability
concerns, including a relatively high risk for developing Clostridium difficile infection and because of their generally broad
spectrum of activity, increasing rates of resistance for uropathogens.
The FDA has communicated safety information about fluoroquinolones, advising that when used systemically, in
the form of tablets, capsules or injectable preparations, fluoroquinolones are associated with disabling and potentially
permanent serious side effects. In December 2018, the FDA warned prescribers of an increase in the occurrence of rare but
serious events of ruptures or tears in the main artery of the body, called the aorta. These tears, called aortic dissections, or
ruptures of an aortic aneurysm can lead to dangerous bleeding or death. Prior communications pertaining to the safety of
fluoroquinolones occurred in July 2018 (significant decreases in blood sugar and certain mental health side effects), July
2016 (disabling side effects of the tendons, muscles, joints, nerves, and central nervous system), May 2016 (restricting use
for certain uncomplicated infections), August 2013 (peripheral neuropathy), and July 2008 (tendinitis and tendon rupture).
The European Medicines Agency, or EMA, has also reviewed this class of antibiotics and has modified prescribing
information to restrict use, and outline some of the safety risks. We believe these concerns have contributed to the increase
in restrictions imposed by hospitals on and overall decline in the use of fluoroquinolones.
Many currently available antibiotic therapies are only available for IV administration and are prescribed for seven
to fourteen days, requiring prolonged hospitalization or a switch to a different orally administered antibiotic, with the
attendant risk that the patient might respond differently.
2
Table of Contents
Effective January 1, 2017, the Joint Commission & Center for Medicare and Medicaid Services, or CMS, began
requiring all U.S. hospitals to have antibiotic management guidelines, also known as “stewardship” committees, in place to
identify antibiotics most appropriate and targeted to each individual patient’s infection. Past efforts to “cast the widest net
possible” with broad-spectrum antibiotics that affect many types of bacteria have caused problems, such as Clostridium
difficile infections, by killing good bacteria or increased antibiotic resistance in other bacteria in different areas of the body.
Additionally, in 2016, the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of
America, or IDSA/SHEA, updated their antibiotic stewardship guidelines for antibiotic use. We believe that three key goals
from these guidelines are applicable to the treatment of CABP:
● Reduce use of antibiotics associated with a high risk of Clostridium difficile infections;
● Increase use of oral antibiotics as a strategy to improve outcomes or decrease costs; and
● Reduce antibiotic therapy to the shortest effective duration.
Consistent with the Antimicrobial Stewardship principles, we believe that XENLETA could be well suited as
either a first-line or second-line empiric monotherapy for the treatment of CABP patients in the hospital setting, outpatient-
transition of care setting or in the community setting, because of its novel mechanism of action, spectrum of activity for
CABP pathogens, including against multidrug resistant strains, achievement of substantial drug concentrations in lung
fluids and lung immune cells, the flexibility to step down from IV to oral administration and a favorable safety and
tolerability profile.
On September 9, 2019, we announced that the oral and IV formulations of XENLETA were available in the
United States for the treatment of CABP in adults through major specialty distributors. This followed the approval by the
FDA of our NDA for XENLETA on August 19, 2019 for the treatment of adults with CABP. XENLETA is the first oral
and IV treatment in the pleuromutilin class of antibiotics available for the systematic administration in humans.
We primarily market XENLETA to community-based physicians. This strategy has been implemented given
XENLETA’s convenient 5-day dosing of its oral formulation and given that it is widely covered under most commercial
insurance plans.
We entered into a license and commercialization agreement in March 2019 with Sunovion Pharmaceuticals
Canada Inc., or Sunovian, for the commercial rights to XENLETA in Canada. On July 16, 2020, we announced that
Sunovian received approval from Health Canada to market oral and IV formulations of XENLETA® (lefamulin) for the
treatment of community-acquired pneumonia, or CAP, in adults, with the related Notice of Compliance from Health
Canada dated July 10, 2020.
On July 28, 2020, we announced that the European Commission, or EC, issued a legally binding decision for
approval of the marketing authorization application for XENLETA™ (lefamulin) for the treatment of CAP, in adults when
it is considered inappropriate to use antibacterial agents that are commonly recommended for initial treatment or when
these agents have failed following a review by the EMA. The EC approved XENLETA for countries of the European
Economic Area, or EEA, and United Kingdom, or U.K. We intend to work with a commercial partner to make XENLETA
available to patients in the EEA and U.K.
In May 2021, Sumitomo Pharmaceuticals (Suzhou) and we announced positive topline results from Sumitomo
Pharmaceuticals (Suzhou)’s Phase 3 clinical trial of lefamulin in Chinese adults with CABP. Sumitomo Pharmaceuticals
(Suzhou)’s multi-center, randomized, double-blind trial was designed to evaluate the safety and efficacy of IV to oral
lefamulin compared to IV/oral moxifloxacin in 125 patients with CABP. The results were similar to those observed in our
global Phase 3 LEAP 1 and LEAP 2 clinical trials of lefamulin conducted. Consistent with previously reported clinical trial
results, lefamulin was observed to be generally well-tolerated, with an overall rate of treatment-emergent adverse events, or
TEAEs, comparable to that of moxifloxacin. The vast majority of TEAEs in both treatment arms were mild-to-moderate in
severity, with serious adverse events occurring in 4% of lefamulin-treated patients and 10% of moxifloxacin-treated
patients. TEAEs leading to discontinuation were uncommon and observed in just 5% of subjects in both treatment arms.
3
Table of Contents
In September 2021, Sumitomo Pharmaceuticals (Suzhou) and we announced Sumitomo Pharmaceuticals (Suzhou)
received approval to market oral and IV formulations of XENLETA for the treatment of community-acquired pneumonia
in adults in Taiwan.
In November 2021, we announced that Sumitomo Pharmaceuticals´ (Suzhou) NDA to market oral and IV
formulations of lefamulin for the treatment of community-acquired pneumonia, or CAP, in adults in mainland China was
accepted for review by the Chinese Center for Drug Evaluation, or CDE, China’s regulatory authority, on November 23,
2021. The expected time for the application review is up to 24 months.
COVID-19 has demonstrated the devastating impact that infectious diseases can have on public health and the
economy. Similar to other acute respiratory virus infections, including influenza virus, patients infected with COVID-19
are at increased risk of developing concomitant bacterial pneumonia. In published reports, bacterial pneumonia has been
shown to affect nearly 50% of hospitalized patients with COVID-19, with an associated mortality of almost 50%. Some
physisians routinely administer broad-spectrum antibiotics as an empiric therapy for bacterial pneumonia to all patients
with COVID-19 and moderate or severe hypoxemia. Other physisians administer antibiotics only for certain situations,
such as the presence of a lobar infiltrate on a chest X-ray, leukocytosis, an elevated serum lactate level, microbiologic data,
or shock. If antimicrobials are initiated, the NIH Panel recommends that their use should be reassessed daily to minimize
the adverse consequences of unnecessary antimicrobial therapy. In addition to XENLETA’s potential role in treating
COVID-19 patients with superimposed bacterial pneumonia, we are assessing the anti-inflammatory activity of XENLETA
and what role, if any, these characteristics may play in the management of patients with COVID-19.
CONTEPO
On July 24, 2018, we completed the acquisition of Zavante Therapeutics, Inc., or Zavante, together with its lead
product candidate CONTEPO™ (fosfomycin for injection, previously referred to as ZTI-01 and ZOLYD), or the
Acquisition. With the Acquisition, Zavante became our wholly owned subsidiary.
The prevalence of antibiotic-resistant bacteria is increasing and is considered a significant threat to global health.
Complicated urinary tract infections, or cUTIs, including acute pyelonephritis, or AP, are among the most common
infections due to multi-drug resistant, or MDR bacteria, including carbapenem-resistant Enterobacteriaceae, or CRE, and
are often healthcare-associated. Global mortality attributable to CRE infections has been estimated in some studies to be
over 20% and reflects the need for safe, alternative, carbapenem-sparing options.
CONTEPO is a novel, potentially first-in-class investigational IV antibiotic in the United States with a broad
spectrum of Gram-negative and Gram-positive activity, including activity against most MDR strains such as extended-
spectrum β-lactamase-, or ESBL-producing Enterobacteriaceae. Intravenous fosfomycin has been approved for a number
of indications and utilized for over 45 years in Europe to treat a variety of serious bacterial infections, including cUTIs.
CONTEPO utilizes a new dosing regimen that optimizes its pharmacokinetics and pharmacodynamics. We believe these
attributes, the extensive worldwide clinical experience and the positive efficacy and safety results from the Phase 2/3
clinical trial support CONTEPO as a first-line treatment for cUTIs, including AP, suspected to be caused by MDR
pathogens. At least 20% of cUTIs are caused by MDR bacteria and limited treatment options are available in the U.S. In
addition, non-clinical data have shown that CONTEPO acts in combination with certain other antibiotics to improve
bacterial killing.
We submitted an NDA for marketing approval of CONTEPO for the treatment of cUTI including AP in adults in
the United States, to the FDA in October 2018. The NDA submission is utilizing the 505(b)(2) regulatory pathway and is
supported by a robust data package, including a pivotal Phase 2/3 clinical trial (known as ZEUS™), which met its primary
endpoint of statistical non-inferiority to high dose piperacillin/tazobactam in patients with cUTI, including AP. In April
2019, the FDA issued a CRL in connection with our NDA for CONTEPO for the treatment of cUTIs, including AP, stating
that it was unable to approve the application in its current form. The CRL requested that issues related to facility
inspections and manufacturing deficiencies at our active pharmaceutical ingredient contract manufacturer be addressed
prior to the FDA approving the NDA. We requested a “Type A” meeting with the FDA to discuss its findings and this
meeting occurred in July 2019. As the FDA did not request any new clinical data and did not raise any other concerns with
regard to the safety or efficacy of CONTEPO in the CRL, the purpose of the meeting was to discuss and
4
Table of Contents
gain clarity on the issues related to facility inspections and manufacturing deficiencies at one of our contract manufacturers
that were described in the CRL and other matters pertaining to the steps required for the resubmission of the NDA for
CONTEPO. We resubmitted our NDA in December 2019 and the FDA acknowledged the resubmission in January 2020.
On June 19, 2020 we received a second CRL from the FDA. Although our European contract manufacturing partners were
prepared for regulatory authority inspections, the CRL cites observations at our manufacturing partners that could not be
resolved due to FDA’s inability to conduct onsite inspections because of travel restrictions. On October 30, 2020, we
participated in a “Type A” meeting with the FDA to obtain any new information related to the FDA´s pending conduct of
inspections of foreign manufacturers during the COVID-19 pandemic that has negatively impacted a number of FDA
product reviews, including our NDA for CONTEPO. On April 14, 2021, the FDA issued industry guidance on remote
interactive evaluations of drug manufacturing and bioresearch monitoring facilities during the COVID-19 pandemic
specifying that when it cannot perform a Pre-Approval Inspection, or PAI, or a Pre-License Inspection, or PLI, or when the
FDA determines that it would be useful to supplement a planned inspection, the agency will consider using tools other than
a physical inspection and select the most appropriate method to address the specific risks that justify the need for the PAI or
PLI. The FDA informed us that onsite inspections of our manufacturing partners in Europe are required in order for the
FDA to complete the review of a potential CONTEPO NDA resubmission. Due to travel restriction related to the COVID-
19 pandemic, the FDA suspended onsite inspections of ex-US manufacturers for all non-COVID products. As a result, we
requested an extension of the timeline for a potential CONTEPO NDA resubmission until June 2023, which the FDA
granted on March 21, 2022. We are awaiting further clarity from the FDA regarding their ability to complete onsite
inspections at our manufacturing partners in Italy and Spain before determining specific timing of the potential NDA
resubmission, which we plan to submit promptly once we have clarity from the FDA. We currently do not have a
forecasted date for the resubmission of our NDA for CONTEPO, for the treatment of cUTI, including AP. The FDA
released the Resiliency Roadmap for FDA Inspectional Oversight that describes the systematic approach that FDA will
utilize to manage postponed inspections and other oversight activities. The prioritization plan considers public health risks
related to conducting an inspection, such as the impact of the product’s availability on public health, as well as investigator
safety and travel restrictions/advisories. In addition, the FDA informed us that, while they cannot predict when an
inspection may occur and when the pandemic may prevent the FDA from completing inspections, tier 1 mission-critical
inspections and tier 2 higher priority inspections, which includes PAIs, will continue to be prioritized going forward. We
cannot predict the outcome of any further interactions with the FDA or when CONTEPO will receive marketing approval,
if at all.
Our Strategy
We are a biopharmaceutical company engaged in the commercialization and research and development of novel
anti-infective agents to treat serious infections. The key elements of our strategy are:
● Maximize the commercial potential of SIVEXTRO for ABSSSIs , XENLETA for CABP, and CONTEPO
for cUTIs. We have established a scalable commercial infrastructure focused on maximizing the value of
SIVEXTRO, XENLETA, and if approved, CONTEPO. We have secured a virtual and in-person sales effort
with community-based expertise with Amplity Health, which is a contract sales organization, to replace our
hospital-based sale force and began a small and focused sales effort for SIVEXTRO and XENLETA in
September 2020. We expanded this effort to 60 sales representatives in 2021 and may expand it further. We
also piloted a virtual promotion effort with incremental sales representatives in the third quarter of 2021. We
may also adjust the allocation of our sales representatives across our portfolio from time to time to maximize
sales. We have distribution rights to SIVEXTRO in the United States under a Sales Promotion and
Distribution Agreement, or the Distribution Agreement, with MSD International GmbH, or MSD, and Merck
Sharp & Dohme Corp., or the Supplier, each a subsidiary of Merck & Co. We own exclusive, worldwide
rights to XENLETA and U.S. rights to CONTEPO and we have out licensed the rights to XENLETA in
Canada and China. We plan to continue to explore licensing of rights to XENLETA in other territories
outside the United States. Our initial target population for SIVEXTRO in the United States focused on
historial SIVEXTRO prescribers for ABSSI. Our initial target patient population for XENLETA in the
United States consists of adult patients with moderate to severe CABP and the initial target population for
CONTEPO is expected to be hospitalized adult patients with cUTIs, including AP. If CONTEPO receives
marketing approval from the FDA, we plan to commercialize it in the United States with either internal or
external sales resources. We believe CONTEPO has an innovative profile which, if
5
Table of Contents
approved, would support its adoption in the United States for adult cUTI patients treated in the hospital.
XENLETA also has the opportunity to be adopted as outpatient transition of care from the hospital, or
emergency department, or as an out-patient treatment in a community setting, each of which we believe
represents a significant commercial opportunity. Outside the United States we expect to utilize a variety of
types of collaboration, distribution and other marketing arrangements with multiple third parties to
commercialize XENLETA in such markets. We currently have a Market Access team that is working with
large payors, including managed care organizations to secure favorable formulary placement for SIVEXTRO
and XENLETA. In addition we offer Patient Assistance Programs to reduce the cost of our drugs at the point
of sale. Medical science liaisons are engaging with health care providers to serve as a resource for learning
about XENLETA.
● Evaluate business development opportunities and potential collaborations. As part of our corporate
strategy, we continue to evaluate business development opportunities and potential collaborations. We may
further expand our product pipeline through opportunistically in licensing or acquiring the rights to
complementary products, product candidates and technologies for the treatment of a range of infectious
diseases or other products that we would efficiently leverage with our commercial infrastructure, including
additional community products, which could involve an acquisition of or combination or other strategic
transaction with another operating business. We plan to evaluate the merits of entering into collaboration
agreements with other pharmaceutical or biotechnology companies that may contribute to our ability to
efficiently advance our product candidates, build our product pipeline, concurrently advance a range of
research and development programs and leverage our commercial infrastructure. We may consider out-
licensing certain products for certain market segments. Potential collaborations may provide us with funding
and access to the scientific, development, regulatory and commercial capabilities of the collaborators. We
expect to continue to explore opportunities from domestic and international governments, foundations, and
non-governmental entities to provide additional funding and support for potential future development
programs.
● Pursue the continued development of XENLETA in additional indications. We are evaluating the cost and
benefits of the continued development of XENLETA for indications in addition to CABP. Pediatric oral
formulation development is ongoing, and a Phase 1 clinical trial of intravenous lefamulin in pediatric patients
is ongoing. We initiated screening of our Phase 1 clinical trial of XENLETA for the treatment of resistant
bacterial infections in patients with cystic fibrosis, or CF, in March 2022, and are on track to begin dosing in
April 2022. Given the ongoing COVD-19 pandemic and the high risk it puts CF patients under, it is difficult
to estimate recruitment timelines at this time. We believe XENLETA may have the potential to treat
infections in patients with CF, acute bacterial skin and skin-structure infection, or ABSSSI, ventilator-
associated bacterial pneumonia, or VABP, or hospital-acquired bacterial pneumonia, or HABP, and sexually
transmitted infections, or STIs. In addition, we may explore longer duration of treatment with XENLETA to
support development of a treatment for osteomyelitis and prosthetic joint infections. We believe that
XENLETA would be differentiated from existing treatment options for these potential indications because of
its novel mechanism of action, spectrum of activity, including activity against multi-drug resistant pathogens,
achievement of substantial concentrations in relevant tissues, availability in both an IV and oral formulation
and favorable safety and tolerability profile. We continue to evaluate these opportunities and consider their
development if and when there is adequate funding which meets our business and financial objectives.
● Continue the development of CONTEPO for a pediatric indication. We are continuing the development of
CONTEPO for use in pediatric patients with cUTIs. In June 2018, we initiated a Phase 1, non-comparative,
open-label study of the pharmacokinetics and safety of a single dose of CONTEPO in pediatric subjects less
than 12 years of age. As a result of COVID-19, research sites were temporarily closed for enrolment for a
large part of 2020, and part of 2021, only a minority of sites are currently screening patients and allowing
access to the institution. As a result, our development timeline for CONTEPO for use in pediatric patients
with cUTIs was modified to reflect approximately a two-year delay due to COVID-19.
6
Table of Contents
Background
Anti-Bacterial Market and Scientific Overview
Antibiotics that are active against both Gram-positive and Gram-negative bacteria are referred to as broad
spectrum, while those that are active only against a select subset of Gram-positive or Gram-negative bacteria are referred to
as narrow spectrum. Bacteria that cause infections are often referred to as bacterial pathogens. Because it often takes from
24 to 72 hours to definitively identify the particular bacterial pathogen causing an infection, and the difficulty associated
with obtaining adequate bacterial cultures in some patients and infections, the causative pathogen(s) often remains
unidentified. Since the introduction of antibiotics in the 1940s, numerous new antibiotic classes have been discovered and
developed for therapeutic use. The development of new antibiotic classes and new antibiotics within a class is important
because of the ability of bacteria to develop resistance to existing mechanisms of action of currently approved antibiotics.
However, the pace of discovery and development of new antibiotic classes slowed considerably in the past few decades.
The CDC estimates that the pathogens responsible for more than 70% of U.S. hospital infections are resistant to at least one
of the antibiotics most commonly used to treat them. The CDC also estimated in 2019 that annually in the United States at
least 2.8 million people become infected with bacteria that are resistant to antibiotics and at least 35,000 people die as a
direct result of these infections.
Antibiotic resistance is primarily caused by genetic mutations in bacteria selected by exposure to antibiotics that do
not kill all of the bacteria. In addition to mutated bacteria being resistant to the drug used for treatment, many bacterial
strains can also become cross-resistant, meaning that they become resistant to multiple classes of antibiotics. As a result,
the effectiveness of many antibiotics has declined, limiting physicians’ options to treat serious infections and exacerbating
a global health issue. For example, the WHO estimated in 2014 that people with infections caused by MRSA, a highly
resistant form of bacteria, are 64% more likely to die than people with a non-resistant form of the bacteria. Resistance can
increase the cost of healthcare because of the potential for lengthier hospital stays and more intensive care. Growing
antibiotic resistance globally, together with the low level of investment in research and development, is considered one of
the biggest global health threats. In 2010, the WHO stated that antibiotic resistance is one of the three greatest threats to
human health. Partially in response to this threat, the U.S. Congress passed the GAIN Act in 2012, which provides
incentives, including access to expedited FDA review for approval, fast track designation and five years of potential data
exclusivity extension for the development of new QIDPs. Additional legislation is also being considered in the United
States, including the Developing an Innovative Strategy for Antimicrobial Resistant Microorganisms Act of 2019, or
DISARM, which is intended to establish a new reimbursement framework to enable product specific reimbursement to
hospitals for anti-infective products. In addition, the CMS has launched an alternative New Technology Add-On Payment,
or NTAP, to increase access to innovative antibiotics for hospital inpatients, by improving reimbursement rates for new
generation anti-infectives, and specifically those considered QIDP. In September 2020, the Centers for Medicare &
Medicaid Services, or CMS, granted a NTAP for XENLETA for injection, when administered in the hospital inpatient
setting. Both the IV and oral formulations of XENLETA were granted QIDP and Fast Track designation by the FDA.
NTAP was also grated for CONTEPO, making it the first QIDP antibiotic to be granted conditional NTAP approval prior to
receiving FDA approval. CONTEPO was granted QIDP and Fast Track Designation by the FDA for the treatment of
complicated urinary tract infections, or cUTIs, including acute pyelonephritis.
In 2018, sales of antibiotics to treat humans totaled approximately $45 billion globally. Although judicious use of
antibiotics is important to reduce the rate of antibiotic resistance, this approach alone cannot fully address the threat from
increasing antibiotic resistance. New antibiotics, and particularly new antibiotic classes, are needed to ensure the
availability of effective antibiotic therapy in the future.
Acute Bacterial Skin and Skin-Structure Infections
Market Overview
ABSSSIs are very common and are characterized by a wide range of disease presentations. Over 10.7 million
unique patients are diagnosed annually with ABSSSIs and lead to over 850,000 hospitalizations based on our market
research. The vast majority of ABSSSI patients are successfully treated in the community setting with oral medications.
7
Table of Contents
The frequency of ABSSSI is increasing. From 2000 to 2004, total hospital admissions attributed to ABSSSIs increased by
30%, followed by another 17% increase from 2005 to 2011. During a similar time period, from 1993 to 2005, the number
of emergency department visits attributed to ABSSSIs almost tripled, from 1.2 million to 3.4 million patients. The increase
in frequency of ABSSSI is attributed to the spread of resistant bacteria, in particular, community-associated methicillin-
resistant Staphylococcus aureus, or CA-MRSA. ABSSSI includes infections of deeper soft tissues, cellulitis, wound
infections, burns, and major abscesses. They often lead to substantial morbidity and mortality, can be resource intensive
and incur high healthcare costs.
Causes of ABSSSIs
ABSSSIs are a frequent reason for seeking care at in both the outpatient and hospital settings. Staphylococcus
aureus is one of the most common pathogens associated with these infections, and the emergence of community-associated
MRSA, has represented a significant challenge in their treatment.
Gram-positive bacteria, in particular Staphylococcus aureus, Staphylococcus pyogenes, and other ß-hemolytic
streptococci are the most common pathogens in ABSSSI. Of increasing concern is the rapidly rising frequency of ABSSSI
caused by MRSA. There has been a dramatic increase in the occurrence of CA-MRSA infections since 2000. In many U.S.
cities CA-MRSA is the most common pathogen cultured from patients with skin and skin structure infections in emergency
departments. The emerging incidence of resistance to multiple antibiotics in pathogens makes ABSSSI increasingly
difficult to treat. The most recent practice guidelines published by the IDSA for the treatment of ABSSSIs reflect the
impact of MRSA, because a large focus is on antibiotic regimens covering Staphylococcus aureus, in particular, MRSA.
The introduction of community-associated MRSA organisms has also influenced the selection of empirical antibiotic
therapy to treat ABSSSIs. Additionally, knowledge of regional microbial resistance and susceptibility patterns is essential
to identify appropriate empirical coverage for MRSA. Therefore, empiric coverage for MRSA has been recommended for
treatment of skin and soft tissue infections, given the high community prevalence of MRSA. Empiric antibiotic therapy
with activity against MRSA is particularly important in the following circumstances:
● History of MRSA infection
● Recurrent infection in the setting of underlying predisposing condition(s)
● Skin and soft tissue infection not associated with purulence, in the setting of inadequate clinical response (within
72 hours) to antibiotic therapy with no activity against MRSA
It is recommended that ABSSSI patients with mild infection (localized involvement with no systemic symptoms),
due to known or suspected MRSA, may be treated with oral antibiotic therapy. However, treatment with IV formulations of
antibiotic therapy may be appropriate in the following circumstances:
● Extensive soft tissue involvement
● Signs of systemic toxicity
● Rapid progression of clinical manifestations
● Persistence or progression of symptoms after 48 to 72 hours of oral therapy
● Immunocompromise
● Proximity of soft tissue infection to an indwelling device (such as a prosthetic joint or a vascular graft); soft tissue
infection should be considered a manifestation of device infection if it originates on the skin directly overlying
the prosthesis site.
8
Table of Contents
About MRSA
According to the CDC, “Antibiotic resistance threats in the United States, 2019” report, in contrast to the 2013
report, while the burden of antibiotic-resistance threats in the U.S. was greater than initially estimated, deaths are
decreasing. However, the number of Americans who must deal with antibiotic resistant infections remains high. According
to the CDC, more than 2.8 million antibiotic-resistant infections occur in the U.S. yearly and lead to the deaths of 35,000
Americans.
One of the serious public health threats identified by the CDC is MRSA, which continues to be a clinical and
economic burden. Based on the CDC 2019 report, there were 323,700 estimated MRSA cases in hospitalized patients in
2017, and an estimated 10,600 deaths in the U.S due to MRSA. The European Centre for Disease Prevention and Control,
or ECDC, estimates that more than four million patients in the European Union, or EU, healthcare acquired infections
annually, resulting in 37,000 deaths and that a large proportion of these deaths are due to the most common multidrug-
resistant bacteria, including MRSA. According to the ECDC, MRSA is still the most commonly identified antimicrobial-
resistant pathogen in hospitals in many parts of the world, including Europe, the Americas, North Africa, the Middle East,
and Asia. Data from the Eurosurveillance journal estimates MRSA infections affect more than 150,000 patients annually in
the EU.
Currently Available Treatment Options
Since it may take as long as 48 to 72 hours to identify the pathogen(s) causing an infection and most of the
currently available oral therapy options that cover resistant pathogens are narrow-spectrum treatments, physicians
frequently prescribe two or more antibiotics to treat a broad-spectrum of potential pathogens. In general, empiric therapy
choice has typically been guided by the patients’ clinical circumstances including regional antibiotic resistance patterns,
allergy history, and concomitant medications. A recent 12 month analysis of oral treatment options in the outpatient setting
by IQVIA indicated cephalosporins (Keflex), sulfonamide/trimethoprim combinations (Bactrim), tetracyclines and
fluroquinolones (Baxdela), are some of the most frequently prescribed oral treatments for certain serious bacterial skin
infections. However, these commonly prescribed therapies must be dosed more frequently, and many have adverse drug
effects such as drug-drug interactions and central nervous system effects. The efficacy of tetracyclines is supported by
susceptibility testing and observational and retrospective reports; however their efficacy for treatment of skin and soft
tissue infections due to MRSA has not been rigorously evaluated or compared in clinical trials. Fluroquinolones are not
recommended as a treatment option for ABSSSIs caused by MRSA because of decreased susceptibility of MRSA to
fluoroquinolones, which also highlights the need for additional treatment options for skin infections that are caused by
fluoroquinolone-resistant organisms.
Limitations of Currently Available Treatment Options
The most common treatments for serious bacterial skin infections are beta-lactams, such as cephalosporins
(cephalexin (Keflex), cefazolin (Anef)) or penicillin, or its derivates such as dicloxacillin, nafcillin or oxacillin. Other
agents include, sulfonamide/trimethoprim combinations (Bactrim), tetracyclines, vancomycin, linezolid and fluroquinolone
(Baxdela). Although many of these agents have an effective oral equivalent of dicloxacilin, some such as vancomycin or
daptomycin (Cubicin) for MRSA infections do not; the lack of an effective bioequivalent oral formulation of these and
many other commonly prescribed antibiotics requires continued IV therapy, which is inconvenient for the patient and may
result in longer hospital stays and greater cost. Alternatively, because of the absence of the same antibiotic in an oral, well-
tolerated formulation, physicians may switch the patient to a different orally available antibiotic at the time of hospital
discharge. This carries the risk of new side effects and possible treatment failure if the oral antibiotic does not cover the
same bacteria that were being effectively treated by the IV antibiotic therapy. While linezolid is a twice-daily IV and oral
therapy, it is a narrow-spectrum treatment that is associated with increasing bacterial resistance, side effects from
interactions with other therapies and other serious safety concerns.
9
Table of Contents
Adverse Effects
Concerns about antibiotic safety and tolerability are among the leading reasons why patients stop treatment and
fail therapy. The most commonly used antibiotics to treat ABSSSIs, such as cephalosporins (Keflex),
sulfonamide/trimethoprim combinations (Bactrim), and fluroquinolones (Baxdela) are associated with safety and
tolerability concerns. For example, Bactrim is associated with severe reactions including Stevens-Johnsons syndrome a rare
and serious disorder of the skin and mucus membranes. As previously noted, fluoroquinolones are associated with tendon
rupture, peripheral neuropathy and, more recently, valvular abnormalities, aortic aneurysm and/or dissection. In addition,
fluoroquinolones have been associated with an increased frequency of Clostridium difficile colitis, an overgrowth of a
bacteria in the colon that produces a toxin that results in inflammation of the colon and repeated bouts of watery diarrhea.
Linezolid should not be taken by patients who are also on many commonly prescribed anti-depressants, such as
monoamine oxidase inhibitors and serotonin reuptake inhibitors.
Our Solution : SIVEXTRO for the treatment of ABSSSI
SIVEXTRO (tedizolid phosphate) is a novel oxazolidinone class antibiotic to treat susceptible Gram-positive
pathogens including MRSA, one of the serious public health threats identified by the CDC.
SIVEXTRO, available in both IV and oral formulations, was approved by the FDA in 2014 for the treatment of
adults with ABSSSI such as cellulitis, wound infections and erysipelas and in 2020 the label was expanded to include
adolescents 12 years of age and older.
Administered once-daily, SIVEXTRO offers an effective, short six-day course of therapy. Convenient dosing
enables greater patient compliance and is one of the key therapeutic and commercial benefits of the drug over existing
treatments, many of which must be taken more frequently and for longer periods of time. SIVEXTRO has proven efficacy
and demonstrated 80% early clinical response in 48-72 hours, so clinicians can have confidence that the drug will work
quickly and is well tolerated with a low incidence of side effects. There is no need for monitoring and no drug-drug
interactions with selective serotonin reuptake inhibitors, or SSRIs, another significant competitive advantage, and
SIVEXTRO is not a substrate for hepatic CYP450. Additionally, many older ABSSSI treatments can only be administered
intravenously, and therefore require hospital treatment leading to increased healthcare costs.
Community-Acquired Bacterial Pneumonia
Market Overview
Our analysis of the LexisNexis data indicates that approximately 2.4 million of adult CABP patients were treated
as inpatients with IV or injectable antibiotics, and we found that the majority of CABP patients enter the hospital inpatient
setting following the initiation of antibiotic therapy during an Emergency Department, or ED, visit. Additionally, our
analyses show that approximately 1.4 million adult CABP patients were treated with antibiotic courses, IV or oral, in the
ED or as hospital outpatients and subsequently released without hospital admission.
Based on data collected from July 1, 2015 through June 30, 2018, on the Medicare.gov Hospital Compare website,
the current national rate of readmissions for Medicare pneumonia patients is 16.6%, which is the percentage of patients
who have had a recent hospital stay that must return to a hospital for unplanned care within 30 days of being discharged.
The national average death rate for Medicare pneumonia patients, excluding Medicare Advantage plan data, is 15.6%,
which is the percentage of patients who die, for any reason, within 30 days of admission to a hospital.
Based on data from LexisNexis Risk Solutions, as well as analysis of data from US hospitals and other healthcare
facilities, we believe that the number of adult CABP patients who were treated with antibiotic therapy in hospitals in the United
States exceeded 3.8 million for full-year 2016. Our analysis of the LexisNexis data also indicates that approximately 2.4 million
of these adult CABP patients were treated as inpatients with IV/injectable antibiotics, and we find that the majority of CABP
patients enter the hospital inpatient setting following the initiation of antibiotic therapy during an ED visit. Additionally, our
analyses show that approximately 1.4 million adult CABP patients were treated with antibiotic courses (IV or oral) in the ED or
as hospital outpatients and subsequently released without hospital admission.
10
Table of Contents
Additionally, approximately 1.4 million adult CABP patients were treated with antibiotic courses (IV or oral) in
the ED or as hospital outpatients and subsequently released without hospital admission. Furthermore, as a result of our
market research in 2017-18, we believe that once adult CABP patients are released from ED or are discharged from U.S.
hospitals, approximately 60-70%, receive oral antibiotic outpatient prescriptions as continuation of their antibiotic
treatment. As hospitals look to minimize the total cost of care and duration of hospital stay for CABP patients toward
improved outcomes, efficient transition of adult CABP inpatients to an oral antibiotic treatment as outpatient therapy can
significantly reduce days of hospitalization and overall treatment cost.
IQVIA estimated that in 2017 approximately 2.0 million adult CABP patients were actively treated with
antibiotics from prescribers in community clinics and at other non-hospital based sites of urgent care. As a result, we
believe that approximately 6 million CABP patients are treated with antibiotics in the United States on an annual basis and
6 out of every 10 adult CABP patients have treatment initiated in a hospital setting versus. the community setting.
Overall, the impact of pneumonia is serious. Based on CDC data, approximately 50,000 patients died from CABP
in the United States in 2014.
Causes of CABP
Pneumonia can be caused by a variety of micro-organisms, with bacteria being the most common identifiable
cause. CABP refers to bacterial pneumonia that is acquired outside of a hospital setting. Signs and symptoms of CABP
include cough, fever, sputum production and chest pain. A number of different types of bacteria can cause CABP, including
both Gram-positive and Gram-negative bacteria. Pneumonia that is caused by atypical bacterial pathogens often has
different symptoms and responds to different antibiotics than pneumonia caused by pathogens referred to as typical
bacteria. However, atypical bacteria are not uncommon. The most common bacterial pathogens noted in current treatment
guidelines from the Infectious Diseases Society of America, or IDSA, for hospitalized CABP patients who are not in the
intensive care unit are Streptococcus pneumoniae, Mycoplasma pneumoniae, Haemophilus influenzae, Chlamydophila
pneumoniae, and Legionella species. In addition, IDSA notes the emergence of resistance to commonly utilized antibiotics
for CABP, specifically drug-resistant Streptococcus pneumoniae and community-acquired MRSA, or CA-MRSA, as a
major consideration in choosing empiric therapy. However, a majority of patients do not have a pathogen identified using
routine diagnostic tests available to physicians.
Currently Available Treatment Options
In 2019, based on the most likely bacteria to cause CABP, IDSA and the American Thoracic Society, or ATS,
updated their recommendations for the empiric treatment of non-severe hospitalized patients with CABP without risk
factors for MRSA and Pseudomonas aeruginosa with either:
● a combination of a cephalosporin plus a macrolide or
● monotherapy with a respiratory fluoroquinolone; or
● combination therapy with a β-lactam and doxycycline when macrolides or fluoroquinolones are
contraindicated.
Given concerns over increasing drug resistance (macrolides) and safety issues (macrolides, fluoroquinolones), the
guidelines noted a need for additional research of new therapeutic agents, like XENLETA, for adults with CABP. As a new
therapeutic agent for the treatment of CABP, we believe the treatment of CABP with XENLETA is consistent with the
guidelines.
Regarding outpatient therapy, the updated guidelines now only conditionally recommend macrolide monotherapy
for CABP patients with or without comorbidities or risk factors only if local pneumococcal macrolide resistance is less
than 25% and reiterated that physicians need to be aware of the local susceptibility profiles of the common bacterial
pathogens associated with CABP because of increasing resistance to first-line antibiotics. For example, rates of
pneumococcal resistance to macrolides now exceed 25% in most areas of the US and resistance to
11
Table of Contents
tetracyclines (another first line outpatient recommended therapy) exceed 25% in some areas, while resistance in
Mycoplasma pneumoniae associated with severe disease has been recently reported by the CDC in the United States.
Antibiotic resistance is widespread to various degrees throughout the world.
Limitations of Currently Available Treatment Options
When confronted with a new patient suffering from a serious infection caused by an unknown pathogen, a
physician may be required to quickly initiate first-line empiric antibiotic treatment, often with a combination of antibiotics,
to stabilize the patient prior to definitively diagnosing the particular bacterial infection. However, currently available
antibiotic therapies for first-line empiric treatment of CABP suffer from significant limitations.
Bacterial Resistance and Spectrum of Activity
As a result of bacterial resistance, the effectiveness of many antibiotics has declined. For example, the CDC
estimates that in 30% of severe Streptococcus pneumoniae cases, the bacterial pathogen is fully resistant to one or more
clinically relevant antibiotics, with 44% of strains resistant to a macrolide in the United States. Antibiotic resistance has a
significant impact on mortality and contributes heavily to healthcare system costs worldwide. According to the CDC, cases
of resistant Pneumococcal pneumonia result in 32,000 additional doctor visits, approximately 19,000 additional
hospitalizations and 7,000 deaths each year. None of the currently available treatment options provides a monotherapeutic,
empiric, narrow spectrum of antibacterial coverage that sufficiently covers all of the most common bacterial causes of
CABP, including multi-drug resistant strains.
Difficult, Inconvenient and Costly Regimens
Currently available antibiotics used to treat CABP and other serious infections can be difficult, inconvenient and
costly to administer. Physicians typically prefer IV administration for patients hospitalized with more serious illness to
ensure adequate delivery of the drug. Many IV antibiotics are prescribed for seven to 14 days or more and patients can be
hospitalized for much or all of this period or require in-home IV therapy. The diagnosis related group, or DRG,
reimbursement system often used in the U.S. hospital setting pays a fixed fee for an episode of CABP that may not fully
compensate hospitals for the duration of hospitalized care. Prolonged IV treatment that extends the period of
hospitalization may cause hospital costs to increase in excess of the fixed reimbursement fee, resulting in significant
negative financial impact on healthcare institutions. In addition, to address all likely bacterial pathogens in a patient with a
more serious illness, IDSA guidelines recommend using a combination of antibiotics. Combination therapy presents the
logistical challenge of administering multiple drugs with different dosing regimens and may increase the risk of drug-drug
interactions. While IV treatment delivers the drug more rapidly than is typical orally, once a patient is stabilized, oral
treatment with the same drug allows for more convenient and cost-effective out-patient treatment. Because many
commonly used antibiotics are only available in IV form, a switch to an oral therapy often requires changing to a different
antibiotic, which may be less effective for the patient due to the different mechanism of action of the drug prescribed upon
discharge.
Adverse Effects
Currently available antibiotic therapies can have serious side effects. These side effects may include severe
allergic reactions, decreased blood pressure, nausea and vomiting, suppression of platelets, pain and inflammation at the
site of injection, muscle, renal and oto-toxicity, optic and peripheral neuropathies, aortic dissection, valvular abnormalities,
tendinopathy, hypoglycemia and headaches. At times, these side effects may be significant and require discontinuation of
therapy. As a result, some treatments require clinicians to closely monitor patients’ blood levels and other parameters,
increasing the expense and inconvenience of treatment. This risk may increase with combination therapy, which exposes
patients to potential adverse effects from each of the antibiotics used in treatment. For example, fluoroquinolones are
associated with tendon rupture, peripheral neuropathy and, more recently, valvular abnormalities, aortic aneurysm and/or
dissection. In addition, fluoroquinolones have been associated with an increased frequency of Clostridium difficile colitis,
an overgrowth of a bacteria in the colon that produces a toxin that results in inflammation of the colon and repeated bouts
of watery diarrhea. This has resulted in limitations on the use of fluoroquinolones in several countries. In November 2015,
the FDA convened an Advisory Committee meeting to review the benefits and risks of
12
Table of Contents
fluoroquinolones in less severe indications, such as uncomplicated UTI, acute bacterial sinusitis and acute bacterial
exacerbations of chronic bronchitis. Based on the committee’s recommendation, in July 2016, the FDA approved changes
to the labels of fluoroquinolones to indicate that fluoroquinolones should be reserved for use in patients who have no other
treatment options for the indications mentioned above, because the risk of these serious side effects generally outweighs
the benefits in these patients. These changes included a requirement that a separate patient Medication Guide be given with
each prescription that describes the safety issues associated with this class of drugs. In December 2018, an FDA review
found that fluoroquinolone antibiotics can increase the occurrence of rare but serious events of ruptures or tears in the
aorta. These tears, called aortic dissections, or ruptures of an aortic aneurysm can lead to dangerous bleeding or even death.
They can occur with fluoroquinolones for systemic use given by mouth or through an injection. As a result,
fluoroquinolone use has declined substantially in recent years.
Our Solution: XENLETA for the treatment of CABP
We believe that XENLETA, which is the first new class of antibiotic approved by the FDA in nearly 20 years for
CABP, can fill the current treatment gap by providing clinicians the ability to treat a patient with suspected or confirmed
CABP where there may be concerns about resistance, or adverse event profiles for available antibiotic classes, or for
elderly patients or patients with co-morbidities where they are at higher risk for negative outcomes from pneumonia.
XENLETA has demonstrated efficacy and a favorable safety profile as an empiric, short-course monotherapy for the
treatment of CABP with targeted activity against Gram-positive, Gram-negative, and atypical bacteria that are commonly
associated with CABP, including drug-resistant strains. The novel mechanism of action of XENLETA provides for a low
risk of resistance development and low probability of cross resistance with other antibiotics, which is important given the
increase in antimicrobial resistance to relevant CABP pathogens. XENLETA, with IV and oral formulations, and no need
for a loading dose, has versatility to meet the health care provider and patient’s clinical needs. For example, XENLETA can
be utilized in patients as an IV antibiotic in the hospital setting with discharge on oral therapy, which provides significant
advantages to the patients’ health while potentially reducing the total cost of care to the hospital. Additionally, we believe a
short course treatment with XENLETA oral monotherapy could benefit moderate to severe CABP patients treated in the
Emergency Department, or ED, by potentially avoiding hospitalization. And finally, XENLETA can be utilized effectively
in the community setting by primary care practitioners who can potentially avoid an ED visit, thereby, reducing patient
hospitalization exposure and related significant associated costs to managed care plans.
Complicated Urinary Tract Infections
Market Overview
Infections due to a bacterial pathogen that are resistant to one or multiple antibiotic classes have become
increasingly common and present a risk to our fight against infectious diseases and the management of complications in
vulnerable patients. According to the CDC, more than 2.8 million hospital infections caused by bacteria resistant to one or
more antibiotics occur every year in the United States, and over 35,000 patients with an antibiotic-resistant pathogen die
each year. The prevalence of β-lactamase enzymes among Gram-negative pathogens threatens the usefulness of many β-
lactam antibiotics and has resulted in greater reliance on last line antibiotics, including carbapenems.
cUTIs, including AP, are among the most common infections due to MDR bacteria, including CRE, and are often
healthcare-associated. Global mortality attributable to CRE infections has been estimated in some studies to be over 20%
and reflects the need for safe, alternative, carbapenem-sparing.
Surveillance and epidemiological studies suggest that some traditional, first line antibiotics may no longer be
acceptable choices for early therapy. In one third party, large scale surveillance study, approximately one out of three
patients hospitalized in the United States with cUTI, hospital associated pneumonia, or a bloodstream infection did not
receive timely effective antibiotic therapy, and this delay was associated with increased morbidity and mortality. Based on
third party studies, the rate of antibiotic resistance appears to be two to four times higher in patients who were admitted to
the hospital from a nursing home or were recently hospitalized. Antibiotic therapy within the past six months has also been
identified in these third party studies as a risk factor for antibiotic resistance.
13
Table of Contents
New classes of antibiotics that are effective against drug-resistant pathogens are needed for early, appropriate
treatment of serious infections in hospitalized patients and to treat patients who have failed to respond to standard, first-line
antibiotics due to acquired drug resistance.
For over 45 years, oral and IV formulations of fosfomycin have been used in the EU, Australia, Canada, Africa,
Asia, and South America, and an oral formulation of fosfomycin has been used in the United States. Oral fosfomycin is
available in the United States as single dose therapy for cystitis and is noted as an appropriate treatment option for cystitis
in treatment guidelines by the IDSA and the CDC. However, oral administration of fosfomycin provides inadequate
concentrations that are required for treatment of more serious infections due to its limited bioavailability and dose limiting
gastrointestinal tolerability.
Outside of the United States, IV fosfomycin is approved for patients with a variety of infections, often severe,
including cUTI, bacteremia, osteomyelitis, nosocomial lower respiratory tract infections, surgical site infections, bone and
joint infections, endocarditis, skin infections and bacterial meningitis. The efficacy and safety profile of IV fosfomycin has
been established by more than 45 years of clinical use outside of the United States and has been evaluated in more than 60
clinical trials. Fosfomycin has retained high in vitro activity with a low and stable resistance profile, and continues to be
suitable for use as a monotherapy for cUTI despite long term use.
Causes of cUTIs
cUTI is defined as a clinical syndrome characterized by pyuria (the presence of puss in the urine) and a
documented microbial pathogen on culture of urine or blood, accompanied by local and systemic signs and symptoms,
including fever, chills, malaise, flank pain, back pain or costo-vertebral angle pain or tenderness that occur in the presence
of a functional or anatomical abnormality of the urinary tract, or in the presence of catheterization. Indwelling urethral
catheters account for 70% to 80% of cUTIs, or 1 million cases per year in the United States. Catheter-associated UTI is the
most common cause of secondary bloodstream infections and is linked to increased morbidity and mortality. Patients with
pyelonephritis, regardless of underlying abnormalities of the urinary tract, are considered a subset of patients with cUTI.
cUTI are usually caused by a greater variety of pathogens, with a greater likelihood of associated antimicrobial
resistance, than uncomplicated UTIs, or uUTIs. Escherichia coli, or E. coli, is isolated in approximately 75% to 95% of
uUTIs and approximately 50% of cUTIs and is the most common etiologic agent of cUTIs. Additional commonly-
identified Gram-negative uropathogens include other Enterobacteriaceae (such as Klebsiella spp., Proteus spp.,
Enterobacter cloacae) and non-fermenting Gram-negative bacilli (such as Pseudomonas aeruginosa and Acinetobacter
spp.). Gram-positive organisms, such as Enterococci and coagulase-negative Staphylococci, may also be contributing
pathogens.
Limitations of Currently Available Treatment Options
We believe bacterial resistance against antimicrobials has created the need for more antibiotic treatment options,
particularly among MDR, Gram-negative bacilli (including CRE, ESBL, producers, and MDR Pseudomonas aeruginosa).
Gram-negative antimicrobial resistance is particularly common among urinary tract pathogens. Enterobacteriaceae,
including E. coli and Klebsiella pneumoniae, may acquire plasmids that encode ESBLs and confer resistance to third-
generation cephalosporins and other broad-spectrum antibiotics. Third-generation cephalosporins and β-lactamase
inhibitors, or BLIs, are also commonly ineffective against Enterobacteriaceae that generate AmpC enzymes.
The recent spread into hospitals of Enterobacteriaceae expressing emergent β-lactamases, including members of
the serine carbapenemases and metallo-β-lactamases, endanger antibiotic options. The lack of available and effective
antibiotic classes for these organisms has created an unmet medical need. For example, infections with CRE are difficult to
treat, as there are limited treatment choices available. Mortality rates as high as 40% to 50% have been associated with
CRE infections, making them a serious threat to public health. The available treatment choices are associated with serious
potential toxicity, in the case of colistin and aminoglycosides, or concerns of allergy or hypersensitivity, in the case of β-
lactams or penicillin derivatives.
14
Table of Contents
Our Solution: CONTEPO for the Treatment of cUTI
● CONTEPO is an IV formulation of fosfomycin and the sole member of the epoxide antibiotic class.
● CONTEPO has a different mechanism of action than other IV antibiotics available in the United States.
● CONTEPO has a broad spectrum of in vitro activity against a variety of clinically important MDR Gram-
negative pathogens, including ESBL-producing Enterobacteriaceae, CRE, and Gram-positive pathogens,
including MRSA and vancomycin-resistant enterococci.
● CONTEPO has demonstrated in vitro additivity or synergy when used in combination with other classes of
antibiotic agents in pre-clinical studies.
● CONTEPO has a small molecular size, which may enable high levels of tissue penetration and facilitate renal
elimination, both of which are important for treatment of cUTIs.
● CONTEPO is supported by a long history of IV fosfomycin use outside the United States in a variety of
indications, including cUTI.
● CONTEPO completed the ZEUS Study, a pivotal registrational Phase 2/3 clinical trial in cUTI, achieving
non-inferiority to an active comparator.
CONTEPO is a potentially first-in-class epoxide IV antibiotic in the United States with a broad spectrum of
bactericidal Gram-negative and Gram-positive activity, including activity against many contemporary MDR strains that
threaten hospitalized patients. IV fosfomycin has an extensive commercial history in markets outside the United States,
where it has been used broadly for over 45 years to treat a variety of indications, including cUTIs, bacteremia, pneumonia
and skin infections with little resistance shown to date.
CONTEPO works differently than other IV antibiotics approved in the United States. CONTEPO inhibits an early
step in bacterial cell wall synthesis, so the cell wall lacks integrity and the bacteria die quickly. We believe that because of
its different mechanism of action, we have not observed any cross resistance to date between CONTEPO and any of the
existing classes of intravenous antibiotics. In addition, CONTEPO has demonstrated in in vitro studies an additive or
synergistic antibacterial effect with other classes of antibiotics when used in combination therapy in preclinical studies, and
has been shown to restore susceptibility of resistant strains.
Our Products and Product Candidate
SIVEXTRO
Overview
SIVEXTRO (tedizolid phosphate) is a novel oxazolidinone class antibiotic to treat susceptible Gram-positive
pathogens including MRSA, one of the serious public health threats identified by the CDC.
SIVEXTRO, available in both IV and oral formulations, was approved by the FDA in 2014 for the treatment of
adults with ABSSSI such as cellulitis, wound infections and erysipelas and in 2020 the label was expanded to include
adolescents 12 years of age and older.
Sales Promotion and Distribution Agreement with Merck & Co.
On July 15, 2020, we entered into a Sales Promotion and Distribution Agreement, or the Distribution Agreement,
with MSD International GmbH, or MSD, and Merck Sharp & Dohme Corp., or Supplier, each a subsidiary of Merck &
Co., Inc. Under the Distribution Agreement and subject to the satisfaction of certain conditions, MSD
15
Table of Contents
appointed us as its sole and exclusive distributor of certain products containing tedizolid phosphate as the active ingredient
previously marketed and sold by Supplier and MSD under the trademark SIVEXTRO® for injection, intravenous use and
oral use, or the Products, in the United States and its territories, or the SIVEXTRO Territory. SIVEXTRO is an
oxazolidinone-class antibacterial indicated in adults and pediatric patients 12 years of age and older for the treatment of
acute bacterial skin and skin structure infections caused by certain susceptible Gram-positive microorganisms. On April 12,
2021, in accordance with the terms of the Distribution Agreement, we began exclusive distribution of SIVEXTRO under
our own National Drug Code, or NDC, and we recognize 100% of net product sales of SIVEXTRO in our results of
operations.
Under the Distribution Agreement and subject to the fulfillment of certain conditions, including us having
engaged sufficient sales representatives, restrictions relating to travel and physician office access in the SIVEXTRO
Territory due to COVID-19 having continued to decrease in a sufficient portion of the SIVEXTRO Territory so as not to
hinder the successful detailing of SIVEXTRO, we have been granted the right by MSD initially to promote the Products in
the SIVEXTRO Territory and, upon satisfaction of additional conditions, including an increase in sales representatives, the
right to exclusively distribute the Products in the SIVEXTRO Territory, including the sole right and responsibility to fill
orders with respect to the Products in the SIVEXTRO Territory. We successfully satisfied those conditions, including the
increase in the number of sales representatives, and began filling orders of SIVEXTRO with our own Nabriva NDC
beginning on April 12, 2021. Subject to applicable law, we are entitled to determine the final selling prices of the Products
charged by us to our customers at our sole discretion, subject to an overall annual limit on price increases, and will be
solely responsible for sales contracting and all market access activities, including bidding, hospital listing and
reimbursement. We are responsible for all costs related to the promotion, sale and distribution of the Products by us, as well
as all costs required to meet our staffing obligations under the Distribution Agreement. We are obligated to use
commercially reasonable efforts to promote and distribute the Products and to maximize the sales of the Products
throughout the SIVEXTRO Territory. We have agreed to employ a sales force or retain the services of a contract sales
organization to fulfill our obligations under the Distribution Agreement. We have secured a virtual and in-person sales
effort with community-based expertise with Amplity Health, which is a contract sales organization, to replace our hospital-
based sale force and began a small and focused sales effort for SIVEXTRO and XENLETA in September 2020. We
expanded this effort to 60 sales representatives in 2021 and may expand it further. We also piloted a virtual promotion
effort with incremental sales representatives in the third quarter of 2021.
Furthermore, a subsidiary of Merck will sell to us, and we have agreed to purchase SIVEXTRO from such
subsidiary at specified prices in such quantities as we may specify. Although we are entitled, subject to appliable law, to
determine the final selling prices of SIVEXTRO in our sole discretion, subject to an overall annual limit on price increases,
we may not be able to sell SIVEXTRO at prices high enough to recoup our investment in a sales force and other
commercialization activities.
XENLETA
Overview
XENLETA is a semi-synthetic derivative of the naturally occurring antibiotic, pleuromutilin, which was originally
identified from a fungus called Pleurotus mutilius. XENLETA is designed to inhibit the synthesis of bacterial protein,
which is required for bacteria to grow. XENLETA acts by binding to the peptidyl transferase center, or PTC, on the
bacterial ribosome in such a way that it interferes with the interaction of protein production at two key sites known as the
“A” site and the “P” site, resulting in the inhibition of bacterial proteins and the cessation of bacterial growth. XENLETA’s
binding occurs with high affinity, high specificity and at molecular sites that are different than other antibiotic classes. We
believe that XENLETA’s novel mechanism of action is responsible for the lack of cross-resistance with other antibiotic
classes that we have observed in our preclinical studies and clinical trials and a low propensity for
16
Table of Contents
development of bacterial resistance to XENLETA. The binding of XENLETA to the PTC on the bacterial ribosome is
depicted in the graphic below.
We believe that XENLETA is well suited to be used empirically as monotherapy for the treatment of respiratory
tract infections, such as CABP, because of its spectrum of antibacterial activity against both the typical and atypical
pathogens causing CABP. XENLETA is a pleuromutilin antibacterial indicated for the treatment of adults with CABP
caused by susceptible microorganisms. In addition, in preclinical studies, XENLETA showed potent antibacterial activity
against a variety of Gram-positive bacteria, Gram-negative bacteria and atypical bacteria, including multi-drug resistant
strains. In preclinical studies and in Phase 1 clinical trials, XENLETA achieved substantial concentrations in the epithelial
lining fluid, or ELF, of the lung, the site infected during pneumonia. XENLETA also provides the ability to switch from IV
to oral therapy and maintain therapy with the same antibacterial treatment. The efficacy of XENLETA in humans has been
shown in a proof-of-concept Phase 2 clinical trial with 207 patients with ABSSSI comparing two XENLETA doses (100
mg and 150 mg i.v. q12 h) with vancomycin (≥ 1,000 mg) over 5-14 days. This trial enrolled patients with severe skin and
skin structure infections, excluding any patients with minor and uncomplicated infections. In total, 90.8 % of patients in the
Modified Intent to Treat, or mITT population had Staphylococcus aureus infection; 69.1 % of patients had MRSA. The
results of the clinical Phase 2 trial in ABSSSI provided the first proof of concept for the systemic use of a pleuromutilin
antibiotic for the treatment of serious bacterial infections in humans. Thereafter, the clinical program for XENLETA
progressed with completion of two Phase 3 clinical trials in CABP (LEAP 1, LEAP 2). These trials demonstrated that
XENLETA treatment, administered as IV only, IV to oral, and oral only regimens, was non-inferior to the standard of care
moxifloxacin for the treatment of adults with CABP. Each trial provided independent evidence of the treatment effect and
safety in this population with unmet medical need. In May 2021, we and Sumitomo Pharmaceuticals (Suzhou) announced
positive topline results from Sumitomo Pharmaceuticals (Suzhou)’s Phase 3 clinical trial of lefamulin in Chinese adults
with CABP. Sumitomo Pharmaceuticals (Suzhou)’s multi-center, randomized, double-blind trial was designed to evaluate
the safety and efficacy of IV to oral lefamulin compared to IV/oral moxifloxacin in 125 subjects with CABP. The results
were similar to those observed in our global Phase 3 LEAP 1 and LEAP 2 clinical trials of lefamulin. Consistent with
previously reported clinical trial results, lefamulin was observed to be generally well-tolerated, with an overall rate of
treatment-emergent adverse events, or TEAEs, comparable to that of moxifloxacin. The vast majority of TEAEs in both
treatment arms were mild-to-moderate in severity, with serious adverse events occurring in 4% of lefamulin-treated
patients and 10% of moxifloxacin-treated patients. TEAEs leading to discontinuation were uncommon and observed in just
5% of subjects in both treatment arms.
17
Table of Contents
The FDA has designated each of the IV and oral formulations of XENLETA as a QIDP, which provides for the
extension of statutory exclusivity periods in the United States for an additional five years upon FDA approval of the
product for the treatment of CABP and granted fast track designation to these formulations of XENLETA. Fast track
designation is granted by the FDA to facilitate the development and expedite the review of drugs that treat serious
conditions and fill an unmet medical need. The fast track designation for the IV and oral formulations of XENLETA will
allow for more frequent interactions with the FDA, the opportunity for a rolling review of any NDAs, eligibility for priority
review and a shortening of the FDA’s goal for taking action on a marketing application from ten months to six months. Two
NDAs for IV and oral formulations of XENLETA for treatment of CABP were submitted to the FDA December 19, 2018
and were approved on August 19, 2019. On July 16, 2020, we announced that Sunovion Pharmaceuticals Canada Inc.,
received approval from Health Canada to market oral and intravenous formulations of XENLETA for the treatment of CAP
in adults, with the Notice of Compliance from Health Canada dated July 10, 2020. On July 28, 2020, we announced that
the EC, issued a legally binding decision for approving of the marketing authorization application for XENLETA for the
treatment of CAP, in adults when it is considered inappropriate to use antibacterial agents that are commonly recommended
for initial treatment or when these agents have failed following a review by the EMA. The EMA approved XENLETA in
the EEA and the U.K. In September 2021, we and Sumitomo Pharmaceuticals (Suzhou) announced the approval received
by Sumitomo Pharmaceuticals (Suzhou) to market oral and IV formulations of XENLETA for the treatment CAP in adults
in Taiwan.
We own exclusive, worldwide rights to XENLETA, other than our rights in People’s Republic of China, Hong
Kong, Macau, and Taiwan, which were licensed to Sumitomo Pharmaceuticals (Suzhou), and Canada, which was licensed
to Sunovian. XENLETA is protected by issued patents in the United States, Europe and Japan covering composition of
matter, which are scheduled to expire no earlier than 2028. We also have been granted patents for XENLETA relating to
process and pharmaceutical crystalline salt forms in the United States, which are scheduled to expire no earlier than 2031
before any regulatory exclusivity such as QIDP or pediatric extensions are applied. In addition, we own a family of
pending patent applications directed to pharmaceutical compositions of XENLETA, which if issued would be scheduled to
expire no earlier than 2036.
Key Attributes of XENLETA
We believe that the combination of the following key attributes of XENLETA, observed in clinical trials and
preclinical studies, differentiates XENLETA from currently available antibiotics and make XENLETA well suited for use
as a first-line or second-line empiric monotherapy for the treatment of CABP.
The preclinical studies and clinical trials we have conducted to date suggest that XENLETA’s novel mechanism of
action is responsible for the low risk of cross resistance observed with other antibiotic classes and a low propensity for
development of bacterial resistance to XENLETA. As a result of the favorable safety and tolerability profile we have
observed in our clinical trials to date, we believe XENLETA has the potential to present fewer complications relative to the
use of current therapies.
Based on our market research, we also believe that the availability of both IV and oral formulations of
XENLETA, and an option to switch to oral treatment, could reduce the length of a patient’s hospital stay and the overall
cost of care.
Targeted Spectrum of Activity for CABP Pathogens and Low Propensity for the Development of Bacterial Resistance
We expect XENLETA’s spectrum of antibacterial activity against typical and atypical pathogens could eliminate
the need to use a combination of antibiotics for the treatment of CABP. In our completed Phase 2 clinical trial, IV
XENLETA achieved a high cure rate against multi-drug resistant Gram-positive bacteria, including MRSA. In addition, in
preclinical studies, XENLETA showed activity against a variety of Gram-positive bacteria, including Streptococcus
pneumoniae and Staphylococcus aureus, that are resistant to other classes of antibiotics, Gram-negative bacteria, including
Haemophilus influenzae and Moraxella catarrhalis, and atypical bacteria, including Chlamydophila pneumoniae,
Mycoplasma pneumoniae and Legionella pneumophila. Included in XENLETA’s spectrum of activity are all bacterial
pathogens identified by IDSA as the most common causes of CABP for hospitalized patients who are not in
18
Table of Contents
the intensive care unit, as well as strains of the above listed bacteria that are resistant to other classes of antibiotics,
including penicillins, cephalosporins, fluoroquinolones and macrolides.
Based on observations from our preclinical studies and clinical trials of XENLETA, as well as industry experience
with pleuromutilins used in veterinary medicine over the last 40 years, we believe that XENLETA’s novel mechanism of
action is responsible for the low risk of cross-resistance observed with other antibiotic classes and a low propensity for
development of bacterial resistance to XENLETA.
Convenient Dosing Regimen; Potential for Switching from IV to Oral Treatment
We have developed both an IV and oral formulation of XENLETA, which we utilized in our clinical trials of
XENLETA for the treatment of CABP. The administration of XENLETA as a monotherapy avoids the need for the
complicated dosing regimens typical of multi-drug cocktails. We believe the availability of both IV and oral administration,
and an option to switch to oral treatment, would be more convenient for patients and could reduce the length of a patient’s
hospital stay and the overall cost of care. The potential reduction in the overall cost of care could be particularly
meaningful to healthcare institutions, as the DRG reimbursement system pays a fixed fee for the treatment of CABP
regardless of the length of hospital stay.
The efficacy and safety of XENLETA in adult patients with CABP was shown in two pivotal Phase 3 clinical
trials (LEAP 1 and LEAP 2). The two trials were designed in accordance with US and EU regulatory guidelines and
conducted in parallel from 2016 to 2018. Design elements of the Phase 3 clinical trials were broadly comparable. Both
were global, multicenter, randomized, double-blind, active-controlled, non-inferiority studies to establish the efficacy and
safety of XENLETA against the standard-of-care moxifloxacin in the treatment of adult subjects with CABP. In LEAP 1,
subjects were treated with IV study drug and could be switched to oral study drug at the discretion of the Investigator after
3 full days (6 doses) of IV treatment if, in the opinion of the Investigator, pre-defined criteria were met. In LEAP 2,
subjects were treated with XENLETA for five days (ten doses) compared to seven days of moxifloxacin (seven doses).
LEAP 1 (IV to Oral) Phase 3 Clinical Trial
In LEAP 1, a total of 551 subjects with Pneumonia Outcomes Research Team (PORT) Risk Class III to V who
required IV antibiotic therapy as initial treatment for the current episode of CABP were randomized 1:1 to treatment with
XENLETA 150 mg IV every 12 hours (n=276) or moxifloxacin 400 mg IV every 24 hours (n=275). Subjects could be
switched from IV to oral study drug (XENLETA 600 mg orally every 12 hours or moxifloxacin 400 mg orally every
24 hours) at the discretion of the Investigator after three full days (six doses) of IV treatment if pre-defined criteria were
met. If the investigator determined that MRSA was a probable pathogen at Screening, adjunctive linezolid 600 mg IV
every 12 hours was to be added to the moxifloxacin group and linezolid placebo was to be added to the XENLETA group.
The protocol defined different primary endpoints for the FDA and EMA to address regional differences in
regulatory requirements for the development of antibacterial drugs to treat CABP. The FDA primary endpoint (EMA
secondary endpoint) was the percentage of subjects with an Early Clinical Response, or ECR, of responder at 96 ± 24-
hours after the first dose of study drug in the Intent-to-treat, or ITT, Analysis Set. The EMA co-primary endpoints (FDA
secondary endpoints) were the percentages of subjects with an Investigator’s Assessment of Clinical Response (IACR) of
success at Test of Cure (TOC) Visit (5 to 10 days after the last dose of study drug) in the mITT and Clinically Evaluable at
Test of Cure, or CE-TOC Analysis Sets.
Of the 551 subjects randomized, 546 received any amount of study drug (Safety Analysis Set: 273 XENLETA,
273 moxifloxacin). The mean total duration of study drug treatment (IV and oral combined) was approximately seven days
in each treatment group. The two treatment groups were generally well balanced with respect to demographics and baseline
characteristics. Overall, 59.9% of subjects were male. The overall mean age was 60.3 years; 43.6% were ≥65 years and
18.1% were ≥75 years. Overall, 72.1% of subjects were classified as PORT Risk Class III, 26.5% were PORT Risk
Class IV, and 1.3% were PORT Risk Class V.
19
Table of Contents
LEAP 1 met its primary objective and demonstrated that XENLETA is non-inferior to moxifloxacin with or
without adjunctive linezolid for the treatment of adult subjects with CABP based on the FDA and EMA primary endpoints.
The ECR responder rate (FDA primary endpoint) was 87.3% in the XENLETA group and 90.2% in the moxifloxacin group
(treatment difference −2.9%; 95% CI: −8.5, 2.8). The lower limit of the 95% CI for the difference in ECR responder rates
was greater than the non-inferiority margin of −12.5%. Success rates for IACR at TOC (EMA co-primary endpoints) were
81.7% in the XENLETA group and 84.2% in the moxifloxacin group (treatment difference −2.6%; 95% CI: −8.9, 3.9) in
the mITT group, and 86.9% in the XENLETA group and 89.4% in the moxifloxacin group (treatment difference −2.5%;
95% CI: −8.4, 3.4) in the CE-TOC group. The lower limit of the 95% CI for the difference in IACR success rates was
greater than the non-inferiority margin of −10% for both groups.
Early Clinical Response rates for the most frequently identified baseline pathogens in the Microbiological Intent-
to-treat, or microITT, group were: Streptococcus pneumoniae (88.2% XENLETA vs 93.8% moxifloxacin), Haemophilus
influenzae (92.2% XENLETA vs 94.7% moxifloxacin), Moraxella catarrhalis (92.0% XENLETA vs 100.0%
moxifloxacin), Mycoplasma pneumoniae (84.2% XENLETA vs 90.0% moxifloxacin), Legionella pneumophila (88.9%
XENLETA vs 85.7% moxifloxacin), and Chlamydophila pneumoniae (90.9% XENLETA vs 94.7% moxifloxacin). ECR
responder rates for Staphylococcus aureus were 100.0% in both treatment groups. Responder rates among resistant
pathogens were high in the XENLETA group (e.g., 100.0% for penicillin-intermediate Streptococcus pneumoniae [PISP],
penicillin-resistant Streptococcus pneumoniae [PRSP], multi-drug resistant Streptococcus pneumoniae, or MDRSP, and
macrolide-resistant Streptococcus pneumoniae), although the number of resistant pathogens was low.
Both XENLETA and moxifloxacin were well tolerated in the IV ± oral treatment regimens administered in the
study. A similar rate of treatment-emergent adverse events, or TEAEs, was observed (38.1% vs 37.7% in the XENLETA
and moxifloxacin groups, respectively). Gastrointestinal events were the most frequently reported TEAEs in both treatment
groups (6.6% XENLETA, 13.6% moxifloxacin), with the difference between groups driven by an imbalance in TEAEs of
diarrhea (0.7% XENLETA, 7.7% moxifloxacin). No gastrointestinal TEAEs led to discontinuation of study drug in either
treatment group.
Administration site reactions of any type occurred more frequently for XENLETA (7.7%) than moxifloxacin
(3.7%). The most common individual TEAE was infusion site pain, affecting eight (2.9%) subjects in the XENLETA
group, and no subjects in the moxifloxacin group. One subject in each treatment group had an infusion site reaction that led
to discontinuation of study drug.
The incidence of TEAEs leading to discontinuation of study drug was 2.9% XENLETA and 4.4% for
moxifloxacin. The only TEAE preferred terms leading to discontinuation for more than 1 subject per treatment group were
electrocardiogram (ECG) QT prolonged (one XENLETA-treated subject and three moxifloxacin-treated subjects) and
infectious pleural effusion (one XENLETA-treated subject and two moxifloxacin-treated subjects).
Serious TEAEs occurred in 7.0% of subjects in the XENLETA group and 4.8% of subjects in the moxifloxacin
group and were most frequently reported in the Infections and Infestations System Organ Class, or SOC (2.9% XENLETA,
1.5% moxifloxacin).
Nine deaths (five in the XENLETA group and, four in the moxifloxacin group) occurred by Day 28. Two
additional deaths were reported after Day 28 (i.e., after the intended Late Follow-up [LFU] Visit): one XENLETA-treated
subject on Day 32 and one moxifloxacin-treated subject on Day 48. None of the deaths was assessed as related to study
drug by the Investigators.
There were no clinically meaningful trends or pattern of changes identified in hematology or chemistry laboratory
parameters. No subjects met Hy’s Law criteria.
LEAP 2 (Oral Only) Phase 3 Clinical Trial
In LEAP 2, a total of 738 subjects with PORT Risk Class II to IV who were appropriate candidates for oral
antibiotic therapy for the current episode of CABP were randomized 1:1 to treatment with XENLETA (n=370) or
20
Table of Contents
moxifloxacin (n=368). Subjects received either XENLETA 600 mg orally every 12 hours for 5 days (10 doses) or
moxifloxacin 400 mg orally every 24 hours for seven days (seven doses). The primary and secondary objectives were
identical to those in LEAP 1.
Of the 738 subjects randomized, 736 received any amount of study drug (Safety Analysis Set: 368 XENLETA,
368 moxifloxacin). The mean duration of exposure to active XENLETA was 5.0 days, compared with 6.7 days of active
moxifloxacin, which reflects the intended duration of active treatment for each drug as per the study design. The two
treatment groups were generally well balanced with respect to demographics and baseline characteristics. Overall, 52.4%
of subjects were male. The overall mean age was 57.5 years; 37.5% were ≥65 years and 16.3% were ≥75 years. Overall,
50.4% of subjects were classified as PORT Risk Class II, 37.7% were PORT Risk Class III, and 11.1% were PORT Risk
Class IV.
LEAP 2 met its primary objective and demonstrated that XENLETA is non-inferior to moxifloxacin for the
treatment of adult subjects with CABP based on the FDA and EMA primary endpoints. The ECR responder rate (FDA
primary endpoint) was 90.8% in the XENLETA group and 90.8% in the moxifloxacin group (treatment difference 0.1%;
95% CI: −4.4, 4.5). The lower limit of the 95% CI for the difference in ECR responder rates was greater than the non-
inferiority margin of −10%. Success rates for IACR at TOC (EMA co-primary endpoints) were 87.5% in the XENLETA
group and 89.1% in the moxifloxacin group (treatment difference −1.6%; 95% CI: −6.3, 3.1) in the mITT group, and
89.7% in the XENLETA group and 93.6% in the moxifloxacin group (treatment difference −3.9%; 95% CI: −8.2, 0.5) in
the CE-TOC group. The lower limit of the 95% CI for the difference in IACR success rates was greater than the non-
inferiority margin of −10% for both groups.
Early Clinical Response rates for the most frequently identified baseline pathogens in the microITT group were:
Streptococcus pneumoniae (89.4% XENLETA vs 91.3% moxifloxacin), Haemophilus influenzae (89.3% XENLETA vs
91.7% moxifloxacin), Mycoplasma pneumoniae (100.0% in both groups), Moraxella catarrhalis (85.7% XENLETA vs
100.0% moxifloxacin), Legionella pneumophila (81.3% XENLETA vs 94.1% moxifloxacin), and Chlamydophila
pneumoniae (93.8% XENLETA vs 100.0% moxifloxacin). ECR responder rates for Staphylococcus aureus were 100.0% in
both treatment groups. Responder rates among resistant pathogens were high in the XENLETA group (e.g., 100.0% for
PISP, PRSP, MDRSP, and MRSA), although the number of resistant pathogens was low.
Both XENLETA and moxifloxacin were well tolerated in the oral treatment regimens administered in the study.
The overall incidence of TEAEs was higher in the XENLETA group (32.6%) than in the moxifloxacin group (25.0%),
which was driven by a difference in the incidence of mild/moderate Gastrointestinal Disorders. For XENLETA and
moxifloxacin, respectively, the most frequently reported individual TEAEs in this category (and for the study overall) were
diarrhea (12.2% vs 1.1%), nausea (5.2% vs 1.9%), and vomiting (3.3% vs 0.8%). Among the XENLETA-treated subjects
reporting each of these TEAEs, approximately 75% had mild events and the remainder had moderate events. The only
severe gastrointestinal adverse event, which was also serious, was a case of inguinal hernia strangulated in a moxifloxacin-
treated subject. There were no severe or serious gastrointestinal adverse events among XENLETA-treated subjects.
Furthermore, gastrointestinal events led to study drug discontinuation for 3 XENLETA-treated subjects (due to vomiting or
abdominal pain) and one moxifloxacin-treated subject (due to vomiting). One patient who had a positive clinical response
to XENLETA was later diagnosed with a Clostridium difficile infection during an extended hospital stay.
The incidence of TEAEs leading to discontinuation of study drug was 3.3% for the XENLETA group and 2.4%
for the moxifloxacin group.
Serious TEAEs occurred in 4.6% of XENLETA-treated subjects and 4.9% of moxifloxacin-treated subjects, most
frequently in the Infections and Infestations category (2.4% and 1.4%, respectively).
In each treatment group, three (0.8%) subjects died by Day 28. Deaths of two additional XENLETA-treated
subjects were reported after Day 28 (i.e., after the intended LFU Visit): one subject on Day 57 and one subject on Day 271.
None of the deaths was assessed as related to study drug by the Investigators.
21
Table of Contents
No clinically meaningful trends or pattern of changes were identified in hematology or chemistry laboratory
parameters. Two unique XENLETA-treated subjects had either an ALT or an aspartate aminotransferase (AST) value
>10 × the upper limit of normal, or ULN; in both cases the transaminase increases were transient with no associated
increase in serum bilirubin. No subjects met Hy’s Law criteria.
Electrocardiogram analyses demonstrated increases from baseline in the QTcF interval in both treatment groups,
but the magnitude of the change in the XENLETA treatment group was smaller than that caused by moxifloxacin. In this
study the mean change from baseline in QTcF interval at the steady state assessment was 9.5 msec for XENLETA and 11.6
msec for moxifloxacin. Post-baseline QTcF increases of >60 msec occurred in 1.1% of XENLETA-treated subjects and
1.9% of moxifloxacin-treated subjects. No associated cardiac arrhythmias of concern were observed. No adverse trends in
vital signs in either treatment group were observed.
Phase 1 Pediatric Clinical Trial
Not unlike treatment of infectious diseases in adults, the management of pediatric infections has become more
difficult due to the continuing rise in resistance in bacteria. Further complicating antimicrobial selection in the pediatric
population is the need for agents to be very well tolerated and available in a final dosage form that can be easily
administered to children. Based upon the in vitro antimicrobial spectrum of activity, along with the safety profile observed
to date, we believe XENLETA is appropriate for evaluation for the treatment of a variety of pediatric infections, including
those affecting the respiratory tract and skin and skin structure. We have an agreed Pediatric Investigation Plan, or PiP, and
Pediatric Study Plan, or PSP, with the EMA and FDA, respectively. Pediatric oral formulation development is ongoing with
initiation of a relative bioavailability and pharmacokinetic study with said oral formulation in 2019, and we initiated a
Phase 1 clinical trial evaluating safety, tolerability and PK of intravenous XENLETA in pediatric patients in mid-2018. As
a result of COVID-19, research sites were temporarily closed for enrollment in 2020 and 2021 as hospitals suspended
access and non-essential clinical research to focus on health care delivery to COVID-19 patients. As of July 2020, trials
started to re-open, where allowed by the institution, and initiated screening of potential subjects at sites.
Additional Potential Indications for XENLETA
Cystic Fibrosis
Cystic fibrosis, or CF, is a genetically inherited multi-system rare disorder caused by defects in the CFTR gene
(CF transmembrane conductance regulatory), located on chromosome 7, with a gene carrier rate of 1 in 25. In many cases,
CF is apparent soon after birth and most patients are diagnosed by age 3. Approximately 10% of those affected were
diagnosed after 18 years of age, but this figure has decreased due to newborn screening.
The disruption in chloride transport at the cellular level leads to dehydrated secretions within the lungs. Hence,
pulmonary disease is the leading cause of morbidity and mortality in patients with CF because impaired muco-ciliary
clearance in the lungs leads to recurrent pulmonary infections, inflammation, bronchiectasis and progressive lung function
decline. One of the major factors influencing the impact on the lungs is infection. Infections are a leading cause of loss of
lung function and take a significant physical and emotional toll, making them a top concern for people with CF. The
treatment landscape for infections is becoming more challenging as antimicrobial resistance (AMR) increases. It is
estimated that approximately half of the CF population will continue to require improved anti-infective treatments over the
next 20 years.
Staphylococcus aureus is a ubiquitous commensal bacterial pathogen isolated in the respiratory tract and is
commonly colonized in the respiratory tracts of CF patients. It is one of the main causes of recurrent acute pulmonary
infections. According to the 2020 CF Foundation Patient Registry, 63.3% of patients with CF have either methicillin-
susceptible Staphylococcus aureus, or MSSA, MRSA, or a combination of the two. Looking at the specific resistance
phenotypes, 48.9% of patients have MSSA. What is concerning many CF clinicians is the prevalence of MRSA, which was
identified in 19.6% of patients because MRSA is associated with greater lung damage, pulmonary function deterioration
and increased risk of death.
22
Table of Contents
Sexually Transmitted Infections
Urethritis and cervicitis caused by Neisseria gonorrhoeae, Chlamydia trachomatis, or Mycoplasma genitalium are
frequently occurring sexually transmitted infections in the United States and Europe. Left untreated, these infections can
cause serious health problems, particularly in women, including chronic pelvic pain, life-threatening ectopic pregnancy and
infertility. Resistance in these organisms to the most commonly prescribed antibacterial treatments poses a serious public
health threat. For example, the CDC estimates that half of all infections of the clinical isolates of Neisseria gonorrhoeae
are resistant to at least one currently available antibiotic.
In preclinical studies, XENLETA has shown high potency against Neisseria gonorrhoeae, Chlamydia trachomatis
and Mycoplasma genitalium, including strains resistant to currently available antibacterial agents.
Osteomyelitis
The incidence of osteomyelitis, which is an infection of the bone, is increasing. The most common causative
organism is Staphylococcus aureus. In the United States, the prevalence of MRSA in these cases ranges from 33% to 55%.
Up to 90% of cases of hematogenous osteomyelitis, most frequently in children, are caused by Staphylococcus aureus. We
believe that XENLETA has the potential to be an effective treatment option for osteomyelitis. XENLETA has shown
substantial tissue penetration and activity against the most common causative organism in all forms of osteomyelitis. We
believe that based on the safety profile observed to date, XENLETA will be well tolerated for the long term use necessary
for the treatment of both adult and pediatric patients with osteomyelitis. The current standard of care for these infections is
treatment with vancomycin. We believe the ability to administer XENLETA by either the IV or oral route would provide a
significant advantage over existing therapies, such as vancomycin, that can only be administered by IV.
Prosthetic Joint Infections
Infection occurs in approximately 1% of joint replacement surgeries. Although the incidence of infection has been
decreasing, the total number of replacement operations has been rising, such that, overall, there is increasing morbidity.
The majority of these infections are caused by three organisms: coagulase negative staphylococci, Staphylococcus aureus
(including MRSA) and streptococci, all organisms that are susceptible to XENLETA. The preferred treatment for joint
infections with MRSA is vancomycin, with daptomycin and linezolid as alternatives. Vancomycin and daptomycin are
administered only by IV for this indication, and linezolid has side effects that affect long term use. We believe that
XENLETA could provide an alternative for both IV and oral therapy for these infections cases.
A 2018 Cochrane Review on interventions for the eradication of MRSA in people with cystic fibrosis reviewed
the available literature to evaluate the effectiveness of current treatment regimens. Despite showing MRSA eradication in
CF patients is possible, it is not clear what the long- term implications are as only two studies were identified and the
quality of the evidence was found to be very low or low for the different outcomes. For acute pulmonary exacerbations due
to MRSA, treatment with trimethoprim-sulfamethoxasole or doxycycline, and for moderate or severe exacerbations or if
the prior regimens fail, treatment with oral linezolid, intravenous vancomycin or intravenous ceftaroline is recommended.
There are limited treatment options in patients and each of the aforementioned drugs have potential safety concerns such as
hypersensitivity reactions, bone marrow suppression or renal toxicity. More information on dosage and administration is
needed to evaluate the effectiveness of antibiotic therapy to ensure optimal patient outcomes. Hence, there is an unmet
need for new treatment options to treat Staphylococcal pulmonary infections, specifically acute pulmonary exacerbations
due to MRSA.
We believe XENLETA has an opportunity to provide CF patients with MRSA infection an alternative treatment
option. XENLETA is a potent anti-staphylococcal antibiotic from the pleuromutilin class. It has been demonstrated to be
highly effective in in vitro and in vivo studies of Staphylococcus aureus infection, both MSSA and MRSA. Further it has
been shown to achieve high concentrations in the lung fluid and lung macrophages. XENLETA has been developed and
approved for the treatment of community-acquired bacterial pneumonia (including those caused by Staphylococcus aureus)
in the U.S., EU, and Canada as an oral tablet and a sterile intravenous product. XENLETA is not metabolized
23
Table of Contents
renally and is not nephrotoxic. We believe the confluence of non-clinical and clinical data, as well as the availability of a
well-tolerated and effective oral formulation uniquely positions lefamulin to potentially address the major unmet need of
exacerbations of cystic fibrosis caused by Staphylococcus aureus, both MSSA and MRSA. We initiated screening of our
Phase 1 clinical trial to evaluate the pharmacokinetics, safety and tolerability of XENLETA in patients with CF in March
2022. Results from this trial will inform further development of XENLETA as a treatment for staphylococcal lung
infections in this patient population.
Sexually Transmitted Infections
The CDC reports gonorrhea (caused by Neisseria gonorrhoeae) as one of the most common STIs in the US, with
more than 800,000 cases estimated to occur each year. Left untreated, these infections can cause serious health problems,
particularly for women, including chronic pelvic pain, life-threatening ectopic pregnancy, and infertility. Gonorrhea
infection also increases a person’s risk of contracting and transmitting human immunodeficiency virus. Chlamydial
infections and gonorrhea are the most frequently reported sexually transmitted and reportable infections in both Europe and
the United States with high occurrence rates among young persons, particularly women.
The WHO has estimated that there are over 1.0 million new STI cases per day globally, the majority of which are
asymptomatic. In 2020, the WHO estimated that there are 374.0 million new STI infections globally each year, of which
129.0 million are infected with Chlamydia trachomatis, 82.0 million are infected with Neisseria gonorrhoeae, 7.1 million
are infected with Treponema pallidu and 156.0 million are infected with Trichomonas vaginalis.
The CDC estimates that approximately 20% of the population of the United States was infected with an STI
organism on any given day in 2018, costing the healthcare system nearly $16.0 billion in healthcare costs alone. The total
number of new cases of Chlamydia trachomatis and Neisseria gonorrhoeae reported to the CDC in 2018 was 4.0 million
and 1.6 million, respectively.
STI organisms are progressively developing resistance to antibiotics prescribed for treatment: sulfonilamides,
penicillin, cephalosporins, azithromycin, tetracycline, and ciprofloxacin, and gonococcal resistance to all of these
antibiotics have been reported globally. Declining susceptibility to cefixime (an oral cephalosporin antibiotic) resulted in a
change to the CDC treatment guidelines in 2015, so that dual therapy with ceftriaxone (an injectable cephalosporin) and
azithromycin is now the only CDC recommended treatment regimen for gonorrhea. The emerging threat of cephalosporin
resistance highlights the need for continued surveillance of Neisseria gonorrhoeae antimicrobial susceptibility. In 2014,
38.2% of all Neisseria gonorrhoeae collected in the national surveillance program exhibited resistance to penicillin,
tetracycline, or ciprofloxacin or reduced susceptibility to cefixime, ceftriaxone, or azithromycin. Resistance or reduced
susceptibility to one antibiotic was identified in 20.8% of isolates, to two in 9.6%, to three in 7.2%, to four in 0.5%, and to
five in 0.1%. In 2019, the prevalence of ciprofloxacin resistance continued to increase to 35.4%, the highest recorded in the
Gonococcal Isolate Surveillance Project (GISP).
Mycoplasma genitalium has become a well-established cause for STIs and several studies have demonstrated the
association between Mycoplasma genitalium and urethritis in men and urethritis, cervicitis, endometritis, and pelvic
inflammatory disease in women. Decreases in the treatment efficacy of azithromycin, and treatment failure after second
line moxifloxacin leaves no validated treatment options for the treatment of Mycoplasma genitalium infections.
XENLETA is a highly potent novel antimicrobial of the pleuromutilin class. Initial in vitro studies demonstrated
high susceptibility of STI pathogens to lefamulin. Notably, susceptibility of Chlamydia trachomatis (MIC50/90, 0.02/0.04
mg/liter) and susceptible and resistant Neisseria gonorrhoeae (MIC50/90, 0.12/0.5 mg/liter) were good, and susceptibility
of Mycoplasma genitalium was excellent (MIC range, 0.002 to 0.063 mg/liter for multi-drug resistant strains). Given this
high degree of in vitro susceptibility and its favorable safety profile, we believe lefamulin holds great promise for a first-
line antibiotic for the syndromic treatment of STIs, particularly in populations with high rates of resistance to standard-of-
care antibiotics.
24
Table of Contents
Acute Bacterial Skin and Skin Structure Infections
The effect of lefamulin in treating ABSSSI was demonstrated in a Phase 2 clinical trial with 207 subjects with
ABSSSI comparing two lefamulin doses (100 mg and 150 mg IV q12h) with vancomycin over 5-14 days. This clinical trial
enrolled patients with significant skin and skin structure infections with a median lesion size of 175.0 cm2 (greater than the
minimum surface area of 75 cm2 specified in the FDA draft guidance), excluding any patients with minor and
uncomplicated infections. In total, 90.8% of patients in the MITT population had Staphylococcus aureus infection; 69.1%
of subjects had MRSA. Lefamulin 100 mg and 150 mg had consistently high efficacy rates across a wide range of clinical
and microbiological outcomes at several time points including the TOC, 7 to 14 days after the completion of therapy. These
response rates were comparable to vancomycin. The clinical success rate at TOC with lefamulin 100 mg and 150 mg q12h
treatment was high for all subgroups of subjects defined by primary infection type, bacteremia status, diabetic status,
baseline fever status, age group, antibiotic therapy category, prior treatment failure status, baseline area of erythema,
baseline body mass index, and gender. No important differences between or among the compared subgroups in the
response to lefamulin treatment were observed. The Day 3 clinical responder rate for lefamulin was also high and
comparable to vancomycin.
We may advance these programs into clinical development based on available funding.
CONTEPO Clinical Development Program
Overview
CONTEPO is under development in the United States for the treatment of cUTI, including AP. The clinical
development plan for CONTEPO utilized a modernized dosing regimen to optimize coverage of the predominant
pathogens in hospital infections, including strains recognized by the CDC as an urgent or serious antibiotic resistant threat
to public health in the United States. The FDA has designated CONTEPO as a QIDP. We submitted an NDA for marketing
approval of CONTEPO for the treatment of cUTI in adults in the United States, to the FDA in October 2018. The NDA
submission utilized the 505(b)(2) regulatory pathway and is supported by a robust data package, including a pivotal Phase
2/3 clinical trial (known as ZEUS™), which met its primary endpoint of statistical non inferiority to
piperacillin/tazobactam in patients with cUTI, including AP. In April 2019, the FDA issued a CRL in connection with our
NDA for CONTEPO for the treatment of cUTIs, including AP, stating that it was unable to approve our application in its
current form. The CRL requested that issues related to facility inspections and manufacturing deficiencies at our active
pharmaceutical ingredient contract manufacturer be addressed prior to the FDA approving the NDA. We requested a “Type
A” meeting with the FDA to discuss its findings and this meeting occurred in July 2019. As the FDA did not request any
new clinical data and did not raise any other concerns with regard to the safety or efficacy of CONTEPO in the CRL, the
purpose of the meeting was to discuss and gain clarity on the issues related to facility inspections and manufacturing
deficiencies at one of our contract manufacturers that were described in the CRL and other matters pertaining to the steps
required for the resubmission of the NDA for CONTEPO. We resubmitted our NDA in December 2019 and the FDA
acknowledged the resubmission in January 2020. On June 19, 2020, the FDA issued a second CRL on the NDA for
CONTEPO. Although our European contract manufacturing partners were prepared for regulatory authority inspections,
the CRL cited observations at our manufacturing partners that could not be resolved due to FDA’s inability to conduct
onsite inspections because of travel restrictions caused by the COVID-19 pandemic. In general, previously identified
product quality and facility inspection related observations at our contract manufacturing partners are required to be
satisfactorily resolved before the NDA may be approved. The FDA did not request any new clinical data and did not raise
any other concerns with regard to the safety or efficacy of CONTEPO in the second CRL. Our contract manufacturers
continue to interact with FDA to discuss its plans for conducting inspections at their sites. On October 30, 2020, we
participated in a “Type A” meeting with the FDA to obtain any new information related to the FDA’s pending conduct of
inspections of foreign manufacturers during the COVID-19 pandemic that has negatively impacted a number of FDA
product reviews, including our NDA for CONTEPO. On April 14, 2021, the FDA issued industry guidance on remote
interactive evaluations of drug manufacturing and bioresearch monitoring facilities during COVID-19 specifying that when
it cannot perform a PAI or PLI or when the FDA determines that it would be useful to supplement a planned inspection, the
agency will consider using tools other than a physical inspection and select the most appropriate method to address the
specific risks that justify the need for the PAI or PLI. The FDA informed us that
25
Table of Contents
onsite inspections of our manufacturing partners in Europe are required in order for the FDA to complete the review of a
potential CONTEPO NDA resubmission. Due to travel restriction related to the COVID-19 pandemic, the FDA suspended
onsite inspections of ex-US manufacturers for all non-COVID products. As a result, we requested an extension of the
timeline for a potential CONTEPO NDA resubmission until June 2023, which the FDA granted on March 21, 2022. We are
awaiting further clarity from the FDA regarding their ability to complete onsite inspections at our manufacturing partners
in Italy and Spain before determining specific timing of the potential NDA resubmission, which we plan to submit
promptly once we have clarity from the FDA. We do not have a forecasted date for the resubmission of our NDA for
CONTEPO for the treatment of cUTI, including AP.The FDA released the Resiliency Roadmap for FDA Inspectional
Oversight that describes the systematic approach that FDA will utilize to manage postponed inspections and other
oversight activities. The prioritization plan considers public health risks related to conducting an inspection, such as the
impact of the product’s availability on public health, as well as investigator safety and travel restrictions/advisories. In
addition, the FDA informed us that, while they cannot predict when an inspection may occur and when the pandemic may
prevent the FDA from completing inspections, tier 1 mission-critical inspections and tier 2 higher priority inspections,
which includes PAIs, will continue to be prioritized going forward. We cannot predict the outcome of any further
interactions with the FDA or when CONTEPO will receive marketing approval, if at all. CONTEPO has been granted
QIDP and Fast Track designations by the FDA for the treatment of serious infections, including cUTI. However, we cannot
predict when the NDA for CONTEPO for the treatment of cUTI, including AP, will be resubmitted or when CONTEPO
would receive marketing approval, if at all.
Phase 2/3 Clinical Trial
The ZEUS Study was a multicenter, randomized, parallel-group, double-blind, pivotal Phase 2/3 clinical trial
designed to evaluate safety, tolerability, efficacy and pharmacokinetics of CONTEPO compared to PIP-TAZ in the
treatment of hospitalized adults with cUTI or AP. PIP-TAZ is a combination antibiotic consisting of a broad-spectrum
antibiotic, piperacillin, plus a β-lactamase inhibitor, tazobactam, which extends the antibiotic spectrum of piperacillin to
include many β-lactamase-producing bacteria that have acquired resistance to piperacillin alone. PIP-TAZ is widely used to
treat serious Gram-negative infections. The primary objective of the ZEUS Study was to demonstrate that CONTEPO was
non-inferior to PIP-TAZ in overall success based on clinical cure and microbiologic eradication in the microbiologic
modified intent-to-treat, or m-MITT, population at the test-of-cure visit, or TOC, which occurred on the 19th to 21st day
after completion of seven days of treatment with the study drug, or after up to 14 days of treatment for patients with
concurrent bacteremia. The m-MITT population consisted of 362 patients, each of whom met the study’s inclusion criteria,
was randomized, received any amount of study drug, and had one or more baseline Gram-negative pathogens growing at
greater than or equal to 10(5) CFU/mL from an appropriately collected, pre-treatment baseline urine or blood sample. The
primary endpoint was a composite of the investigator’s determination of clinical cure, meaning complete resolution or
significant improvement of signs and symptoms that were present at baseline and no new symptoms, such that no further
antimicrobial therapy is warranted, plus microbiologic eradication, meaning that the baseline bacterial pathogen was
reduced to less than 10(4) CFU/mL on urine culture and, if applicable, negative on repeat blood culture, both in the m-
MITT population at TOC. Any missing or presumed eradications were classified as indeterminates, and conservatively
counted as failures in the overall success analysis.
All pathogens isolated from patients who had a baseline and TOC pathogen underwent blinded, post-hoc, pulsed-
field gel electrophoresis, or PFGE, typing analysis. Microbiologic outcome was also defined utilizing the PFGE results,
whereby microbiologic persistence required the same genus and species of baseline and post-baseline pathogens, as well as
PFGE-confirmed genetic identity.
Patients eligible for the trial were required to be 18 years of age or older and have cUTI or AP that was considered
by the clinical investigator to be serious enough to require hospitalization and IV antibiotic therapy. The diagnosis was
based on pyuria, or the presence of pus or white blood cells in the urine, and cUTI or AP with at least two additional
symptoms such as chills, rigors, or warmth associated with fever, nausea or vomiting, painful, difficult or frequent
urination, lower abdominal or pelvic pain, or acute flank pain. Patients with cUTI were also required to have at least one
risk factor, such as use of intermittent or indwelling bladder catheterization; functional or anatomical abnormality of the
urogenital tract; complete or partial hindrance of normal urine flow; blood urea nitrogen greater than 20 mg/dL, blood urea
greater than 42.8 mg/dL, or serum creatinine greater than 1.4 mg/dL, due to known prior renal disease; or, in male patients,
chronic urinary retention. A baseline urine culture specimen was obtained within 48 hours
26
Table of Contents
prior to randomization, and any indwelling bladder catheters were required to be removed or replaced, unless such removal
was considered unsafe or contraindicated, before or within 24 hours after randomization.
Eligible patients were randomly assigned to receive either CONTEPO (6 grams IV fosfomycin) or PIP-TAZ (4
grams piperacillin/0.5 grams tazobactam) as one-hour infusions three times daily for seven days, except patients with
concurrent bacteremia, who could have received treatment for up to 14 days at the clinical investigator’s discretion. Oral
step down therapy was prohibited. Throughout the study, all patients were monitored for signs and symptoms of cUTI or
AP and the occurrence of adverse events. Laboratory data, including chemistry panels, complete blood counts,
electrocardiograms, and samples for urine and blood cultures were collected from all patients at specified times throughout
the study.
Of the total of 465 patients randomized across 92 sites in 16 countries, with studies conducted at 74 sites in 15
countries, 464 (99.8%) received at least one dose of the study drug. Of the 464 patients who received at least one dose of
study drug, 233 patients were in the CONTEPO treatment group, and 231 patients were in the PIP-TAZ treatment group.
The incidence of premature discontinuation from study drug was low and similar between treatment groups (6.0% in the
CONTEPO treatment group compared to 3.9% in the PIP-TAZ treatment group), and the incidence of not completing the
study through the last follow-up visit, or LFU, which occurred on the 24th through 28th day after completion of seven days
of treatment with the study drug, or after up to 14 days of treatment for patients with concurrent bacteremia, was 5.2% in
the CONTEPO group compared to 0.9% in the PIP-TAZ group.
In the ZEUS Study, CONTEPO was non-inferior to PIP-TAZ for the primary efficacy outcome of overall success,
which was defined as clinical cure and microbiologic eradication at TOC. Overall success occurred in 64.7% of CONTEPO
patients and 54.5% of PIP-TAZ patients. The treatment difference between the CONTEPO and PIP-TAZ groups was
10.2%, with a 95% confidence interval (−0.4, 20.8). Additionally, the lower bound of the 95% confidence interval met the
pre-specified non-inferiority margin of −15%, demonstrating that CONTEPO was non-inferior to PIP-TAZ in the study. In
a post-hoc primary efficacy analysis using results of blinded PFGE molecular typing of urinary tract pathogens, this
difference was even greater (69.0% CONTEPO patients compared to 57.3% PIP-TAZ patients, with a treatment difference
of 11.7%, with a 95% confidence interval (1.3, 22.1). Overall success rates were driven by microbiologic eradication rates,
as clinical cure rates were greater than 90% and treatment differences were small at TOC. Using the PFGE molecular
typing, the microbiologic eradication rates in the m-MITT population at the TOC were 70.7% for patients receiving
CONTEPO compared to 60.1% for patients receiving PIP-TAZ. These rates were consistent with those observed in some
contemporary cUTI studies, and most patients with microbiologic persistence at TOC had identifiable reasons or risk
factors for persistence, such as functional or anatomical abnormalities of the urogenital tract, recent or indwelling urinary
tract catheterization, elevated minimum inhibitory concentration, or MIC, to the study drug received, abbreviated study
drug therapy, or other underlying co-morbidities. Of note, a majority of patients with microbiologic persistence at TOC
were clinical cures at TOC, did not require rescue antimicrobial therapy, and remained sustained cures at LFU.
The identity and frequency of pathogens recovered at baseline from patients in the ZEUS Study were similar in
both the CONTEPO and PIP-TAZ treatment groups. The most common pathogens identified were Enterobacteriaceae,
identified in 96.2% of the CONTEPO patients and 94.9% of the PIP-TAZ patients, including E. coli, identified in 72.3% of
the CONTEPO patients and 74.7% of the PIP-TAZ patients; Klebsiella pneumoniae, identified in 14.7% of the CONTEPO
patients and 14.0% of the PIP-TAZ patients; Enterobacter cloacae species complex, identified in 4.9% of the CONTEPO
patients and 1.7% of the PIP-TAZ patients; and Proteus mirabilis, identified in 4.9% of the CONTEPO patients and 2.8%
of the PIP-TAZ patients. Gram-negative aerobes other than Enterobacteriaceae included Pseudomonas aeruginosa, which
was identified in 4.3% of the CONTEPO patients and 5.1% of the PIP-TAZ patients, and Acinetobacter baumannii-
calcoaceticus species complex, identified in 1.1% of the CONTEPO patients and no PIP-TAZ patients. These pathogens
are representative of the pathogens that have been recovered in other studies of patients with cUTI or AP. For the
predominant pathogens E. coli and Klebsiella pneumoniae, the clinical cure rates at TOC for CONTEPO were greater than
90% for both pathogens, and microbiologic eradication rates were 68.4%, or 72.9% with PFGE analysis, for E. coli, and
66.7% for Klebsiella pneumoniae on both a non-PFGE analysis and PFGE analysis-basis.
A total of 42.1% of CONTEPO patients and 32.0% of PIP-TAZ patients experienced at least one TEAE. Most
TEAEs were mild or moderate in severity, and severe TEAEs were uncommon (2.1% of CONTEPO patients and 1.7%
27
Table of Contents
of PIP-TAZ patients). The most common TEAEs in both treatment groups were transient, asymptomatic laboratory
abnormalities and gastrointestinal events. Treatment-emergent serious adverse events, or SAEs, were uncommon in both
treatment groups (2.1% of CONTEPO patients and 2.6% of PIP-TAZ patients). There were no deaths in the study and one
SAE in each treatment group was deemed related to the study drug (hypokalemia in a CONTEPO patient and renal
impairment in a PIP-TAZ patient), leading to study drug discontinuation in the PIP-TAZ patient. Study drug
discontinuations due to TEAEs were infrequent and similar between treatment groups (3.0% of CONTEPO patients and
2.6% of PIP-TAZ patients).
The most common laboratory abnormality TEAEs were increases in the levels of alanine aminotransferase (8.6%
of CONTEPO patients and 2.6% of PIP-TAZ patients) and aspartate transaminase (7.3% of CONTEPO patients and 2.6%
of PIP-TAZ patients). None of the aminotransferase elevations were symptomatic or treatment-limiting, and none of the
patients met the criteria for Hy’s Law. Outside of the United States, elevated liver aminotransferases are listed among
undesirable effects in labeling for IV fosfomycin.
Hypokalemia occurred in 71 of 232 (30.6%) CONTEPO patients and 29 of 230 (12.6%) PIP-TAZ patients. Most
decreases in potassium levels were mild to moderate in severity. Shifts in potassium levels from normal at baseline to
hypokalemia, as determined by worst post-baseline hypokalemia values, were more frequent in the CONTEPO group than
the PIP-TAZ group for mild (17.7% compared to 11.3%), moderate (11.2% compared to 0.9%), and severe (1.7%
compared to 0.4%) categories of hypokalemia. Hypokalemia was deemed a TEAE in 6.4% of patients receiving
CONTEPO and 1.3% of patients receiving PIP-TAZ, and all cases were transient and asymptomatic. While no significant
cardiac adverse events were observed in the ZEUS Study, post-baseline QT intervals calculated using Fridericia’s formula,
or QTcF, of greater than 450 to less than or equal to 480 msec (baseline QTcF of less than or equal to 450 msec) occurred at
a higher frequency in CONTEPO patients (7.3%) compared to PIP-TAZ patients (2.5%). In the CONTEPO arm, these
results appear to be associated with the hypokalemia associated with the salt load of the IV formulation.
Phase 1 Pediatric Clinical Trial
In June 2018, we initiated a Phase 1, non-comparative, open-label study of the pharmacokinetics and safety of a
single dose of CONTEPO in pediatric subjects less than 12 years of age receiving standard-of-care antibiotic therapy for
proven or suspected infection or peri-operative prophylaxis. A total of 24 patients are expected to be enrolled at up to ten
clinical sites in the United States. As a result of COVID-19, research sites were temporarily closed in 2020 and 2021 and
only a minority of sites are currently screening patients and allowing access to the institution. As a result, our development
timeline for CONTEPO for use in pediatric patients with cUTIs has been modified to reflect a two-year delay due to
COVID-19.
Potential Additional Indications for CONTEPO
Fosfomycin has a long history of use outside the United States in a variety of indications beyond cUTI. The FDA
has granted both Fast Track and QIDP designations for the investigation of CONTEPO for the following indications in
addition to cUTI:
● Complicated intra-abdominal infections
● Hospital-acquired bacterial pneumonia
● Ventilator-associated bacterial pneumonia
● Acute bacterial skin and skin structure infections
Although we have no current plans to develop CONTEPO for indications other than cUTI, including AP, these
designations make CONTEPO eligible for Fast Track and GAIN incentives. We may advance these programs in the clinic
based on available funding.
28
Table of Contents
In August 2017, Zavante entered into an agreement with the United States National Institute of Allergy and
Infectious Diseases, or NIAID, under which NIAID will conduct a clinical trial to assess CONTEPO’s intrapulmonary
penetration and pharmacokinetics in support of the product candidate’s potential future development as a treatment for
HABP and VABP. This bronchoalveolar lavage study, or the BAL study, will measure CONTEPO’s pulmonary penetration
by assessing drug concentrations in the lining of study subjects’ bronchial pathways. Diffusion and saturation of antibiotics
in patients’ airways are considered important factors in assessing a drug’s ability to effectively treat lower-respiratory tract
infections. Prior preclinical and clinical investigations of IV fosfomycin have demonstrated that the product candidate
penetrates rapidly into tissues and achieves clinically relevant concentrations in urine, soft tissues, lungs and other organs,
supporting CONTEPO’s potential versatility as an antibiotic treatment option. The Phase 1 BAL clinical trial is currently
enrolling study subjects.
China Region License Agreement
In March 2018, we entered into the China Region License Agreement, with Sinovant Sciences, Ltd., or Sinovant,
an affiliate of Roivant Sciences, Ltd., to develop and commercialize lefamulin in the greater China region. As part of the
China Region License Agreement, Nabriva Therapeutics Ireland DAC and Nabriva Therapeutics GmbH, our wholly owned
subsidiaries, granted Sinovant an exclusive license to develop and commercialize, and a non-exclusive license to
manufacture, certain products containing lefamulin, or the China Region Licensed Products, in the People’s Republic of
China, Hong Kong, Macau, and Taiwan, together the Extended China Territory. In May 2021, we entered into an
assignment, assumption and novation agreement, or the Assignment Agreement, pursuant to which we consented to the
assignment by Sinovant, an affiliate of Roivant Sciences, Ltd., of the China Region License Agreement to develop and
commercialize lefamulin in the greater China region to Sumitomo Pharmaceuticals (Suzhou), a wholly-owned subsidiary
of Sumitomo Dainippon Pharma Co., Ltd., or Sumitomo. Pursuant to the Assignment Agreement, we agreed to release
Sinovant and its affiliates from their obligations under the China Region License Agreement and consented to Sumitomo
Pharmaceuticals (Suzhou)’s assumption of such obligations. In addition, Sumitomo has agreed to guarantee all of the
obligations of Sumitomo Pharmaceuticals (Suzhou) under the China Region License Agreement.
Under the China Region License Agreement, Sumitomo Pharmaceuticals (Suzhou) and our subsidiaries have
established a joint development committee, or the JDC, to review and oversee development and commercialization plans in
the Extended China Territory. The China Region License Agreement includes milestone events consisting of a non-
refundable $5.0 million upfront payment, an additional $91.5 million in milestone payments upon the achievement of
certain regulatory and commercial milestone events related to lefamulin for CABP, plus an additional $4.0 million in
milestone payments if any China Region Licensed Product receives a second or any subsequent regulatory approval in the
People’s Republic of China. We received the $5.0 million upfront payment, a $1.5 million payment for the submission of a
clinical trial application, or CTA, by Sinovant to the Chinese FDA, which was received in the first quarter of 2019 and a
$5.0 million milestone payment in the third quarter of 2019 in connection with the Chinese FDA approval for lefamulin.
We will also be eligible to receive low double-digit royalties on sales, if any, of China Region Licensed Products in the
Extended China Territory. In December 2020, we announced the restructuring of our China Region License Agreement.
The restructured agreement provided for additional manufacturing collaboration and regulatory support to be provided by
us that is expected to help expedite the delivery of XENLETA to patients in the Extended China Territory. The restructured
agreement also accelerated $3.0 million of the $5.0 million milestone payment to us that was previously payable upon
regulatory approval of XENLETA in China, including a non-refundable upfront payment of $1.0 million which was
received in the fourth quarter of 2020 and a $1.0 million milestone achieved during the first quarter of 2021.
Except for the manufacturing collaboration and regulatory support discussed above, Sumitomo Pharmaceuticals
(Suzhou) will be solely responsible for all costs related to developing, obtaining regulatory approval of and
commercializing China Region Licensed Products in the Extended China Territory and is obligated to use commercially
reasonable efforts to develop, obtain regulatory approval for and commercialize China Region Licensed Products in the
Extended China Territory. We are obligated to use commercially reasonable efforts to supply, pursuant to supply
agreements to be negotiated by the parties, to Sumitomo Pharmaceuticals (Suzhou) a sufficient supply of lefamulin for
Sumitomo Pharmaceuticals (Suzhou) to manufacture finished drug products for development and commercialization of the
China Region Licensed Products in the Extended China Territory.
29
Table of Contents
Unless earlier terminated, the China Region License Agreement will expire upon the expiration of the last royalty
term for the last China Region Licensed Product in the Extended China Territory, which we expect will occur in 2033.
Following the expiration of the last royalty term, the license granted to Sumitomo Pharmaceuticals (Suzhou) will become
non-exclusive, fully-paid, royalty-free and irrevocable. The China Region License Agreement may be terminated in its
entirety by Sumitomo Pharmaceuticals (Suzhou) upon 180 days’ prior written notice at any time. Either party may, subject
to specified cure periods, terminate the China Region License Agreement in the event of the other party’s uncured material
breach. Either party may also terminate the China Region License Agreement under specified circumstances relating to the
other party’s insolvency. We have the right to terminate the China Region License Agreement immediately if Sumitomo
Pharmaceuticals (Suzhou) does not reach certain development milestones by certain specified dates (subject to specified
cure periods). The China Region License Agreement contemplates that we will enter into ancillary agreements with
Sumitomo Pharmaceuticals (Suzhou), including clinical and commercial supply agreements and a pharmacovigilance
agreement.
Sunovion License Agreement
In March 2019, we entered into the Sunovion License Agreement with Sunovion Pharmaceuticals Canada Inc., or
Sunovion. As part of the Sunovion License Agreement, Nabriva Therapeutics Ireland DAC, our wholly owned subsidiary,
granted Sunovion an exclusive license under certain patent rights, trademark rights and know-how to commercialize certain
products containing XENLETA in the forms clinically developed by us or any of our affiliates, or the Sunovion Licensed
Products in Canada in all uses in humans in CABP and in any other indication for which the Sunovion Licensed Products
have received regulatory approval in Canada. Under the Sunovion License Agreement, Sunovion and Nabriva Therapeutics
Ireland DAC established a joint development committee, or the Sunovion JDC, to review and oversee regulatory approval
and commercialization plans in Canada. Sunovion will be solely responsible for all costs related to obtaining regulatory
approval of and commercializing Sunovion Licensed Products in the Canada and is obligated to use commercially
reasonable efforts to develop, obtain regulatory approval for, and commercialize Licensed Product in the Canada.
On November 7, 2019, we, through Sunovion, submitted a New Drug Submission, or NDS to market oral and
intravenous formulations of XENLETA for the treatment of CAP in adults. Health Canada determined there was a
screening deficiency in December 2019 and a response from us/Sunovion was provided on December 18, 2019 and
acknowledged by Health Canada on January 13, 2020. Sunovion received approval from Health Canada to market oral and
intravenous formulations of XENLETA for the treatment of community-acquired pneumonia in adults, with the Notice of
Compliance from Health Canada dated July 10, 2020.
Named Patient Program Agreement with WE Pharma Ltd.
On June 30, 2020 we announced that WE Pharma Ltd., or WEP Clinical, a specialist pharmaceutical services
company, had signed an exclusive agreement with us to supply XENLETA on a named patient or expanded access basis in
certain countries outside of the US, China and Canada. The Named Patient Program, or NPP, is designed to ensure that
physicians, contingent on meeting the necessary eligibility criteria and receiving approval, can request IV or oral
XENLETA on behalf of patients who live in certain countries where it is not yet available and have an unmet medical need.
Commercialization Strategy
We have distribution rights to SIVEXTRO in the United States pursuant to a Sales Promotion and Distribution
Agreement, or the Distribution Agreement, with MSD International GmbH, or MSD, and Merck Sharp & Dohme Corp., or
the Supplier, each a subsidiary of Merck & Co. Our initial target population for SIVEXTRO consisted of healthcare
professionals who had historically prescribed SIVEXTRO for patients with ABSSSI. Other than in greater China and
Canada where we have licensed development and commercialization rights to XENLETA, we own exclusive, worldwide
rights to XENLETA and U.S. rights to CONTEPO. Our initial target population for XENLETA consisted of patients with
moderate to severe CABP whose antibiotic treatment is hospital initiated. We received approval for XENLETA from the
FDA in August 2019 and launched the product in September 2019. We previously utilized our own targeted hospital sales
force and marketing organization and in early 2020 began to target high value primary care physicians in
30
Table of Contents
the community near our target hospitals. Based on our market research, we believe XENLETA has an innovative profile
supporting adoption in the United States for adult hospital initiated CABP patients, treated both as in patients as well as
outpatient transition of care from the hospital to the community, which we believe represents a significant commercial
opportunity. Due to market factors in 2020, including the COVID-19 pandemic, we transitioned to a community-based
sales effort. In the third quarter of 2020 we secured a contract sales organization and began promoting SIVEXTRO and
XENLETA to community-based healthcare providers. We anticipate that we will effectively be able to communicate
SIVEXTRO’s and XENLETA’s differentiating characteristics and key attributes to clinicians and payors with the goal of
establishing favorable reimbursement for patients. Outside of the United States, we expect to utilize a variety of types of
collaboration, distribution and other marketing arrangements with one or more third parties to commercialize XENLETA.
Along with additional market research, we believe that medical education will be a key component of our
commercialization efforts and, plan to invest in these activities to optimize the commercial potential of XENLETA. We
believe that XENLETA’s novel mechanism of action, status as the only member of a new class of systemically
administered pleuromutilins and anticipated clinical profile will support its potential favorable reimbursement, its potential
inclusion on formularies and in local and national treatment guidelines.
We plan to evaluate the merits of entering into collaboration agreements with other pharmaceutical or
biotechnology companies that may contribute to our ability to efficiently advance our product candidates, build our product
pipeline and concurrently advance a range of research and development programs for a variety of indications outside the
United States.
We own exclusive U.S. rights to CONTEPO. Our strategic intention, supported by CONTEPO’s differentiated
profile, is to establish CONTEPO, if approved, as the standard of care in the United States for hospitalized patients with
serious infections caused by suspected or confirmed MDR bacteria. We plan to seek a hospital based sales force to promote
CONTEPO, and potentially XENLETA, to hospital-based healthcare professionals in key locations within the United
States where MDR infections, including CRE, are concentrated. These include roughly 900 hospitals in high resistance
locations such as New York City, Los Angeles and Chicago, and other major population centers.
Manufacturing
We do not own or operate, and currently have no plans to establish, manufacturing facilities for the production of
clinical or commercial quantities of XENLETA, CONTEPO, or any of the other compounds that we are evaluating in our
discovery program. We currently rely, and expect to continue to rely, on third parties for the manufacture of XENLETA,
CONTEPO and any further products that we may develop. We have significant in-house knowledge and experience in the
relevant chemistry associated with XENLETA and CONTEPO; and the relevant manufacturing and supply chain processes
associated with the commercial supply of XENLETA and CONTEPO. In addition to these internal resources, we engage
third-party consultants, to assist in the management of our third-party manufacturers. We procure our supply of
SIVEXTRO from Merck & Co., Inc.
We have engaged a limited number of third-party manufacturers to provide all of our starting materials, drug
substance and finished product for use in clinical trials. The active pharmaceutical ingredients, or API, and drug products
have been produced under master service contracts and specific work orders from these manufacturers pursuant to
agreements that include specific supply timelines and volume and quality expectations. We choose the third-party
manufacturers of the drug substance based on the volume required and the regulatory requirements at the relevant stage of
development. All lots of drug substance and drug products used in clinical trials are manufactured under current good
manufacturing practices. Separate third-party manufacturers have been responsible for fill and finish services, and for
labeling and shipment of the final drug product to the clinical trial sites.
SIVEXTRO
In July 2020, we entered into a Sales Promotion and Distribution Agreement, with subsidiaries of Merck pursuant
to which a subsidiary of Merck will sell, and we have agreed to purchase, SIVEXTRO at specified prices. We
31
Table of Contents
will rely on a subsidiary of Merck to supply SIVEXTRO to us, who in turn, relies on third party manufacturers for the
production, packaging, and serialization of SIVEXTRO for our distribution.
XENLETA
We have entered into a long-term commercial supply agreement with SEL Biochem Xinjiang Co., Ltd, or SEL,
and Fountain International Development Holding Limited for the supply of pleuromutilin, which is the key intermediate for
XENLETA API production. Under this agreement, SEL is required to manufacture and supply and we are required to
purchase from SEL a specified percentage of our commercial requirements of pleuromutilin. The initial term of the
agreement expires on August 28, 2022, subject to automatic renewal for successive three-year periods. It will remain in
force until it is terminated by either party with two-year prior written notice, expiring on or at any time after the expiry of a
then-current three-year period renewal term. Either party may terminate the agreement for the other party’s uncured
material breach or upon the occurrence of specified bankruptcy events. The agreement includes customary supply terms,
including product specifications, price, payment terms, requirements forecasting, delivery mechanics and quality
assurance. Under the agreement, we have also negotiated a quality technical agreement pursuant to which SEL will
conduct all quality control and release testing for the pleuromutilin produced under the agreement.
In November 2018 we entered into a long-term commercial supply agreement with Arran Chemical Company
Limited, or Arran, for the supply of the chiral acid starting material required in the synthesis of XENLETA API. Under this
agreement Arran is required to manufacture and supply, and we are required to purchase from Arran the amount forecast
for the first six months of a twelve-month rolling forecast provided monthly by us. The agreement term expires on
November 12, 2023 and continues thereafter unless terminated by either party with not less than twelve months written
notice. Either party may terminate the agreement for the other party’s uncured material breach or upon the occurrence of
insolvency or bankruptcy events. The agreement includes customary supply terms including material specifications, price,
payment terms, demand forecasting, delivery mechanics, and quality assurance.
We have entered into a long-term commercial supply agreement with Hovione Limited, or Hovione, for the supply
of XENLETA API. Under this agreement, Hovione is required to manufacture and supply and we are required to purchase
from Hovione a specified percentage of our commercial requirements of XENLETA API. The agreement includes
customary supply terms, including product specifications, price, payment terms, requirements forecasting, delivery
mechanics and quality assurance. Under the agreement, we have also negotiated a quality technical agreement pursuant to
which Hovione will conduct all quality control and release testing for the pleuromutilin produced under the agreement. On
August 4, 2021, we entered into an amendment to the agreement, under which Hovione agreed to cancel our May 2021
purchase order for XENLETA API, which represented our minimum purchase requirement under the Hovione Supply
Agreement. In addition, pursuant to the First Amendment, Hovione agreed to reduce our annual minimum purchase
requirements for XENLETA API to no minimum purchase requirement in 2021, by 50% from 2022 to 2024 and by 25% in
2025, in consideration for cash payments from us totaling €3.2 million and the right to a low single-digit royalty on total
net sales of XENLETA in the United States for a period commencing on August 4, 2021 and ending on November 22,
2030, or the Royalty Term, which royalty payments shall be no greater than an aggregate of €10.0 million. If the aggregate
amount of royalties payments received by Hovione under the First Amendment is less than an aggregate of €4.0 million,
we are obligated to pay Hovione the difference in a lump sum payment at the end of the Royalty Term. In addition,
pursuant to the First Amendment, Hovione agreed to extend the duration of the Hovione Supply Agreement from
November 22, 2025 to November 22, 2030 with annual minimum purchase requirements for 2026 to 2030 at the newly
agreed annual minimum purchase amount for 2025. Pursuant to the First Amendment, upon the occurrence of certain
events of insolvency for us, any unpaid minimum annual commitment amounts and royalty amounts under the agreement
will become immediately due and payable.
We have also entered into a long-term commercial supply agreement with Patheon UK Limited, or Patheon, for
the supply of IV vials of XENLETA. Under this agreement, Patheon is required to supply and we are required to purchase a
specified percentage of our commercial requirements of IV vials of XENLETA. The initial term of the agreement expires
on December 31, 2023, but it will remain in force until it is terminated by either party upon 24-months prior written notice,
expiring on or at any time after the expiry of the initial term. Either party may also terminate the agreement for the other
party’s uncured material breach or upon the occurrence of specified bankruptcy events. We may also terminate the
agreement if a governmental authority takes action that prevents us from importing,
32
Table of Contents
exporting, purchasing or selling the IV vials of XENLETA. Finally, Patheon may terminate the agreement if we assign any
of our rights under the agreement to an assignee that it does not consider to be a creditworthy substitute or is a competitor
of Patheon. The agreement includes customary supply terms, including product specifications, batch size requirements,
price, payment terms, requirements forecasting, delivery mechanics and quality assurance. Under the agreement, we have
also negotiated a quality agreement pursuant to which Patheon will conduct all quality control testing for the IV vials of
XENLETA. In November 2021, we entered into a side agreement effective January 1, 2021 to the long-term commercial
supply agreement, reducing the annual binding volume requirements for IV vials of XENLETA for the years 2022 to 2025.
The side agreement also provides for a discount on the amount due to Patheon for the minimum annual conversion revenue
commitment for years 2020 and 2021.
In addition, we have entered into a long-term commercial supply agreement with Almac Pharma Services Limited,
or Almac, for the commercial supply of XENLETA tablets. Under this agreement, Almac is required to supply and we are
required to purchase services relating to the manufactured tablets equaling a specified minimum annual spend. The initial
term of the agreement expires on August 7, 2022, but it will remain in force until it is terminated by either party with 24-
months prior written notice, expiring on or at any time after the expiry of the initial term. Either party may also terminate
the agreement for the other party’s uncured material breach or upon the occurrence of specified bankruptcy events. The
agreement includes customary supply terms, including payment terms, requirements forecasting, delivery mechanics and
quality assurance. Under the agreement, we have also negotiated a quality technical agreement pursuant to which Almac
will conduct all quality control testing for the tablets.
In August 2018, we entered into a commercial packaging and supply agreement, or the Packaging Agreement with
Sharp Corporation, or Sharp, for the commercial packaging of XENLETA acetate for oral and intravenous administration.
Under the Packaging Agreement, Sharp has agreed to provide certain packaging services to us, including labeling,
serialization and final packaging of the packaged products. The Packaging Agreement has an initial five-year term ending
December 31, 2023 and will automatically renew after the initial term for additional one-year terms unless either party
gives notice of its intention to terminate the Packaging Agreement at least 90 days prior to the end of the then-current term.
In addition, either party may terminate the Packaging Agreement for the other party’s uncured material breach, in addition
to other specified events, including with respect to bankruptcy proceedings and governmental actions, in each case subject
to notice, cure periods and other conditions set forth in the Packaging Agreement. The Packaging Agreement includes
customary supply terms, including product specifications, batch size requirements, price, payment terms, requirements
forecasting, delivery mechanics and quality assurance. Under the agreement, we have also negotiated a quality agreement
pursuant to which Sharp will conduct quality control testing for the packaged products.
XENLETA is a semi-synthetic organic compound of low molecular weight. The pleuromutilin core of the
molecule is produced by fermentation and is manufactured on a significant scale by various manufacturers. The second part
of the molecule is established from a readily accessible chiral starting material. The development stage production of
XENLETA was carried out at a significant scale and we believe, if required, the synthetic route to XENLETA is amenable
to further scale-up. The synthetic route does not require unusual, or specialized, equipment in the manufacturing process.
Therefore, if any of our current or future drug substance manufacturers were to become unavailable for any reason, we
believe there are a number of potential replacements, although delays may be incurred in identifying and qualifying such
replacements.
CONTEPO
Effective July 28, 2016, Zavante, Laboratorios ERN, S.A., or ERN, and Ercros, S.A., or Ercros entered into an
amended and restated three-way agreement (the “Three-Way Agreement”), which established the basis for related supply
agreements with ERN and Ercros in anticipation of FDA approval of fosfomycin disodium and succinic acid injection for
intravenous use filled, finished and packaged into containers for use by end users, or Product, in the United States.
Pursuant to the Three-Way Agreement, Zavante has the direct responsibility for the manufacture and supply of the
commercial Product in the United States. Under the Three-Way Agreement, (i) ERN has agreed to provide Zavante with
certain technical documentation, or Technical Documentation, and data required for submission of an NDA or Abbreviated
New Drug Application, or ANDA, as applicable, for the Product , and other assistance in connection with the submission
of an NDA or ANDA, pursuant to the ERN Supply Agreement (as defined below); (ii) Ercros has agreed
33
Table of Contents
to provide Zavante with certain Technical Documentation and the manufacture and supply of a blend of fosfomycin
disodium and succinic acid, or API Mixture, for the manufacture of the Product, pursuant to the terms of the Ercros Supply
Agreement (as defined below); and (iii) Zavante has agreed to obtain the commercial supply of the Product, under one or
more separate agreements with third party manufacturers. The rights and obligations of each of the parties are set forth in
each of the ERN Supply Agreement and the Ercros Supply Agreement. In addition, pursuant to the Three-Way Agreement,
Zavante is required to (i) contract with one or more third party manufacturers to provide quantities of the Product required
by Zavante for commercial sale in the United States, perform validation activities as required by the FDA, and obtain FDA
approval of such third party manufacturer’s facilities and quality systems; (ii) use commercially reasonable efforts to file an
NDA within one year of its receipt of all Technical Documentation for the NDA from ERN and Ercros; (iii) obtain and own
all trademarks to be used for the Product in the United States and (iv) bear the cost and manage all clinical trials necessary
for obtaining FDA approval of the Product and keep ERN and Ercros updated regarding the progress of such clinical trials.
The Three-Way-Agreement will continue in force and effect until the Ercros Supply Agreement and the ERN Supply
Agreement have both been terminated or expired in accordance with the respective terms therein, or if the Three-Way
Agreement is terminated upon mutual written agreement of all of the parties. The Three-Way Agreement contains, among
other provisions, customary provisions relating to legal compliance and publicity.
Effective July 28, 2016, Zavante and Ercros entered into a manufacturing and supply agreement (the “Ercros
Supply Agreement”) pursuant to the Three-Way Agreement. Under the Ercros Supply Agreement, Ercros has agreed,
pursuant to purchase orders entered into under the Ercros Supply Agreement, to manufacture (i) the exclusive supply of the
API Mixture for Zavante in support of filing an NDA or an ANDA, as applicable, and (ii) the commercial supply of
fosfomycin disodium and succinic acid injection for intravenous use in the United States. In addition, Ercros has agreed to
provide access to certain technical documentation as may be requested by Zavante in connection with the filing of an NDA.
The Ercros Supply Agreement has an initial ten-year term ending July 28, 2026 and will automatically renew after the
initial term for additional two-year terms unless either party gives notice of its intention to terminate the Ercros Supply
Agreement at least 18 months prior to the end of the then-current term. Either party may terminate the Ercros Supply
Agreement for the other party’s uncured material breach, in addition to other specified events, including with respect to
bankruptcy proceedings, governmental actions and legal proceedings, in each case subject to notice, cure periods and other
conditions set forth in the Ercros Supply Agreement. The Ercros Supply Agreement contains customary supply terms,
including requirements forecasting, purchase orders, product specifications, price, payment terms, delivery mechanics and
quality insurance. In addition, the Ercros Supply Agreement contains, among other provisions, customary representations
and warranties by the parties, a grant by Ercros to Zavante of certain limited license rights to Ercros’ intellectual property
in connection with Zavante’s performance under the Ercros Supply Agreement, certain indemnification rights in favor of
both parties and customary confidentiality provisions. Under the Ercros Supply Agreement, Zavante and Ercros have also
entered into a quality agreement, pursuant to which Ercros will conduct all quality control and release testing for the API
Mixture produced under the Ercros Supply Agreement.
Effective July 28, 2016, Zavante and ERN entered into an amended and restated pharmaceutical manufacturing
and exclusive supply agreement, as amended on December 1, 2016, March 1, 2017, May 1, 2017 and December 20, 2017,
pursuant to the Three-Way Agreement (the ERN Supply Agreement). Under the ERN Supply Agreement, each party is
required to use commercially reasonable efforts to complete certain development activities required for submission of an
NDA or an ANDA for fosfomycin sodium and succinic acid (the bulk formulation of CONTEPO). In addition, ERN has
agreed to provide to Zavante (i) certain technical documentation and data as required by the International Council for
Harmonisation of Technical Requirements for Pharmaceuticals for Human Use’s guidelines and the FDA for submission of
an NDA or an ANDA for the bulk formulation of CONTEPO, and (ii) certain regulatory support in connection with the
bulk formulation of CONTEPO sold or intended for commercial sale and human use. Upon the first commercial sale of the
bulk formulation of CONTEPO, Zavante is obligated to make a one-time cash payment to ERN and subsequent quarterly
payments thereafter based on the number of vials of the bulk formulation of CONTEPO sold during each calendar quarter.
The ERN Supply Agreement has an initial ten-year term ending July 28, 2026 and will automatically renew after the initial
term for additional two-year terms unless either party gives notice of its intention to terminate the ERN Supply Agreement
at least 18 months prior to the end of the then-current term. Either party may terminate the ERN Supply Agreement by
mutual written agreement and for the other party’s uncured material breach, in addition to other specified events, including
with respect to bankruptcy proceedings and governmental actions, in each case subject to notice, cure periods and other
conditions set forth in the ERN Supply Agreement. The ERN
34
Table of Contents
Supply Agreement contains, among other provisions, customary representations and warranties by the parties, a grant to
each party by the other party of certain limited license rights to such other party’s intellectual property in connection with
the parties’ performance of the services under the ERN Supply Agreement, certain indemnification rights in favor of both
parties and customary confidentiality provisions.
On April 25, 2017, Zavante and Fisiopharma, S.r.l., or Fisiopharma, entered into a manufacturing and supply
agreement, as amended on May 8, 2017, or the Fisiopharma Supply Agreement. Under the Fisiopharma Supply
Agreement, Fisiopharma has agreed, pursuant to purchase orders entered into under the Fisiopharma Supply Agreement, to
manufacture and supply fosfomycin disodium for intravenous injection in bulk drug vials, or the Bulk Drug Vials, to
Zavante in support of filing an NDA or an ANDA, as applicable, and a specified percentage of Zavante’s commercial
requirements of Bulk Drug Vials for the United States. The Fisiopharma Supply Agreement has an initial ten-year term
ending April 25, 2027 and will automatically renew after the initial term for additional one-year terms unless Zavante gives
notice of its intention to terminate the Fisiopharma Supply Agreement at least six months prior to the end of the then-
current term. Either party may terminate the Fisiopharma Supply Agreement for the other party’s uncured material breach
or upon the occurrence of specified bankruptcy events, and Zavante may terminate the Fisiopharma Supply Agreement
upon the occurrence of other specified events, including with respect to governmental actions and legal proceedings
instituted against Fisiopharma, in each case subject to notice, cure periods and other conditions set forth in the Fisiopharma
Supply Agreement. The Fisiopharma Supply Agreement contains customary supply terms, including requirements
forecasting, purchase orders, product specifications, price, payment terms, delivery mechanics and quality insurance. In
addition, it contains, among other provisions, customary representations and warranties by the parties, a grant to
Fisiopharma of certain limited license rights of Zavante’s intellectual property in connection with Fisiopharma’s
performance of services under the Fisiopharma Supply Agreement, certain indemnification rights in favor of both parties,
limitations of liability and customary confidentiality provisions. Under the Fisiopharma Supply Agreement, Zavante and
Fisiopharma have also entered into a quality control agreement, pursuant to which Fisiopharma will conduct all quality
control and release testing for the bulk drug vials produced under the Fisiopharma Supply Agreement. Any default under
the quality control agreement constitutes a default under the Ercros Supply Agreement.
On December 26, 2017, Zavante entered into a commercial packaging agreement, or the PCI Packaging
Agreement, with AndersonBrecon Inc., doing business as PCI of Illinois, or PCI for the commercial packaging of
fosfomycin disodium for intravenous injection in bulk drug vials, or the Packaged Product. Under the PCI Packaging
Agreement, PCI had agreed to provide certain packaging services to Zavante, including labeling, serialization and final
packaging of the PCI Packaged Product. The PCI Packaging Agreement has been extended until December 26, 2022.
These five commercial supply agreements relating to CONTEPO are filed as exhibits to this Form 10-K. Other
than these five agreements, we do not have long-term agreements with any other third parties for the manufacture of
commercial supplies of CONTEPO, but we may enter into additional agreements with third-party contract manufacturers
for additional commercial supplies of CONTEPO pending potential regulatory approval.
Competition
The biotechnology and pharmaceutical industries are characterized by rapidly advancing technologies, intense
competition and a strong emphasis on proprietary products. While we believe that our technologies, knowledge, experience
and scientific resources provide us with competitive advantages, we face potential competition from many different
sources, including major pharmaceutical, specialty pharmaceutical and biotechnology companies, academic institutions,
government agencies and private and public research institutions. Our products compete, and any product candidates that
we successfully develop and commercialize will compete with existing therapies and new therapies that may become
available in the future.
Many of our competitors may have significantly greater financial resources and expertise in research and
development, manufacturing, preclinical testing, conducting clinical trials, obtaining regulatory approvals and marketing
approved products than we do. These competitors also compete with us in recruiting and retaining qualified scientific and
management personnel and establishing clinical trial sites and patient registration for clinical trials, as well as in acquiring
technologies complementary to, or necessary for, our programs. Smaller or early stage companies may also
35
Table of Contents
prove to be significant competitors, particularly through collaborative arrangements with large and established companies.
Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize
products that are safer, more effective, have fewer or less severe side effects, are more convenient or are less expensive
than any products that we may develop. Our competitors also may obtain marketing approvals for their products more
rapidly than we obtain approval for ours, which could result in our competitors establishing a strong market position before
we are able to enter the market. In addition, our ability to compete may be affected because in some cases insurers or other
third-party payors seek to encourage the use of generic products. This may have the effect of making branded products less
attractive, from a cost perspective, to buyers. SIVEXTRO and XENLETA are priced at a significant premium over
competitive generic products. This may make it difficult for us to replace existing therapies with SIVEXTRO and
XENLETA.
The key competitive factors affecting the success of SIVEXTRO, XENLETA and CONTEPO are likely to be their
efficacy, safety, convenience, price and the availability of coverage and reimbursement from government and other third-
party payors.
There are a variety of available therapies marketed for the treatment of ABSSSI and CABP. Currently, the
treatment of CABP is dominated by generic products. For hospitalized patients, combination therapy is frequently used.
Many currently approved drugs are well-established therapies and are widely accepted by physicians, patients and third-
party payors. We also are aware of various drugs under development or recently approved by the FDA for the treatment of
ABSSSI and CABP, including omadacycline (Nuzyra approved by the FDA in October 2018 on behalf of Paratek
Pharmaceuticals Inc. for both ABSSSI and CABP), delafloxacin (Baxdela approved by the FDA for ABSSSI in June 2017
and expanded for CABP in October 2019 on behalf of Melinta Therapeutics Inc.), and oral nafithromycin (Phase 2 clinical
development by Wockhardt Ltd. for CABP).
If approved, we expect CONTEPO will face competition from commercially available antibiotics such as
ceftazidime-avibactam, meropenem-vaborbactam, ceftolozane-tazobactam, imipenem-cilastatin-relebactam, cefiderocol,
tigecycline, plazomicin, and from other product candidates currently in development for the treatment of cUTI, including
AP, such as ceftazidime-avibactam (Avycaz), meropenem-vaborbactam (vabomere), plazomicin (Zemdri), ceftolozane-
tazobactam (Zerbaxa), as well as imipenem-cilastatin-relebactam (Recarbrio approved by the FDA in July 2019 on behalf
of Merck & Co., Inc. ), cefiderocol (Fetroja approved by the FDA in November 2019 on behalf of Shionogi Inc.), or drugs
under development such as tebipenem HBr (NDA to FDA for the Treatment of Complicated Urinary Tract Infections
including Pyelonephritis in October 2021– Spero Therapeutics), cefepime-taniborbactam (under Phase 3 clinical
development by Venatorx Pharmaceuticals), cefepime-enmetazobactam (under Phase 3 clinical development by Allecra
Therapeutics), ETX0282-cefpodoxime proxetil (under Phase 1 clinical development by Entasis Therapeutics) tebipenem
(under development by Spero), sulopenem (under development by Iterum Therapeutics), and LYS228 (under development
by Novartis).
Intellectual Property
Our success depends in large part on our ability to obtain and maintain proprietary protection for our approved
product, product candidates, technology and know-how, to operate without infringing the proprietary rights of others and to
prevent others from infringing our proprietary rights. We strive to protect the proprietary technology that we believe is
important to our business by, among other methods, seeking and maintaining patents, where available, that are intended to
cover our approved product, product candidates, compositions and formulations, their methods of use and processes for
their manufacture and any other inventions that are commercially important to the development of our business. We also
rely on trade secrets, know-how, continuing technological innovation and in-licensing opportunities to develop and
maintain our proprietary and competitive position.
As of January 31, 2022, we owned 26 different families of patents and patent applications, including 24 families
directed to the various pleuromutilin derivatives as compositions of matter, processes for their manufacture, and their use in
pharmaceutical compositions and methods of treating disease. The remaining two families are directed to ß lactamase
inhibitors and siderophore cephalosporin conjugates. Our patent portfolio includes 20 issued U.S. patents, 23
36
Table of Contents
granted European patents 10 granted Chinese patents, 11 granted patents in Taiwan, 6 granted patents in Canada, 12
granted patents in Hong Kong and 16 granted Japanese patents, as well as patents in other jurisdictions. We also have
pending patent applications in the United States, Europe, China, Taiwan, Canada, Hong Kong, Japan and other countries
and regions, including Asia, Australia, Eastern Europe, and South America, including notably Brazil, Israel and India
among others.
All of these patents and patent applications are assigned solely to us and were either originally filed by us or
originally filed by Sandoz and subsequently assigned to us.
As of January 31, 2022, XENLETA, was protected by the following six patent families:
● The first patent family includes patents and applications with claims that specifically recite XENLETA
and/or its use in the treatment of microbial infections. This family includes two issued patents in each of the
United States, Europe, China, Hong Kong and Japan and one issued patent in Taiwan and Canada, as well as
issued patents in 16 other jurisdictions and 4 pending patent applications in other jurisdictions, including one
divisional application in the United States. The standard term for patents in this family expires in 2028. A
patent term adjustment of 303 days has already been obtained in the United States for one patent. A patent
term extension for this patent has been filed extending the term to 2033. A patent term extension application
for the second United States patent has also been filed extending the term of this patent to 2032.
Supplementary Patent Certificates, or SPCs, have been filed for the first granted European patent extending
the patent term to 2033. Similarly, a Certificate of Supplementary Protection was filed for the granted patent
in Canada extending the patent term to 2030.
● The second patent family includes patents and applications with claims directed to the processes for the
manufacture of XENLETA, crystalline intermediates useful in the processes, and the resulting crystalline
salts. This family includes 23 granted patents including issued patents in the United States, Europe, China,
Taiwan, Canada, Hong Kong and Japan and 8 pending patent applications in other jurisdictions. The standard
term for patents in this family expires in 2031. A patent term extension application for the United States
patent has been filed extending the term to 2033.
● The third patent family includes patents and applications with claims directed to processes for the synthetic
manufacture of crystalline intermediates useful in the manufacture of XENLETA. This family includes
granted patents in the United States, Europe, China, Taiwan, Hong Kong and Japan and 2 granted patents in
other jurisdictions. The standard term for patents in this family expires in 2031.
● The fourth patent family includes patents and applications with claims directed to pharmaceuticals and
treatments for Helicobacter infection, including pleuromutilins, such as XENLETA. This family includes
issued patents in the United States, Europe and Hong Kong. The standard term for patents in this family
expires in 2023. A patent term adjustment of 921 days has already been obtained for the U.S. patent.
● The fifth patent family is directed to pharmaceutical compositions of XENLETA and covers 11 granted
patents including issued patent in Europe, China, Taiwan, Hong Kong and Japan and 6 pending patent
applications in various other jurisdictions including the United States and Canada. The standard term for
patents in this family expires 2036.
● The sixth patent family is directed to methods for purification of pleuromutilin, key intermediate in the
XENLETA drug substance synthesis, and covers 5 granted patents including an issued patent in the United
States, Europe and 6 pending patent applications in various jurisdictions such as China, Taiwan, Canada,
Hong Kong and Japan. The standard term for patents in this family expires in 2038.
Our second most advanced product candidate, BC-7013, is covered specifically in one patent family with patents
granted in the United States, Europe, and Japan. In other jurisdictions ten patents of this family are granted. The standard
term for patents in this family expires in 2027.
37
Table of Contents
The remaining 17 pleuromutilin patent families are directed to either molecules in the intellectual property
landscape surrounding our approved product and product candidates in development including specific medical use or
molecules which can be potentially further developed by us but have not yet been pursued. All patent applications in these
families have been filed at least in the United States and/or Europe, and most have been filed in other countries. Many of
these patent applications have already resulted in granted patents.
Finally, we own one patent family directed to ß lactamase inhibitor compounds and one patent family directed to
siderophore cephalosporin conjugates. Patent applications in the ß lactamase inhibitors family have been filed and granted
in the United States and Europe. The standard term for patents in this family expires in 2030. The published PCT patent
application for the siderophore cephalosporin conjugates will be nationalized on or before the filing deadline.
Zavante holds two issued United States patents (U.S. 9,345,717 and U.S. 10,086,006) directed to methods for
identifying dosing regimens that decrease the potential for on-therapy drug resistance. Zavante filed patent applications
directed to dosing regimens of Fosfomycin in renally impaired patients. Additionally, Zavante has filed a patent application
based on results from the ZEUS Study that relates to methods for treating patients with resistant bacterial infections and,
specifically, Gram-negative bacterial infections. However, these patents may not ensure exclusivity through the patent
terms and we may not be able to secure any additional patent protection. We plan to rely on regulatory protection afforded
to CONTEPO TM through QIDP designation, data exclusivity, and market exclusivity where available.
The term of individual patents depends upon the legal term for patents in the countries in which they are obtained.
In most countries, including the United States, the patent term is 20 years from the filing date of a non provisional patent
application. In the United States, a patent’s term may, in certain cases, be lengthened by patent term adjustment, which
compensates a patentee for administrative delays by the U.S. Patent and Trademark Office, or the USPTO, in examining
and granting a patent, or may be shortened if a patent is terminally disclaimed over an earlier filed patent. The term of a
U.S. patent that covers a drug, biological product or medical device approved pursuant to a pre market approval, or PMA,
may also be eligible for patent term extension when FDA approval is granted, provided that certain statutory and regulatory
requirements are met. The length of the patent term extension is related to the length of time the drug is under regulatory
review while the patent is in force. The Drug Price Competition and Patent Term Restoration Act of 1984, or the Hatch
Waxman Act, permits a patent term extension of up to five years beyond the expiration date set for the patent. Patent
extension cannot extend the remaining term of a patent beyond a total of 14 years from the date of product approval, only
one patent applicable to each regulatory review period may be granted an extension and only those claims reading on the
approved drug may be extended. Similar provisions are available in Europe, Canada, Taiwan and certain other foreign
jurisdictions to extend the term of a patent that covers an approved drug, provided that statutory and regulatory
requirements are met. Thus, in the future, if and when our product candidates receive approval by the FDA or foreign
regulatory authorities, we expect to apply for additional patent term extensions on issued patents covering those products,
depending upon the length of the clinical trials for each drug and other factors. The expiration dates of our patents and
patent applications referred to above are without regard to potential patent term extension or other market exclusivity that
may be available to us unless otherwise indicated that a patent term extension application has been filed.
In addition to patents, we may rely, in some circumstances, on trade secrets to protect our technology and maintain
our competitive position. However, trade secrets can be difficult to protect. We seek to protect our proprietary technology
and processes, in part, by confidentiality agreements with our employees, corporate and scientific collaborators,
consultants, scientific advisors, contractors and other third parties. 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.
Government Regulation
Government authorities in the United States, at the federal, state and local level, and in other countries and
jurisdictions, including the European Union, extensively regulate, among other things, the research, development, testing,
manufacture, quality control, approval, pricing, reimbursement, packaging, storage, recordkeeping, labeling, advertising,
promotion, distribution, marketing, post-approval monitoring and reporting, and import and export of
38
Table of Contents
pharmaceutical products. The processes for obtaining regulatory approvals in the United States and in foreign countries and
jurisdictions, along with subsequent compliance with applicable statutes and regulations and other regulatory authorities,
require the expenditure of substantial time and financial resources.
Review and Approval of Drugs in the United States
In the United States, the FDA reviews, approves and regulates drugs under the federal Food, Drug, and Cosmetic
Act, or FDCA, and associated implementing regulations. A company, institution, or organization which takes responsibility
for the initiation and management of a clinical development program for such products, and for their regulatory approval, is
typically referred to as a sponsor. The failure to comply with the applicable U.S. requirements at any time during the
product development process, approval process or post-approval may result in delays to the conduct of study, regulatory
review and subject a sponsor to a variety of administrative or judicial sanctions.
A sponsor seeking approval to market and distribute a new drug product in the United States must typically
undertake the following before a product candidate will be approved by the FDA:
● completion of preclinical laboratory tests, animal studies and formulation studies in compliance with the
FDA’s good laboratory practice, or GLP, regulations;
● design of a clinicial protocol and submission to the FDA of an investigational new drug application, or IND,
which must take effect before human clinical trials may begin;
● approval by an independent institutional review board, or IRB, representing each clinical site before each
clinical trial may be initiated;
● performance of adequate and well-controlled human clinical trials in accordance with good clinical practices,
or GCP, to establish the safety and efficacy of the proposed drug product for each indication;
● preparation and submission to the FDA of a new drug application, or NDA, summarizing available data to
support the proposed approval of the new drug product for the proposed use;
● review of the product application by an FDA advisory committee, where appropriate or if applicable and as
may be requested by the FDA;
● satisfactory completion of one or more FDA inspections of the manufacturing facility or facilities at which
the product, or components thereof, are produced to assess compliance with current Good Manufacturing
Practices, or cGMP, requirements and to assure that the facilities, methods and controls are adequate to
preserve the product’s identity, strength, quality and purity;
● satisfactory completion of FDA audits of clinical trial sites to assure compliance with GCPs and the integrity
of the clinical data;
● payment of PDUFA fees and securing FDA approval of the NDA; and
● compliance with any post-approval requirements, including the potential requirement to implement a Risk
Evaluation and Mitigation Strategy, or REMS, where applicable, and the potential to conduct post-approval
studies required by the FDA.
Preclinical Studies
Before a sponsor begins testing a compound with potential therapeutic value in humans, the drug candidate enters
the preclinical testing stage. Preclinical studies include laboratory evaluation of the purity and stability of the manufactured
drug substance or active pharmaceutical ingredient and the formulated drug or drug product, as well as in
39
Table of Contents
vitro and animal studies to assess the safety and activity of the drug for initial testing in humans and to establish a rationale
for therapeutic use. The conduct of preclinical studies is subject to federal regulations and requirements, including GLP
regulations and standards and the United States Department of Agriculture’s Animal Welfare Act, if applicable.The results
of the preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature
and plans for clinical studies, among other things, are submitted to the FDA as part of an IND. Additional long-term
preclinical testing, such as animal tests of reproductive adverse events and carcinogenicity, may continue after the IND is
submitted.
Companies usually must complete some long-term preclinical testing, such as animal tests of long term exposure
and reproductive adverse events, and must also develop additional information about the chemistry and physical
characteristics of the investigational product and finalize a process for manufacturing the product in commercial quantities
in accordance with cGMP requirements. The manufacturing process must be capable of consistently producing quality
batches of the candidate product and, among other things, the manufacturer must develop methods for testing the identity,
strength, quality and purity of the final product. Additionally, appropriate packaging must be selected and tested and
stability studies must be conducted to demonstrate that the candidate product does not undergo unacceptable deterioration
over its shelf life.
The IND and IRB Processes
An IND is an exemption from the FDCA that allows an unapproved drug to be shipped in interstate commerce for
use in an investigational clinical trial and a request for FDA authorization to administer an investigational drug to humans.
Such authorization must be secured prior to interstate shipment and administration of any new drug that is not the subject
of an approved NDA. In support of a request for an IND, sponsors must submit a protocol for each clinical trial and any
subsequent protocol amendments must be submitted to the FDA as part of the IND. In addition, the results of the
preclinical tests, together with manufacturing information, analytical data, any available clinical data or literature and plans
for clinical trials, among other things, are submitted to the FDA as part of an IND. The FDA requires a 30-day waiting
period after the filing of each IND before clinical trials may begin. This waiting period is designed to allow the FDA to
review the IND to determine whether human research subjects will be exposed to unreasonable health risks. At any time
during this 30-day period, the FDA may raise concerns or questions about the conduct of the trials as outlined in the IND
and impose a clinical hold or partial clinical hold. In this case, the IND sponsor and the FDA must resolve any outstanding
concerns before clinical trials can begin.
Following commencement of a clinical trial under an IND, the FDA may also place a clinical hold or partial
clinical hold on that trial. A clinical hold is an order issued by the FDA to the sponsor to delay a proposed clinical
investigation or to suspend an ongoing investigation. A partial clinical hold is a delay or suspension of only part of the
clinical work requested under the IND. For example, a specific protocol or part of a protocol is not allowed to proceed,
while other protocols may do so. No more than 30 days after imposition of a clinical hold or partial clinical hold, the FDA
will provide the sponsor a written explanation of the basis for the hold. Following issuance of a clinical hold or partial
clinical hold, an investigation may only resume after the FDA has notified the sponsor that the investigation may proceed.
The FDA will base that determination on information provided by the sponsor correcting the deficiencies previously cited
or otherwise satisfying the FDA that the investigation can proceed.
A sponsor may choose, but is not required, to conduct a foreign clinical study under an IND. When a foreign
clinical study is conducted under an IND, all FDA IND requirements must be met unless waived. When the foreign clinical
study is not conducted under an IND, the sponsor must ensure that the study complies with FDA regulatory requirements,
including GCP requirements, in order to use the study as support for an IND or application for marketing approval. The
FDA’s regulations are intended to help ensure the protection of human subjects enrolled in non-IND foreign clinical
studies, as well as the quality and integrity of the resulting data. They further help ensure that non-IND foreign studies are
conducted in a manner comparable to that required for IND studies.
In addition to the foregoing IND requirements, an IRB representing each institution participating in the clinical
trial must review and approve the plan for any clinical trial before it commences at that institution, and the IRB must
conduct continuing review and reapprove the study at least annually. The IRB must review and approve, among other
things, the study protocol and informed consent information to be provided to study subjects. An IRB must operate in
40
Table of Contents
compliance with FDA regulations. An IRB can suspend or terminate approval of a clinical trial at its institution, or an
institution it represents, if the clinical trial is not being conducted in accordance with the IRB’s requirements or if the
product candidate has been associated with unexpected serious harm to patients.
Additionally, some trials are overseen by an independent group of qualified experts organized by the trial
applicant, known as a data safety monitoring board or committee, or DSMB. This group provides authorization as to
whether or not a trial may move forward at designated check points based on unblinded safety data from the study to which
only the DSMB has access. Suspension or termination of development during any phase of clinical trials may occur if it is
determined that the participants or patients are being exposed to an unacceptable health risk. Other reasons for suspension
or termination may be made by us based on evolving business objectives and/or competitive climate.
Human Clinical Studies in Support of an NDA
Clinical trials involve the administration of the investigational product to human subjects under the supervision of
qualified investigators in accordance with GCP requirements, which include, among other things, the requirement that all
research subjects provide their informed consent in writing before their participation in any clinical trial. Clinical trials are
conducted under written study protocols detailing, among other things, the inclusion and exclusion criteria, the objectives
of the study, the parameters to be used in monitoring safety and the effectiveness criteria to be evaluated.
Human clinical trials are typically conducted in the following four sequential phases, which may overlap or be
combined:
● Phase 1: The drug is initially introduced into healthy human subjects or, in certain indications such as cancer,
patients with the target disease or condition and tested for safety, dosage tolerance, absorption, metabolism,
distribution, excretion and, if possible, to gain an early indication of its effectiveness and to determine
optimal dosage.
● Phase 2: The drug is administered to a limited patient population to identify possible adverse effects and
safety risks, to preliminarily evaluate the efficacy of the product for specific targeted diseases and to
determine dosage tolerance and optimal dosage.
● Phase 3: The drug is administered to an expanded patient population, generally at geographically dispersed
clinical trial sites, in well-controlled clinical trials to generate enough data to statistically evaluate the
efficacy and safety of the product for approval, to establish the overall risk-benefit profile of the product, and
to provide adequate information for the labeling of the product.
● Phase 4: Post-approval studies, which are conducted following initial approval, are typically conducted to
gain additional experience and data from treatment of patients in the intended therapeutic indication.
A clinical trial may combine the elements of more than one phase and the FDA often requires more than one
Phase 3 trial to support marketing approval of a product candidate. A pivotal trial is a clinical trial that is believed to satisfy
FDA requirements for the evaluation of a product candidate’s safety and efficacy such that it can be used, alone or with
other pivotal or non-pivotal trials, to support regulatory approval. Generally, pivotal trials are Phase 3 trials, but they may
be Phase 2 trials if the design provides a well-controlled and reliable assessment of clinical benefit, particularly in an area
of unmet medical need.
Progress reports detailing the results of the clinical trials must be submitted at least annually to the FDA and more
frequently if serious adverse events occur. In addition, IND safety reports must be submitted to the FDA for any of the
following: serious and unexpected suspected adverse reactions; findings from other studies or animal or in vitro testing that
suggest a significant risk in humans exposed to the drug; and any clinically important increase in the case of a serious
suspected adverse reaction over that listed in the protocol or investigator brochure. Phase 1, Phase 2 and Phase 3 clinical
trials may not be completed successfully within any specified period, or at all. The FDA will typically inspect one or more
clinical sites to assure compliance with GCP and the integrity of the clinical data submitted.
41
Table of Contents
Concurrent with clinical trials, companies often complete additional animal studies and must also develop
additional information about the chemistry and physical characteristics of the drug as well as finalize a process for
manufacturing the product in commercial quantities in accordance with cGMP requirements. The manufacturing process
must be capable of consistently producing quality batches of the drug candidate and, among other things, must develop
methods for testing the identity, strength, quality, purity, and potency of the final drug. Additionally, appropriate packaging
must be selected and tested and stability studies must be conducted to demonstrate that the drug candidate does not undergo
unacceptable deterioration over its shelf life.
Finally, sponsors of clinical trials are required to register and disclose certain clinical trial information on a public
registry (clinicaltrials.gov) maintained by the U.S. National Institutes of Health. In particular, information related to the
product, patient population, phase of investigation, study sites and investigators and other aspects of the clinical trial is
made public as part of the registration of the clinical trial. The failure to submit clinical trial information to
clinicaltrials.gov, as required, is a prohibited act under the FDCA with violations subject to potential civil monetary
penalties of up to $10,000 for each day the violation continues.
Expanded Access to an Investigational Drug for Treatment Use
Expanded access, sometimes called “compassionate use”, is the use of investigational new drug products outside
of clinical trials to treat patients with serious or immediately life-threatening diseases or conditions when there are no
comparable or satisfactory alternative treatment options. The rules and regulations related to expanded access are intended
to improve access to investigational drugs for patients who may benefit from investigational therapies. FDA regulations
allow access to investigational drugs under an IND by the company or the treating physician for treatment purposes on a
case-by-case basis for: individual patients (single-patient IND applications for treatment in emergency settings and non-
emergency settings); intermediate-size patient populations; and larger populations for use of the drug under a treatment
protocol or Treatment IND Application.
When considering an IND application for expanded access to an investigational product with the purpose of
treating a patient or a group of patients, the sponsor and treating physicians or investigators will determine suitability when
all of the following criteria apply: patient(s) have a serious or immediately life-threatening disease or condition, and there
is no comparable or satisfactory alternative therapy to diagnose, monitor, or treat the disease or condition; the potential
patient benefit justifies the potential risks of the treatment and the potential risks are not unreasonable in the context or
condition to be treated; and the expanded use of the investigational drug for the requested treatment will not interfere
initiation, conduct, or completion of clinical investigations that could support marketing approval of the product or
otherwise compromise the potential development of the product.
There is no obligation for a sponsor to make its drug products available for expanded access; however, as required
by the 21st Century Cures Act, or Cures Act, passed in 2016, sponsors are required to make policies for evaluating and
responding to requests for expanded access for patients publicly available upon the earlier of initiation of a Phase 2 or
Phase 3 clinical trial, or 15 days after the investigational drug or biologic receives designation as a breakthrough therapy,
fast track product, or regenerative medicine advanced therapy.
In addition, on May 30, 2018, the Right to Try Act, was signed into law. The law, among other things, provides a
federal framework for certain patients to access certain investigational new drug products that have completed a Phase 1
clinical trial and that are undergoing investigation for FDA approval. Under certain circumstances, eligible patients can
seek treatment without enrolling in clinical trials and without obtaining FDA permission under the FDA expanded access
program. There is no obligation for a drug manufacturer to make its drug products available to eligible patients as a result
of the Right to Try Act, but the manufacturer must develop an internal policy and respond to patient requests according to
that policy.
Special Protocol Assessment Agreements
A Special Protocol Assessment, or SPA, agreement is an agreement between a drug manufacturer and the FDA on
the design and size of studies and clinical trials that can be used for approval of a drug or biological product. The FDA’s
guidance on such agreements states that an agreement may not be changed by the manufacturer or the agency
42
Table of Contents
unless through a written agreement of the two entities or if FDA determines a substantial scientific issue essential to
determining the safety or effectiveness of the drug. The protocols that are eligible for SPA agreements are: animal
carcinogenicity protocols, final product stability protocols and clinical protocols for Phase 3 trials whose data will form the
primary basis for an efficacy claim.
Specifically, under the FDCA, the FDA may meet with sponsors, provided certain conditions are met, for the
purpose of reaching a SPA agreement on the design and size of clinical trials intended to form the primary basis of an
efficacy claim in a marketing application. If a sponsor makes a reasonable written request to meet with the FDA for the
purpose of reaching agreement on the design and size of a clinical trial, then the FDA will meet with the sponsor. If an
agreement is reached, the FDA will reduce the agreement to writing and make it part of the administrative record. An
agreement may not be changed by the sponsor or FDA after the trial begins, except with the written agreement of the
sponsor and FDA, or if the director of the FDA reviewing division determines that “a substantial scientific issue essential
to determining the safety or effectiveness of the drug” was identified after the testing began. If a sponsor and the FDA meet
regarding the design and size of a clinical trial and the parties cannot agree that the trial design is adequate to meet the
goals of the sponsor, the FDA will clearly state the reasons for the disagreement in a letter to the sponsor.
Pediatric Studies
Under the Pediatric Research Equity Act of 2003, or PREA, a marketing application or supplement thereto must
contain data that are adequate to assess the safety and effectiveness of the product for the claimed indications in all relevant
pediatric subpopulations, and to support dosing and administration for each pediatric subpopulation for which the product
is safe and effective. Sponsors must also submit an initial Pediatric Study Plan, or PSP, within 60 days of an end-of-phase 2
meeting or as may be agreed between the sponsor and the FDA. Those plans must contain an outline of the proposed
pediatric study or studies the sponsor plans to conduct, including study objectives and design, any deferral or waiver
requests, and other information required by regulation. The sponsor, the FDA, and the FDA’s internal review committee
must then review the information submitted, consult with each other, and agree upon a final plan. The FDA or the sponsor
may request an amendment to the plan at any time.
The FDA may, on its own initiative or at the request of the sponsor, grant deferrals for submission of some or all
pediatric data until after approval of the product for use in adults, or full or partial waivers from the pediatric data
requirements. A deferral may be granted for several reasons, including a finding that the therapeutic candidate is ready for
approval for use in adults before pediatric trials are complete or that additional safety or effectiveness data needs to be
collected before the pediatric trials begin. The law requires the FDA to send a PREA Non-Compliance letter to sponsors
who have failed to submit their pediatric assessments required under PREA, have failed to seek or obtain a deferral or
deferral extension or have failed to request approval for a required pediatric formulation. Unless otherwise required by
regulation, the pediatric data requirements do not apply to products with orphan designation, although FDA has recently
taken steps to limit what it considers abuse of this statutory exemption. The FDA maintains a list of diseases that are
exempt from PREA requirements due to low prevalence of disease in the pediatric population.
Submission of an NDA to the FDA
Assuming successful completion of required clinical testing and other requirements, the results of the preclinical
and clinical studies, together with detailed information relating to the product’s chemistry, manufacture, controls and
proposed labeling, among other things, are submitted to the FDA as part of an NDA requesting approval to market the drug
product for one or more indications. Under federal law, the submission of most NDAs is subject to an application user fee,
which for federal fiscal year 2022 is $3,117,218 for an application requiring clinical data. The sponsor of an approved
NDA is also subject to an annual program fee, which for fiscal year 2022 is $369,413. Exceptions or waivers for these fees
exist for a small company (fewer than 500 employees, including employees and affiliates) satisfying certain requirements
and products with orphan drug designation for a particular indication are not subject to a fee provided there are no other
intended uses in the NDA.
Following submission of an NDA, the FDA conducts a preliminary review of an NDA within 60 calendar days of
its receipt and must inform the sponsor at that time or before whether the application is sufficiently complete to permit
substantive review. In the event that FDA determines that an application does not satisfy this standard, it will issue a
43
Table of Contents
Refuse to File, or RTF, determination to the sponsor. The FDA may request additional information rather than accept an
NDA for filing and the application may be resubmitted with the additional information. The resubmitted application is also
subject to review before the FDA accepts it for filing.
Once the submission is accepted for filing, the FDA begins an in-depth substantive review. The FDA has agreed
to certain performance goals in the review process of NDAs. Standard review, representing most such applications are
meant to be reviewed within ten months from the date of filing. Priority review applications are meant to be reviewed
within six months of filing. The review process and the Prescription Drug User Fee Act goal date may be extended by the
FDA for three additional months to consider new information or clarification provided by the sponsor to address an
outstanding deficiency identified by the FDA following the original submission.
In connection with its review of an NDA, the FDA typically will inspect the facility or facilities where the product
is or will be manufactured. These pre-approval inspections may cover all facilities associated with an NDA submission,
including drug component manufacturing (such as active pharmaceutical ingredients), finished drug product
manufacturing, and control testing laboratories. The FDA will not approve an application unless it determines that the
manufacturing processes and facilities are in compliance with cGMP requirements and adequate to assure consistent
production of the product within required specifications. Additionally, before approving an NDA, the FDA will typically
inspect one or more clinical sites to assure compliance with GCP and the integrity of the data in support of the application.
In addition, as a condition of approval, the FDA may require the sponsor to develop a REMS. REMS use risk
minimization strategies beyond the professional labeling to ensure that the benefits of the product outweigh the potential
risks. To determine whether a REMS is needed, the FDA will consider the size of the population likely to use the product,
seriousness of the disease, expected benefit of the product, expected duration of treatment, seriousness of known or
potential adverse events, and whether the product is a new molecular entity. REMS can include medication guides,
physician communication plans for healthcare professionals, and elements to assure safe use, or ETASU. ETASU may
include, but are not limited to, special training or certification for prescribing or dispensing, dispensing only under certain
circumstances, special monitoring, and the use of patient registries. The FDA may require a REMS before approval or
post-approval if it becomes aware of a serious risk associated with use of the product. The requirement for a REMS can
materially affect the potential market and profitability of a product.
The FDA may refer an application for a novel drug to an advisory committee or explain why such referral was not
made. Typically, an advisory committee is a panel of independent experts, including clinicians and other scientific experts,
that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what
conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such
recommendations carefully when making decisions relating to approval of a new drug product.
Expedited Review Programs
The FDA is authorized to expedite the review of NDAs in several ways. Under the Fast Track program, the
sponsor of a product candidate may request the FDA to designate the product for a specific indication as a Fast Track
product concurrent with or after the filing of the IND. Candidate products are eligible for Fast Track designation if they are
intended to treat a serious or life-threatening condition and demonstrate the potential to address unmet medical needs for
the condition. Fast Track designation applies to the combination of the product candidate and the specific indication for
which it is being studied. In addition to other benefits, such as the ability to have greater interactions with the FDA, the
FDA may initiate review of sections of a Fast Track application before the application is complete, a process known as
rolling review.
Any product candidate submitted to the FDA for marketing, including under a Fast Track program, may be
eligible for other types of FDA programs intended to expedite development and review, such as breakthrough therapy
designation, priority review and accelerated approval.
● Breakthrough therapy designation. To qualify for the breakthrough therapy program, product candidates
must be intended to treat a serious or life-threatening disease or condition and preliminary clinical evidence
44
Table of Contents
must indicate that such product candidates may demonstrate substantial improvement on one or more
clinically significant endpoints over existing therapies. The FDA will seek to ensure the sponsor of a
breakthrough therapy product candidate receives intensive guidance on an efficient drug development
program, intensive involvement of senior managers and experienced staff on a proactive, collaborative and
cross-disciplinary review and rolling review.
● Priority review. A product candidate is eligible for priority review if it treats a serious condition and, if
approved, it would be a significant improvement in the safety or effectiveness of the treatment, diagnosis or
prevention compared to marketed products. FDA aims to complete its review of priority review applications
within six months as opposed to 10 months for standard review.
● Accelerated approval. Drug or biologic products studied for their safety and effectiveness in treating serious
or life-threatening illnesses and that provide meaningful therapeutic benefit over existing treatments may
receive accelerated approval. Accelerated approval means that a product candidate may be approved on the
basis of adequate and well controlled clinical trials establishing that the product candidate has an effect on a
surrogate endpoint that is reasonably likely to predict a clinical benefit, or on the basis of an effect on a
clinical endpoint other than survival or irreversible morbidity or mortality or other clinical benefit, taking
into account the severity, rarity and prevalence of the condition and the availability or lack of alternative
treatments. As a condition of approval, the FDA may require that a sponsor of a drug or biologic product
candidate receiving accelerated approval perform adequate and well controlled post-marketing clinical trials.
In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional
materials.
● Regenerative advanced therapy. With passage of the 21st Century Cures Act, or the Cures Act, in December
2016, Congress authorized the FDA to accelerate review and approval of products designated as regenerative
advanced therapies. A product is eligible for this designation if it is a regenerative medicine therapy that is
intended to treat, modify, reverse or cure a serious or life-threatening disease or condition and preliminary
clinical evidence indicates that the product candidate has the potential to address unmet medical needs for
such disease or condition. The benefits of a regenerative advanced therapy designation include early
interactions with the FDA to expedite development and review, benefits available to breakthrough therapies,
potential eligibility for priority review and accelerated approval based on surrogate or intermediate
endpoints.
None of these expedited programs change the standards for approval but they may help expedite the development
or approval process of product candidates.
Limited Population Antibacterial Drug Pathway
With passage of the CURES Act, Congress authorized FDA to approve an antibacterial or antifungal drug, alone
or in combination with one or more other drugs, as a “limited population drug”. To qualify for this approval pathway, the
drug must be intended to treat a serious or life-threatening infection in a limited population of patients with unmet needs;
the standards for approval of drugs and biologics under the FDCA and PHSA must be satisfied; and FDA must receive a
written request from the sponsor to approve the drug as a limited population drug pursuant to this provision. The FDA’s
determination of safety and effectiveness for such a product must reflect the benefit-risk profile of such drug in the
intended limited population, taking into account the severity, rarity, or prevalence of the infection the drug is intended to
treat and the availability or lack of alternative treatment in such a limited population.
Any drug or biologic approved under this pathway must be labeled with the statement “Limited Population” in a
prominent manner and adjacent to the proprietary name of the drug or biological product. The prescribing information must
also state that the drug is indicated for use in a limited and specific population of patients and copies of all promotional
materials relating to the drug must be submitted to FDA at least 30 days prior to dissemination of the materials. If FDA
subsequently approves the drug for a broader indication, the agency may remove any post-marketing conditions, including
requirements with respect to labeling and review of promotional materials applicable to the
45
Table of Contents
product. Nothing in this pathway to approval of a limited population drug prevents sponsors of such products from seeking
designation or approval under other provisions of the FDCA, such as accelerated approval.
The FDA’s Decision on an NDA
The FDA reviews an application to determine, among other things, whether the product is safe and whether it is
effective for its intended use(s), with the latter determination being made on the basis of substantial evidence. The FDA has
interpreted this evidentiary standard to require at least two adequate and well-controlled clinical investigations to establish
effectiveness of a new product. Under certain circumstances, however, the FDA has indicated that a single trial with certain
characteristics and additional information may satisfy this standard. Ultimately, the FDA will determine whether the
expected benefits of the drug product outweigh its potential risks to patients.
On the basis of the FDA’s evaluation of the NDA and accompanying information, including the results of the
inspection of the manufacturing facilities, the FDA may issue a complete response letter, or CRL, or an approval letter. A
CRL generally outlines the deficiencies in the submission and may require additional, sometimes substantial, testing or
information in order for the FDA to reconsider the application. If and when those deficiencies have been addressed to the
FDA’s satisfaction in a resubmission of the NDA, the FDA will issue an approval letter. The FDA has committed to
reviewing such resubmissions in two or six months depending on the type of information included. Even with submission
of this additional information, the FDA ultimately may decide that the application does not satisfy the regulatory criteria
for approval.
An approval letter, on the other hand, authorizes commercial marketing of the product with specific prescribing
information for specific indications. The FDA approves a new product, it may limit the approved indications for use for the
product, require that contraindications, warnings or precautions be included in the product labeling, require that post-
approval studies, including Phase 4 clinical trials, be conducted to further assess the drug’s safety after approval, require
testing and surveillance programs to monitor the product after commercialization, or impose other conditions, including
distribution restrictions or other risk management mechanisms, including REMS, which can materially affect the potential
market and profitability of the product. The FDA may prevent or limit further marketing of a product based on the results
of post-market studies or surveillance programs. After approval, many types of changes to the approved product, such as
adding new indications, manufacturing changes and additional labeling claims, are subject to further testing requirements
and FDA review and approval.
Post-Approval Regulation
Drugs manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation
by the FDA, including, among other things, requirements relating to recordkeeping, periodic reporting, product sampling
and distribution, advertising and promotion and reporting of adverse experiences with the product. After approval, most
changes to the approved product, such as adding new indications or other labeling claims, are subject to prior FDA review
and approval. There also are continuing, annual user fee requirements for any marketed products and the establishments at
which such products are manufactured, as well as new application fees for supplemental applications with or without
clinical data.
In addition, drug manufacturers and other entities involved in the manufacture and distribution of approved drugs
are required to register their establishments with the FDA and state agencies, and are subject to periodic unannounced
inspections by the FDA and these state agencies for compliance with cGMP requirements. Changes to the manufacturing
process are strictly regulated and often require prior FDA approval before being implemented. FDA regulations also
require investigation and correction of any deviations from cGMP and impose reporting and documentation requirements
upon the sponsor and any third-party manufacturers that the sponsor may decide to use. Accordingly, manufacturers must
continue to expend time, money and effort in the area of production and quality control to maintain cGMP compliance.
Once an approval is granted, the FDA may withdraw the approval if compliance with regulatory requirements and
standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously
unknown problems with a product, including adverse events of unanticipated severity or frequency, or with
46
Table of Contents
manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved
labeling to add new safety information; imposition of post-market studies or clinical trials to assess new safety risks; or
imposition of distribution or other restrictions under a REMS program. Other potential consequences include, among other
things:
● restrictions on the marketing or manufacturing of the product, suspension of the approval, or complete
withdrawal of the product from the market or product recalls;
● fines, warning letters or holds on post-approval clinical trials;
● refusal of the FDA to approve pending NDAs or supplements to approved NDAs, or suspension or
revocation of product license approvals;
● product seizure or detention, or refusal to permit the import or export of products; or
● injunctions or the imposition of civil or criminal penalties.
The FDA strictly regulates the marketing, labeling, advertising and promotion of prescription drug products
placed on the market. This regulation includes, among other things, standards and regulations for direct-to-consumer
advertising, communications regarding unapproved uses, industry-sponsored scientific and educational activities, and
promotional activities involving the Internet and social media. Promotional claims about a drug’s safety or effectiveness are
prohibited before the drug is approved. After approval, a drug product generally may not be promoted for uses that are not
approved by the FDA, as reflected in the product’s prescribing information. In the United States, health care professionals
are generally permitted to prescribe drugs for such uses not described in the drug’s labeling, known as off-label uses,
because the FDA does not regulate the practice of medicine. However, FDA regulations impose rigorous restrictions on
manufacturers’ communications and prohibit the promotion of off-label uses. It may be permissible, under very specific,
narrow conditions, for a manufacturer to engage in non-promotional, non-misleading communication regarding off-label
information, such as distributing scientific or medical journal information. In September 2021, the FDA published final
regulations which describe the types of evidence that the agency will consider in determining the intended use of a drug
product.
If a company is found to have promoted off-label uses, it may become subject to adverse public relations and
administrative and judicial enforcement by the FDA, the Department of Justice, or the Office of the Inspector General of
the Department of Health and Human Services, as well as state authorities. This could subject a company to a range of
penalties that could have a significant commercial impact, including civil and criminal fines and agreements that materially
restrict the manner in which a company promotes or distributes drug products. The federal government has levied large
civil and criminal fines against companies for alleged improper promotion, and has also requested that companies enter
into consent decrees or permanent injunctions under which specified promotional conduct is changed or curtailed.
In addition, the distribution of prescription pharmaceutical products is subject to the Prescription Drug Marketing
Act, or PDMA, and its implementing regulations, as well as the Drug Supply Chain Security Act, or DSCA, which regulate
the distribution and tracing of prescription drug samples at the federal level, and set minimum standards for the regulation
of drug distributors by the states. The PDMA, its implementing regulations and state laws limit the distribution of
prescription pharmaceutical product samples and the DSCA imposes requirements to ensure accountability in distribution
and to identify and remove counterfeit and other illegitimate products from the market.
Section 505(b)(2) NDAs
NDAs for most new drug products are based on two full clinical studies which must contain substantial evidence
of the safety and efficacy of the proposed new product for the proposed use. These applications are submitted under
Section 505(b)(1) of the FDCA. The FDA is, however, authorized to approve an alternative type of NDA under
Section 505(b)(2) of the FDCA. This type of application allows the sponsor to rely, in part, on the FDA’s previous findings
of safety and efficacy for a similar product, or published literature. Specifically, Section 505(b)(2) applies to
47
Table of Contents
NDAs for a drug for which the investigations made to show whether or not the drug is safe for use and effective in use and
relied upon by the sponsor for approval of the application “were not conducted by or for the sponsor and for which the
sponsor has not obtained a right of reference or use from the person by or for whom the investigations were conducted”.
Thus, Section 505(b)(2) authorizes the FDA to approve an NDA based on safety and effectiveness data that were
not developed by the applicant. NDAs filed under Section 505(b)(2) may provide an alternate and potentially more
expeditious pathway to FDA approval for new or improved formulations or new uses of previously approved products. If
the Section 505(b)(2) applicant can establish that reliance on the FDA’s previous approval is scientifically appropriate, the
applicant may eliminate the need to conduct certain preclinical or clinical studies of the new product. The FDA may also
require companies to perform additional studies or measurements to support the change from the approved product. The
FDA may then approve the new drug candidate for all or some of the label indications for which the referenced product has
been approved, as well as for any new indication sought by the Section 505(b)(2) applicant.
Abbreviated New Drug Applications for Generic Drugs
In 1984, with passage of the Hatch-Waxman Amendments to the FDCA, Congress authorized the FDA to approve
generic drugs that are the same as drugs previously approved by the FDA under the NDA provisions of the statute. To
obtain approval of a generic drug, a sponsor must submit an abbreviated new drug application, or ANDA, to the agency. In
support of such applications, a generic manufacturer may rely on the preclinical and clinical testing previously conducted
for a drug product previously approved under an NDA, known as the reference listed drug, or RLD.
Specifically, in order for an ANDA to be approved, the FDA must find that the generic version is identical to the
RLD with respect to the active ingredients, the route of administration, the dosage form, and the strength of the drug. At
the same time, the FDA must also determine that the generic drug is “bioequivalent” to the innovator drug. Under the
statute, a generic drug is bioequivalent to a RLD if “the rate and extent of absorption of the drug do not show a significant
difference from the rate and extent of absorption of the listed drug”.
Upon approval of an ANDA, the FDA indicates whether the generic product is “therapeutically equivalent” to the
RLD in its publication “Approved Drug Products with Therapeutic Equivalence Evaluations”, also referred to as the
“Orange Book”. Physicians and pharmacists consider a therapeutic equivalent generic drug to be fully substitutable for the
RLD. In addition, by operation of certain state laws and numerous health insurance programs, the FDA’s designation of
therapeutic equivalence often results in substitution of the generic drug without the knowledge or consent of either the
prescribing physician or patient.
Under the Hatch-Waxman Amendments, the FDA may not approve an ANDA until any applicable period of non-
patent exclusivity for the RLD has expired. The FDCA provides a period of five years of non-patent data exclusivity for a
new drug containing a new chemical entity. For the purposes of this provision, a new chemical entity, or NCE, is a drug
that contains no active moiety that has previously been approved by the FDA in any other NDA. This interpretation of the
FDCA by the FDA was confirmed with enactment of the Ensuring Innovation Act in April 2021. An active moiety is the
molecule or ion responsible for the physiological or pharmacological action of the drug substance. In cases where such
exclusivity has been granted, an ANDA may not be filed with the FDA until the expiration of five years unless the
submission is accompanied by a Paragraph IV certification, in which case the applicant may submit its application four
years following the original product approval.
The FDCA also provides for a period of three years of exclusivity if the NDA includes reports of one or more new
clinical investigations, other than bioavailability or bioequivalence studies, that were conducted by or for the applicant and
are essential to the approval of the application. This three-year exclusivity period often protects changes to a previously
approved drug product, such as a new dosage form, route of administration, combination or indication. Three-year
exclusivity would be available for a drug product that contains a previously approved active moiety, provided the statutory
requirement for a new clinical investigation is satisfied. Unlike five-year NCE exclusivity, an award of three-year
exclusivity does not block the FDA from accepting ANDAs seeking approval for generic versions of the drug
48
Table of Contents
as of the date of approval of the original drug product. The FDA typically makes decisions about awards of data exclusivity
shortly before a product is approved.
Hatch-Waxman Patent Certification and the 30-Month Stay
Upon approval of an NDA or a supplement thereto, NDA sponsors are required to list with the FDA each patent
with claims that cover the applicant’s product or an approved method of using the product. Each of the patents listed by the
NDA sponsor is published in the Orange Book. The FDA’s regulations governing patient listings were largely codified into
law with enactment of the Orange Book Modernization Act in January 2021. When an ANDA applicant files its application
with the FDA, the applicant is required to certify to the FDA concerning any patents listed for the reference product in the
Orange Book, except for patents covering methods of use for which the ANDA applicant is not seeking approval. To the
extent that the Section 505(b)(2) applicant is relying on studies conducted for an already approved product, the applicant is
required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to the same
extent that an ANDA applicant would.
Specifically, the applicant must certify with respect to each patent that:
● the required patent information has not been filed;
● the listed patent has expired;
● the listed patent has not expired, but will expire on a particular date and approval is sought after patent
expiration; or
● the listed patent is invalid, unenforceable or will not be infringed by the new product.
A certification that the new product will not infringe the already approved product’s listed patents or that such
patents are invalid or unenforceable is called a Paragraph IV certification. If the applicant does not challenge the listed
patents or indicates that it is not seeking approval of a patented method of use, the ANDA application will not be approved
until all the listed patents claiming the referenced product have expired (other than method of use patents involving
indications for which the ANDA applicant is not seeking approval).
If the ANDA applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice
of the Paragraph IV certification to the NDA and patent holders once the ANDA has been accepted for filing by the FDA.
The NDA and patent holders may then initiate a patent infringement lawsuit in response to the notice of the Paragraph IV
certification. The filing of a patent infringement lawsuit within 45 days after the receipt of a Paragraph IV certification
automatically prevents the FDA from approving the ANDA until the earlier of 30 months after the receipt of the
Paragraph IV notice, expiration of the patent, or a decision in the infringement case that is favorable to the ANDA
applicant.
To the extent that the Section 505(b)(2) applicant is relying on studies conducted for an already approved product,
the applicant is required to certify to the FDA concerning any patents listed for the approved product in the Orange Book to
the same extent that an ANDA applicant would. As a result, approval of a Section 505(b)(2) NDA can be stalled until all
the listed patents claiming the referenced product have expired, until any non-patent exclusivity, such as exclusivity for
obtaining approval of a new chemical entity, listed in the Orange Book for the referenced product has expired, and, in the
case of a Paragraph IV certification and subsequent patent infringement suit, until the earlier of 30 months, settlement of
the lawsuit or a decision in the infringement case that is favorable to the Section 505(b)(2) applicant.
Pediatric Exclusivity
Pediatric exclusivity is a type of non-patent marketing exclusivity in the United States and, if granted, provides for
the attachment of an additional six months of regulatory exclusivity to the term of any existing patent or non-patent
49
Table of Contents
regulatory exclusivity, including orphan exclusivity, for a drug product. This six-month exclusivity may be granted if an
NDA sponsor submits pediatric data that fairly respond to a written request from the FDA for such data. The data does not
need to show the product to be effective in the pediatric population studied; rather, if the clinical trial is deemed to fairly
respond to the FDA’s request, the additional protection is granted. If reports of requested pediatric studies are submitted to
and accepted by the FDA within the statutory time limits, whatever statutory or regulatory periods of exclusivity or patent
protection cover the product are extended by six months. This is not a patent term extension, but it effectively extends the
regulatory period during which the FDA cannot approve another application.
GAIN Exclusivity for Antibiotics
In 2012, Congress passed legislation known as the Generating Antibiotic Incentives Now Act, or GAIN Act. This
legislation is designed to encourage the development of antibacterial and antifungal drug products that treat pathogens that
cause serious and life-threatening infections. To that end, the law grants an additional five years of exclusivity upon the
approval of an NDA for a drug product designated by FDA as a QIDP. Thus, for a QIDP, the periods of five-year new
chemical entity exclusivity, three-year new clinical investigation exclusivity, and seven-year orphan drug exclusivity,
would become ten years, eight years, and twelve years, respectively.
A QIDP is defined in the GAIN Act to mean “an antibacterial or antifungal drug for human use intended to treat
serious or life-threatening infections, including those caused by (1) an antibacterial or antifungal resistant pathogen,
including novel or emerging infectious pathogens” or (2) certain “qualifying pathogens”. A “qualifying pathogen” is a
pathogen that has the potential to pose a serious threat to public health (such as resistant Gram-positive pathogens, multi-
drug resistant Gram-negative bacteria, multi-drug resistant tuberculosis, and Clostridium difficile) and that is included in a
list established and maintained by FDA. A drug sponsor may request the FDA to designate its product as a QIDP any time
before the submission of an NDA. The FDA must make a QIDP determination within 60 days of the designation request. A
product designated as a QIDP will be granted priority review by the FDA and can qualify for “fast track” status.
The additional five years of exclusivity under the GAIN Act for drug products designated by the FDA as QIDPs
applies only to a drug that is first approved on or after July 9, 2012. Additionally, the five year exclusivity extension does
not apply to: a supplement to an application under FDCA Section 505(b) for any QIDP for which an extension is in effect
or has expired; a subsequent application filed with respect to a product approved by the FDA for a change that results in a
new indication, route of administration, dosing schedule, dosage form, delivery system, delivery device or strength; or a
product that does not meet the definition of a QIDP under Section 505(g) based upon its approved uses. The FDA has
designated IV fosfomycin, and each of the IV and oral formulations of XENLETA as a QIDP and also granted fast track
designations.
Patent Term Restoration and Extension
A patent claiming a new drug product may be eligible for a limited patent term extension under the Hatch-
Waxman Act, which permits a patent restoration of up to five years for patent term lost during product development and the
FDA regulatory review. The restoration period granted on a patent covering a product is typically one-half the time
between the effective date of the IND and the submission date of an application, plus the time between the submission date
of an application and the ultimate approval date. Patent term restoration cannot be used to extend the remaining term of a
patent past a total of 14 years from the product’s approval date. Only one patent applicable to an approved drug product is
eligible for the extension, and the application for the extension must be submitted prior to the expiration of the patent in
question. A patent that covers multiple products for which approval is sought can only be extended in connection with one
of the approvals. The United States Patent and Trademark Offices reviews and approves the application for any patent term
extension or restoration in consultation with the FDA.
Regulation Outside the United States
In order to market any product outside of the United States, a company must also comply with numerous and
varying regulatory requirements of other countries and jurisdictions regarding quality, safety and efficacy and governing,
among other things, clinical trials, marketing authorization, commercial sales and distribution of drug products.
50
Table of Contents
Although FDA approval for XENLETA has been obtained, we are required to obtain the necessary approvals by the
comparable foreign regulatory authorities before we can commence clinical trials or marketing of the product in those
countries or jurisdictions. The approval process ultimately varies between countries and jurisdictions and can involve
additional product testing and additional administrative review periods. The time required to obtain approval in other
countries and jurisdictions might differ from and be longer than that required to obtain FDA approval. Regulatory approval
in one country or jurisdiction does not ensure regulatory approval in another, but a failure or delay in obtaining regulatory
approval in one country or jurisdiction may negatively impact the regulatory process in others.
Regulation and Marketing Authorization in the European Union
The process governing approval of medicinal products in the European Union follows essentially the same lines as
in the United States and, likewise, generally involves satisfactorily completing each of the following:
● preclinical laboratory tests, animal studies and formulation studies all performed in accordance with the
applicable E.U. Good Laboratory Practice regulations;
● submission to the relevant national authorities of a clinical trial application, or CTA, which must be approved
before human clinical trials may begin;
● performance of adequate and well-controlled clinical trials to establish the safety and efficacy of the product
for each proposed indication;
● submission to the relevant competent authorities of a marketing authorization application, or MAA, which
includes the data supporting safety and efficacy as well as detailed information on the manufacture and
composition of the product in clinical development and proposed labelling;
● satisfactory completion of an inspection by the relevant national authorities of the manufacturing facility or
facilities, including those of third parties, at which the product is produced to assess compliance with strictly
enforced cGMP;
● potential audits of the non-clinical and clinical trial sites that generated the data in support of the MAA; and
● review and approval by the relevant competent authority of the MAA before any commercial marketing, sale
or shipment of the product.
Preclinical Studies
Preclinical tests include laboratory evaluations of product chemistry, formulation and stability, as well as studies
to evaluate toxicity in animal studies, in order to assess the potential safety and efficacy of the product. The conduct of the
preclinical tests and formulation of the compounds for testing must comply with the relevant E.U. regulations and
requirements. The results of the preclinical tests, together with relevant manufacturing information and analytical data, are
submitted as part of the CTA.
Clinical Trial Approval
Requirements for the conduct of clinical trials in the European Union including Good Clinical Practice, or GCP,
are set forth in the Clinical Trials Directive 2001/20/EC and the GCP Directive 2005/28/EC. Pursuant to
Directive 2001/20/EC and Directive 2005/28/EC, as amended, a system for the approval of clinical trials in the European
Union has been implemented through national legislation of the E.U. member states. Under this system, approval must be
obtained from the competent national authority of each E.U. member state in which a study is planned to be conducted. To
this end, a CTA is submitted, which must be supported by an investigational medicinal product dossier, or IMPD, and
further supporting information prescribed by Directive 2001/20/EC and Directive 2005/28/EC and other
51
Table of Contents
applicable guidance documents. Furthermore, a clinical trial may only be started after a competent ethics committee has
issued a favorable opinion on the clinical trial application in that country. On January 31, 2022, the new Clinical Trials
Regulation (EU) No 536/2014 cecomes applicable.
The new Clinical Trials Regulation aims to simplify and streamline the approval of clinical trial in the European
Union. The main characteristics of the regulation include:
● a streamlined application procedure via a single entry point, the E.U. portal;
● a single set of documents to be prepared and submitted for the application as well as simplified reporting
procedures that will spare sponsors from submitting broadly identical information separately to various
bodies and different member states;
● a harmonized procedure for the assessment of applications for clinical trials, which is divided in two parts.
Part I is assessed jointly by all member states concerned. Part II is assessed separately by each member state
concerned;
● strictly defined deadlines for the assessment of clinical trial applications; and
● the involvement of the ethics committees in the assessment procedure in accordance with the national law of
the member state concerned but within the overall timelines defined by the Clinical Trials Regulation.
The new regulation did not change the preexisting requirement that a sponsor must obtain prior approval from the
competent national authority of the EU Member State in which the clinical trial is to be conducted. If the clinical trial is
conducted in different EU Member States, the competent authorities in each of these EU Member States must provide their
approval for the conduct of the clinical trial. Furthermore, the sponsor may only start a clinical trial at a specific study site
after the applicable ethics committee has issued a favorable opinion.
As in the United States, similar requirements for posting clinical trial information are present in the European
Union (EudraCT) website: https://eudract.ema.europa.eu/ and other countries.
Marketing Authorization
Authorization to market a product in the member states of the European Union proceeds under one of four
procedures: a centralized authorization procedure, a mutual recognition procedure, a decentralized procedure or a national
procedure.
Centralized Authorization Procedure
The centralized procedure enables sponsors to obtain a marketing authorization that is valid in all E.U. member
states based on a single application. Certain medicinal products, including products developed by means of
biotechnological processes must undergo the centralized authorization procedure for marketing authorization, which, if
granted by the European Commission, is automatically valid in all 28 E.U. member states. The EMA and the European
Commission administer this centralized authorization procedure pursuant to Regulation (EC) No 726/2004.
Pursuant to Regulation (EC) No 726/2004, this procedure is mandatory for:
● medicinal products developed by means of one of the following biotechnological processes:
● recombinant DNA technology;
● controlled expression of genes coding for biologically active proteins in prokaryotes and eukaryotes
including transformed mammalian cells; and
52
Table of Contents
● hybridoma and monoclonal antibody methods;
● advanced therapy medicinal products as defined in Article 2 of Regulation (EC) No 1394/2007 on advanced
therapy medicinal products;
● medicinal products for human use containing a new active substance that, on the date of effectiveness of this
regulation, was not authorized in the European Union, and for which the therapeutic indication is the
treatment of any of the following diseases:
● acquired immune deficiency syndrome;
● cancer;
● neurodegenerative disorder;
● diabetes;
● auto-immune diseases and other immune dysfunctions; and
● viral diseases; and
● medicinal products that are designated as orphan medicinal products pursuant to Regulation (EC)
No 141/2000.
The centralized authorization procedure is optional for other medicinal products if they contain a new active
substance or if the sponsor shows that the medicinal product concerned constitutes a significant therapeutic, scientific or
technical innovation or that the granting of authorization is in the interest of patients in the European Union.
Administrative Procedure
Under the centralized authorization procedure, the EMA’s Committee for Medicinal Products for Human Use, or
CHMP serves as the scientific committee that renders opinions about the safety, efficacy and quality of medicinal products
for human use on behalf of the EMA. The CHMP is composed of experts nominated by each member state’s national
authority for medicinal products, with one of them appointed to act as Rapporteur for the co-ordination of the evaluation
with the possible assistance of a further member of the Committee acting as a Co-Rapporteur. After approval, the
Rapporteur(s) continue to monitor the product throughout its life cycle. The CHMP has 210 days, to adopt an opinion as to
whether a marketing authorization should be granted. The process usually takes longer in case additional information is
requested, which triggers clock-stops in the procedural timelines. The process is complex and involves extensive
consultation with the regulatory authorities of member states and a number of experts. When an application is submitted
for a marketing authorization in respect of a drug that is of major interest from the point of view of public health and in
particular from the viewpoint of therapeutic innovation, the sponsor may pursuant to Article 14(9) Regulation (EC)
No 726/2004 request an accelerated assessment procedure. If the CHMP accepts such request, the time-limit of 210 days
will be reduced to 150 days but it is possible that the CHMP can revert to the standard time-limit for the centralized
procedure if it considers that it is no longer appropriate to conduct an accelerated assessment. Once the procedure is
completed, a European Public Assessment Report, or EPAR, is produced. If the opinion is negative, information is given as
to the grounds on which this conclusion was reached. After the adoption of the CHMP opinion, a decision on the MAA
must be adopted by the European Commission, after consulting the E.U. member states, which in total can take more than
60 days.
Conditional Approval
In specific circumstances, E.U. legislation (Regulation (EC) No 726/2004 and Regulation (EC) No 507/2006 on
Conditional Marketing Authorizations for Medicinal Products for Human Use) enables sponsors to obtain a conditional
53
Table of Contents
marketing authorization prior to obtaining the comprehensive clinical data required for an application for a full marketing
authorization. Such conditional approvals may be granted for product candidates (including medicines designated as
orphan medicinal products), if (1) the risk-benefit balance of the product candidate is positive, (2) it is likely that the
sponsor will be in a position to provide the required comprehensive clinical trial data, (3) the product fulfills unmet medical
needs and (4) the benefit to public health of the immediate availability on the market of the medicinal product concerned
outweighs the risk inherent in the fact that additional data are still required. A conditional marketing authorization may
contain specific obligations to be fulfilled by the marketing authorization holder, including obligations with respect to the
completion of ongoing or new studies, and with respect to the collection of pharmacovigilance data. Conditional marketing
authorizations are valid for one year, and may be renewed annually, if the risk-benefit balance remains positive, and after
an assessment of the need for additional or modified conditions and/or specific obligations. The timelines for the
centralized procedure described above also apply with respect to the review by the CHMP of applications for a conditional
marketing authorization.
Marketing Authorization Under Exceptional Circumstances
Under Regulation (EC) No 726/2004, products for which the sponsor can demonstrate that comprehensive data (in
line with the requirements laid down in Annex I of Directive 2001/83/EC, as amended) cannot be provided (due to specific
reasons foreseen in the legislation) might be eligible for marketing authorization under exceptional circumstances. This
type of authorization is reviewed annually to reassess the risk-benefit balance. The fulfillment of any specific
procedures/obligations imposed as part of the marketing authorization under exceptional circumstances is aimed at the
provision of information on the safe and effective use of the product and will normally not lead to the completion of a full
dossier/approval.
Market Authorizations Granted by Authorities of E.U. Member States
In general, if the centralized procedure is not followed, there are three alternative procedures to obtain a marketing
authorization in (one or several) E.U. member states as prescribed in Directive 2001/83/EC:
● The decentralized procedure allows sponsors to file identical applications to several E.U. member states and
receive simultaneous national approvals based on the recognition by E.U. member states of an assessment by
a reference member state.
● The national procedure is only available for products intended to be authorized in a single E.U. member state.
● A mutual recognition procedure similar to the decentralized procedure is available when a marketing
authorization has already been obtained in at least one E.U. member state.
A marketing authorization may be granted only to a sponsor established in the European Union.
Pediatric Studies
Prior to obtaining a marketing authorization in the E.U., sponsors have to demonstrate compliance with all
measures included in an EMA-approved Pediatric Investigation Plan, or PIP, covering all subsets of the pediatric
population, unless the EMA has granted a product-specific waiver, a class waiver, or a deferral for one or more of the
measures included in the PIP. The respective requirements for all marketing authorization procedures are set forth in
Regulation (EC) No 1901/2006, which is referred to as the Pediatric Regulation. This requirement also applies when a
company wants to add a new indication, pharmaceutical form or route of administration for a medicine that is already
authorized. The Pediatric Committee of the EMA, or PDCO, may grant deferrals for some medicines, allowing a company
to delay development of the medicine in children until there is enough information to demonstrate its effectiveness and
safety in adults. The PDCO may also grant waivers when development of a medicine in children is not needed or is not
appropriate, such as for diseases that only affect the elderly population.
54
Table of Contents
Before a marketing authorization application can be filed, or an existing marketing authorization can be amended,
the EMA determines that companies actually comply with the agreed studies and measures listed in each relevant PIP.
Period of Authorization and Renewals
A marketing authorization, other than a conditional marketing authorization, is initially valid for five years and the
marketing authorization may be renewed after five years on the basis of a re-evaluation of the risk-benefit balance by the
EMA or by the competent authority of the authorizing member state. To this end, the marketing authorization holder must
provide the EMA or the competent authority with a consolidated version of the file in respect of quality, safety and
efficacy, including all variations introduced since the marketing authorization was granted, at least six months before the
marketing authorization ceases to be valid. Once renewed, the marketing authorization is valid for an unlimited period,
unless the European Commission or the competent authority decides, on justified grounds relating to pharmacovigilance, to
proceed with one additional five-year renewal. Any authorization which is not followed by the actual placing of the drug
on the E.U. market (in case of centralized procedure) or on the market of the authorizing member state within three years
after authorization ceases to be valid (the so-called sunset clause).
Regulatory Data Protection
European Union legislation also provides for a system of regulatory data and market exclusivity. According to
Article 14(11) of Regulation (EC) No 726/2004, as amended, and Article 10(1) of Directive 2001/83/EC, as amended, upon
receiving marketing authorization, new chemical entities approved on the basis of complete independent data package
benefit from eight years of data exclusivity and an additional two years of market exclusivity. Data exclusivity prevents
regulatory authorities in the European Union from referencing the innovator’s data to assess a generic (abbreviated)
application. During the additional two-year period of market exclusivity, a generic marketing authorization application can
be submitted, and the innovator’s data may be referenced, but no generic medicinal product can be marketed until the
expiration of the market exclusivity. The overall ten-year period will be extended to a maximum of eleven years if, during
the first eight years of those ten years, the marketing authorization holder, or MAH, obtains an authorization for one or
more new therapeutic indications which, during the scientific evaluation prior to their authorization, are held to bring a
significant clinical benefit in comparison with existing therapies. Even if a compound is considered to be a new chemical
entity and the innovator is able to gain the period of data exclusivity, another company nevertheless could also market
another version of the drug if such company obtained marketing authorization based on an MAA with a complete
independent data package of pharmaceutical test, preclinical tests and clinical trials.
Transparency
There is an increasing trend in the E.U. towards greater transparency and, while the manufacturing or quality
information in marketing authorization dossiers is currently generally protected as confidential information, the EMA and
national regulatory authorities are now liable to disclose much of the non-clinical and clinical information, including the
full clinical study reports, in response to freedom of information requests after the marketing authorization has been
granted. In October 2014, the EMA adopted a policy under which clinical study reports would be posted on the agency’s
website following the grant, denial or withdrawal of a marketing authorization application, subject to procedures for
limited redactions and protection against unfair commercial use. Additional transparency provisions are contained in the
new Clinical Trials Regulation (EU) No 536/2014.
Regulatory Requirements After a Marketing Authorization has been Obtained
If we obtain authorization for a medicinal product in the European Union, we will be required to comply with a
range of requirements applicable to the manufacturing, marketing, promotion and sale of medicinal products:
Pharmacovigilance and Other Requirements
We will, for example, have to comply with the E.U.’s stringent pharmacovigilance or safety reporting rules,
pursuant to which post-authorization studies and additional monitoring obligations can be imposed. E.U. regulators may
55
Table of Contents
conduct inspections to verify our compliance with applicable requirements, and we will have to continue to expend time,
money and effort to remain compliant. Non-compliance with E.U. requirements regarding safety monitoring or
pharmacovigilance, and with requirements related to the development of products for the pediatric population, can also
result in significant financial penalties in the European Union. Similarly, failure to comply with the European Union’s
requirements regarding the protection of individual personal data can also lead to significant penalties and sanctions.
Individual E.U. member states may also impose various sanctions and penalties in case we do not comply with locally
applicable requirements.
Manufacturing
The manufacturing of authorized drugs, for which a separate manufacturer’s license is mandatory, must be
conducted in strict compliance with the EMA’s GMP requirements and comparable requirements of other regulatory bodies
in the European Union, which mandate the methods, facilities and controls used in manufacturing, processing and packing
of drugs to assure their safety and identity. The EMA enforces its GMP requirements through mandatory registration of
facilities and inspections of those facilities. The EMA may have a coordinating role for these inspections while the
responsibility for carrying them out rests with the member states competent authority under whose responsibility the
manufacturer falls. Failure to comply with these requirements could interrupt supply and result in delays, unanticipated
costs and lost revenues, and could subject the sponsor to potential legal or regulatory action, including but not limited to
warning letters, suspension of manufacturing, seizure of product, injunctive action or possible civil and criminal penalties.
Marketing and Promotion
The marketing and promotion of authorized drugs, including industry-sponsored continuing medical education
and advertising directed toward the prescribers of drugs and/or the general public, are strictly regulated in the European
Union under Directive 2001/83EC, as amended. The applicable regulations aim to ensure that information provided by
holders of marketing authorizations regarding their products is truthful, balanced and accurately reflects the safety and
efficacy claims authorized by the EMA or by the competent authority of the authorizing member state. Failure to comply
with these requirements can result in adverse publicity, warning letters, corrective advertising and potential civil and
criminal penalties.
Patent Term Extension
To compensate the patentee for delays in obtaining a marketing authorization for a patented product, a
supplementary certificate, or SPC, may be granted extending the exclusivity period for that specific product by up to five
years. Applications for SPCs must be made to the relevant patent office in each E.U. member state and the granted
certificates are valid only in the member state of grant. An application has to be made by the patent owner within six
months of the first marketing authorization being granted in the European Union (assuming the patent in question has not
expired, lapsed or been revoked) or within six months of the grant of the patent (if the marketing authorization is granted
first). In the context of SPCs, the term “product” means the active ingredient or combination of active ingredients for a
medicinal product and the term “patent” means a patent protecting such a product or a new manufacturing process or
application for it. The duration of an SPC is calculated as the difference between the patent’s filing date and the date of the
first marketing authorization, minus five years, subject to a maximum term of five years.
A six-month pediatric extension of an SPC may be obtained where the patentee has carried out an agreed pediatric
investigation plan, the authorized product information includes information on the results of the studies and the product is
authorized in all member states of the European Union.
Brexit and the Regulatory Framework in the United Kingdom
The United Kingdom’s withdrawal from the European Union took place on January 31, 2020. The European
Union and the United Kingdom reached an agreement on their new partnership in the Trade and Cooperation Agreement,
or the Agreement, which was applied provisionally beginning on January 1, 2021 and which entered into force on May 1,
2021. The Agreement focuses primarily on free trade by ensuring no tariffs or quotas on trade in goods,
56
Table of Contents
including healthcare products such as medicinal products. Thereafter, the European Union and the United Kingdom will
form two separate markets governed by two distinct regulatory and legal regimes. As such, the Agreement seeks to
minimize barriers to trade in goods while accepting that border checks will become inevitable as a consequence that the
United Kingdom is no longer part of the single market. As of January 1, 2021, the Medicines and Healthcare products
Regulatory Agency, or the MHRA, became responsible for supervising medicines and medical devices in Great Britain,
comprising England, Scotland and Wales under domestic law whereas Northern Ireland continues to be subject to European
Union rules under the Northern Ireland Protocol. The MHRA will rely on the Human Medicines Regulations 2012 (SI
2012/1916) (as amended), or the HMR, as the basis for regulating medicines. The HMR has incorporated into the domestic
law the body of EU law instruments governing medicinal products that pre-existed prior to the United Kingdom’s
withdrawal from the European Union.
Furthermore, while the Data Protection Act of 2018 in the United Kingdom that “implements” and complements
the E.U. General Data Protection Regulation, or GDPR, is now effective in the United Kingdom, it is still unclear whether
transfer of data from the EEA to the United Kingdom will remain lawful under GDPR. The Trade and Cooperation
Agreement provides for a transitional period during which the United Kingdom will be treated like an E.U. Member State
in relation to processing and transfers of personal data for four months from January 1, 2021. This may be extended by two
further months. After such period, the United Kingdom will be a “third country” under the GDPR unless the European
Commission adopts an adequacy decision in respect of transfers of personal data to the United Kingdom. The United
Kingdom has already determined that it considers all of the European Union and EEA member states to be adequate for the
purposes of data protection, ensuring that data flows from the United Kingdom to the European Union and EEA remain
unaffected. We may, however, incur liabilities, expenses, costs, and other operational losses under GDPR and applicable
E.U. Member States and the United Kingdom privacy laws in connection with any measures we take to comply with them.
General Data Protection Regulation
The collection, use, disclosure, transfer, or other processing of personal data regarding individuals in the E.U.,
including personal health data, is subject to the E.U. General Data Protection Regulation, or the GDPR, which became
effective on May 25, 2018. The GDPR is wide-ranging in scope and imposes numerous requirements on companies that
process personal data, including requirements relating to processing health and other sensitive data, obtaining consent of
the individuals to whom the personal data relates, providing information to individuals regarding data processing activities,
implementing safeguards to protect the security and confidentiality of personal data, providing notification of data
breaches, and taking certain measures when engaging third-party processors. The GDPR also imposes strict rules on the
transfer of personal data to countries outside the E.U., including the U.S., and permits data protection authorities to impose
large penalties for violations of the GDPR, including potential fines of up to €20 million or 4% of annual global revenues,
whichever is greater. The GDPR also confers a private right of action on data subjects and consumer associations to lodge
complaints with supervisory authorities, seek judicial remedies, and obtain compensation for damages resulting from
violations of the GDPR. Compliance with the GDPR will be a rigorous and time-intensive process that may increase the
cost of doing business or require companies to change their business practices to ensure full compliance.
Pharmaceutical Coverage, Pricing and Reimbursement
In the United States and markets in other countries, patients who are prescribed treatments for their conditions and
providers performing the prescribed services generally rely on third-party payors to reimburse all or part of the associated
healthcare costs. Significant uncertainty exists as to the coverage and reimbursement status of products approved by the
FDA and other government authorities. Thus, even if a product candidate is approved, sales of the product will depend, in
part, on the extent to which third-party payors, including government health programs in the United States such as
Medicare and Medicaid, commercial health insurers and managed care organizations, provide coverage, and establish
adequate reimbursement levels for, the product. The process for determining whether a payor will provide coverage for a
product may be separate from the process for setting the price or reimbursement rate that the payor will pay for the product
once coverage is approved. Third-party payors are increasingly challenging the prices charged, examining the medical
necessity, and reviewing the cost-effectiveness of medical products and services and
57
Table of Contents
imposing controls to manage costs. Third-party payors may limit coverage to specific products on an approved list, also
known as a formulary, which might not include all of the approved products for a particular indication.
To secure coverage and reimbursement for any product that might be approved for sale, a company may need to
conduct expensive pharmacoeconomic studies in order to demonstrate the medical necessity and cost-effectiveness of the
product, in addition to the costs required to obtain FDA or other comparable marketing approvals. Nonetheless, product
candidates may not be considered medically necessary or cost effective. A decision by a third-party payor not to cover a
product candidate could reduce physician utilization once the product is approved and have a material adverse effect on
sales, results of operations and financial condition. Additionally, a payor’s decision to provide coverage for a product does
not imply that an adequate reimbursement rate will be approved. Further, one payor’s determination to provide coverage
for a drug product does not assure that other payors will also provide coverage and reimbursement for the product, and the
level of coverage and reimbursement can differ significantly from payor to payor.
The containment of healthcare costs also has become a priority of federal, state and foreign governments and the
prices of drugs have been a focus in this effort. Governments have shown significant interest in implementing cost-
containment programs, including price controls, restrictions on reimbursement and requirements for substitution of generic
products. Adoption of price controls and cost-containment measures, and adoption of more restrictive policies in
jurisdictions with existing controls and measures, could further limit a company’s revenue generated from the sale of any
approved products. Coverage policies and third-party reimbursement rates may change at any time. Even if favorable
coverage and reimbursement status is attained for one or more products for which a company or its collaborators receive
marketing approval, less favorable coverage policies and reimbursement rates may be implemented in the future.
Outside the United States, ensuring adequate coverage and payment for a product also involves challenges.
Pricing of prescription pharmaceuticals is subject to governmental control in many countries. Pricing negotiations with
governmental authorities can extend well beyond the receipt of regulatory marketing approval for a product and may
require a clinical trial that compares the cost effectiveness of a product to other available therapies. The conduct of such a
clinical trial could be expensive and result in delays in commercialization.
In the European Union, pricing and reimbursement schemes vary widely from country to country. Some countries
provide that products may be marketed only after a reimbursement price has been agreed. Some countries may require the
completion of additional studies that compare the cost-effectiveness of a particular drug candidate to currently available
therapies or so called health technology assessments, in order to obtain reimbursement or pricing approval. For example,
the European Union provides options for its member states to restrict the range of products for which their national health
insurance systems provide reimbursement and to control the prices of medicinal products for human use. E.U. European
Union member states may approve a specific price for a product or it may instead adopt a system of direct or indirect
controls on the profitability of the company placing the product on the market. Other member states allow companies to fix
their own prices for products, but monitor and control prescription volumes and issue guidance to physicians to limit
prescriptions. Recently, many countries in the European Union have increased the amount of discounts required on
pharmaceuticals and these efforts could continue as countries attempt to manage healthcare expenditures, especially in light
of the severe fiscal and debt crises experienced by many countries in the European Union. The downward pressure on
health care costs in general, particularly prescription drugs, has become intense. As a result, increasingly high barriers are
being erected to the entry of new products. Political, economic and regulatory developments may further complicate
pricing negotiations, and pricing negotiations may continue after reimbursement has been obtained. Reference pricing used
by various European Union member states, and parallel trade, i.e., arbitrage between low-priced and high-priced member
states, can further reduce prices. There can be no assurance that any country that has price controls or reimbursement
limitations for pharmaceutical products will allow favorable reimbursement and pricing arrangements for any products, if
approved in those countries.
Healthcare Law and Regulation
Healthcare providers and third-party payors play a primary role in the recommendation and prescription of drug
products that are granted marketing approval. Arrangements with providers, consultants, third party payors and customers
are subject to broadly applicable fraud and abuse, anti-kickback, false claims laws, reporting of payments to physicians and
teaching physicians and patient privacy laws and regulations and other healthcare laws and regulations
58
Table of Contents
that may constrain business and/or financial arrangements. Restrictions under applicable federal and state healthcare laws
and regulations, include the following:
● the federal Anti-Kickback Statute prohibits, among other things, persons and entities from knowingly and
willfully soliciting, offering, paying, receiving or providing remuneration, directly or indirectly, in cash or in
kind, to induce or reward either the referral of an individual for, or the purchase, order or recommendation of,
any good or service, for which payment may be made, in whole or in part, under a federal healthcare program
such as Medicare and Medicaid;
● the federal civil and criminal false claims laws, including the civil False Claims Act and civil monetary
penalty laws, which prohibit individuals or entities from, among other things, knowingly presenting, or
causing to be presented, to the federal government, claims for payment that are false, fictitious or fraudulent
or knowingly making, using or causing to be made or used a false record or statement to avoid, decrease or
conceal an obligation to pay money to the federal government;
● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created additional
federal criminal laws that prohibit, among other things, knowingly and willfully executing, or attempting to
execute, a scheme to defraud any healthcare benefit program or making false statements relating to
healthcare matters;
● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and their
regulations, including the Final Omnibus Rule published in January 2013, which impose obligations,
including mandatory contractual terms, with respect to safeguarding the privacy, security and transmission of
individually identifiable health information;
● the federal false statements statute, which prohibits knowingly and willfully falsifying, concealing or
covering up a material fact or making any materially false statement in connection with the delivery of or
payment for healthcare benefits, items or services;
● the Foreign Corrupt Practices Act, or FCPA, which prohibits companies and their intermediaries from
making, or offering or promising to make improper payments to non-U.S. officials for the purpose of
obtaining or retaining business or otherwise seeking favorable treatment;
● the federal transparency requirements known as the federal Physician Payments Sunshine Act, under the
Patient Protection and Affordable Care Act, as amended by the Health Care Education Reconciliation Act, or
the Affordable Care Act, which requires certain manufacturers of drugs, devices, biologics and medical
supplies to report annually to the Centers for Medicare & Medicaid Services, or CMS, within the United
States Department of Health and Human Services, information related to payments and other transfers of
value made by that entity to physicians, other healthcare providers and teaching hospitals, as well as
ownership and investment interests held by physicians, other healthcare providers and their immediate family
members; and
● analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which
may apply to healthcare items or services that are reimbursed by non-governmental third-party payors,
including private insurers.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary
compliance guidelines and the relevant compliance guidance promulgated by the federal government in addition to
requiring drug manufacturers to report information related to payments to physicians and other health care providers or
marketing expenditures. State and foreign laws also govern the privacy and security of health information in some
circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus
complicating compliance efforts.
59
Table of Contents
Healthcare Reform
A primary trend in the United States healthcare industry and elsewhere is cost containment. There have been a
number of federal and state proposals during the last few years regarding the pricing of pharmaceutical and
biopharmaceutical products, limiting coverage and reimbursement for drugs and other medical products, government
control and other changes to the healthcare system in the United States.
In March 2010, the United States Congress enacted the Affordable Care Act, or the ACA, which, among other
things, includes changes to the coverage and payment for products under government health care programs. Among the
provisions of the Affordable Care Act of importance to potential drug candidates are:
● an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs
and biologic agents, apportioned among these entities according to their market share in certain government
healthcare programs, although this fee would not apply to sales of certain products approved exclusively for
orphan indications;
● expansion of eligibility criteria for Medicaid programs by, among other things, allowing states to offer
Medicaid coverage to certain individuals with income at or below 133% of the federal poverty level, thereby
potentially increasing a manufacturer’s Medicaid rebate liability;
● expanded manufacturers’ rebate liability under the Medicaid Drug Rebate Program by increasing the
minimum rebate for both branded and generic drugs and revising the definition of “average manufacturer
price”, or AMP, for calculating and reporting Medicaid drug rebates on outpatient prescription drug prices
and extending rebate liability to prescriptions for individuals enrolled in Medicare Advantage plans;
● addressed a new methodology by which rebates owed by manufacturers under the Medicaid Drug Rebate
Program are calculated for drugs that are inhaled, infused, instilled, implanted or injected;
● expanded the types of entities eligible for the 340B drug discount program;
● established the Medicare Part D coverage gap discount program by requiring manufacturers to provide a 50%
point-of-sale-discount off the negotiated price of applicable brand drugs to eligible beneficiaries during their
coverage gap period as a condition for the manufacturers’ outpatient drugs to be covered under Medicare
Part D;
● a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct
comparative clinical effectiveness research, along with funding for such research;
● the Independent Payment Advisory Board, or IPAB, which has authority to recommend certain changes to
the Medicare program to reduce expenditures by the program that could result in reduced payments for
prescription drugs. However, the IPAB implementation has been not been clearly defined. ACA provided that
under certain circumstances, IPAB recommendations will become law unless Congress enacts legislation that
will achieve the same or greater Medicare cost savings; and
● established the Center for Medicare and Medicaid Innovation within CMS to test innovative payment and
service delivery models to lower Medicare and Medicaid spending, potentially including prescription drug
spending. Funding has been allocated to support the mission of the Center for Medicare and Medicaid
Innovation from 2011 to 2019.
In addition, other legislative changes have been proposed and adopted since the ACA was enacted. In August
2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress. A Joint
Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for
the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s
60
Table of Contents
automatic reduction to several government programs. These changes included aggregate reductions to Medicare payments
to providers of up to 2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2029 unless
additional Congressional action is taken. The Coronavirus Aid, Relief, and Economic Security Act, or the CARES Act,
suspended the 2% Medicare sequester from May 1, 2020 through December 31, 2020, and extended the sequester by one
year, through 2031. The Medicare sequester reductions have been suspended through the end of March 2022. From April
2022 through June 2022 a 1% sequester cut will be in effect, with the full 2% cut resuming thereafter. The American
Taxpayer Relief Act of 2012, among other things, reduced Medicare payments to several providers and increased the
statute of limitations period for the government to recover overpayments to providers from three to five years. These new
laws may result in additional reductions in Medicare and other healthcare funding and otherwise affect the prices we may
obtain for any of our product candidates for which we may obtain regulatory approval or the frequency with which any
such product candidate is prescribed or used.
Since enactment of the ACA, there have been, and continue to be, numerous legal challenges and Congressional
actions to repeal and replace provisions of the law. For example, with enactment of the Tax Cuts and Jobs Act of 2017, or
the Tax Act, which was signed by President Trump on December 22, 2017, Congress repealed the “individual mandate.”
The repeal of this provision, which requires most Americans to carry a minimal level of health insurance, became effective
in 2019. On December 14, 2018, a U.S. District Court judge in the Northern District of Texas ruled that the individual
mandate portion of the ACA is an essential and inseverable feature of the ACA, and therefore because the mandate was
repealed as part of the Tax Act, the remaining provisions of the ACA are invalid as well. The U.S. Supreme Court heard
this case on November 10, 2020 and, on June 17, 2021, dismissed this action after finding that the plaintiffs do not have
standing to challenge the constitutionality of the ACA. Litigation and legislation over the ACA are likely to continue, with
unpredictable and uncertain results.
The Trump Administration also took executive actions to undermine or delay implementation of the ACA,
including directing federal agencies with authorities and responsibilities under the ACA to waive, defer, grant exemptions
from, or delay the implementation of any provision of the ACA that would impose a fiscal or regulatory burden on states,
individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical devices. On January 28,
2021, however, President Biden rescinded those orders and issued a new Executive Order which directs federal agencies to
reconsider rules and other policies that limit Americans’ access to health care, and consider actions that will protect and
strengthen that access. Under this Order, federal agencies are directed to re-examine: policies that undermine protections
for people with pre-existing conditions, including complications related to COVID-19; demonstrations and waivers under
Medicaid and the ACA that may reduce coverage or undermine the programs, including work requirements; policies that
undermine the Health Insurance Marketplace or other markets for health insurance; policies that make it more difficult to
enroll in Medicaid and the ACA; and policies that reduce affordability of coverage or financial assistance, including for
dependents. This Executive Order also directs the U.S. Department of Health and Human Services to create a special
enrollment period for the Health Insurance Marketplace in response to the COVID-19 pandemic.
In addition, the Centers for Medicare & Medicaid Services, or CMS, has proposed regulations that would give
states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have
the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces. On
November 30, 2018, CMS announced a proposed rule that would amend the Medicare Advantage and Medicare Part D
prescription drug benefit regulations to reduce out of pocket costs for plan enrollees and allow Medicare plans to negotiate
lower rates for certain drugs. Among other things, the proposed rule changes would allow Medicare Advantage plans to use
pre authorization, or PA, and step therapy, or ST, for six protected classes of drugs, with certain exceptions, permit plans to
implement PA and ST in Medicare Part B drugs; and change the definition of “negotiated prices” in the regulations. It is
unclear whether these proposed changes will be accepted, and if so, what effect such changes will have on our business.
We expect that these healthcare reforms, as well as other healthcare reform measures that may be adopted in the
future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new
payment methodologies and additional downward pressure on the price that we receive for any approved product and/or
the level of reimbursement physicians receive for administering any approved product we might bring to market.
Reductions in reimbursement levels may negatively impact the prices we receive or the frequency with which our
61
Table of Contents
products are prescribed or administered. Any reduction in reimbursement from Medicare or other government programs
may result in a similar reduction in payments from private payors.
Pharmaceutical Prices
The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United
States. There have been several recent U.S. congressional inquiries, as well as proposed and enacted state and federal
legislation designed to, among other things, bring more transparency to pharmaceutical pricing, review the relationship
between pricing and manufacturer patient programs, and reduce the costs of pharmaceuticals under Medicare and
Medicaid. In 2020, President Trump issued several executive orders intended to lower the costs of prescription products
and certain provisions in these orders have been incorporated into regulations. These regulations include an interim final
rule implementing a most favored nation model for prices that would tie Medicare Part B payments for certain physician-
administered pharmaceuticals to the lowest price paid in other economically advanced countries, effective January 1, 2021.
That rule, however, has been subject to a nationwide preliminary injunction and, on December 29, 2021, CMS issued a
final rule to rescind it. With issuance of this rule, CMS stated that it will explore all options to incorporate value into
payments for Medicare Part B pharmaceuticals and improve beneficiaries' access to evidence-based care.
In addition, in October 2020, HHS and the FDA published a final rule allowing states and other entities to develop
a Section 804 Importation Program, or SIP, to import certain prescription drugs from Canada into the United States. The
final rule is currently the subject of ongoing litigation, but at least six states (Vermont, Colorado, Florida, Maine, New
Mexico, and New Hampshire) have passed laws allowing for the importation of drugs from Canada with the intent of
developing SIPs for review and approval by the FDA. Further, on November 20, 2020, HHS finalized a regulation
removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D,
either directly or through pharmacy benefit managers, unless the price reduction is required by law. The implementation of
the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in response to ongoing
litigation. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as well as a new safe
harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the implementation of
which have also been delayed by the Biden administration until January 1, 2023.
On July 9, 2021, President Biden signed Executive Order 14063, which focuses on, among other things, the price
of pharmaceuticals. The Order directs the Department of Health and Human Services, or HHS, to create a plan within 45
days to combat “excessive pricing of prescription pharmaceuticals and enhance domestic pharmaceutical supply chains, to
reduce the prices paid by the federal government for such pharmaceuticals, and to address the recurrent problem of price
gouging.” On September 9, 2021, HHS released its plan to reduce pharmaceutical prices. The key features of that plan are
to: (1) make pharmaceutical prices more affordable and equitable for all consumers and throughout the health care system
by supporting pharmaceutical price negotiations with manufacturers; (2) improve and promote competition throughout the
prescription pharmaceutical industry by supporting market changes that strengthen supply chains, promote biosimilars and
generic drugs, and increase transparency; and (3) foster scientific innovation to promote better healthcare and improve
health by supporting public and private research and making sure that market incentives promote discovery of valuable and
accessible new treatments.
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations
designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints,
discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some
cases, designed to encourage importation from other countries and bulk purchasing. A number of states, for example,
require drug manufacturers and other entities in the drug supply chain, including health carriers, pharmacy benefit
managers, wholesale distributors, to disclose information about pricing of pharmaceuticals. In addition, regional healthcare
organizations and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical
products and which suppliers will be included in their prescription pharmaceutical and other healthcare programs. These
measures could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing. We
expect that additional state and federal healthcare reform measures will be adopted in the future, any of which could limit
the amounts that federal and state governments will pay for healthcare products and services, which could result in reduced
demand for our product candidates or additional pricing pressures.
62
Table of Contents
Federal and State Data Privacy Laws
There are multiple privacy and data security laws that may impact our business activities, in the United States and
in other countries where we conduct trials or where we may do business in the future. These laws are evolving and may
increase both our obligations and our regulatory risks in the future. In the health care industry generally, under the federal
Health Insurance Portability and Accountability Act of 1996, or HIPAA, the U.S. Department of Health and Human
Services, or HHS, has issued regulations to protect the privacy and security of protected health information, or PHI, used or
disclosed by covered entities including certain healthcare providers, health plans and healthcare clearinghouses. HIPAA
also regulates standardization of data content, codes and formats used in healthcare transactions and standardization of
identifiers for health plans and providers. HIPAA also imposes certain obligations on the business associates of covered
entities that obtain protected health information in providing services to or on behalf of covered entities. HIPAA may apply
to us in certain circumstances and may also apply to our business partners in ways that may impact our relationships with
them. Our clinical trials are regulated by the Common Rule, which also includes specific privacy-related provisions. In
addition to federal privacy regulations, there are a number of state laws governing confidentiality and security of health
information that may be applicable to our business. In addition to possible federal civil and criminal penalties for HIPAA
violations, state attorneys general are authorized to file civil actions for damages or injunctions in federal courts to enforce
HIPAA and seek attorney’s fees and costs associated with pursuing federal civil actions. In addition, state attorneys general
(along with private plaintiffs) have brought civil actions seeking injunctions and damages resulting from alleged violations
of HIPAA’s privacy and security rules. State attorneys general also have authority to enforce state privacy and security
laws. New laws and regulations governing privacy and security may be adopted in the future as well.
At the state level, California has enacted legislation that has been dubbed the first “GDPR-like” law in the United
States. Known as the California Consumer Privacy Act, or CCPA, it creates new individual privacy rights for consumers
(as that word is broadly defined in the law) and places increased privacy and security obligations on entities handling
personal data of consumers or households. The CCPA went into effect on January 1, 2020 and requires covered companies
to provide new disclosures to California consumers, provide such consumers new ways to opt-out of certain sales of
personal information, and allow for a new cause of action for data breaches. Additionally, effective starting on January 1,
2023, the California Privacy Rights Act, or CPRA, will significantly modify the CCPA, including by expanding
consumers’ rights with respect to certain sensitive personal information. The CPRA also creates a new state agency that
will be vested with authority to implement and enforce the CCPA and the CPRA. The CCPA and CPRA could impact our
business activities depending on how it is interpreted and exemplifies the vulnerability of our business to not only cyber
threats but also the evolving regulatory environment related to personal data and individually identifiable health
information. These provisions may apply to some of our business activities. In addition, other states, including Virginia and
Colorado, already have passed state privacy laws and other states will likely be considering similar laws in the near future.
Because of the breadth of these laws and the narrowness of the statutory exceptions and regulatory safe harbors
available under such laws, it is possible that some of our current or future business activities, including certain clinical
research, sales and marketing practices and the provision of certain items and services to our customers, could be subject to
challenge under one or more of such privacy and data security laws. The heightening compliance environment and the need
to build and maintain robust and secure systems to comply with different privacy compliance and/or reporting requirements
in multiple jurisdictions could increase the possibility that a healthcare company may fail to comply fully with one or more
of these requirements. If our operations are found to be in violation of any of the privacy or data security laws or
regulations described above that are applicable to us, or any other laws that apply to us, we may be subject to penalties,
including potentially significant criminal, civil and administrative penalties, damages, fines, contractual damages,
reputational harm, diminished profits and future earnings, additional reporting requirements and/or oversight if we become
subject to a consent decree or similar agreement to resolve allegations of non-compliance with these laws, and the
curtailment or restructuring of our operations, any of which could adversely affect our ability to operate our business and
our results of operations. To the extent that any product candidates we may develop, once approved, are sold in a foreign
country, we may be subject to similar foreign laws.
63
Table of Contents
Employees and Human Capital
As of January 31, 2022, we had 73 employees, 3 employees are located in Dublin, Ireland, 27 of our employees
are located in Vienna, Austria and 43 of our employees are located in the U.S., with 38 located in Fort Washington,
Pennsylvania, one located in San Diego, California and the remaining four employees in the field.
Our employees in Austria are subject to the collective bargaining agreement of the chemical industry. This is an
annual agreement between the employer representatives and the trade union of an industry. It defines conditions of
employment, such as minimum wages, working hours and conditions, overtime payments, vacations and other matters.
Our human capital resources objectives include, as applicable, identifying, recruiting, retaining, incentivizing and
integrating our existing and additional employees. The principal purposes of our equity incentive plans are to attract, retain
and motivate selected employees, consultants and directors through the granting of stock-based compensation awards. We
utilize third party consultants to review and update our compensation practices annually. We understand that attracting,
retaining, engaging and supporting our talented team and maintaining a diverse and inclusive organization is critical to our
success and to increase the value we can provide for patients, shareholders and all stakeholders. We consider our relations
with our employees to be good.
In response to the COVID-19 pandemic and related mitigation efforts, we assembled a COVID-19 task force,
which consists of senior leaders from various departments within our organization and is responsible for the safety of our
employees, consultants and contractors throughout the world, collectively our workers, and to maintain business continuity.
Our COVID-19 task force continues to monitor safety protocols and procedures to protect our workers as well as business
essential operations. These protocols include: (i) limiting access to our facilities and requiring a majority of our workers to
work from home (except when access to facilities is necessary) while providing additional equipment to operate
successfully remotely, (ii) increasing physical distancing in workspaces for workers working onsite, (iii) adjusting
schedules for workers working onsite to minimize the number of individuals in a facility at one time, (iv) requiring masks
to be worn in all of our locations, (v) enhancing our cleaning protocols across all facilities, (vi) establishing emergency
worker testing procedures to immediately respond to potential onsite exposure risks with subsequent testing, tracing,
quarantining and re-testing to ensure a safe work environment. Our COVID-19 task force periodically provides updates to
our executive team and our board of directors and provides timely communications to employees.
Our Corporate Information
On March 1, 2017, Nabriva Therapeutics plc, or Nabriva Ireland was incorporated in Ireland under the name
Hyacintho 2 plc, and was renamed to Nabriva Therapeutics plc on April 10, 2017, in order to effectuate the change of the
jurisdiction of incorporation of the ultimate parent company of the Nabriva Group from Austria to Ireland. Nabriva Ireland
replaced Nabriva Therapeutics AG, or Nabriva Austria as the ultimate parent company on June 23, 2017, following the
conclusion of a tender offer in which holders of the outstanding share capital of Nabriva Austria exchanged their holdings
for ordinary shares, $0.01 nominal value per share, of Nabriva Ireland. The ordinary shares of Nabriva Ireland were issued
on a one-for-ten basis to the holders of the Nabriva Austria common shares and on a one-for-one basis to the holders of the
Nabriva Austria American Depositary Shares, or Nabriva Austria ADSs. On June 26, 2017, the ordinary shares of Nabriva
Ireland began trading on the Nasdaq Global Select Market under the symbol “NBRV”, the same symbol under which the
Nabriva Austria ADSs were previously traded. This transaction was accounted for as a merger between entities under
common control; accordingly, the historical financial statements of Nabriva Austria for periods prior to this transaction are
considered to be the historical financial statements of Nabriva Ireland. Our executive offices are located at 25-28 North
Wall Quay IFSC, Dublin 1, Ireland, and our telephone number is +353 1 649 2000.
The predecessor of Nabriva Ireland, Nabriva Austria, was incorporated in Austria as a spin-off from
Sandoz GmbH in October 2005 under the name Nabriva Therapeutics Forschungs GmbH, a limited liability company
organized under Austrian law and commenced operations in February 2006. In 2007, Nabriva Austria transformed into a
stock corporation (Aktiengesellschaft) under the name Nabriva Therapeutics AG. On October 19, 2017, Nabriva Austria
was converted into a private limited liability company under Austrian law and renamed Nabriva Therapeutics GmbH.
64
Table of Contents
Our U.S. operations are conducted by our wholly-owned subsidiary Nabriva Therapeutics US, Inc., a Delaware
corporation established in August 2014 and located at 414 Commerce Drive, Fort Washington, Pennsylvania 19034.
Our website address is www.nabriva.com. The information contained on, or that can be accessed from, our
website does not form part of this Annual Report.
Available Information
We make available free of charge through our website our annual report on Form 10-K, quarterly reports on
Form 10-Q, current reports on Form 8-K and amendments to those reports filed or furnished pursuant to Sections 13(a) and
15(d) of the Securities Exchange Act of 1934, as amended, or the Exchange Act. We make these reports available through
our website (www.nabriva.com) as soon as reasonably practicable after we electronically file such reports with, or furnish
such reports to, the SEC. Previously, as a foreign private issuer, we filed our Annual Report on Form 20-F and furnished
information on Form 6-K. You can review our electronically filed reports and other information that we file with the SEC
on the SEC’s web site at http://www.sec.gov. We also make available, free of charge on our website, the reports filed with
the SEC by our executive officers, directors and 10% shareholders pursuant to Section 16 under the Exchange Act as soon
as reasonably practicable after copies of those filings are provided to us by those persons. The information contained on, or
that can be accessed through, our website is not a part of or incorporated by reference in this Annual Report on Form 10-K.
ITEM 1A. RISK FACTORS.
You should consider carefully the risks and uncertainties described below, together with all of the other information in this
Annual Report on Form 10-K. If any of the following risks are realized, our business, financial condition, results of
operations and prospects could be materially and adversely affected. The risks described below are not the only risks
facing us. Risks and uncertainties not currently known to us or that we currently deem to be immaterial also may materially
adversely affect our business, financial condition, results of operations and/or
prospects.
Risks Related to Our Financial Position and Need for Additional Capital
We have incurred significant losses since our inception. We expect to incur losses for at least the next several years and
may never generate profits from operations or maintain profitability.
Since inception, we have incurred significant operating losses. Our net losses were $49.5 million for the year
ended December 31, 2021, $69.5 million for the year ended December 31, 2020 and $82.8 million for the year ended
December 31, 2019. As of December 31, 2021, we had an accumulated deficit of $595.7 million. To date, we have financed
our operations primarily through the sale of our equity securities, convertible and term debt financings and research and
development support from governmental grants and loans and proceeds from our licensing agreements. We have devoted
most of our efforts to research and development, including clinical trials and the commercial sale of our products.
XENLETA is approved in the United States for the treatment of community-acquired bacterial pneumonia, or CABP, in
adults. In July 2020, we entered into a Sales Promotion and Distribution Agreement, with subsidiaries of Merck Sharp &
Dohme Corp. pursuant to which we licensed the right, subject to specified conditions, to promote, distribute and sell
SIVEXTRO for acute bacterial skin and skin structure infections, or ABSSSIs, caused by certain susceptible Gram-positive
microorganisms in the United States and its territories, or the SIVEXTRO Territory. We have secured a virtual and in-
person sales effort with community-based expertise with Amplity Health, which is a contract sales organization, to replace
our hospital-based sale force and began a small and focused sales effort for SIVEXTRO and XENLETA in September
2020. We expanded this effort to 60 sales representatives in 2021 and may expand it further. We also piloted a virtual
promotion effort with incremental sales representatives in the third quarter of 2021. We expect to continue to incur
significant expenses and increasing operating losses for at least the next several years, including in connection with our
regulatory approval efforts, supply chain investments and commercialization of XENLETA, the promotion and distribution
efforts for SIVEXTRO, and, if it receives marketing approval, the commercialization of CONTEPO. The net losses we
incur may fluctuate significantly from quarter-to-quarter and year-to-year.
65
Table of Contents
We expect to continue to invest in critical commercial promotion and distribution, medical affairs and other
commercialization activities, as well as investing in our supply chain for the commercialization of SIVEXTRO, XENLETA
and the potential launch of CONTEPO. We expect to seek additional funding in future periods to support these activities. In
December 2019, we resubmitted an NDA for CONTEPO for the treatment of cUTIs, including AP. On June 19, 2020 we
received a second Complete Response Letter from the FDA in connection with our NDA for CONTEPO for the treatment
of cUTIs, including AP. Although our European contract manufacturing partners were prepared for regulatory authority
inspections, the CRL cited observations at our manufacturing partners that could not be resolved due to FDA’s inability to
conduct onsite inspections because of travel restrictions. Our contract manufacturers continue to interact with FDA to
discuss its plans for conducting inspections at their sites. On October 30, 2020, we participated in a “Type A” meeting with
the FDA to obtain any new information related to the FDA’s pending conduct of inspections of foreign manufacturers
during the COVID-19 pandemic that has negatively impacted a number of FDA product reviews, including our NDA for
CONTEPO for the treatment of cUTIs, including AP. The FDA informed us that it has not yet determined how it will
conduct international inspections during the COVID-19 pandemic. On April 14, 2021, the FDA issued industry guidance
on remote interactive evaluations of drug manufacturing and bioresearch monitoring facilities during COVID-19
specifying that when it cannot perform a Pre-Approval Inspection, or PAI, or a Pre-License Inspection, or PLI, or when the
FDA determines that it would be useful to supplement a planned inspection, the agency will consider using tools other than
a physical inspection and select the most appropriate method to address the specific risks that justify the need for the PAI or
PLI. The FDA informed us that onsite inspections of our manufacturing partners in Europe are required in order for the
FDA to complete the review of a potential CONTEPO NDA resubmission. Due to travel restriction related to the COVID-
19 pandemic, the FDA suspended onsite inspections of ex-US manufacturers for all non-COVID products. As a result, we
requested an extension of the timeline for a potential CONTEPO NDA resubmission until June 2023, which the FDA
granted on March 21, 2022. We are awaiting further clarity from the FDA regarding their ability to complete onsite
inspections at our manufacturing partners in Italy and Spain before determining specific timing of the potential NDA
resubmission, which we plan to submit promptly once we have clarity from the FDA. The FDA released the Resiliency
Roadmap for FDA Inspectional Oversight that describes the systematic approach that FDA will utilize to manage
postponed inspections and other oversight activities. The prioritization plan considers public health risks related to
conducting an inspection, such as the impact of the product’s availability on public health, as well as investigator safety
and travel restrictions/advisories. In addition, the FDA informed us that, while they cannot predict when an inspection may
occur and when the pandemic may prevent the FDA from completing inspections, tier 1 mission-critical inspections and
tier 2 higher priority inspections, which includes PAIs, will continue to be prioritized going forward. We cannot predict the
outcome of any further interactions with the FDA or when CONTEPO will receive marketing approval, if at all. Our
contract manufacturers continue to interact with FDA to discuss its plans for conducting inspections at their sites. If we
obtain marketing approval of CONTEPO for cUTI, including AP, or another indication, we also expect to incur significant
additional sales, marketing, distribution and manufacturing expense.
In addition, our expenses will increase if and as we:
● initiate or continue the research and development of XENLETA and CONTEPO for additional indications
and of our other product candidates;
● seek to develop additional product candidates;
● seek marketing approval for any product candidates that successfully complete clinical development;
● are required by the FDA, EMA or other regulators to conduct additional clinical trials prior to or after
approval;
● continue to build or re-build a medical affairs, sales, marketing and distribution infrastructure and scale up
manufacturing capabilities to commercialize SIVEXTRO, XENLETA and any other product candidates for
which we receive marketing approval;
● in-license or acquire other products, product candidates or technologies, including additional community
products;
66
Table of Contents
● maintain, expand and protect our intellectual property portfolio;
● expand our physical presence in the United States and Ireland;
● incur additional debt;
● establish and expand manufacturing arrangements with third parties; and
● add operational, financial and management information systems and personnel, including personnel to
support our product development and our operations as a public company in addition to our
commercialization efforts.
Our ability to generate profits from operations, and to become and remain profitable, depends on our ability to
successfully develop and commercialize drugs that generate significant revenue. Based on our current plans, we do not
expect to generate significant revenue unless and until we obtain marketing approval for CONTEPO, and successfully
commercialize XENLETA and, if approved, CONTEPO and actively promote SIVEXTRO. In April 2020, we announced a
plan to restructure our hospital-based commercial sales force and transition to a community-based sales effort. This
restructuring intended to reduce costs and to align the capabilities of our sales effort with our strategic re-focus on making
sales of XENLETA to community health care professionals. This restructuring resulted in the termination of 66 employees,
consisting of our entire hospital-based sales personnel and certain members of our sales force leadership team. Additional
reductions in headcount occurred in the third quarter of 2020 including the restructuring of the commercial organization,
which led to the elimination of the role of our Chief Commercial Officer. Our commercial operations now report directly to
our Chief Executive Officer. We have secured a virtual and in-person sales effort with community-based expertise with
Amplity Health, which is a contract sales organization, to replace our hospital-based sale force and began a small and
focused sales effort for SIVEXTRO and XENLETA in September 2020. We expanded this effort to 60 sales representatives
in 2021 and may expand it further. We also piloted a virtual promotion effort with incremental sales representatives in the
third quarter of 2021. Our ability to generate significant revenue will require us to be successful in a range of challenging
activities, including:
● maintaining and expanding a community-based sales effort;
● obtaining marketing approval for CONTEPO;
● establishing and maintaining medical affairs, sales, marketing and distribution capabilities to effectively
market and sell SIVEXTRO, XENLETA and CONTEPO, if approved, in the United States;
● establishing and maintaining collaboration, distribution or other marketing arrangements with third parties to
commercialize XENLETA in markets outside the United States;
● protecting our rights to our intellectual property portfolio related to XENLETA and CONTEPO;
● minimizing cyber-security and similar risks, which could result in the disclosure of confidential information,
disruption of our technology support systems, legal exposure and financial losses;
● assessing any material effects of climate change transition risks, such as policy and regulatory changes,
which could impose operational and compliance burdens in certain jurisdictions or impact market trends;
● establishing and maintaining arrangements for the manufacture of and obtaining commercial quantities of
SIVEXTRO, XENLETA and CONTEPO, if approved; and
● negotiating and securing adequate reimbursement from third-party payors for SIVEXTRO, XENLETA and
CONTEPO, if approved.
67
Table of Contents
We may never succeed in these activities and, even if we do, may never generate revenues that are significant
enough to generate profits from operations. Even if we do generate profits from operations, we may not be able to sustain
or increase profitability on a quarterly or annual basis. Our failure to generate profits from operations, and to become and
remain profitable, would decrease the value of our company and could impair our ability to raise capital, expand our
business, maintain our research and development efforts, diversify our product offerings, conduct commercial activities,
maintain our commercial efforts or continue our operations. A decline in the value of our company could also cause our
shareholders to lose all or part of their investment.
We have identified conditions and events that raise substantial doubt about our ability to continue as a going concern.
We may be forced to delay or reduce the scope of our development programs and/or limit or cease our operations
if we are unable to obtain additional funding to support our current operating plan. We have identified conditions and
events that raise substantial doubt about our ability to continue as a going concern. As of December 31, 2021, we had cash
and cash equivalents, restricted cash and short-term investments of $47.9 million. Based on our available cash resources,
we believe we do not have sufficient cash on hand to support current operations for more than twelve months from the date
of filing this Annual Report on Form 10-K. This condition raises substantial doubt about our ability to continue as a going
concern within one year after the date the consolidated financial statements included elsewhere in this Annual Report on
Form 10-K are issued. Management’s plans in this regard are described in Note 1 of the consolidated financial statements
included elsewhere in this Annual Report on Form 10-K. However, we cannot guarantee that we will be able to obtain
sufficient additional funding when needed or that such funding, if available, will be obtainable.
We will need substantial additional funding. If we are unable to raise capital when needed or on acceptable terms, we
could be forced to delay, reduce or eliminate our product development programs or commercialization efforts.
We expect to continue to incur substantial costs in connection with our ongoing activities. These activities include
the commercialization of SIVEXTRO and XENLETA, the process of obtaining marketing approval for CONTEPO and,
possibly, other product candidates or additional indications for our products, and our ongoing research activities. Our
expenses will increase if we suffer any regulatory delays or are required to conduct additional clinical trials to satisfy
regulatory requirements.
Furthermore, we expect to continue to incur additional costs to service our current debt and any potential future
draws on the Loan Agreement (as defined below) and costs associated with operating as a public company and as a
company with a commercial rather than a research and development focus. Accordingly, we will need to obtain substantial
additional funding in connection with our continuing operations. If we are unable to raise capital when needed or on
attractive terms, we could be forced to further delay, reduce or eliminate our research and development programs or reduce
our commercialization efforts.
On March 11, 2020, we entered into an amendment, or the Third Amendment, to our Loan and Security
Agreement, or the Loan Agreement, with Hercules Capital, Inc., or Hercules, as administrative agent, collateral agent and
lender. Pursuant to the Third Amendment, we repaid Hercules in March 2020, $30.0 million of the $35.0 million in
aggregate principal amount of debt outstanding under the Loan Agreement, which we refer to as the Prepayment. We
determined to enter into the Third Amendment following the effectiveness of a performance covenant in February 2020
under which we became obligated to either (1) achieve 80% of our net product revenue sales target over a trailing six-
month period, or (2) maintain an amount of cash and cash equivalents in accounts pledged to Hercules plus a specified
amount of eligible accounts receivables equal to the greater of the amount outstanding under the Loan Agreement or $40.0
million, which we refer to as the liquidity requirement. Under the Third Amendment, we and Hercules agreed to defer the
end of term loan charge payment in the amount of approximately $2.1 million that would have otherwise become payable
on the date of the Prepayment and to reduce the prepayment charge with respect to the Prepayment from $600,000 to
$300,000 and to defer its payment, in each case, until June 1, 2023 or such earlier date on which all loans under the Loan
Agreement are repaid or become due and payable. The Third Amendment also reset the revenue performance covenant to
70% of targeted revenue based on a revised net product revenue forecast and lowered our minimum liquidity requirement
to $3.0 million in cash and cash equivalents, in each case, following the Prepayment.
68
Table of Contents
The new minimum liquidity requirement will not apply if CONTEPO receives regulatory approval from the U.S. Food and
Drug Administration and we achieve at least 70% of our revised net product revenue targets under the Loan Agreement.
On June 2, 2021, we entered into a further amendment, or the Fourth Amendment, to our Loan Agreement with Hercules.
Pursuant to the Fourth Amendment, the date on which we must commence repaying principal under the Loan Agreement
was extended to April 1, 2022, which date may be extended until July 1, 2022, subject to our receipt of a specified amount
of additional net financing proceeds and the achievement of a specified product revenue milestone. Additionally, the time
during which the Tranche Advance (as defined in Note 7 to our consolidated financial statements) may be requested by us
under the Loan Agreement, was extended until the Amortization Date. In addition, pursuant to the Fourth Amendment, the
minimum liquidity requirement of $3.0 million in cash and cash equivalents will be waived at any time we have recognized
$15.0 million of net product revenue during the applicable trailing three months. In light of the COVID-19 pandemic, the
associated disruption to the healthcare delivery and the uncertainty of resuming full direct physician promotion, future
sales are uncertain. Based on our current operating plans, we expect that our existing cash resources as of the date of this
Annual Report on Form 10-K will be sufficient to enable us to fund our operations, debt service obligations and capital
expenditure requirements well into the fourth quarter of 2022. We have based this estimate on assumptions that may prove
to be wrong, and we could use our capital resources sooner than we currently expect. This estimate assumes, among other
things, that we do not obtain any additional funding through grants and clinical trial support, collaboration agreements, or
equity or debt financings. This estimate also assumes that we remain in compliance with the covenants and no event of
default occurs under the Loan Agreement.
We expect to continue to invest in critical commercial and medical affairs activities, as well as investing in our
supply chain for the commercialization of SIVEXTRO and XENLETA and the potential commercial launch of CONTEPO.
We expect to seek additional funding in future periods to support these activities.
Our future capital requirements will depend on many factors, including:
● the costs and timing of process development and manufacturing scale-up activities associated with
XENLETA and, if approved, CONTEPO;
● the costs, timing and outcome of regulatory review of CONTEPO;
● the costs of commercialization activities for SIVEXTRO, XENLETA and CONTEPO if we receive
marketing approval for CONTEPO, including the costs and timing of establishing product sales, marketing
distribution and outsourced manufacturing capabilities, including the costs of building finished product
inventory and its components in preparation of initial marketing of CONTEPO;
● revenue received from commercial sales of SIVEXTRO, XENLETA and, subject to the resubmission of the
CONTEPO NDA and potential receipt of marketing approval, CONTEPO;
● the costs of developing XENLETA and CONTEPO for the treatment of additional indications;
● the impact of the COVID-19 pandemic;
● our ability to establish collaborations on favorable terms, if at all;
● the scope, progress, results and costs of product development of any other product candidates that we may
develop;
● the extent to which we in-license or acquire rights to other products, product candidates or technologies,
including additional community products;
● the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual
property rights and defending against intellectual property-related claims;
69
Table of Contents
● the continued availability of Austrian governmental grants;
● the costs of our physical presence in the United States, Ireland and Austria;
● interest expense on our debt and the eventual repayment of our debt obligations which is scheduled to begin
in April 2022;
● the requirement to keep minimum cash balances per the terms of our debt obligations as well as our ability to
remain in compliance with our debt covenants;
● the costs of operating as a company with a commercial rather than a research and development focus; and
● the costs of operating as a public company in the United States.
Our commercial revenues will be derived from sales of SIVEXTRO, XENLETA and from CONTEPO, if
approved, or any other products that we successfully develop, in-license or acquire. SIVEXTRO, XENLETA or, if
approved, CONTEPO or any other product candidate that we develop, in-license or acquire may not achieve commercial
success. Additionally, the reliance on a commercial sales organization may adversely impact our sales of SIVEXTRO and
XENLETA. If we fail to generate sufficient revenues from the sale of SIVEXTRO, XENLETA, or the commercialization
of CONTEPO, if approved, or any other product candidate that we successfully develop, in-license or acquire, we will need
to obtain substantial additional financing to achieve our business objectives.
Adequate additional financing may not be available to us on acceptable terms, or at all. Under General Instruction
I.B.6 to Form S-3, or the Baby Shelf Rule, the amount of funds we can raise through primary public offerings of securities
in any 12-month period using our registration statement on Form S-3 is limited to one-third of the aggregate market value
of the ordinary shares held by our non-affiliates. As of March 28, 2022, the aggregate market value of our ordinary shares
held by our non-affiliates was approximately $32.1 million, based on 61,197,667 ordinary shares held by non-affiliates and
a price of $0.525 per share, which was the last reported sale price of our ordinary shares on the Nasdaq Global Select
Market on February 9, 2022. We therefore are limited by the Baby Shelf Rule as of the filing of this Annual Report on
Form 10-K, until such time as our public float exceeds $75.0 million. We will need substantial additional funding. If we are
unable to raise capital when needed or on acceptable terms, we could be forced to delay, reduce or eliminate our product
development programs or commercialization efforts.
In addition, as part of our corporate strategy, we continue to evaluate business development opportunities and
potential collaborations. We may further expand our product pipeline through opportunistically in-licensing or acquiring
the rights to complementary products, product candidates and technologies for the treatment of a range of infectious
diseases or other products that we would market with our commercial infrastructure, including additional community
products, which could involve an acquisition of or combination or other strategic transaction with another operating
business. To the extent any additional business development opportunity is consummated, our capital expenditures may
increase significantly.
Raising additional capital may cause dilution to our security holders, restrict our operations or require us to relinquish
certain rights to our technologies, products or product candidates.
Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs
through a combination of equity offerings, debt financings, collaborations, and funding from local and international
government entities and non-government organizations in the disease areas addressed by our products or product
candidates and marketing, distribution or licensing arrangements. To the extent that we raise additional capital through the
sale of equity or convertible debt securities, our security holders’ ownership interests will be diluted, and the terms of these
securities may include liquidation or other preferences that adversely affect the rights of our security holders. Additional
debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to take
specific actions, such as incurring additional debt, making capital expenditures or declaring dividends. In
70
Table of Contents
addition, debt service obligations under any debt financings may limit the availability of our cash for other purposes, and
we may be unable to make interest payments or repay the principal of such debt financings when due.
In June 2019, we entered into an Open Market Sale AgreementSM, or the Jefferies ATM Agreement, with
Jefferies, pursuant to which, from time to time, we may offer and sell ordinary shares, for aggregate gross sale proceeds of
up to $50.0 million through Jefferies by any method permitted that is deemed an “at the market offering” as defined in Rule
415(a)(4) promulgated under the Securities Act of 1933, as amended.
In May 2021, we entered into an Open Market Sale AgreementSM, or the New Sale Agreement, with Jefferies, as
agent, pursuant to which we may offer and sell ordinary shares, nominal value $0.01 per share for aggregate gross sale
proceeds of up to $50.0 million, from time to time through Jefferies, by any method permitted that is deemed an “at the
market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended. Upon entry into
the New Sale Agreement, our existing Jefferies ATM Agreement was terminated. We did not incur any termination
penalties as a result of the replacement of the Jefferies ATM Agreement. As of the effective date of the termination of the
Jefferies ATM Agreement, we had sold an aggregate of 5,925,699 of our ordinary shares pursuant to the Jefferies ATM
Agreement for aggregate gross proceeds of $33.7 million and net proceeds to us of $31.9 million, after deducting
commissions and offering expenses payable by us. The approximately $16.3 million of ordinary shares that had been
available for sale pursuant to the Jefferies ATM Agreement remained unsold at the time of its replacement. The
replacement of the Jefferies ATM Agreement terminated any future sales of ordinary shares through the Jefferies ATM
Agreement.
As of December 31, 2021, we have issued and sold an aggregate of 18,232,689 ordinary shares pursuant to the
New Sale Agreement and received gross proceeds of $30.5 million and net proceeds of $29.3 million, after deducting
commissions to Jefferies and other offering expenses. From January 1, 2022 and through the date of this filing, we have
issued and sold an aggregate of 1,338,282 ordinary shares pursuant to the New Sale Agreement and received gross
proceeds of $595,000 and net proceeds of $580,000, after deducting commissions to Jefferies and other offering expenses.
On December 20, 2019, we sold to certain institutional investors in a registered direct offering an aggregate of
1,379,310 ordinary shares, and accompanying warrants to purchase up to an aggregate of 1,379,310 ordinary shares. Each
share was issued and sold together with an accompanying warrant at a combined price of $14.50 per security. The proceeds
to us from the offering were $20.0 million gross and $18.3 million net, after deducting the placement agent’s fees and other
offering expenses. As of December 31, 2021, there were 1,379,310 warrants outstanding from the offering, where each
warrant has an exercise price of $19.00 per share and will expire on the date that is three years and six months after the
initial issuance date.
On May 29, 2020, we entered into a securities purchase agreement with certain institutional investors, including
Fidelity Management & Research Company, LLC pursuant to which we issued and sold in a registered direct offering an
aggregate of 4,144,537 ordinary shares and accompanying warrants to purchase up to an aggregate of 4,144,537 ordinary
shares. Each share we issued and sold together with an accompanying warrant at a combined price of $9.1686. The
proceeds to us from the offering were $38.0 million gross and $35.2 million net, after deducting the placement agent’s fees
and other offering expenses. Each warrant was immediately exercisable and will expire on the two-year anniversary of the
issuance date. As of December 31, 2021, there were 4,059,532 warrants outstanding from the offering at an exercise price
of $7.92 per share.
On March 1, 2021, we entered into a securities purchase agreement with certain institutional investors pursuant to
which we issued and sold in a registered direct offering (1) an aggregate of 9,761,010 ordinary shares, $0.01 nominal value
per share, and accompanying warrants to purchase up to an aggregate of 4,880,505 ordinary shares and (2) pre-funded
warrants to purchase up to an aggregate of 600,000 ordinary shares and accompanying ordinary share warrants to purchase
up to an aggregate of 300,000 ordinary shares. Each share was issued and sold together with an accompanying ordinary
share warrant at a combined price of $2.4525, and each pre-funded warrant was issued and sold together with an
accompanying ordinary share warrant at a combined price of $2.4425. The proceeds to us from the offering were $25.4
million gross and $23.4 million net after deducting the placement agent’s fees and estimated offering expenses. Each pre-
funded warrant had an exercise price per ordinary share equal to $0.01 and each pre-funded warrant was
71
Table of Contents
exercised in full on the issuance date. Each warrant has an exercise price per ordinary share equal to $2.39, is exercisable
on the date of issuance and will expire on the five-year anniversary of the date of issuance. As of December 31, 2021, there
were 5,180,505 warrants outstanding from the offering at an exercise price of $2.39 per share.
On September 24, 2021, we entered into a purchase agreement, or Purchase Agreement, with Lincoln Park Capital
Fund, LLC, or Lincoln Park, which, subject to the terms and conditions, provides that we have the right to sell to Lincoln
Park and Lincoln Park is obligated to purchase up to $23.0 million of our ordinary shares. In addition, under the Purchase
Agreement, we agreed to issue a commitment fee of 632,474 ordinary shares, or the Commitment Shares, as consideration
for Lincoln Park entering into the Purchase Agreement and for the payment of $0.01 per Commitment Share. Under the
Purchase Agreement, we may from time to time, at our discretion, direct Lincoln Park to purchase on any single business
day, or a Regular Purchase, up to (i) 400,000 ordinary shares if the closing sale price of our ordinary shares is not below
$0.25 per share on Nasdaq, (ii) 600,000 ordinary shares if the closing sale price of our ordinary shares is not below $2.00
per share on Nasdaq or (iii) 800,000 ordinary shares if the closing sale price of our ordinary shares is not below $3.00 per
share on Nasdaq. In addition to Regular Purchases, we may also direct Lincoln Park to purchase other amounts as
accelerated purchases or as additional accelerated purchases on the terms and subject to the conditions set forth in the
Purchase Agreement. In any case, Lincoln Park’s commitment in any single Regular Purchase may not exceed $2.5 million
absent a mutual agreement to increase such amount. As of December 31, 2021, we have issued and sold an aggregate of
2,400,000 ordinary shares pursuant to the Purchase Agreement and received net proceeds of $2.4 million. From January 1,
2022 and through the date of this filing, we have issued and sold an aggregate of 3,600,000 ordinary shares pursuant to the
Purchase Agreement and received net proceeds of $1.6 million. As of the date of this filing, we may issue and sell ordinary
shares for gross proceeds of up to $19.0 million under the Purchase Agreement, subject to the Nasdaq rules which may
limit our ability to make sales of our ordinary shares to Lincoln Park in excess of a specified amount without prior
shareholder approval.
In addition, in connection with the closing of the acquisition of Zavante Therapeutics, Inc., or Zavante, together
with its lead product candidate CONTEPO, or the Acquisition, we issued 733,690 of our ordinary shares to former Zavante
stockholders as initial upfront consideration and following the one year anniversary of the closing of the Acquisition on
July 25, 2019, we issued an additional 81,518 ordinary shares to the former Zavante stockholders that had been subject to
reduction in respect of certain indemnification and other obligations pursuant to the Merger Agreement. Such shares are
able to be freely sold in the public market, subject to any requirements and restrictions, including any applicable volume
limitations, imposed by Rule 144 under the Securities Act. In addition, the Merger Agreement provides that we may issue
up to an additional $97.5 million in our ordinary shares to former Zavante stockholders upon the achievement of specified
regulatory and commercial milestones in the future, and obligates us to provide registration rights with respect to the
registration for resale of such additional ordinary shares that may become issuable upon the achievement of such
milestones. The issuance of our ordinary shares to satisfy the milestone payments will cause dilution to our security
holders, and the sale or resale of these shares in the public market, or the market’s expectation of such sales, may result in
an immediate and substantial decline in our share price. Such a decline would adversely affect our investors and also might
make it difficult for us to sell equity securities in the future at a time and at a price that we deem appropriate.
If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing
arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams,
research programs or product candidates or to grant licenses on terms that may not be favorable to us. If we are unable to
raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or
terminate our product development or commercialization efforts or grant rights to develop and market product candidates
that we would otherwise prefer to develop and market ourselves.
Our limited operating history may make it difficult for you to evaluate the success of our business to date and to assess
our future viability.
Our operations to date have been limited to organizing and staffing our company, developing and securing our
technology, raising capital, undertaking preclinical studies and clinical trials of our product candidates, preparing and filing
NDAs for our product candidates, the commercial launch of XENLETA and the direct selling of SIVEXTRO. We have not
yet demonstrated our ability to conduct sales and marketing activities necessary for successful product
72
Table of Contents
commercialization. Consequently, any predictions you make about our future success or viability may not be as accurate as
they could be if we had a longer operating history.
In addition, we may encounter unforeseen expenses, difficulties, complications, delays and other known and
unknown factors. Also, we may encounter delays or difficulties in our efforts to, or fail to, successfully integrate
CONTEPO into our business strategy. Moreover, we are in the process of transitioning from a company with a research and
development focus to a company capable of supporting commercial activities. We may not be successful in such a
transition.
Our level of indebtedness and debt service obligations could adversely affect our financial condition and may make it
more difficult for us to fund our operations.
On March 11, 2020, we entered into the Amendment to the Loan Agreement pursuant to which we agreed to repay
to Hercules $30.0 million of the $35.0 million in aggregate principal amount of debt outstanding under the Loan
Agreement. Following the Prepayment, there remains outstanding $5.0 million in principal amount under the Loan
Agreement, the end of term loan charge payment of $2.4 million and the Prepayment fee of $300,000, and we are eligible
to request to borrow an additional $5.0 million subject to the lender’s sole discretion. We plan to begin to repay the
outstanding principal amount under the Loan Agreement in April 2022.
Our obligations under the Loan Agreement are secured by substantially all of our personal property, intellectual
property and other assets owned or later acquired by us and our subsidiaries. This indebtedness may create additional
financing risk for us, particularly if our business or prevailing financial market conditions are not conducive to paying off
or refinancing our outstanding debt obligations at maturity. This indebtedness could also have important negative
consequences, including:
● the need to repay our indebtedness by making payment of interest only initially and then interest and
principal, which will reduce the amount of funds available to finance our operations, our research and
development efforts and our general corporate activities;
● our failure to comply with the restrictive covenants in the Loan Agreement or the occurrence of an event that
has a material adverse effect on our business, operations, properties, assets, condition, our ability to pay any
amounts due, the collateral securing our obligations under the Loan Agreement or the ability of Hercules to
enforce any of its rights under the Loan Agreement could result in an event of default that, if not cured or
waived, would accelerate our obligation to repay this indebtedness and permit the lender to enforce its
security interest in the assets securing such indebtedness, including the cash accounts pledged to it; and
● the need to maintain minimum cash balances under specified circumstances, which restricts our ability to
invest in the business and fund our operations.
To the extent additional debt is added to our current debt levels, the risks described above could increase.
We may not have cash available to us in an amount sufficient to enable us to make interest or principal payments on
our indebtedness when due or to comply with minimum cash balance requirements.
Failure to satisfy our current and future debt obligations under the Loan Agreement, or the occurrence of a
material adverse effect as defined in the Loan Agreement, could result in an event of default and, as a result, the lender
under the Loan Agreement could accelerate all of the amounts due. In the event of an acceleration of amounts due under
the Loan Agreement as a result of an event of default, we may not have sufficient funds or may be unable to arrange for
additional financing to repay our indebtedness. In addition, the lender could seek to enforce their security interests in the
assets securing such indebtedness.
73
Table of Contents
We are subject to certain restrictive covenants which, if breached, could have a material adverse effect on our business
and prospects.
The Loan Agreement imposes operating and other restrictions on us. Such restrictions will affect, and in many
respects limit or prohibit, our ability and the ability of any future subsidiary to, among other things:
● declare dividends or redeem or repurchase equity interests;
● incur additional indebtedness and liens;
● make loans and investments;
● engage in mergers, acquisitions and asset sales;
● undertake certain transactions with affiliates
● undergo a change in control;
● add or change business locations; and
● settle in cash potential milestone payment obligations that may become payable by us in the future to former
security holders of Zavante.
We are also required to satisfy certain financial covenants, including an obligation to maintain specified minimum
amounts of cash and cash equivalents in accounts pledged to Hercules. Under the Third Amendment, we and Hercules
agreed to defer the end of term loan charge payment in the amount of approximately $2.1 million that would have
otherwise become payable on the date of the Prepayment and to reduce the prepayment charge with respect to the
Prepayment from $600,000 to $300,000 and to defer its payment, in each case, until June 1, 2023 or such earlier date on
which all loans under the Loan Agreement are repaid or become due and payable. The Third Amendment also reset the
revenue performance covenant to 70% of targeted revenue based on a revised net product revenue forecast and lowered our
minimum liquidity requirement to $3.0 million in cash and cash equivalents. The new minimum liquidity requirement will
not apply if CONTEPO receives regulatory approval from the U.S. Food and Drug Administration and we achieve at least
70% of our revised net product revenue targets under the Loan Agreement. Pursuant to the Fourth Amendment, the date on
which we must commence repaying principal under the Loan Agreement was extended to April 1, 2022, which date may
be extended until July 1, 2022, subject to our receipt of a specified amount of additional net financing proceeds and the
achievement of a specified product revenue milestone. Additionally, the time during which the Tranche Advance (as
defined in Note 7 to our consolidated financial statements) may be requested by us under the Loan Agreement was
extended until the Amortization Date. In addition, pursuant to the Fourth Amendment, the minimum liquidity requirement
of $3.0 million in cash and cash equivalents will be waived at any time we have recognized $15.0 million of net product
revenue during the applicable trailing three months.
These restrictive covenants may prevent us from undertaking an action that we feel is in the best interests of our
business. In addition, if we were to breach any of these restrictive covenants, or if a material adverse effect as defined
under the Loan Agreement occurs, Hercules could accelerate our indebtedness under the Loan Agreement or enforce its
security interest against our assets, either of which would materially adversely affect our ability to continue to operate our
business.
74
Table of Contents
We have relied on, and expect to continue to rely on, certain government grants and funding from the Austrian
government. Should these funds cease to be available, or our eligibility be reduced, or if we are required to repay any of
these funds, this could impact our ongoing need for funding and the timeframes within which we currently expect
additional funding will be required.
As a company that carried out extensive research and development activities, we have benefited from the Austrian
research and development support regime, under which we were eligible to receive a research premium from the Austrian
government equal to 14% (12% for the fiscal years 2016 and 2017 and 10%, in the case of fiscal years prior to 2016) of a
specified research and development cost base. Qualifying expenditures largely comprised research and development
activities conducted in Austria, however, the research premium was also available for certain related third-party expenses
with additional limitations. We received research premiums of $1.4 million for the year ended December 31, 2020 and $1.3
million for the year ended December 31, 2019. We have not received any research premium for our qualified 2021
expenditures as of December 31, 2021. As we expand our business outside of Austria, we may not be able to continue to
claim research premiums to the same extent as we have in previous years or at all, as some research and development
activities may no longer be considered to occur in Austria. As research premiums that have been paid out already may be
audited by the tax authorities, there is a risk that parts of the submitted cost base may not be considered as eligible and
therefore repayments may have to be made.
The intended efficiency of our corporate structure depends on the application of the tax laws and regulations in the
countries where we operate, and we may have exposure to additional tax liabilities or our effective tax rate could
change, which could have a material impact on our results of operations and financial position.
As a company with international operations, we are subject to income taxes, as well as non-income based taxes, in
both the United States and various foreign jurisdictions. We have designed our corporate structure, the manner in which we
develop and use our intellectual property, and our intercompany transactions between our subsidiaries in a way that is
intended to enhance our operational and financial efficiency. The application of the tax laws and regulations of various
countries in which we operate and to our global operations is subject to interpretation. We also must operate our business in
a manner consistent with our corporate structure to realize such efficiencies. The tax authorities of the countries in which
we operate may challenge our methodologies for valuing developed technology or for transfer pricing. If, for one or more
of these reasons, tax authorities determine that the manner in which we operate results in our business not achieving the
intended tax consequences, our effective tax rate could increase and harm our financial position and results of operations.
A change in the tax law in the jurisdictions in which we do business, including an increase in tax rates, an adverse
change in the treatment of an item of income or expense, a decrease in tax rates in a jurisdiction in which we have
significant deferred tax assets, or a new or different interpretation of applicable tax law could result in a material increase
in tax expense.
Risks Related to Product Development and Commercialization
Business interruptions resulting from the SARS-CoV-2 infection causing COVID-19 outbreak or similar public health
crises have caused a disruption of the development of our product candidates and adversely impacted our business.
Beginning in 2019, a novel strain of a virus named SARS-CoV-2 (severe acute respiratory syndrome coronavirus
2), or coronavirus, which causes coronavirus disease 2019, or COVID-19, surfaced in Wuhan, China and spread to
countries across the world, including Ireland, Austria and the United States, where our offices and laboratory space are
located. COVID-19 caused federal, state and local governments to implement measures to slow the spread of the outbreak
through quarantines, strict travel restrictions and bans, heightened border scrutiny and other measures. The outbreak and
government measures taken in response have also had a significant impact, both direct and indirect, on businesses and
commerce, as worker shortages have occurred; supply chains have been disrupted; facility inspections by regulatory
authorities and production have been suspended; and demand for certain goods and services, such as medical services and
supplies, has spiked, while demand for other goods and services has fallen significantly.
75
Table of Contents
Public health crises such as pandemics or similar outbreaks could adversely impact our business. The COVID-19
pandemic is evolving, and to date has led to the implementation of various responses, including government-imposed
quarantines, business closures, school closures, travel restrictions and other public health safety measures, as well as
reported adverse impacts on healthcare resources, facilities and providers across the United States and in other countries
including Ireland and Austria. The extent to which COVID-19 further impacts our operations or those of our third-party
partners will depend on future developments, including the extent there is any resurgence of the COVID-19 virus or any
variant strains of the virus, the availability and effectiveness of vaccines and the impact of the foregoing on our business,
which are highly uncertain and cannot be predicted with confidence.
Additionally, timely completion of clinical trials is dependent upon the availability of, for example, clinical trial
sites, researchers and investigators, site monitors, screening of study subjects, regulatory agency personnel, and materials,
which may be adversely affected by global health matters, such as pandemics. Our Phase 1 clinical trial CONTEPO for use
in pediatric patients with cUTIs, for example, has been significantly delayed by the COVID-19 pandemic.
In particular, shelter-in-place orders and other mandated local travel prohibitions restricted the activities of our
sales force and caused us to determine to terminate our entire hospital-based sales force in April 2020.
We have implemented a hybrid-remote-working policy for all of our U.S. employees, and we may take further
actions that alter our operations as may be required by federal, state, or local authorities, or which we determine are in our
best interests. While most of our operations can be performed remotely, there is no guarantee that we will be as effective
while working remotely because our team is dispersed, many employees may have additional personal needs to attend to
(such as looking after children as a result of school closures or family who become sick), and employees may become sick
themselves and be unable to work. Decreased effectiveness of our team could adversely affect our results due to our
inability to meet in person with customers and physicians, or other decreases in productivity that could seriously harm our
business.
The effects of COVID-19 pandemic also disrupted the FDA’s review of our NDA for CONTEPO. On March 10,
2020, the FDA announced that it would restrict travel of its employees to Europe for inspections as a result of the spread of
COVID-19. On June 19, 2020 we received a CRL for CONTEPO in connection with our NDA for CONTEPO for the
treatment of cUTIs, including AP. Although our European contract manufacturing partners were prepared for regulatory
authority inspections, the CRL cited observations at our manufacturing partners that could not be resolved due to FDA’s
inability to conduct onsite inspections because of travel restrictions. We do not have a forecasted date for the resubmission
of our NDA for CONTEPO for the treatment of cUTIs, including AP.
Additionally, certain of the activities of our former collaborator, Sinovant, were delayed in China. If these delays
continue and impact Sumitomo Pharmaceuticals (Suzhou)’s, Sinovant’s successor, efforts to develop and commercialize
lefamulin in China, our receipt of future milestone payments or potential royalties on sales of the China Region Licensed
Products may be delayed. Also, the spread of COVID-19 may affect the ability of our third-party manufacturers to supply
XENLETA, CONTEPO or any future product candidates. We have secured a virtual and in-person sales effort with
community-based expertise with Amplity Health, which is a contract sales organization, to replace our hospital-based sale
force and began a small and focused sales effort for SIVEXTRO and XENLETA in September 2020. We expanded this
effort to 60 sales representatives in 2021 and may expand it further. We also piloted a virtual promotion effort with
incremental sales representatives in the third quarter of 2021.
The COVID-19 pandemic has already caused significant disruptions in the financial markets, and may continue to
cause such disruptions, which could impact our ability to raise additional funds through public offerings and may also
impact the volatility of our ordinary share price and trading in our ordinary shares. Moreover, the significant ongoing
impact of the pandemic on economies worldwide could result in more extensive adverse effects on our business and
operations. We cannot be certain what the overall impact of the COVID-19 pandemic will be on our business and it has the
potential to significantly and adversely affect our business, financial condition, results of operations and prospects.
In April 2020, we announced a plan to restructure our hospital-based commercial sales force and transition to a
community-based sales effort.
In April 2020, we announced a plan to restructure our hospital-based commercial sales force and transition to a
community-based sales effort. This restructuring reduced costs to align the capabilities of our sales efforts with our
strategic re-focus on making sales of XENLETA to community health care professionals, This restructuring resulted in
76
Table of Contents
the termination of 66 employees, consisting of our entire hospital-based sales personnel and certain members of our sales
force leadership team. Additional reductions in headcount occurred in the third quarter of 2020 including the restructuring
of the commercial organization, which led to the elimination of the role of the Chief Commercial Officer. Our commercial
operations now report directly to our Chief Executive Officer. We have secured a virtual and in-person sales effort with
community-based expertise with Amplity Health, which is a contract sales organization, to replace our hospital-based sale
force and began a small and focused sales effort for SIVEXTRO and XENLETA in September 2020. We expanded this
effort to 60 sales representatives and may expand it further. We also piloted a virtual promotion effort with incremental
sales representatives in the third quarter of 2021.
We depend heavily on the success of XENLETA, which the FDA has approved for oral and IV use for the treatment of
CABP, SIVEXTRO, approved by the FDA for oral and IV use of adults and adolescents for the treatment of ABSSSI,
and CONTEPO, which we are developing for the treatment of cUTI, including AP. If we are unable to obtain marketing
approval for CONTEPO, or if we fail in our commercialization efforts for SIVEXTRO, XENLETA, or, if approved,
CONTEPO, or experience significant delays in doing so, our business will be materially harmed.
We have invested a significant portion of our efforts and financial resources in the development of XENLETA
and, more recently, in CONTEPO. There remains a significant risk that we will fail to successfully develop CONTEPO for
cUTI or any other indication and that we may fail to successfully commercialize XENLETA for CABP and SIVEXTRO
for ABSSSI.
On August 19, 2019, the FDA approved the oral and IV formulations of XENLETA. On July 28, 2020, the
European Commission issued a legally binding decision for approval of the marketing authorization application for
XENLETA for the treatment of CAP in adults following a review by the EMA. In July 2020, Sunovion Pharmaceuticals
Canada Inc. additionally received approval from Health Canada to market oral and IV formulations of XENLETA for the
treatment of CAP in adults, upon receipt of the Notice of Compliance from Health Canada. In mid-2018, we initiated a
Phase 1, non-comparative, open-label study of the pharmacokinetics and safety of a single dose of IV XENLETA in
pediatric subjects from birth to 18 years of age. As a result of COVID-19, research sites were temporarily closed for
enrollment in 2020 and 2021 as hospitals suspended access and non-essential clinical research to focus on health care
delivery to COVID-19 patients. As of July 2020, trials started to re-open, where allowed by the institution, and initiated
screening of potential subjects at sites.
In June 2016, Zavante initiated the ZEUS Study. In April 2017, Zavante announced positive topline results of the
ZEUS Study. We submitted an NDA for marketing approval of CONTEPO for the treatment of cUTI in adults in the
United States, utilizing the FDA’s 505(b)(2) pathway, in October 2018. In April 2019, the FDA issued a CRL in connection
with our NDA for CONTEPO for the treatment of cUTIs, including AP, stating that it was unable to approve the
application in its current form. In December 2019, we resubmitted our NDA for CONTEPO for the treatment of cUTIs,
including AP. On June 19, 2020 we received a second CRL from the FDA. Although our European contract manufacturing
partners were prepared for regulatory authority inspections, the CRL cited observations at our manufacturing partners that
could not be resolved due to FDA’s inability to conduct onsite inspections because of travel restrictions. On October 30,
2020, we participated in a “Type A” meeting with the FDA to obtain any new information related to the FDA´s pending
conduct of inspections of foreign manufacturers during the COVID-19 pandemic that has negatively impacted a number of
FDA product reviews, including our NDA for CONTEPO. On April 14, 2021, the FDA issued industry guidance on remote
interactive evaluations of drug manufacturing and bioresearch monitoring facilities during COVID-19 specifying that when
it cannot perform a PAI or PLI or when the FDA determines that it would be useful to supplement a planned inspection, the
agency will consider using tools other than a physical inspection and select the most appropriate method to address the
specific risks that justify the need for the PAI or PLI. The FDA informed us that onsite inspections of our manufacturing
partners in Europe are required in order for the FDA to complete the review of a potential CONTEPO NDA resubmission.
Due to travel restriction related to the COVID-19 pandemic, the FDA suspended onsite inspections of ex-US
manufacturers for all non-COVID products. As a result, we requested an extension of the timeline for a potential
CONTEPO NDA resubmission until June 2023, which the FDA granted on March 21, 2022. We are awaiting further clarity
from the FDA regarding their ability to complete onsite inspections at our manufacturing partners in Italy and Spain before
determining specific timing of the potential NDA resubmission, which we plan to submit promptly once we have clarity
from the FDA. The FDA released the Resiliency Roadmap for FDA Inspectional Oversight that describes the systematic
approach that FDA will utilize to manage
77
Table of Contents
postponed inspections and other oversight activities. The prioritization plan considers public health risks related to
conducting an inspection, such as the impact of the product’s availability on public health, as well as investigator safety
and travel restrictions/advisories. In addition, the FDA informed us that, while they cannot predict when an inspection may
occur and when the pandemic may prevent the FDA from completing inspections, tier 1 mission-critical inspections and
tier 2 higher priority inspections, which includes PAIs, will continue to be prioritized going forward. We cannot predict the
outcome of any further interactions with the FDA or when CONTEPO will receive marketing approval, if at all.
In June 2018, we initiated a Phase 1, non-comparative, open-label study of the pharmacokinetics and safety of a
single dose of CONTEPO in pediatric subjects less than 12 years of age receiving standard-of-care antibiotic therapy for
proven or suspected infection or peri-operative prophylaxis. A total of 24 patients are expected to be enrolled at up to ten
clinical sites in the United States. As a result of COVID-19, research sites were temporarily closed in 2020 and 2021 and
only a minority of sites are currently screening patients and allowing access to the institution. As a result, our development
timeline for CONTEPO for use in pediatric patients with cUTIs has been modified to reflect a two-year delay due to
COVID-19.
In July 2020, we entered into a Sales Promotion and Distribution Agreement, or the Distribution Agreement, with
subsidiaries of Merck pursuant to which we licensed the right, subject to specified conditions, to promote, distribute and
sell SIVEXTRO for ABSSSIs, caused by certain susceptible Gram-positive microorganisms in the SIVEXTRO Territory.
We expect to incur significant additional sales, marketing, distribution and manufacturing expenses for the
commercialization of SIVEXTRO, XENLETA and CONTEPO, if approved. We expect to continue to invest in critical
commercial promotion and distribution, medical affairs and other commercialization activities, as well as investing in our
supply chain for the commercialization of SIVEXTRO, XENLETA and the potential launch of CONTEPO. We expect to
seek additional funding in future periods to support these activities.
Our ability to generate meaningful product revenues will depend heavily on the successful commercialization of
SIVEXTRO and XENLETA and our obtaining marketing approval for CONTEPO. The success of SIVEXTRO,
XENLETA and, if approved, CONTEPO will depend on a number of factors, including the following:
● establishing and maintaining arrangements with third-party manufacturers for commercial supply and
receiving regulatory approval of our manufacturing processes and our third-party manufacturers’ facilities
from applicable regulatory authorities;
● the resubmission of our NDA for CONTEPO and potential receipt of marketing approval from the FDA for
CONTEPO for the treatment of cUTI, including AP;
● re-establishing an effective sales and marketing organization to successfully generate recurring sales of
SIVEXTRO, XENLETA and, if and when approved, CONTEPO;
● acceptance of SIVEXTRO, XENLETA and, if and when approved, CONTEPO by patients, the medical
community and third-party payors, including hospital formularies;
● achieving approval of favorable prescribing information;
● effectively competing with other therapies;
● the continued acceptable safety profile of SIVEXTRO, XENLETA and, if approved, CONTEPO;
● securing contracts to allow SIVEXTRO, XENLETA and, if approved, CONTEPO to be paid for by private
and public health insurance plans;
78
Table of Contents
● obtaining and maintaining patent and trade secret protection and regulatory exclusivity;
● protecting our rights in our intellectual property portfolio;
● obtaining and maintaining adequate distribution levels of SIVEXTRO, XENLETA and, if approved,
CONTEPO at all appropriate trade channels; and
● resolution of the COVID-19 pandemic.
Successful development of XENLETA and CONTEPO for the treatment of additional indications, if any, or for
use in other patient populations and our ability to broaden the labels for XENLETA and, if approved, CONTEPO will
depend on similar factors. If we do not achieve one or more of these factors in a timely manner or at all, we could
experience significant delays or an inability to successfully commercialize XENLETA for CABP or for any other
indication or CONTEPO for cUTI, including AP or for any other indication, which would materially harm our business.
SIVEXTRO, XENLETA and any other product candidate that receives marketing approval may fail to achieve the
degree of market acceptance by physicians, patients, third-party payors and others in the medical community necessary
for commercial success and the market opportunity for such products and product candidates, if approved, may be
smaller than we estimate.
SIVEXTRO, XENLETA and any other product candidate that receives marketing approval may nonetheless fail to
gain sufficient market acceptance by physicians, patients, third-party payors and others in the medical community. For
example, current treatments for ABSSSI, CABP and cUTI, including generic options, are well established in the medical
community, and doctors may continue to rely on these treatments without SIVEXTRO, XENLETA, CONTEPO or any of
our other product candidates that receive marketing authorization. In addition, our efforts to effectively communicate the
differentiating characteristics and key attributes of SIVEXTRO, XENLETA, CONTEPO or any of our other product
candidates that receive marketing authorization to clinicians and hospital pharmacies with the goal of establishing
favorable formulary status for SIVEXTRO, XENLETA, CONTEPO or any of our other product candidates that receive
marketing authorization may fail or may be less successful than we expect. If SIVEXTRO, XENLETA, CONTEPO or any
of our other product candidates that receive marketing authorization do not achieve an adequate level of acceptance, we
may not generate significant product revenues or any profits from operations. The degree of market acceptance of our
products and product candidates, if approved for commercial sale, will depend on a number of factors, including:
● the efficacy and potential advantages compared to alternative treatments;
● the ability of SIVEXTRO, XENLETA, CONTEPO or any other anti-infective product candidate to limit the
development of bacterial resistance in the pathogens it targets;
● the prevalence and severity of any side effects;
● the ability to offer our product candidates for sale at competitive prices, including in comparison to generic
competition;
● convenience and ease of administration compared to alternative treatments;
● the willingness of the target patient population to try new therapies, physicians to prescribe these therapies
and hospitals to approve the cost and use by their physicians of these therapies;
● our investment in and the strength of sales, marketing, patient access and distribution capabilities;
● the availability of third-party coverage and adequate reimbursement;
● the timing of any marketing approval in relation to other approvals of competitive products; and
79
Table of Contents
● obtaining and maintaining adequate distribution of our products to the appropriate trade channels.
Bacteria might develop resistance to SIVEXTRO, XENLETA, CONTEPO or any future product candidates more
rapidly or to a greater degree than we anticipate. If bacteria develop resistance or if SIVEXTRO, XENLETA, CONTEPO
or any future product candidates is not effective against drug-resistant bacteria, the efficacy of these products or product
candidates would decline, which would negatively affect our potential to generate revenues from these products and
product candidates.
Our ability to negotiate, secure and maintain third-party coverage and reimbursement may be affected by political,
economic and regulatory developments in the United States, the EU and other jurisdictions. Governments continue to
impose cost containment measures, and third-party payors are increasingly challenging prices charged for medicines and
examining their cost effectiveness, in addition to their safety and efficacy. If the level of reimbursement is below our
expectations, our revenue and gross margins would be adversely affected.
Hospital formulary approval of SIVEXTRO, XENLETA, CONTEPO or any future product candidates that receive
marketing authorization is an important component of our commercialization strategy. Accordingly, sales of IV
formulations of SIVEXTRO, XENLETA, CONTEPO or any future IV product candidates will depend substantially on the
extent to which hospital formulary approval is obtained. Hospital formulary approval may depend upon several factors,
including the determination that use of a product is:
● safe, effective and medically necessary;
● appropriate for the specific patient population;
● cost-effective; and
● neither experimental nor investigational.
Obtaining formulary approval from third-party payors can be an expensive and time-consuming process that will
require us to provide supporting scientific, clinical and cost-effectiveness data. We may not be able to provide data
sufficient to gain acceptance with respect to hospital formulary approval. We cannot be certain if and when we will obtain
hospital formulary approval to allow us to sell SIVEXTRO, XENLETA, if approved, CONTEPO or any future product
candidates that receive marketing authorization into our target markets. Even if we do obtain hospital formulary approval,
third-party payors, such as government or private health care insurers, carefully review and increasingly question the
coverage of, and challenge the prices charged for, drugs. Increasing efforts by hospitals in the United States and abroad to
cap or reduce healthcare costs may cause such organizations to limit formulary approval. We have experienced and expect
to continue to experience pricing pressures in connection with the sale of XENLETA in the hospital setting due to the trend
toward reducing hospital costs, managed healthcare, the increasing influence of health maintenance organizations and
additional legislative changes. These and other similar developments could significantly limit the degree of market
acceptance of SIVEXTRO, XENLETA, CONTEPO or any of our other product candidates that receive marketing
approval. To address this uncertainty, in early 2020 we began to utilize our hospital based sales force to call upon
approximately 7,800 high prescriber community doctors in an effort to potentially increase our penetration rates in the
community setting while maintaining sales efforts in the hospital setting before determining to terminate our entire sales
force. This effort ceased with the termination of our entire hospital-based sales force in April 2020. Additional reductions
in headcount occurred in the third quarter of 2020 including the restructuring of the commercial organization, which led to
the elimination of the role of the Chief Commercial Officer. Our commercial operations now report directly to our Chief
Executive Officer. We have secured a virtual and in-person sales effort with community-based expertise with Amplity
Health, which is a contract sales organization, to replace our hospital-based sale force and began a small and focused sales
effort for SIVEXTRO and XENLETA in September 2020. We expanded this effort to 60 sales representatives and may
expand it further. We also piloted a virtual promotion effort with incremental sales representatives in the third quarter of
2021.
80
Table of Contents
If we are unable to establish or maintain sales, marketing and distribution capabilities or enter into or maintain sales,
marketing and distribution agreements with third parties, we may not be successful in commercializing SIVEXTRO,
XENLETA, CONTEPO or any other product candidate if and when they are approved.
We have a limited sales, marketing, patient access and distribution infrastructure, and as a company we have
limited experience in the sale, marketing or distribution of pharmaceutical products and XENLETA is the first product that
we are commercializing. To achieve commercial success for SIVEXTRO, XENLETA and any other approved product, we
must re- establish and maintain an adequate sales, marketing, commercial operations, patient access and distribution
organization or outsource these functions to third parties. We have secured a virtual and in-person sales effort with
community-based expertise with Amplity Health, which is a contract sales organization, to replace our hospital-based sale
force and began a small and focused sales effort for SIVEXTRO and XENLETA in September 2020. We expanded this
effort to 60 sales representatives in 2021 and may expand it further. We also piloted a virtual promotion effort with
incremental sales representatives in the third quarter of 2021. In addition, we expect to utilize a variety of types of
collaboration, distribution and other marketing arrangements with one or more third parties to commercialize XENLETA in
markets outside the United States. We plan to commercialize CONTEPO, if approved, in the United States with targeted
sales efforts, but we do not have the right to commercialize CONTEPO in any markets outside the United States.
There are risks involved with establishing our own sales, marketing, commercial operations, patient access and
distribution capabilities and entering into arrangements with third parties to perform these services. If we do not establish
adequate sales, marketing, commercial operations, patient access and distribution capabilities prior to or in connection with
the commercial launch of any of our products, such products may fail to gain sufficient market acceptance by physicians,
patients, third-party payors and others in the medical community and may fail commercially or be less successful than we
expect. If the commercial launch of a product candidate for which we establish marketing and distribution capabilities is
delayed or does not occur for any reason, we would have prematurely or unnecessarily incurred these commercialization
expenses. This may be costly, and our investment would be lost if we cannot retain or reposition our sales and marketing
personnel.
Factors that may inhibit our efforts to commercialize our products on our own include:
● our inability to recruit, train and retain adequate numbers of effective sales, patient access, commercial
operations and marketing personnel;
● our inability to recruit, train and retain adequate numbers of effective headquarter and field personnel;
● the inability of sales personnel to obtain access to or persuade adequate numbers of physicians to prescribe
SIVEXTRO, XENLETA or any future products;
● the lack of complementary products to be offered by sales personnel, which may put our sales representatives
at a competitive disadvantage relative to sales representatives from companies with more extensive product
lines;
● the COVID-19 pandemic;
● unforeseen costs and expenses associated with creating an independent sales, marketing, commercial
operations, patient access and distribution organization; and
● a change in strategy resulting in the decrease or elimination of sales personnel.
If we enter into arrangements with third parties to perform sales, marketing, commercial operations, patient access
and distribution services, our product revenues or the profitability of these product revenues to us are likely to be lower
than if we were to market, sell and distribute ourselves any products that we develop. In addition, we may not be successful
in entering into arrangements with third parties to sell, market and distribute our product candidates or may be
81
Table of Contents
unable to do so on terms that are favorable to us. We likely will have little control over such third parties, and any of them
may fail to devote the necessary resources and attention to sell and market our products effectively. If we do not re-
establish and maintain sales, marketing and distribution capabilities successfully, either on our own or in collaboration with
third parties, we will not be successful in commercializing SIVEXTRO, XENLETA, or, if approved, CONTEPO.
We face substantial competition, which may result in others discovering, developing or commercializing products before
or more successfully than we do.
The development and commercialization of new drug products is highly competitive. We face competition with
respect to SIVEXTRO, XENLETA, CONTEPO and any other products we may seek to develop or commercialize in the
future from major pharmaceutical companies, specialty pharmaceutical companies and biotechnology companies
worldwide. Potential competitors also include academic institutions, government agencies and other public and private
research organizations that conduct research, seek patent protection and establish collaborative arrangements for research,
development, manufacturing and commercialization.
There are a variety of available therapies marketed for the treatment of ABSSSI, CABP and cUTI. Currently the
treatment of ABSSSI, CABP and cUTI is dominated by generic products. For both hospitalized and community patients,
combination therapy is frequently used for CABP and at times for cUTI. Many currently approved drugs are well-
established therapies and are widely accepted by physicians, patients, medical association guidelines and third-party payors
for the treatment of CABP and ABSSSI. We also are aware of various drugs under development or recently approved by
the FDA for the treatment of CABP and ABSSSI, including omadacycline (Nuzyra approved by the FDA in October 2018
on behalf of Paratek Pharmaceuticals Inc. for both CABP and ABSSSI)), delafloxacin (Baxdela approved by the FDA for
ABSSSI in June 2017 and expanded for CABP in October 2019 on behalf of Melinta Therapeutics Inc.), and oral
nafithromycin (Phase 2 clinical development by Wockhardt Ltd. for CABP). If approved, we expect CONTEPO will face
competition from commercially available branded antibiotics for the treatment of UTI such as ceftazidime-avibactam
(Avycaz), meropenem-vaborbactam (vabomere), plazomicin (Zemdri), ceftolozane-tazobactam (Zerbaxa), as well as
imipenem-cilastatin-relebactam (Recarbrio approved by the FDA in July 2019 on behalf of Merck & Co., Inc. ),
cefiderocol (Fetroja approved by the FDA in November 2019 on behalf of Shionogi Inc.), or drugs under development such
as tebipenem HBr (NDA to FDA for the Treatment of Complicated Urinary Tract Infections including Pyelonephritis in
October 2021– Spero Therapeutics), cefepime-taniborbactam (under Phase 3 clinical development by Venatorx
Pharmaceuticals), cefepime-enmetazobactam (under Phase 3 clinical development by Allecra Therapeutics), ETX0282-
cefpodoxime proxetil (under Phase 1 clinical development by Entasis Therapeutics) tebipenem (under development by
Spero), sulopenem (under development by Iterum Therapeutics), and LYS228 (under development by Novartis), as well as
generically available agents including piperacillin-tazobactam, fluoroquinolones, carbapenems, aminoglycosides,
tigecycline, and polymyxins.
Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products
that are safer, more effective, have fewer or less severe side effects, are approved for broader indications or patient
populations, are more convenient or are less expensive than any products that we may develop. Our competitors may also
obtain marketing approvals for their products more rapidly than we may obtain approval for ours, which could result in our
competitors establishing a strong market position before we are able to enter the market. In addition, our ability to compete
may be affected because in some cases insurers or other third-party payors seek to encourage the use of generic products.
This may have the effect of making branded products less attractive, from a cost perspective, to buyers. We expect that
SIVEXTRO, XENLETA and, if approved, CONTEPO will be priced at a significant premium over competitive generic
products. This pricing difference may make it difficult for us to replace existing therapies with SIVEXTRO, XENLETA
and CONTEPO. The key competitive factors affecting the success of our products and product candidates are likely to be
their efficacy, safety, convenience, price and the availability of coverage and reimbursement from government and other
third-party payors.
Many of our competitors may have significantly greater financial resources and expertise in research and
development, manufacturing, preclinical testing, conducting clinical trials, obtaining approvals from regulatory authorities
and marketing approved products than we do. Mergers and acquisitions in the pharmaceutical and biotechnology industries
may result in even more resources being concentrated among a smaller number of our competitors. Smaller and other early
stage companies may also prove to be significant competitors, particularly through
82
Table of Contents
collaborative arrangements with large and established companies. These third parties compete with us in recruiting and
retaining qualified scientific and management personnel, establishing clinical trial sites and patient registration for clinical
trials, as well as in acquiring technologies complementary to or necessary for our programs.
Even if we are able to successfully commercialize SIVEXTRO, XENLETA, CONTEPO or any other product candidate
that we develop, the product may become subject to unfavorable pricing regulations, third-party reimbursement
practices or healthcare reform initiatives, which would harm our business.
The regulations that govern marketing approvals, pricing, coverage and reimbursement for new drug products,
including XENLETA, vary widely from country to country. Current and future legislation may significantly change the
approval requirements in ways that could involve additional costs and cause delays in obtaining approvals. Some countries
require approval of the sale price of a drug before it can be marketed. In many countries, the pricing review period begins
after marketing or product licensing approval is granted. In some foreign markets, prescription pharmaceutical pricing
remains subject to continuing governmental control even after initial approval is granted. As a result, we might obtain
marketing approval for a product in a particular country, but then be subject to price regulations that delay our commercial
launch of the product, possibly for lengthy time periods, and negatively impact the revenues we are able to generate from
the sale of the product in that country. Adverse pricing limitations may hinder our ability to recoup our investment in one
or more product candidates, even if our product candidates obtain marketing approval.
Our ability to commercialize SIVEXTRO, XENLETA, CONTEPO or any other product candidate successfully
also will depend in part on its availability on hospital formularies and the extent to which coverage and adequate
reimbursement for these products and related treatments will be available from government health administration
authorities, private health insurers and other organizations. Government authorities and other third-party payors, such as
private health insurers and health maintenance organizations, decide which medications they will pay for and establish
reimbursement levels. A major trend in the healthcare industries in the European Union and the United States and
elsewhere is cost containment. Government authorities and other third-party payors have attempted to control costs by
limiting coverage and the amount of reimbursement for particular medications. Increasingly, third-party payors are
requiring that drug companies provide them with predetermined discounts from list prices and are challenging the prices
charged for medical products. We cannot be sure that coverage and reimbursement will be available for SIVEXTRO,
XENLETA, CONTEPO or any other product that we commercialize and, if coverage and reimbursement are available, the
level of reimbursement. Reimbursement may impact the demand for, or the price of, any product candidate for which we
obtain marketing approval. Obtaining and maintaining adequate reimbursement for SIVEXTRO, XENLETA and
CONTEPO may be particularly difficult because of the number of generic drugs, which are typically available at lower
prices, that are available to treat ABSSSI, CABP and cUTI. In addition, third-party payors are likely to impose strict
requirements for reimbursement of a higher priced drug, such as SIVEXTRO, XENLETA and CONTEPO. If
reimbursement is not available or is available only to limited levels, we may not be able to successfully commercialize
SIVEXTRO, XENLETA, CONTEPO or other product candidates for which we obtain marketing approval.
There may be significant delays in obtaining coverage and reimbursement for newly approved drugs, and
particularly in the hospital, coverage may be more limited than the purposes for which the drug is approved by the
applicable regulatory authority. Moreover, eligibility for coverage and reimbursement does not imply that any drug will be
paid for in all cases or at a rate that covers our costs, including research, development, manufacture, sale and distribution.
Interim reimbursement levels for new drugs, if applicable, may also not be sufficient to cover our costs and may not be
made permanent. Reimbursement rates may vary according to the use of the drug and the clinical setting in which it is
used, may be based on reimbursement levels already set for lower cost drugs, and may be incorporated into existing
payments for other services. Net prices for drugs may be reduced by mandatory discounts or rebates required by
government healthcare programs or private payors and by any future relaxation of laws that presently restrict imports of
drugs from countries where they may be sold at lower prices than in the United States. In the United States, third-party
payors often rely upon Medicare coverage policy and payment limitations in setting their own reimbursement policies. In
the European Union, reference pricing systems and other measures may lead to cost containment and reduced prices. Our
inability to promptly obtain coverage and adequate reimbursement rates from both government-funded and private payors
for any approved products that we develop could have a material adverse effect on our operating results, our ability to raise
capital needed to commercialize products and our overall financial condition.
83
Table of Contents
Product liability lawsuits against us could divert our resources, cause us to incur substantial liabilities and to limit
commercialization of SIVEXTRO, XENLETA and any other products that we may develop or in-license.
We face an inherent risk of product liability exposure related to the testing of XENLETA, CONTEPO and any
other product candidate that we develop in human clinical trials and an even greater risk related to the commercial sale of
SIVEXTRO, XENLETA and any other products that we may develop or in-license. If we cannot successfully defend
ourselves against claims that SIVEXTRO, XENLETA or our other product candidates caused injuries, we will incur
substantial liabilities. Regardless of merit or eventual outcome, liability claims may result in:
● reduced resources of our management to pursue our business strategy;
● decreased demand for SIVEXTRO, XENLETA, or any other product candidates that we may develop;
● injury to our reputation and significant negative media attention;
● withdrawal of clinical trial participants;
● significant costs to defend the related litigation;
● substantial monetary awards to trial participants or patients;
● loss of revenue; and
● the inability to commercialize any products that we may develop.
We maintain clinical trial liability insurance that covers bodily injury to patients participating in our clinical trials
up to a $10.0 million annual aggregate limit and subject to a per event deductible. This amount of insurance may not be
adequate to cover all liabilities that we may incur. We maintain $10.0 million in product liability insurance coverage for our
marketed products. Insurance coverage is increasingly expensive. We may not be able to maintain insurance coverage at a
reasonable cost or in an amount adequate to satisfy any liability that may arise.
If we fail to comply with our reporting and payment obligations under the Medicaid Drug Rebate Program or
other governmental pricing programs in the United States, we could be subject to additional reimbursement requirements,
penalties, sanctions and fines which could have a material adverse effect on our business, financial condition, results of
operations and growth prospects.
We participate in the Medicaid Drug Rebate Program and a number of other federal and state government pricing
programs in the United States in order to obtain coverage for SIVEXTRO and XENLETA by certain government
healthcare programs. These programs generally require us to pay rebates or provide discounts to certain private purchasers
or government payers in connection with our products when dispensed to beneficiaries of these programs. In some cases,
such as with the Medicaid Drug Rebate Program, the rebates are based on pricing and rebate calculations that we report on
a monthly and quarterly basis to the government agencies that administer the programs. The terms, scope and complexity
of these government pricing programs change frequently. We may also have reimbursement obligations or be subject to
penalties if we fail to provide timely and accurate information to the government, pay the correct rebates or offer the
correct discounted pricing. Changes to the price reporting or rebate requirements of these programs would affect our
obligations to pay rebates or offer discounts. Responding to current and future changes may increase our costs and the
complexity of compliance, will be time-consuming, and could have a material adverse effect on our results of operations.
84
Table of Contents
If clinical trials of XENLETA, CONTEPO or any of our other product candidates fail to demonstrate safety and
efficacy to the satisfaction of the FDA, regulatory authorities in the European Union, or other regulatory authorities or
do not otherwise produce favorable results, we may incur additional costs or experience delays in completing, or
ultimately be unable to complete, the development and commercialization of XENLETA, CONTEPO or any other
product candidate.
Before obtaining marketing approval from regulatory authorities for the sale of any product candidate, we must
complete preclinical development and early clinical trials, including Phase 1 clinical trials, in addition to extensive later-
stage Phase 3 clinical trials, to demonstrate the safety and efficacy of our product candidates in humans. Clinical testing is
expensive, difficult to design and implement, can take many years to complete and is uncertain as to outcome. A failure of
one or more clinical trials can occur at any stage of testing. The outcome of preclinical testing and early clinical trials may
not be predictive of the success of later clinical trials, and interim results of a clinical trial do not necessarily predict final
results. The design of a clinical trial can determine whether its results will support approval of a product, and flaws in the
design of a clinical trial may not become apparent until the clinical trial is well advanced or completed. Moreover,
preclinical and clinical data are often susceptible to varying interpretations and analyses, and many companies that have
believed their product candidates performed satisfactorily in preclinical studies and clinical trials have nonetheless failed to
obtain marketing approval of their products. In connection with the ZEUS Study in which CONTEPO met the primary
endpoint of statistical non-inferiority versus piperacillin/tazobactam, Zavante conducted a post-hoc primary efficacy
analysis of CONTEPO using results of blinded pulsed-field gel electrophoresis molecular typing of urinary tract pathogens.
Regulatory authorities typically give greater weight to results from pre-specified analyses and less weight to results from
post-hoc, retrospective analyses. While we believe this post-hoc analysis is illustrative information, the FDA may
ultimately have a different interpretation of any of our data that may be based on such post-hoc analysis, or the FDA may
conduct its own analyses and modify analysis populations which could lead to different numerical results or conclusions.
If we are required to conduct additional clinical trials or other testing or studies of XENLETA, CONTEPO or any
other product candidate that we develop beyond those that we contemplate; if we are unable to successfully complete our
clinical trials or other testing or studies; if the results of these trials, tests or studies are not positive or are only modestly
positive; if there are safety concerns; or if they are otherwise not acceptable to the FDA, we may:
● be delayed in obtaining marketing approval for our product candidates;
● not obtain marketing approval at all;
● obtain approval for indications or patient populations that are not as broad as intended or desired;
● obtain approval with labeling that includes significant use or distribution restrictions or safety warnings,
including boxed warnings;
● be subject to additional post-marketing testing requirements or restrictions;
● have the product removed from the market after obtaining marketing approval;
● be unable to obtain reimbursement for use of the product; or
● need to raise capital before we otherwise would or on terms less favorable to us.
The occurrence of any of the developments listed above could materially harm our business, financial condition,
results of operations and prospects.
85
Table of Contents
If we experience any of a number of possible unforeseen events in connection with our clinical trials, the potential
marketing approval or commercialization of XENLETA, CONTEPO or other product candidates could be delayed or
prevented.
We may experience numerous unforeseen events during, or as a result of, our clinical trials of XENLETA and
CONTEPO or other product candidates that could delay or prevent our ability to receive marketing approval or
commercialize XENLETA, CONTEPO or our other product candidates, including:
● clinical trials may produce negative or inconclusive results, and we may decide, or regulators may require us,
to conduct additional clinical trials or abandon product development programs;
● the number of patients required for clinical trials may be larger than we anticipate, enrollment in these
clinical trials may be slower than we anticipate, or participants may drop out of these clinical trials at a
higher rate than we anticipate;
● our third-party contractors may fail to comply with regulatory requirements or meet their contractual
obligations to us in a timely manner, or at all;
● regulators, institutional review boards or independent ethics committees may not authorize us or our
investigators to commence a clinical trial or conduct a clinical trial at a prospective trial site or may require
that we or our investigators suspend or terminate clinical research for various reasons, including
noncompliance with regulatory requirements or a finding that the participants are being exposed to
unacceptable health risks;
● we may experience delays in reaching or fail to reach agreement on acceptable clinical trial contracts or
clinical trial protocols with prospective trial sites;
● we may have to suspend or terminate clinical trials of our product candidates for various reasons, including a
finding that the participants are being exposed to unacceptable health or safety risks;
● the cost of clinical trials of our product candidates may be greater than we anticipate;
● the supply or quality of our product candidates or other materials necessary to conduct clinical trials of our
product candidates may be insufficient or inadequate;
● ongoing or future restrictions resulting from the COVID-19 pandemic and its collateral consequences may
result in internal and external operational delays and limitations; and
● our product candidates may have undesirable side effects or other unexpected characteristics, causing us or
our investigators, regulators, institutional review boards or independent ethics committees to suspend or
terminate the trials.
Our product development costs will increase if we experience delays in enrollment in our clinical development
program or our non-clinical development program or in obtaining marketing approvals. We do not know whether any
additional non-clinical tests or clinical trials will be required, or if they will begin as planned, or if they will need to be
restructured or will be completed on schedule, or at all. Significant non-clinical development program delays, including
chemistry, manufacturing and control activities, or clinical trial delays also could shorten any periods during which we may
have the exclusive right to commercialize our product candidates or allow our competitors to bring products to market
before we do and impair our ability to successfully commercialize our product candidates and may harm our business and
results of operations.
86
Table of Contents
If we experience delays or difficulties in the enrollment of patients in our clinical trials, our receipt of necessary
marketing approvals could be delayed or prevented.
We may not be able to initiate or continue clinical trials for our product candidates, including with respect to
XENLETA, CONTEPO or any other product candidate that we develop, if we are unable to locate and enroll a sufficient
number of eligible patients to participate in these clinical trials, including our Phase 1 clinical trial of IV XENLETA in
pediatric patients. In addition, the COVID-19 pandemic has resulted in enrollment temporary and long-term suspension
globally for many clinical trials. For example, research sites were temporarily closed for enrolment for a large part of 2020,
and inpart of 2021 for our clinical trial to evaluate CONTEPO for use in pediatric patients with cUTIs. Some of our
competitors have ongoing clinical trials for product candidates that could be competitive with XENLETA and CONTEPO,
and patients who would otherwise be eligible for our clinical trials may instead enroll in clinical trials of our competitors’
product candidates.
Patient enrollment is affected by other factors including:
● severity of the disease under investigation;
● eligibility criteria for the clinical trial in question;
● perceived risks and benefits of the product candidate under study;
● approval of other therapies to treat the disease under investigation;
● efforts to facilitate timely enrollment in clinical trials;
● patient referral practices of physicians;
● the time of year in which the trial is initiated or conducted;
● the geographic distribution of global trial sites;
● the ability to monitor patients adequately during and after treatment;
● proximity and availability of clinical trial sites for prospective patients;
● delays in the receipt of required regulatory approvals, or the failure to receive required regulatory approvals,
in the jurisdictions in which clinical trials are expected to be conducted;
● restrictions resulting from the COVID-19 pandemic and its collateral consequences;
● willingness of potential patients to participate in our trials; and
● delays in the receipt of approvals, or the failure to receive approvals, from the relevant institutional review
board or ethics committee at clinical trial sites.
Enrollment delays in our clinical trials may result in increased development costs for our product candidates,
which would cause the value of the company to decline and limit our ability to obtain additional financing. Our inability to
enroll a sufficient number of patients in any of our clinical trials would result in significant delays or may require us to
abandon one or more clinical trials altogether.
87
Table of Contents
If serious adverse or undesirable side effects are identified in SIVEXTRO, XENLETA, or CONTEPO or any other
product candidate that we develop or following their approval and commercialization, we may need to modify, abandon
or limit our development or marketing of that product or product candidate.
It is impossible to predict when or if the FDA, EMA or other regulators will view any of our product candidates as
effective and safe in humans or if we will receive marking approval for any of our product candidates, and it is impossible
to ensure that safety or efficacy issues will not arise following the marketing approval. If our products or product
candidates are associated with undesirable side effects or have characteristics that are unexpected, we may need to modify
or abandon their marketing or development or limit marketing or development to certain uses or subpopulations in which
the undesirable side effects or other characteristics are less prevalent, less severe or more acceptable from a risk-benefit
perspective. Similarly, if we are not able to comply with post-approval regulatory requirements, including safety
requirements, with respect to XENLETA or any other approved product that we may develop, we could have the marketing
approvals for such products withdrawn by regulatory authorities. Many compounds that initially showed promise in clinical
or earlier stage testing have later been found to cause side effects or other safety issues that prevented further development
of the compound.
In the ZEUS Study, the incidence of premature discontinuation from study drug was low and similar between
treatment groups (6.0% in the CONTEPO treatment group compared to 3.9% in the PIP-TAZ treatment group), and the
incidence of not completing the study through the last follow-up visit, which occurred on the 24th through 28th day after
completion of seven days of treatment with the study drug, or after up to 14 days of treatment for patients with concurrent
bacteremia, was 5.2% in the CONTEPO group compared to 0.9% in the PIP-TAZ group. A total of 42.1% CONTEPO
patients and 32.0% PIP-TAZ patients experienced at least one treatment-emergent adverse event. Most treatment-emergent
adverse events were mild or moderate in severity, and severe TEAEs were uncommon (2.1% of CONTEPO patients and
1.7% of PIP-TAZ patients). The most common TEAEs in both treatment groups were transient, asymptomatic laboratory
abnormalities and gastrointestinal events. TEAEs were uncommon in both treatment groups (2.1% of CONTEPO patients
and 2.6% of PIP-TAZ patients). There were no deaths in the study and one TEAE in each treatment group was deemed
related to study drug (hypokalemia in a CONTEPO patient and renal impairment in a PIP-TAZ patient), leading to study
drug discontinuation in the PIP-TAZ patient. Study drug discontinuations due to the TEAEs were infrequent and similar
between treatment groups (3.0% of CONTEPO patients and 2.6% of PIP-TAZ patients).
The most common laboratory abnormality treatment-emergent adverse events in the ZEUS Study were increases
in the levels of alanine aminotransferase, or ALT, (8.6% of CONTEPO patients and 2.6% of PIP-TAZ patients) and
aspartate transaminase, or AST, (7.3% of CONTEPO patients and 2.6% of PIP-TAZ patients). None of the ALT or AST
elevations were symptomatic or treatment-limiting, and none of the patients met the criteria for Hy’s Law. Outside the
United States, elevated liver aminotransferases are listed among undesirable effects in the labeling for IV fosfomycin.
In the ZEUS Study, hypokalemia occurred in 71 of 232 (30.6%) CONTEPO patients and 29 of 230 (12.6%) PIP-
TAZ patients. Most decreases in potassium levels were mild to moderate in severity. Shifts in potassium levels from normal
at baseline to hypokalemia, as determined by worst post-baseline hypokalemia values, were more frequent in the
CONTEPO group than the PIP-TAZ group for mild (17.7% compared to 11.3%), moderate (11.2% compared to 0.9%), and
severe (1.7% compared to 0.4%) categories of hypokalemia. Hypokalemia was deemed a treatment-emergent adverse event
in 6.4% of patients receiving CONTEPO and 1.3% of patients receiving PIP-TAZ, and all cases were transient and
asymptomatic.
While no significant cardiac adverse events were observed in the ZEUS Study, post-baseline QT intervals
calculated using Fridericia’s formula, or QTcF, of greater than 450 to less than or equal to 480 msec (baseline QTcF of less
than or equal to 450 msec) occurred at a higher frequency in CONTEPO patients (7.3%) compared to PIP-TAZ patients
(2.5%). In the CONTEPO arm, these results appeared to be associated with the hypokalemia associated with the salt load
of the IV formulation. Only one patient in the PIP-TAZ arm had a baseline QTcF of less than or equal to 500 msec and a
post-baseline QTcF of greater than 500 msec.
88
Table of Contents
If we elect or are forced to suspend or terminate any clinical trial of XENLETA, CONTEPO or any other product
candidates that we are developing, the commercial prospects of XENLETA, CONTEPO or such other product candidates
will be harmed and our ability to generate product revenues from XENLETA, CONTEPO or any of these other product
candidates will be delayed or eliminated. In addition, a higher rate of adverse events in XENLETA or CONTEPO as
compared to the standard of care, even if slight, could negatively impact commercial adoption of XENLETA or CONTEPO
by physicians. Any of these occurrences could materially harm our business, financial condition, results of operations and
prospects.
Risks Related to Our Dependence on Third Parties
Use of third parties to manufacture our product candidates or products may increase the risk that we will not have
sufficient quantities of our product candidates or products or such quantities at an acceptable quality or cost, which
could delay, prevent or impair our development or commercialization efforts.
We do not own or operate manufacturing facilities for the production of XENLETA or CONTEPO that could be
used in product candidate development, including clinical trial supply, or for commercial supply, or for the supply of any
other compound that we are developing or evaluating in our research program. We have limited personnel with experience
in drug manufacturing and lack the resources and the capabilities and facilities to manufacture any of our product
candidates or products on a clinical or commercial scale. We currently rely on third parties for supply of XENLETA and
CONTEPO, and our strategy is to outsource all manufacturing, packaging, testing, serialization and distribution of our
product candidates and products to third parties. We also procure supply of SIVEXTRO from Merck & Co., Inc.
We have entered into agreements, and expect to enter into additional agreements, with third-party manufacturers
for the long-term commercial supply of XENLETA and CONTEPO. For example, prior to June 2015, we obtained the
pleuromutilin starting material for the clinical trial supply of XENLETA from a single third-party manufacturer, Sandoz
GmbH, or Sandoz, a division of Novartis AG, or Novartis. . We were required to identify and enter into a commercial
supply agreement with an alternative supplier that provides pleuromutilin starting material for the commercial supply of
XENLETA as a result of Novartis discontinuing its manufacture of pleuromutilin starting material.
Another third-party manufacturer synthesizes XENLETA starting from pleuromutilin and a readily accessible
chiral building block and provides our supply of the active pharmaceutical ingredient, or API. We have initiated
engagement with a potential secondary supplier to synthesize XENLETA, with a preliminary technology transfer and pilot
scale manufacture. However, our current operating plans do not include completing technology transfer, scale-up and
validation of this potential secondary supplier until they have demonstrated that they can successfully manufacture the API
at pilot scale and until we obtain additional funding. We engage separate manufacturers to provide tablets, sterile vials, and
sterile diluent that we are using in our clinical trials of XENLETA. We have entered into commercial supply agreements
with these same manufacturers to support the commercialization of XENLETA in the United States and, if approved
outside of the United States, to support future demand outside of the United States. We also entered into a long-term
commercial supply agreement with Arran Chemical Company Limited, or Arran, for the supply of the chiral acid starting
material required in the synthesis of XENLETA API and a commercial packaging and supply agreement with Sharp
Corporation for the secondary packaging of XENLETA for distribution in the United States.
In addition, we have entered into a manufacturing and supply agreement with Ercros, S.A., pursuant to which
Ercros, S.A. supplies to us, on an exclusive basis, the API mixture for CONTEPO in support of our NDA filing and, if
CONTEPO is approved, will supply the commercial API mixture for CONTEPO in the United States. We have also
entered into a manufacturing and exclusive supply agreement with Laboratorios ERN, S.A., pursuant to which
Laboratorios ERN, S.A. has agreed to supply us with certain technical documentation and data as required for our NDA
filing for CONTEPO and certain regulatory support in connection with the commercial sale and use of CONTEPO in the
United States, if approved. We entered into a commercial packaging agreement with AndersonBrecon, Inc. for the
commercial packaging and serialization of CONTEPO. Alternatively, we have engaged Sharp Corporation for the
secondary packaging and serialization of CONTEPO completed under our existing commercial packaging and supply
agreement with Sharp Corporation. We also entered into a manufacturing and supply agreement with Fisiopharma S.r.l.,
89
Table of Contents
or Fisiopharma, for the supply, on a minimum commitment basis, of a percentage of our commercial requirements of
CONTEPO in bulk drug vials for the United States as well as the supply of bulk drug vials of CONTEPO in connection
with the submission of an NDA.
We may be unable to maintain our current arrangements for commercial supply, or conclude agreements for
commercial supply with additional third-party manufacturers, or we may be unable to do so on acceptable terms. Even if
we are able to establish and maintain arrangements with third-party manufacturers, reliance on third-party manufacturers
entails additional risks, including:
● reliance on the third party for regulatory compliance and quality assurance;
● reliance on the third party for the timely supply of our products or product candidates;
● an event at one of our manufacturers or suppliers causing an unforeseen disruption of the manufacture or
supply of our products or product candidates;
● the possible breach of the manufacturing agreement by the third party;
● the possible misappropriation of our proprietary information, including our trade secrets and know-how; and
● the possible termination or nonrenewal of the agreement by the third party at a time that is costly or results in
an interruption to the supply chain for our products.
Third-party manufacturers may not be able to comply with current good manufacturing practice, or cGMP,
regulations or similar regulatory requirements outside the United States. Our failure, or the failure of our third-party
manufacturers, to comply with applicable regulations could result in sanctions being imposed on us, including fines,
injunctions, civil penalties, delays, suspension or withdrawal of approvals, license revocation, seizures or recalls of product
candidates or products, operating restrictions and criminal prosecutions, any of which could significantly and adversely
affect supplies of our product candidates and products. Such failure could also result in the delay of our obtaining
regulatory approval of our product candidates. Also, the spread of COVID-19 may affect the ability of our third-party
manufacturers to supply SIVEXTRO, XENLETA, CONTEPO or any future product candidates.
In April 2019, the FDA issued a CRL in connection with our NDA for CONTEPO for the treatment of cUTIs,
including AP, stating that it was unable to approve the application in its current form. Specifically, the CRL requested us to
address issues related to facility inspections and manufacturing deficiencies at our API contract manufacturer prior to the
FDA approving the NDA. In December 2019, we resubmitted our NDA for CONTEPO for the treatment of cUTIs,
including AP. On June 19, 2020 we received a second CRL from the FDA. Although our European contract manufacturing
partners were prepared for regulatory authority inspections, the CRL cited observations at our manufacturing partners that
could not be resolved due to FDA’s inability to conduct onsite inspections because of travel restrictions. We do not have a
forecasted date for the resubmission of our NDA for CONTEPO for the treatment of cUTIs, including AP . On October 30,
2020, we participated in a “Type A” meeting with the FDA to obtain any new information related to the FDA´s pending
conduct of inspections of foreign manufacturers during the COVID-19 pandemic that has negatively impacted a number of
FDA product reviews, including the our NDA for CONTEPO for the treatment of cUTIs, including AP. On April 14, 2021,
the FDA issued industry guidance on remote interactive evaluations of drug manufacturing and bioresearch monitoring
facilities during COVID-19 specifying that when it cannot perform a PAI or a PLI or when the FDA determines that it
would be useful to supplement a planned inspection, the agency will consider using tools other than a physical inspection
and select the most appropriate method to address the specific risks that justify the need for the PAI or PLI. The FDA
informed us that onsite inspections of our manufacturing partners in Europe are required in order for the FDA to complete
the review of a potential CONTEPO NDA resubmission. Due to travel restriction related to the COVID-19 pandemic, the
FDA suspended onsite inspections of ex-US manufacturers for all non-COVID products. As a result, we requested an
extension of the timeline for a potential CONTEPO NDA resubmission until June 2023, which the FDA granted on March
21, 2022. We are awaiting further clarity from the FDA regarding their ability to complete onsite inspections at our
manufacturing partners in Italy
90
Table of Contents
and Spain before determining specific timing of the potential NDA resubmission, which we plan to submit promptly once
we have clarity from the FDA. The FDA released the Resiliency Roadmap for FDA Inspectional Oversight that describes
the systematic approach that FDA will utilize to manage postponed inspections and other oversight activities. The
prioritization plan considers public health risks related to conducting an inspection, such as the impact of the product’s
availability on public health, as well as investigator safety and travel restrictions/advisories. In addition, the FDA informed
us that, while they cannot predict when an inspection may occur and when the pandemic may prevent the FDA from
completing inspections, tier 1 mission-critical inspections and tier 2 higher priority inspections, which includes PAIs, will
continue to be prioritized going forward. Our contract manufacturers continue to interact with FDA to discuss its plans for
conducting inspections at their sites. If these manufacturing issues are not resolved to the FDA’s satisfaction, or if we or
any of our third-party manufacturers, or suppliers are the subject of any other open or unresolved regulatory inspections,
inspection reports, or FDA Form 483s identifying noncompliance with applicable regulations, we would be delayed in
obtaining or may fail to obtain regulatory approval of our product candidates, including CONTEPO.
Our product candidates and any products that we have developed or may develop may compete with other product
candidates and products for access to manufacturing facilities. There are a limited number of manufacturers that operate
under cGMP regulations and that might be capable of manufacturing for us.
If the third parties that we engage to supply any materials or manufacture product for our non-clinical testing and
clinical trials should cease to continue to do so for any reason, we likely would experience delays in advancing these trials
while we identify and qualify replacement suppliers, and we may be unable to obtain replacement supplies on terms that
are favorable to us. For example, there are only a limited number of known manufacturers that produce the pleuromutilin
starting material used in the synthesis of XENLETA. In early 2015, Novartis completed the sale of its animal health
division, including its veterinary products, to a third party. As a result, we were required to identify an alternative supplier
for pleuromutilin starting material for XENLETA. If we are not able to obtain adequate supplies of our product candidates
or products, or the drug substances used to manufacture them, it will be more difficult for us to develop or commercialize
our product candidates and compete effectively.
Our current and anticipated future dependence upon others for the manufacture of our product candidates and
products may adversely affect our revenues and our ability to develop product candidates and commercialize any products
that receive marketing approval on a timely and competitive basis. In addition, slower than forecasted commercialization of
our products in approved territories, or delayed introduction of our product in approved territories, or disruptions in the
supply of our approved products may adversely affect our revenue and profit margins. Moreover, disruption in the supply
of our approved product may impact the availability of our approved products at retail pharmacies and may adversely
impact our reputation and the willingness of physicians to prescribe our products, which could materially harm our
business, financial condition, results of operations and prospects. In addition, our failure or potential failure to comply with
contractual minimum order commitments or minimum revenue commitments with our third party suppliers could impact
the uninterrupted supply of our products and/or subject us to additional costs. For example, in August 2021, we entered
into an amendment to our supply agreement for the API for XENLETA to reduce our minimum purchase obligations under
the supply agreement in exchange for cash payments to the supplier and a royalty on net sales of XENLETA in the United
States.
We have entered into a Sales Promotion and Distribution Agreement with Merck & Co. related to the promotion,
distribution and sale of SIVEXTRO. If our collaboration with Merck is not successful, we may incur significant
expenses related to the distribution of SIVEXTRO without realizing any value from the agreement.
In July 2020, we entered into the Distribution Agreement with subsidiaries of Merck pursuant to which we
licensed the right, subject to specified conditions, to promote, distribute and sell SIVEXTRO for ABSSSIs, caused by
certain susceptible Gram-positive microorganisms in the SIVEXTRO Territory.
Under the Distribution Agreement and subject to the fulfillment of certain conditions, including our engaging
sufficient sales representatives, restrictions relating to travel and physician office access in the SIVEXTRO Territory due to
COVID-19 having continued to decrease in a sufficient portion of the SIVEXTRO Territory so as not to hinder the
successful detailing of SIVEXTRO, we have been granted the right to initially promote SIVEXTRO in the SIVEXTRO
Territory and, upon satisfaction of additional conditions, including an increase in the number of our sales representatives,
91
Table of Contents
the right to exclusively distribute SIVEXTRO in the SIVEXTRO Territory, including the sole right and responsibility to fill
orders with respect to SIVEXTRO in the SIVEXTRO Territory. In April 2021, we successfully satisfied those conditions,
including the increase in the number of sales representatives, and began filling orders of SIVEXTRO with our own Nabriva
NDC.
A subsidiary of Merck will sell, and we have agreed to purchase, SIVEXTRO at specified prices in such quantities
as we may specify. Although we are entitled, subject to appliable law, to determine the final selling prices of SIVEXTRO
in our sole discretion, subject to an overall annual limit on price increases, we may not be able to sell SIVEXTRO at prices
high enough to recoup our investment in a sales force and other commercialization activities. In addition, we will rely on a
subsidiary of Merck to supply SIVEXTRO to us, who in turn, relies on third party manufacturers for the production,
packaging, and serialization of SIVEXTRO for our distribution. Relying on a third-party manufacturer subjects us to a
number of additional risks, including the risk that we may not have sufficient supply of SIVEXTRO available for sale. See
“Risk Factors—Risks Related to Our Dependence on Third Parties—Use of third parties to manufacture our product
candidates or products may increase the risk that we will not have sufficient quantities of our product candidates or
products or such quantities at an acceptable quality or cost, which could delay, prevent or impair our development or
commercialization efforts.”
We rely on third parties to conduct our clinical trials and those third parties may not perform satisfactorily, including
failing to meet deadlines for the completion of such trials.
We do not independently conduct clinical trials for our product candidates. We rely on third parties, such as
contract research organizations, clinical data management organizations, medical institutions and clinical investigators, to
perform this function. We expect to continue to rely on such third parties in conducting our clinical trials of XENLETA and
CONTEPO, and expect to rely on these third parties to conduct clinical trials of any other product candidate that we
develop. Any of these third parties may terminate their engagements with us at any time. If we need to enter into
alternative arrangements, it would delay our product development activities.
Our reliance on these third parties for clinical development activities reduces our control over these activities but
does not relieve us of our responsibilities. For example, we remain responsible for ensuring that each of our clinical trials is
conducted in accordance with the general investigational plan and protocols for the trial. Moreover, the FDA requires us to
comply with standards, commonly referred to as Good Clinical Practices, or GCP, for conducting, recording and reporting
the results of clinical trials to assure that data and reported results are credible and accurate and that the rights, integrity and
confidentiality of trial participants are protected. We also are required to register ongoing clinical trials and post the results
of completed clinical trials on a U.S. government-sponsored database, ClinicalTrials.gov, within certain timeframes.
Failure to do so can result in fines, adverse publicity and civil and criminal sanctions. Similar GCP and transparency
requirements apply in the European Union. Failure to comply with such requirements, including with respect to clinical
trials conducted outside the European Union, can also lead regulatory authorities to refuse to take into account clinical trial
data submitted as part of an MAA.
Furthermore, third parties that we rely on for our clinical development activities may also have relationships with
other entities, some of which may be our competitors. If these third parties do not successfully carry out their contractual
duties, meet expected deadlines or conduct our clinical trials in accordance with regulatory requirements or our stated
protocols, we will not be able to obtain, or may be delayed in obtaining, marketing approvals for our product candidates
and will not be able to, or may be delayed in our efforts to, successfully commercialize our product candidates. Our product
development costs will increase if we experience delays in testing or obtaining marketing approvals.
We also rely on other third parties to store and distribute drug supplies for our clinical trials. Any performance
failure on the part of our distributors could delay clinical development or marketing approval of our product candidates or
commercialization of our products, producing additional losses and depriving us of potential product revenue.
92
Table of Contents
We have entered into and may enter into additional collaborations with third parties for the development or
commercialization of XENLETA, CONTEPO and our other product candidates. If those collaborations are not
successful, we may not be able to capitalize on the market potential of these product candidates.
We are commercializing XENLETA and expect to commercialize CONTEPO, if approved, in the United States
with targeted sales and marketing efforts. Outside the United States, we expect to utilize a variety of types of collaboration,
distribution and other marketing arrangements with one or more third parties to commercialize XENLETA. For example,
we are party to a license agreement with Sumitomo Pharmaceuticals (Suzhou), pursuant to which we granted Sumitomo
Pharmaceuticals (Suzhou)certain rights to manufacture and commercialize XENLETA in the People’s Republic of China,
Hong Kong, Macau and Taiwan and we have also entered into a license agreement with Sunovion pursuant to which we
granted Sunovion certain rights to commercialize XENLETA in Canada. We also may seek third-party collaborators for
development and commercialization of other product candidates or for XENLETA for indications other than CABP.
Our likely future collaborators for any sales, marketing, distribution, development, licensing or broader
collaboration arrangements include large and mid-size pharmaceutical companies, regional and national pharmaceutical
companies and biotechnology companies. Under our license agreements with Sumitomo Pharmaceuticals (Suzhou) and
Sunovion, we have, and under any such arrangements we enter into with any third parties in the future we will likely have,
limited control over the amount and timing of resources that our collaborators dedicate to the development or
commercialization of our product candidates. Our ability to generate revenues from these arrangements will depend on our
collaborators’ abilities and efforts to successfully perform the functions assigned to them in these arrangements.
Our current collaborations pose, and any future collaborations likely will pose, numerous risks to us, including the
following:
● collaborators have significant discretion in determining the efforts and resources that they will apply to these
collaborations and may not perform their obligations as expected;
● collaborators may deemphasize or not pursue development and commercialization of our product candidates
or may elect not to continue or renew development or commercialization programs based on clinical trial
results, changes in the collaborators’ strategic focus, product and product candidate priorities, available
funding, or external factors such as an acquisition that diverts resources or creates competing priorities;
● collaborators may need to conduct clinical trials, and these clinical trials may not be successful;
● collaborators may delay clinical trials, provide insufficient funding for a clinical trial program, stop a clinical
trial or abandon a product candidate, repeat or conduct new clinical trials or require a new formulation of a
product candidate for clinical testing;
● collaborators could independently develop, or develop with third parties, products that compete directly or
indirectly with our products or product candidates if the collaborators believe that competitive products are
more likely to be successfully developed or can be commercialized under terms that are more economically
attractive than ours;
● a collaborator with marketing and distribution rights to one or more products may not commit sufficient
resources to the marketing and distribution of such product or products;
● collaborators may not properly maintain or defend our intellectual property rights or may use our proprietary
information in such a way as to invite litigation that could jeopardize or invalidate our intellectual property or
proprietary information or expose us to potential litigation;
93
Table of Contents
● collaborators may infringe the intellectual property rights of third parties, which may expose us to litigation
and potential liability;
● disputes may arise between the collaborator and us as to the ownership of intellectual property arising during
the collaboration;
● we may grant exclusive rights to our collaborators, which would prevent us from collaborating with others;
● collaborators may be unable to enforce our intellectual property rights in territories where we have licensed,
or may license, them such rights, which may expose us to material adverse tax and other consequences;
● disputes may arise between the collaborators and us that result in the delay or termination of the development
or commercialization of our products or product candidates or that result in costly litigation or arbitration that
diverts management attention and resources; and
● collaborations may be terminated and, if terminated, may result in a need for additional capital to pursue
further development or commercialization of the applicable product candidates;
● collaborators may elect to delay commercialization in an effort to gain more commercially favorable product
pricing and reimbursement in their territory.
For example, under our license agreement with Sumitomo Pharmaceuticals (Suzhou), if any court, tribunal or
governmental agency in the People’s Republic of China, Hong Kong, Macau or Taiwan determines that the exclusive
license granted to Sumitomo Pharmaceuticals (Suzhou) pursuant to the license agreement is not sufficiently exclusive such
that Sumitomo Pharmaceuticals (Suzhou) does not have sufficient rights to enforce the licensed patent rights in such
territories, we and our subsidiary, Nabriva Therapeutics GmbH, have agreed to take such commercially reasonable steps as
Sumitomo Pharmaceuticals (Suzhou) reasonably requests to grant Sumitomo Pharmaceuticals (Suzhou) such rights. If a
court in such jurisdictions were to determine that our license to Sumitomo Pharmaceuticals (Suzhou) was not sufficiently
exclusive and that Sumitomo Pharmaceuticals (Suzhou) did not have the rights to enforce the licensed patent rights in the
licensed territories, Sumitomo Pharmaceuticals (Suzhou) may require us to take such actions that it deems reasonable but
that we do not and which may have a material adverse effect on our business, including requiring us to make changes to
our organizational structure that may result in adverse tax and other consequences, or to conduct other activities that may
cause us to incur significant expenses.
Collaboration agreements may not lead to development or commercialization of product candidates in the most
efficient manner or at all. If a collaborator of ours were to be involved in a business combination, the continued pursuit and
emphasis on our product development or commercialization program could be delayed, diminished or terminated.
If we are not able to establish additional collaborations, we may have to alter our development and commercialization
plans.
The commercialization of XENLETA, potential commercialization of CONTEPO, if approved, and the
development and potential commercialization of other product candidates will require substantial additional cash to fund
expenses. For some of our product candidates, we may decide to further collaborate with pharmaceutical and
biotechnology companies for the development and potential commercialization of those product candidates. For example,
we intend to seek to commercialize XENLETA through a variety of types of additional collaboration arrangements outside
the United States.
We face significant competition in seeking appropriate collaborators. Whether we reach a definitive agreement for
additional collaborations outside greater China and Canada will depend, among other things, upon our assessment of the
collaborator’s resources and expertise, the terms and conditions of the proposed collaboration and the proposed
collaborator’s evaluation of a number of factors. Those factors may include the design or results of clinical trials, the
94
Table of Contents
likelihood of approval by the FDA or similar regulatory authorities outside the United States, the potential market for the
subject product candidate, the costs and complexities of manufacturing and delivering such product candidate to patients,
the potential of competing products, the existence of uncertainty with respect to our ownership of technology, which can
exist if there is a challenge to such ownership without regard to the merits of the challenge, and industry and market
conditions generally. The collaborator may also consider alternative product candidates or technologies for similar
indications that may be available to collaborate on and whether such a collaboration could be more attractive than the one
with us for our product candidate. Mergers and acquisitions in the pharmaceutical and biotechnology industries may also
reduce the number of potential collaborators with whom we could partner. We may also be restricted under future license
agreements from entering into agreements on certain terms with potential collaborators. Collaborations are complex and
time-consuming to negotiate and document. In addition, there have been recent business combinations among large
pharmaceutical companies that have resulted in a reduced number of potential future collaborators.
If we are unable to reach agreements with suitable collaborators on a timely basis, on acceptable terms, or at all,
we may have to curtail the development of a product candidate, reduce or delay its development program or one or more of
our other development programs, delay its potential commercialization or reduce the scope of any sales or marketing
activities, or increase our expenditures and undertake development or commercialization activities at our own expense. If
we elect to fund and undertake development or commercialization activities on our own, we may need to obtain additional
expertise and additional capital, which may not be available to us on acceptable terms or at all. If we fail to enter into
additional collaborations and do not have sufficient funds or expertise to undertake the necessary development and
commercialization activities, we may not be able to further develop our product candidates or bring them to market and
generate product revenue.
We enter into various contracts in the normal course of our business in which we agree to indemnify the other party to
the contract. In the event we have to perform under these indemnification provisions, it could have a material adverse
effect on our business, financial condition and results of operations.
In the normal course of business, we periodically enter into academic, commercial, service, collaboration,
licensing, consulting and other agreements that contain indemnification provisions. With respect to our academic and other
research agreements, we typically agree to indemnify the institution and related parties from losses arising from claims
relating to the products, processes or services made, used, sold or performed pursuant to the agreements for which we have
secured licenses, and from claims arising from our or our sub licensees’ exercise of rights under the agreement. With
respect to our commercial agreements, we have agreed to indemnify our vendors from any third-party product liability
claims that could result from the production, use or consumption of the product, as well as for alleged infringements of any
patent or other intellectual property right by a third party. With respect to consultants, we typically agree to indemnify them
from claims arising from the good faith performance of their services.
Should our obligation under an indemnification provision exceed applicable insurance coverage or if we were
denied insurance coverage or not covered by insurance, our business, financial condition and results of operations could be
adversely affected. Similarly, if we are relying on a collaborator or other third party to indemnify us and the collaborator or
other third party is denied insurance coverage or otherwise does not have assets available to indemnify us, our business,
financial condition and results of operations could be adversely affected.
Risks Related to Our Intellectual Property
If we are unable to obtain and maintain patent protection for our technology, products and product candidates, or if the
scope of the patent protection is not sufficiently broad, our competitors could develop and commercialize technology,
products and product candidates similar or identical to ours, and our ability to successfully commercialize our
technology, products and product candidates may be adversely affected.
Our success depends in large part on our ability to obtain and maintain patent protection in the United States and
other countries with respect to our proprietary technology, products and product candidates. We seek to protect our
proprietary position by filing patent applications in the United States, Europe and in certain additional foreign jurisdictions
related to our novel technologies, products and product candidates that are important to our business. This process is
expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent
95
Table of Contents
applications at a reasonable cost or in a timely manner. It is also possible that we will fail to identify patentable aspects of
our research and development output before it is too late to obtain patent protection. Moreover, if we license technology,
products or product candidates from third parties, these license agreements may not permit us to control the preparation,
filing and prosecution of patent applications, or to maintain or enforce the patents, covering this intellectual property. These
agreements could also give our licensors the right to enforce the licensed patents without our involvement, or to decide not
to enforce the patents at all. Therefore, in these circumstances, these patents and applications may not be prosecuted,
maintained and enforced in a manner consistent with the best interests of our business.
The patent position of biotechnology and pharmaceutical companies generally is highly uncertain, involves
complex legal and factual questions and has in recent years been the subject of much litigation. As a result, the issuance,
scope, validity, enforceability and commercial value of our patent rights are highly uncertain. Our pending and future
patent applications may not result in patents being issued which protect our technology, products or product candidates, in
whole or in part, or which effectively prevent others from commercializing competitive technologies, products and product
candidates. Changes in either the patent laws or interpretation of the patent laws in the United States and other countries
may diminish the value of our patents or narrow the scope of our patent protection.
The laws of foreign countries may not protect our rights to the same extent as the laws of the United States. As a
result, we may encounter significant problems in protecting and defending our licensed and owned intellectual property
both in the U.S. and abroad. For example, European patent law restricts the patentability of methods of treatment of the
human body more than U.S. law does. In addition, China and certain other developing countries, where we currently have a
number of licensed patents and licensed patent applications, currently affords less protection to a company’s intellectual
property than some other jurisdictions. Furthermore, certain developing countries, including China and India, have
compulsory licensing laws under which a patent owner may be compelled to grant licenses to third parties. In those
countries, we and our licensors may have limited remedies if patents are infringed or if we or our licensors are compelled
to grant a license to a third-party, which could materially diminish the value of those patents. In addition, many countries
limit the enforceability of patents against government agencies or government contractors. This could also limit our
potential revenue opportunities. As such, the lack of strong patent and other intellectual property protection in China and
elsewhere may significantly increase our vulnerability regarding unauthorized disclosure or use of our intellectual property
and undermine our competitive position. Proceedings to enforce our future patent rights, if any, in foreign jurisdictions
could result in substantial cost and divert our efforts and attention from other aspects of our business, could put our patents
at risk of being invalidated or interpreted narrowly and our patent applications at risk of not issuing and could provoke
third parties to assert claims against us. We may not prevail in any lawsuits that we initiate, and the damages or other
remedies awarded, if any, may not be commercially meaningful. We also may not pursue or obtain patent protection in all
major markets or may not obtain protection that enables us to prevent the entry of third parties onto the market. Assuming
the other requirements for patentability are met, currently, the first to file a patent application is generally entitled to the
patent. However, prior to March 16, 2013, in the United States, the first to invent was entitled to the patent. Publications of
discoveries in the scientific literature often lag behind the actual discoveries, and patent applications in the United States
and other jurisdictions are typically not published until 18 months after filing, or in some cases not at all. Therefore, we
cannot know with certainty whether we were the first to make the inventions claimed in our U.S. patents or pending U.S.
patent applications, or that we were the first to file for patent protection of such inventions.
Moreover, we may be subject to a third-party pre-issuance submission of prior art to the U.S. Patent and
Trademark Office, or USPTO, or become involved in opposition, derivation, reexamination, inter partes review, post grant
review, interference proceedings or other patent office proceedings or litigation, in the United States or elsewhere,
challenging our patent rights or the patent rights of others. For example, we have received a Notice of Request for
Invalidation of our lefamulin compound patent in China in October 2021. We filed a response defending the validity of our
patent, and the petitioner withdrew his invalidation request in January 2022, so this matter is concluded. An adverse
determination in any such submission, proceeding or litigation could reduce the scope of, or invalidate, our patent rights,
allow third parties to commercialize our technology, products or product candidates and compete directly with us, without
payment to us, or result in our inability to manufacture or commercialize products and product candidates without
infringing third-party patent rights. In addition, if the breadth or strength of protection provided by our patents
96
Table of Contents
and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or
commercialize current or future technology, products or product candidates.
Even if our patent applications issue as patents, they may not issue in a form that will provide us with any
meaningful protection, prevent competitors from competing with us or otherwise provide us with any competitive
advantage. Our competitors may be able to circumvent our owned or any licensed patents by developing similar or
alternative technologies, products or product candidates in a non-infringing manner. In addition, other companies may
attempt to circumvent any regulatory data protection or market exclusivity that we obtain under applicable legislation,
which may require us to allocate significant resources to preventing such circumvention. Legal and regulatory
developments in the European Union and elsewhere may also result in clinical trial data submitted as part of an MAA
becoming publicly available. Such developments could enable other companies to circumvent our intellectual property
rights and use our clinical trial data to obtain marketing authorizations in the European Union and in other jurisdictions.
Such developments may also require us to allocate significant resources to prevent other companies from circumventing or
violating our intellectual property rights. Our attempts to prevent third parties from circumventing our intellectual property
and other rights may ultimately be unsuccessful. We may also fail to take the required actions or pay the necessary fees to
maintain our patents.
The issuance of a patent is not conclusive as to its inventorship, scope, validity or enforceability, and our owned
and licensed patents may be challenged in the courts or patent offices in the United States and abroad. Such challenges may
result in loss of exclusivity or freedom to operate or in patent claims being narrowed, invalidated or held unenforceable, in
whole or in part, which could limit our ability to stop others from using or commercializing similar or identical technology,
products and product candidates, or limit the duration of the patent protection of our technology, products and product
candidates. Given the amount of time required for the development, testing and regulatory review of new product
candidates, patents protecting such candidates might expire before or shortly after such candidates are commercialized. As
a result, our patent portfolio may not provide us with sufficient rights to exclude others from commercializing products
similar or identical to ours.
We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be
expensive, time consuming and unsuccessful.
Competitors may infringe our patents, trademarks, copyrights or other intellectual property. To counter such
infringement or unauthorized use, we may be required to file claims, which can be expensive, time consuming and a
distraction to management. Any claims we assert against perceived infringers could provoke these parties to assert
counterclaims against us alleging our patents, trademarks, copyrights or other intellectual property are invalid or
unenforceable or that we infringe their intellectual property. In addition, in a patent infringement proceeding, a court may
decide that a patent of ours is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or may
refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology
in question.
Third parties may initiate legal proceedings alleging that we are infringing their intellectual property rights, the
outcome of which would be uncertain and could have a material adverse effect on the success of our business.
Our commercial success depends upon our ability and the ability of our collaborators to develop, manufacture,
market and sell our product candidates and use our proprietary technologies without infringing the intellectual property and
other proprietary rights of third parties. There is considerable intellectual property litigation in the biotechnology and
pharmaceutical industries, and we may become party to, or threatened with, future adversarial proceedings or litigation
regarding intellectual property rights with respect to our products, product candidates and technology, including
interference, derivation, inter partes review or post-grant review proceedings before the USPTO. The risks of being
involved in such litigation and proceedings may increase as our product candidates approach commercialization, and as we
gain greater visibility as a public company with commercial products. Third parties may assert infringement claims against
us based on existing or future intellectual property rights. We may not be aware of all such intellectual property rights
potentially relating to our products and product candidates. Any freedom-to-operate search or analysis previously
conducted may not have uncovered all relevant patents and patent applications, and there may be pending or future patent
applications that, if issued, would block us from commercializing XENLETA®, CONTEPO™ or SIVEXTRO®.
97
Table of Contents
Thus, we do not know with certainty whether XENLETA, CONTEPO, SIVEXTRO or any other product candidate, or our
commercialization thereof, does not and will not infringe any third party’s intellectual property.
If we are found to infringe a third party’s intellectual property rights, or to avoid or settle litigation, we could be
required to obtain a license to continue developing and marketing our technology, products and product candidates.
However, we may not be able to obtain any required license on commercially reasonable terms or at all. Even if we were
able to obtain a license, it could be non-exclusive, thereby giving our competitors access to the same technologies licensed
to us and could require us to make substantial payments. We could be forced, including by court order, to cease
commercializing the infringing technology, products or product candidates. In addition, we could be found liable for
monetary damages, including treble damages and attorneys’ fees if we are found to have willfully infringed a patent or
other intellectual property right. A finding of infringement could prevent us from commercializing our technology,
products and product candidates or force us to cease some of our business operations, which could materially harm our
business. Claims that we have misappropriated the confidential information or trade secrets of third parties could have a
similar negative impact on our business.
We may be subject to claims by third parties asserting that we or our employees have misappropriated their intellectual
property, or claiming ownership of what we regard as our own intellectual property.
Many of our employees were previously employed at universities or other biotechnology or pharmaceutical
companies, including our competitors or potential competitors. Although we try to ensure that our employees do not use
the proprietary information or know-how of others in their work for us, we may be subject to claims that we or these
employees have used or disclosed intellectual property, including trade secrets or other proprietary information, of any such
employee’s former employer. Litigation may be necessary to defend against these claims.
In addition, while we typically require our employees and contractors who may be involved in the development of
intellectual property to execute agreements assigning such intellectual property to us, we may be unsuccessful in executing
such an agreement with each party who in fact develops intellectual property that we regard as our own. Our pleuromutilin
business was founded as a spin-off from Sandoz. Although all patents and patent applications are fully owned by us and
were either filed by Sandoz with all rights fully transferred to us, or filed in our sole name, because we acquired certain of
our patent rights from Sandoz, we must rely on their prior practices, with regard to the assignment of such intellectual
property. Similarly, for any patents and patent applications we acquired from Zavante in connection with the Acquisition,
we must rely on Zavante’s prior practices with regard to the assignment of intellectual property.
Our and their assignment agreements may not be self-executing or may be breached, and we may be forced to
bring claims against third parties, or defend claims they may bring against us, to determine the ownership of what we
regard as our intellectual property.
If we fail in prosecuting or defending any such claims, in addition to paying monetary damages, we may lose
valuable intellectual property rights or personnel. Even if we are successful in prosecuting or defending against such
claims, litigation could result in substantial costs and be a distraction to management.
Intellectual property litigation could cause us to spend substantial resources and could distract our personnel from their
normal responsibilities.
Even if resolved in our favor, litigation or other legal proceedings relating to intellectual property claims may
cause us to incur significant expenses and could distract our technical and management personnel from their normal
responsibilities. In addition, there could be public announcements of the results of hearings, motions or other interim
proceedings or developments. If securities analysts or investors perceive these results to be negative, it could have a
substantial adverse effect on the price of our ordinary shares. Such litigation or proceedings could substantially increase
our operating losses and reduce the resources available for development, sales, marketing or distribution activities. We may
not have sufficient financial or other resources to adequately conduct such litigation or proceedings. Some of our
competitors may be able to sustain the costs of such litigation or proceedings more effectively than we can because of their
greater financial resources. Uncertainties resulting from the initiation and continuation of patent litigation or other
proceedings could have a material adverse effect on our ability to compete in the marketplace.
98
Table of Contents
If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be
harmed.
In addition to seeking patents for some of our technology, products and product candidates, we also rely on trade
secrets, including unpatented know-how, technology and other proprietary information, to maintain our competitive
position. We seek to protect our trade secrets, know-how, technology and other proprietary information, in part, by entering
into non-disclosure and confidentiality agreements with parties who have access to them, such as our employees, corporate
collaborators, outside scientific collaborators, contract manufacturers, consultants, advisors and other third parties. We also
enter into confidentiality and invention or patent assignment agreements with our employees and consultants. However, we
cannot guarantee that we have executed these agreements with each party that may have or has had access to our trade
secrets and other confidential information or that the agreements we have executed will provide adequate protection. Any
party with whom we have executed such an agreement may breach that agreement and disclose our proprietary
information, including our trade secrets, and we may not be able to obtain adequate remedies for such breaches. Enforcing
a claim that a party illegally disclosed or misappropriated a trade secret is difficult, expensive and time-consuming, and the
outcome is unpredictable. In addition, some courts inside and outside the United States are less willing or unwilling to
protect trade secrets. If any of our trade secrets were to be lawfully obtained or independently developed by a competitor,
we would have no right to prevent them, or those to whom they communicate it, from using that technology or information
to compete with us. If any of our trade secrets were to be obtained or independently developed by a competitor, our
competitive position would be harmed.
We have not yet registered our trademarks in all of our potential markets, and failure to secure those registrations could
adversely affect our business.
Our trademark applications may not be allowed for registration, and our registered trademarks may not be
maintained or enforced. During trademark registration proceedings, we may receive rejections. Although we are given an
opportunity to respond to those rejections, we may be unable to overcome such rejections. In addition, in the USPTO and
in comparable agencies in many foreign jurisdictions, third parties are given an opportunity to oppose pending trademark
applications and to seek to cancel registered trademarks. Opposition or cancellation proceedings may be filed against our
trademarks, and our trademarks may not survive such proceedings. If we do not secure registrations for our trademarks, we
may encounter more difficulty in enforcing them against third parties than we otherwise would.
Risks Related to Regulatory Approval and Marketing of Our Product Candidates and Other Legal Compliance
Matters
Even if we complete the necessary non-clinical studies and clinical trials, the marketing approval process is
expensive, time-consuming and uncertain and may prevent us from obtaining approvals for the commercialization of
some or all of our product candidates. If we are not able to obtain, or if there are delays in obtaining, required
regulatory approvals, in particular in the United States or the European Union, we will not be able to commercialize our
product candidates in those markets, and our ability to generate revenue will be materially impaired.
XENLETA, CONTEPO, and any other product candidates that we develop, and the activities associated with their
development and commercialization, including their design, testing, manufacture, safety, efficacy, recordkeeping, labeling,
storage, approval, advertising, promotion, sale and distribution, are subject to comprehensive regulation by the FDA and, in
the case of XENLETA, by comparable authorities in other countries. Failure to obtain marketing approval for a product
candidate will prevent us from commercializing the product candidate. On August 19, 2019, we received approval from the
FDA to market the oral and intravenous formulations of XENLETA to treat CABP in the United States. Further, on July
28, 2020, the European Commission issued a legally binding decision for approval of the marketing authorization
application for XENLETA for the treatment of community-acquired pneumonia in adults following a review by the
European Medicines Agency. Sunovion Pharmaceuticals Canada Inc. additionally received approval from Health Canada to
market oral and intravenous formulations of XENLETA for the treatment of community-acquired pneumonia in adults,
with the Notice of Compliance from Health Canada dated July 10, 2020. We have entered into a license and
commercialization agreement in March 2019 with Sunovion Pharmaceuticals Canada Inc. for XENLETA in Canada. In
September 2021, we and Sumitomo Pharmaceuticals (Suzhou) announced the approval received by Sumitomo
Pharmaceuticals (Suzhou) to market oral and intravenous formulations of XENLETA for the
99
Table of Contents
treatment of community-acquired pneumonia in adults in Taiwan. We have not received approval to market XENLETA in
any jurisdiction other than those mentioned above or for any other indication, and we have not received approval to market
CONTEPO or any of our other product candidates from regulatory authorities in any jurisdiction, and we do not intend to
seek approval to market CONTEPO outside the United States. In April 2019, the FDA issued a Complete Response Letter
in connection with our NDA for CONTEPO for the treatment of cUTIs, including AP, stating that it was unable to approve
the application in its current form. Specifically, the Complete Response Letter requested us to address issues related to
facility inspections and manufacturing deficiencies at our API contract manufacturer prior to the FDA approving the NDA.
In December 2019, we resubmitted the NDA for CONTEPO. On June 19, 2020 we received a second Complete Response
Letter from the FDA. Although our European contract manufacturing partners were prepared for regulatory authority
inspections, the CRL cited observations at our manufacturing partners that could not be resolved due to FDA’s inability to
conduct onsite inspections because of travel restrictions. We do not have a forecasted date for the resubmission of our NDA
for CONTEPO for the treatment of cUTI, including AP.
Even after obtaining marketing approval for XENLETA, we have limited experience in filing and supporting the
applications necessary to obtain marketing approvals for product candidates and we have and expect to continue to rely on
third parties to assist us in this process. Securing marketing approval requires the submission of extensive non-clinical and
clinical data and supporting information to various regulatory authorities for each therapeutic indication to establish the
product candidate’s safety and efficacy. Securing marketing approval also requires the submission of information about the
product manufacturing process to, and inspection of manufacturing facilities by, the regulatory authorities. Regulatory
authorities may determine that XENLETA, CONTEPO or any of our other product candidates are not effective or only
moderately effective, or have undesirable or unintended side effects, toxicities, safety profiles or other characteristics that
preclude us from obtaining marketing approval or that prevent or limit commercial use.
The process of obtaining marketing approvals is expensive, may take many years, if approval is obtained at all,
and can vary substantially based upon a variety of factors, including the type, complexity and novelty of the product
candidates involved. Changes in marketing approval policies during the development period, changes in or the enactment
of additional statutes or regulations, or changes in regulatory review for each submitted product application, may cause
delays in the approval or rejection of an application.
The FDA and comparable regulatory authorities in other countries have substantial discretion in the approval
process and may refuse to accept any application or may decide that our data are insufficient for approval and require
additional preclinical, clinical or other studies. In addition, varying interpretations of the data obtained from non-clinical
and clinical testing could delay, limit or prevent marketing approval of a product candidate. Any marketing approval we
ultimately obtain may be limited or subject to restrictions or post-approval commitments that render the approved product
not commercially viable.
Accordingly, if we or our collaborators experience delays in obtaining approval or if we or they fail to obtain
approval of our product candidates, the commercial prospects for our product candidates may be harmed and our ability to
generate revenues will be materially impaired.
Our failure to obtain marketing approval in jurisdictions other than the United States and Europe would prevent our
product candidates from being marketed in these other jurisdictions, and any approval we are granted for our product
candidates in the United States and Europe would not assure approval of product candidates in other jurisdictions.
In order to market and sell XENLETA and our other product candidates in jurisdictions other than the United
States, Canada and Europe, we must obtain separate marketing approvals and comply with numerous and varying
regulatory requirements. The approval process varies among countries and can involve additional testing. The time
required to obtain approval may differ from that required to obtain FDA approval or approvals from regulatory authorities
in the European Union. The regulatory approval process outside the United States, Canada and Europe generally includes
all of the risks associated with obtaining FDA approval or approvals from regulatory authorities in the European Union. In
addition, some countries outside the United States, Canada and Europe require approval of the sales price of a drug before
it can be marketed. In many countries, separate procedures must be followed to obtain reimbursement and a product may
not be approved for sale in the country until it is also approved for reimbursement. We may not obtain marketing, pricing
or reimbursement approvals outside the United States, Canada and Europe on a
100
Table of Contents
timely basis, if at all. Approval by the FDA or regulatory authorities in the European Union does not ensure approval by
regulatory authorities in other countries or jurisdictions, and approval by one regulatory authority outside the United States
and Europe does not ensure approval by regulatory authorities in other countries or jurisdictions or by the FDA or
regulatory authorities in the European Union. We may not be able to file for marketing approvals and may not receive
necessary approvals to commercialize our products in any market. Marketing approvals in countries outside the United
States and Europe do not ensure pricing approvals in those countries or in any other countries, and marketing approvals and
pricing approvals do not ensure that reimbursement will be obtained.
Additionally, we could face heightened risks with respect to seeking marketing approval in the United Kingdom as
a result of the recent withdrawal of the United Kingdom from the European Union, commonly referred to as Brexit. The
United Kingdom and European Union entered into a Trade and Cooperation Agreement in connection with Brexit that sets
out certain procedures for approval and recognition of medical products in each jurisdiction. Since the regulatory
framework for pharmaceutical products in the United Kingdom covering the quality, safety and efficacy of pharmaceutical
products, clinical trials, marketing authorization, commercial sales and distribution of pharmaceutical products is derived
from European Union directives and regulations, Brexit could materially impact the future regulatory regime that applies to
products and the approval of product candidates in the United Kingdom. Any delay in obtaining, or an inability to obtain,
any marketing approvals, as a result of the Trade and Cooperation Agreement would prevent us from commercializing any
product candidates in the United Kingdom and/or the European Union and restrict our ability to generate revenue and
achieve and sustain profitability. If any of these outcomes occur, we may be forced to restrict or delay efforts to seek
regulatory approval in the United Kingdom and/or European Union for any product candidates, which could significantly
and materially harm our business.We expect that we will be subject to additional risks in commercializing any of our
product candidates that receive marketing approval outside the United States, including tariffs, trade barriers and regulatory
requirements; economic weakness, including inflation, or political instability in particular foreign economies and markets;
compliance with tax, employment, immigration and labor laws for employees living or traveling abroad; foreign currency
fluctuations, which could result in increased operating expenses and reduced revenue, and other obligations incident to
doing business in another country; and workforce uncertainty in countries where labor unrest is more common than in the
United States.
Any product candidate for which we obtain marketing approval will be subject to strict enforcement of post-marketing
requirements and we could be subject to substantial penalties, including withdrawal of our product from the market, if
we fail to comply with all regulatory requirements or if we experience unanticipated problems with our product
candidates, when and if any of them are approved.
XENLETA and any other product candidate for which we obtain marketing approval, along with the
manufacturing processes, post-approval clinical data, labeling, advertising and promotional activities for such product, will
be subject to continual requirements of and review by the FDA and other regulatory authorities. These requirements
include, but are not limited to, restrictions governing promotion of an approved product, submissions of safety and other
post-marketing information and reports, registration and listing requirements, cGMP requirements relating to
manufacturing, quality control, quality assurance and corresponding maintenance of records and documents, and
requirements regarding the distribution of samples to physicians and recordkeeping. In addition, even if marketing
approval of a product candidate is granted, the approval may be subject to limitations on the indicated uses for which the
product may be marketed or to the conditions of approval. In addition, laws and regulations govern the distribution and
tracing of prescription drugs and prescription drug samples, including the Prescription Drug Marketing Act of 1976 and the
Drug Supply Chain Security Act, which regulate the distribution and tracing of prescription drugs and prescription drug
samples at the United States federal level and set minimum standards for the regulation of drug distributors by the states.
The FDA and other federal and state agencies, including the U.S. Department of Justice, or DOJ, closely regulate
compliance with all requirements governing prescription drug products, including requirements pertaining to marketing
and promotion of drugs subject to the provisions of the approved labeling and manufacturing of products in accordance
with cGMP requirements. The FDA and DOJ impose stringent restrictions on manufacturers’ communications regarding
off-label use and if we do not market our products for their approved indications, we may be subject to enforcement action
for off-label marketing. Violations of such requirements may lead to investigations alleging violations of the Food, Drug
and Cosmetic Act and other statutes, including the False Claims Act and other
101
Table of Contents
federal and state health care fraud and abuse laws as well as state consumer protection laws. Accordingly, we may not
promote XENLETA in the United States for use in any indications other than the treatment of CABP, and all promotional
claims must be consistent with the FDA-approved labeling of XENLETA.
Our failure to comply with all regulatory requirements, and later discovery of previously unknown adverse events
or other problems with our products, manufacturers or manufacturing processes, may yield various results, including:
● litigation involving patients taking our products;
● restrictions on such products, manufacturers or manufacturing processes;
● restrictions on the labeling or marketing of a product;
● restrictions on product distribution or use;
● requirements to conduct post-marketing studies or clinical trials;
● warning or untitled letters;
● withdrawal of the products from the market;
● refusal to approve pending applications or supplements to approved applications that we submit;
● recall of products;
● fines, restitution or disgorgement of profits or revenues;
● suspension or withdrawal of marketing approvals;
● damage to relationships with any potential collaborators;
● unfavorable press coverage and damage to our reputation;
● refusal to permit the import or export of our products;
● product seizure;
● exclusion from participation in federal healthcare reimbursement programs or debarment or the imposition of
Corporate Integrity Agreements; or
● injunctions or the imposition of civil or criminal penalties.
Non-compliance by us or any future collaborator with regulatory requirements regarding safety monitoring or
pharmacovigilance, and with requirements related to the development of products for the pediatric population, can also
result in significant financial penalties. Similarly, failure to comply with regulatory requirements regarding the protection
of personal information can also lead to significant penalties and sanctions.
Similar restrictions apply to the approval of our products in the EU. The holder of a marketing authorization is
required to comply with a range of requirements applicable to the manufacturing, marketing, promotion and sale of
medicinal products. These include: compliance with the EU’s stringent pharmacovigilance or safety reporting rules, which
can impose post-authorization studies and additional monitoring obligations; the manufacturing of authorized
102
Table of Contents
medicinal products, for which a separate manufacturer’s license is mandator; and the marketing and promotion of
authorized drugs, which are strictly regulated in the EU and are also subject to EU member state laws.
Accordingly, with respect to XENLETA and any other product candidates for which we receive marketing
approval, we and our contract manufacturers will continue to expend time, money and effort in all areas of regulatory
compliance, including manufacturing, production, product surveillance and quality control. If we are not able to comply
with post-approval regulatory requirements, we could have the marketing approvals for our products, including
XENLETA, withdrawn by regulatory authorities and our ability to market any future products could be limited, which
could adversely affect our ability to achieve or sustain profitability. Thus, the cost of compliance with post-approval
regulations may have a negative effect on our operating results and financial condition.
Inadequate funding for the FDA, the SEC and other government agencies could hinder their ability to hire and retain
key leadership and other personnel, prevent new products and services from being developed or commercialized in a
timely manner or otherwise prevent those agencies from performing normal business functions on which the operation
of our business may rely, which could negatively impact our business.
The ability of the FDA to review and approve new products can be affected by a variety of factors, including
government budget and funding levels, ability to hire and retain key personnel and accept the payment of user fees, and
statutory, regulatory, and policy changes. Average review times at the agency have fluctuated in recent years as a result. In
addition, government funding of the SEC and other government agencies on which our operations may rely, including
those that fund research and development activities is subject to the political process, which is inherently fluid and
unpredictable.
Disruptions at the FDA and other agencies have delayed the time necessary for new drugs to be reviewed and/or
approved by necessary government agencies, which has adversely affected our business. The FDA announced that in order
to bring new therapies to patients sick with COVID-19 as quickly as possible, it has redeployed medical and regulatory
staff from other areas to work on COVID-19 therapies. On June 19, 2020 we received a second Complete Response Letter
in connection with our NDA for CONTEPO for the treatment of cUTIs, including AP due to issues at our third party
manufacturers that could not be inspected by the FDA owing to operational restrictions placed on the FDA by COVID-19.
Additionally, over the last several years, the U.S. government has shut down several times and certain regulatory agencies,
such as the FDA and the SEC, have had to furlough critical FDA, SEC and other government employees and stop critical
activities. If a prolonged government shutdown occurs, it could significantly impact the ability of the FDA to timely review
and process our regulatory submissions, which could have a material adverse effect on our business. Future government
shutdowns could impact our ability to access the public markets and obtain necessary capital in order to properly capitalize
and continue our operations.
As of May 26, 2021, the FDA noted it was continuing to ensure timely reviews of applications for medical
products during the ongoing COVID-19 pandemic in line with its user fee performance goals and conducting mission
critical domestic and foreign inspections to ensure compliance of manufacturing facilities with FDA quality standards.
However, the FDA may not be able to continue its current pace and review timelines could be extended, including where a
pre-approval inspection or an inspection of clinical sites is required and due to the ongoing COVID-19 pandemic and travel
restrictions, the FDA is unable to complete such required inspections during the review period. Regulatory authorities
outside the U.S. may adopt similar restrictions or other policy measures in response to the COVID-19 pandemic and may
experience delays in their regulatory activities.
A Fast Track or Priority Review designation by the FDA may not lead to a faster development or regulatory review or
approval process and does not assure FDA approval of our product candidates.
If a product candidate is intended for the treatment of a serious or life threatening condition and the product
candidate demonstrates the potential to address unmet medical need for this condition, the sponsor may apply to the FDA
for fast track designation. For fast track products, sponsors may have greater interactions with the FDA, and the FDA may
initiate review of sections of a fast track product’s application before the application is complete. This rolling review may
be available if the FDA determines, after preliminary evaluation of clinical data submitted by the sponsor,
103
Table of Contents
that a fast track product may be effective. The FDA has designated the IV formulation of CONTEPO as a qualified
infectious disease product, or QIDP, and granted a fast track designation for this formulation of CONTEPO.
Further, if FDA determines that a product candidate offers major advances in treatment or provides a treatment
where no adequate therapy exists, the FDA may designate the product candidate for priority review. Significant
improvement may be illustrated by evidence of increased effectiveness in the treatment of a condition, elimination or
substantial reduction of a treatment-limiting product reaction, documented enhancement of patient compliance that may
lead to improvement in serious outcomes, and evidence of safety and effectiveness in a new subpopulation. A priority
review designation means that the goal for the FDA to review an application is six months, rather than the standard review
period of ten months. CONTEPO has been granted priority review by the FDA.
We may seek these and other expedited review designations for our product candidates. The FDA has broad
discretion with respect to whether or not to grant these designations to a product candidate, so even if we believe a
particular product candidate is eligible for such designation or status, the FDA may decide not to grant it. Moreover, a fast
track or breakthrough therapy designation does not necessarily mean a faster regulatory review process or necessarily
confer any advantage with respect to approval compared to conventional FDA procedures. As a result, while we may seek
and receive these designations for our product candidates, we may not experience a faster development process, review or
approval compared to conventional FDA procedures. In addition, the FDA may withdraw these designations if it believes
that the designation is no longer supported by data from our clinical development program.
Designation of CONTEPO as a Qualified Infectious Disease Product does not assure FDA approval of this product
candidate.
A QIDP is an antibacterial or antifungal drug intended to treat serious or life-threatening infections, including
those caused by an antibacterial or antifungal resistant pathogen, including novel or emerging infectious pathogens or
certain “qualifying pathogens”. Upon the approval of an NDA for a drug product designated by the FDA as a QIDP, the
product is granted an additional period of five years of regulatory exclusivity. Even though we have received a QIDP
designation for CONTEPO, there is no assurance that CONTEPO will be approved by the FDA.
If the FDA does not conclude that our product candidates satisfy the requirements under Section 505(b)(2) of the
Federal Food Drug and Cosmetics Act, or if the requirements for such product candidates under Section 505(b)(2) are
not as we expect, the approval pathway for those product candidates may take longer, cost more and entail greater
complications and risks than anticipated, and may not be successful.
We submitted an NDA for marketing approval of CONTEPO for the treatment of cUTI in adults in the United
States in October 2018, and we resubmitted the NDA in December 2019, utilizing Section 505(b)(2) of the Food, Drug and
Cosmetic Act, or the FDCA, which was enacted as part of the Drug Price Competition and Patent Term Restoration Act of
1984, otherwise known as the Hatch-Waxman Act. Section 505(b)(2) permits the submission of an NDA where at least
some of the information required for approval comes from studies not conducted by or for the applicant and for which the
applicant has not obtained a right of reference.
For NDAs submitted under Section 505(b)(2) of the FDCA, the patent certification and related provisions of the
Hatch-Waxman Act apply. In accordance with the Hatch-Waxman Act, such NDAs may be required to include
certifications, known as Paragraph IV certifications, that certify any patents listed in the Orange Book publication in
respect to any product referenced in the 505(b)(2) application are invalid, unenforceable and/or will not be infringed by the
manufacture, use or sale of the product that is the subject of the 505(b)(2) application. Under the Hatch-Waxman Act, the
holder of the NDA which the 505(b)(2) application references may file a patent infringement lawsuit after receiving notice
of the Paragraph IV certification. Filing of a patent infringement lawsuit triggers a one-time automatic 30-month stay of the
FDA’s ability to approve the 505(b)(2) application. We have not conducted a comprehensive freedom-to-operate review
with regard to CONTEPO.
Accordingly, we may invest a significant amount of time and expense in the development of CONTEPO or any
other product candidate we may develop and experience significant delays and patent litigation before such products may
be commercialized, if at all. A Section 505(b)(2) application also may not be approved until any non-patent
104
Table of Contents
exclusivity, such as exclusivity for obtaining approval of a new chemical entity, listed in the Orange Book for the
referenced product has expired. The FDA may also require us to perform one or more additional clinical studies or
measurements to support the change from the approved product. The FDA may then approve the new formulation for all or
only some of the indications sought by us. The FDA may also reject our future Section 505(b)(2) submissions and may
require us to file such submissions under Section 501(b)(1) of the FDCA, which could be considerably more expensive and
time consuming.
In addition, notwithstanding the approval of a number of products by the FDA under Section 505(b)(2) over the
last few years, certain competitors and others have objected to the FDA’s interpretation of Section 505(b)(2). If the FDA’s
interpretation of Section 505(b)(2) is successfully challenged, the FDA may be required to change its 505(b)(2) policies
and practices, which could delay or even prevent the FDA from approving any NDA that we submit under Section 505(b)
(2). It is not uncommon for a manufacturer of an approved product to file a citizen petition with the FDA seeking to delay
approval of, or impose additional approval requirements for, pending competing products. If successful, such petitions can
significantly delay, or even prevent, the approval of the new product. However, even if the FDA ultimately denies such a
petition, the FDA may substantially delay approval while it considers and responds to the petition. Thus, even if we are
able to utilize the Section 505(b)(2) regulatory pathway, there is no guarantee this would ultimately lead to faster product
development or earlier approval.
If the FDA does not conclude that CONTEPO, or any of our other product candidates for which we may utilize
the 505(b)(2) pathway, satisfies the requirements for the 505(b)(2) regulatory approval pathway, or if the requirements for
approval of any of our product candidates, including CONTEPO, under Section 505(b)(2) are not as we expect, the
approval pathway for CONTEPO and any of our other product candidates for which we may utilize the 505(b)(2) pathway
will likely take significantly longer, cost significantly more and encounter significantly greater complications and risks than
anticipated, and in any case may not be successful.
Our relationships with healthcare providers, physicians and third-party payors will be subject to applicable anti-
kickback, fraud and abuse and other healthcare laws and regulations, which in the event of a violation could expose us
to criminal sanctions, civil penalties, contractual damages, reputational harm and diminished profits and future
earnings.
Healthcare providers, physicians and third-party payors will play a primary role in the recommendation and
prescription of any of our products, including SIVEXTRO, XENLETA, and product candidates, including CONTEPO, for
which we obtain marketing approval. Our future arrangements with healthcare providers, physicians and third-party payors
may expose us to broadly applicable fraud and abuse and other healthcare laws and regulations that may constrain the
business or financial arrangements and relationships through which we market, sell and distribute SIVEXTRO, XENLETA,
and any other products for which we obtain marketing approval. Restrictions under applicable federal, state, and foreign
healthcare laws and regulations, include the following:
● the federal Anti-Kickback Statute prohibits, among other things, persons from knowingly and willfully
soliciting, offering, receiving or providing remuneration, directly or indirectly, in cash or in kind, to induce or
reward, or in return for, either the referral of an individual for, or the purchase, order or recommendation or
arranging of, any good or service, for which payment may be made under a federal healthcare program such
as Medicare and Medicaid;
● the federal False Claims Act imposes criminal and civil penalties, including through civil whistleblower or
qui tam actions, against individuals or entities for, among other things, knowingly presenting, or causing to
be presented, false or fraudulent claims for payment by a federal healthcare program or making a false
statement or record material to payment of a false claim or avoiding, decreasing or concealing an obligation
to pay money to the federal government, with potential liability including mandatory treble damages and
significant per-claim penalties;
● the federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, imposes criminal and
civil liability for executing a scheme to defraud any healthcare benefit program or making false statements
relating to healthcare matters;
105
Table of Contents
● HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act and its
implementing regulations, also imposes obligations, including mandatory contractual terms, with respect to
safeguarding the privacy, security and transmission of individually identifiable health information;
● the federal Physician Payments Sunshine Act requires applicable manufacturers of covered products to report
payments and other transfers of value to physicians, other healthcare providers and teaching hospitals, with
data collection beginning in August 2013; and
● analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws and
transparency statutes, and foreign anti-corruption laws, may apply to sales or marketing arrangements and
claims involving healthcare items or services reimbursed by non-governmental third party payors, including
private insurers.
Some state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary
compliance guidelines and the relevant compliance guidance promulgated by the federal government and may require
product manufacturers to report information related to payments and other transfers of value to physicians and other
healthcare providers or marketing expenditures. State and foreign laws also govern the privacy and security of health
information in some circumstances, many of which differ from each other in significant ways and often are not pre-empted
by HIPAA, thus complicating compliance efforts.
If our operations are found to be in violation of any of the laws described above or any governmental regulations
that apply to us, we may be subject to penalties, including civil and criminal penalties, damages, fines and the curtailment
or restructuring of our operations. Any penalties, damages, fines, curtailment or restructuring of our operations could
adversely affect our financial results. We have developed and implemented a corporate compliance program designed to
ensure that we will market and sell any approved products in compliance with all applicable laws and regulations, but we
cannot guarantee that this program will protect us from governmental investigations or other actions or lawsuits stemming
from a failure to be in compliance with such laws or regulations. If any such actions are instituted against us and we are not
successful in defending ourselves or asserting our rights, those actions could have a significant impact on our business,
including the imposition of significant fines or other sanctions.
Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws
and regulations will involve substantial costs. It is possible that governmental authorities will conclude that our business
practices may not comply with current or future statutes, regulations or case law involving applicable fraud and abuse or
other healthcare laws and regulations. If our operations are found to be in violation of any of these laws or any other
governmental regulations that may apply to us, we may be subject to significant civil, criminal and administrative
penalties, damages, fines, imprisonment, exclusion of products from government funded healthcare programs, such as
Medicare and Medicaid, and the curtailment or restructuring of our operations. If any of the physicians or other healthcare
providers or entities with whom we do business is found to be not in compliance with applicable laws, they may be subject
to criminal, civil or administrative sanctions, including exclusions from government funded healthcare programs.
Reporting and payment obligations under the Medicaid Drug Rebate Program and other governmental drug pricing
programs are complex and may involve subjective decisions. Any failure to comply with those obligations could subject
us to penalties and sanctions.
As a condition of reimbursement by various federal and state health insurance programs, pharmaceutical
companies are required to calculate and report certain pricing information to federal and state agencies. The regulations
governing the calculations, price reporting and payment obligations are complex and subject to interpretation by various
government and regulatory agencies, as well as the courts. Reasonable assumptions have been made where there is lack of
regulations or clear guidance and such assumptions involve subjective decisions and estimates. Pharmaceutical companies
are required to report any revisions to our calculation, price reporting and payment obligations previously reported or paid.
Such revisions could affect liability to federal and state payers and also adversely impact reported financial results of
operations in the period of such restatement.
106
Table of Contents
Uncertainty exists as new laws, regulations, judicial decisions, or new interpretations of existing laws, or
regulations related to our calculations, price reporting or payments obligations increases the chances of a legal challenge,
restatement or investigation. If a company becomes subject to investigations, restatements, or other inquiries concerning
compliance with price reporting laws and regulations, it could be required to pay or be subject to additional
reimbursements, penalties, sanctions or fines, which could have a material adverse effect on the business, financial
condition and results of operations. In addition, it is possible that future healthcare reform measures could be adopted,
which could result in increased pressure on pricing and reimbursement of products and thus have an adverse impact on
financial position or business operations.
Further, state Medicaid programs may be slow to invoice pharmaceutical companies for calculated rebates
resulting in a lag between the time a sale is recorded and the time the rebate is paid. This results in a company having to
carry a liability on its consolidated balance sheets for the estimate of rebate claims expected for Medicaid patients. If actual
claims are higher than current estimates, the company’s financial position and results of operations could be adversely
affected.
In addition to retroactive rebates and the potential for 340B Program refunds, if a pharmaceutical firm is found to
have knowingly submitted any false price information related to the Medicaid Drug Rebate Program to the Centers for
Medicare & Medicaid Services, or CMS , it may be liable for civil monetary penalties. Such failure could also be grounds
for CMS to terminate the Medicaid drug rebate agreement, pursuant to which companies participate in the Medicaid
program. In the event that CMS terminates a rebate agreement, federal payments may not be available under government
programs, including Medicaid or Medicare Part B, for covered outpatient drugs.
Additionally, if a pharmaceutical company overcharges the government in connection with the FSS program or
Tricare Retail Pharmacy Program, whether due to a misstated Federal Ceiling Price or otherwise, it is required to refund the
difference to the government. Failure to make necessary disclosures and/or to identify contract overcharges can result in
allegations against a company under the FCA and other laws and regulations. Unexpected refunds to the government, and
responding to a government investigation or enforcement action, would be expensive and time-consuming, and could have
a material adverse effect on our business, financial condition, results of operations and growth prospects.
Our collaborators are also subject to similar requirements outside of the U.S. and thus the attendant risks and uncertainties.
If our collaborators suffer material and adverse effects from such risks and uncertainties, our rights and benefits for our
licensed products could be negatively impacted, which could have a material and adverse impact on our revenues.
Current and future legislation may increase the difficulty and cost for us and any future collaborators to obtain
marketing approval of and commercialize our products and product candidates and affect the prices we, or they, may
obtain.
In the United States and some foreign jurisdictions, there have been a number of legislative and regulatory
changes and proposed changes regarding the healthcare system that could, among other things, prevent or delay marketing
approval of CONTEPO or any of our other product candidates, restrict or regulate post-approval activities and affect our
ability, or the ability of any collaborators, to profitably sell any products, including SIVEXTRO, XENLETA, or product
candidates, including CONTEPO, for which we, or they, obtain marketing approval. We expect that current laws, as well as
other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and in
additional downward pressure on the price that we, or any future collaborators, may receive for any approved products.
In March 2010, President Obama signed into law the Patient Protection and Affordable Care Act, as amended by
the Health Care and Education Reconciliation Act, or collectively the ACA. Among the provisions of the ACA of potential
importance to our business and our product candidates are the following:
● an annual, non-deductible fee on any entity that manufactures or imports specified branded prescription
products and biologic agents;
107
Table of Contents
● an increase in the statutory minimum rebates a manufacturer must pay under the Medicaid Drug Rebate
Program;
● expansion of healthcare fraud and abuse laws, including the civil False Claims Act and the federal Anti-
Kickback Statute, new government investigative powers and enhanced penalties for noncompliance;
● a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70%
point-of-sale discounts off negotiated prices;
● extension of manufacturers’ Medicaid rebate liability;
● expansion of eligibility criteria for Medicaid programs;
● expansion of the entities eligible for discounts under the Public Health Service pharmaceutical pricing
program;
● new requirements to report certain financial arrangements with physicians and teaching hospitals;
● a new requirement to annually report product samples that manufacturers and distributors provide to
physicians; and
● a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct
comparative clinical effectiveness research, along with funding for such research.
In addition, other legislative changes have been proposed and adopted since the ACA was enacted. In August
2011, the Budget Control Act of 2011, among other things, created measures for spending reductions by Congress. A Joint
Select Committee on Deficit Reduction, tasked with recommending a targeted deficit reduction of at least $1.2 trillion for
the years 2013 through 2021, was unable to reach required goals, thereby triggering the legislation’s automatic reduction to
several government programs. These changes included aggregate reductions to Medicare payments to providers of up to
2% per fiscal year, which went into effect in April 2013 and will remain in effect through 2031 under the Coronavirus Aid,
Relief, and Economic Security Act, or the CARES Act. Pursuant to subsequent legislation, however, these Medicare
sequester reductions have been suspended through the end of March 2022. From April 2022 through June 2022 a 1%
sequester cut will be in effect, with the full 2% cut resuming thereafter. The American Taxpayer Relief Act of 2012, among
other things, reduced Medicare payments to several providers and increased the statute of limitations period for the
government to recover overpayments to providers from three to five years. These new laws may result in additional
reductions in Medicare and other healthcare funding and otherwise affect the prices we may obtain for any of our product
candidates for which we may obtain regulatory approval or the frequency with which any such product candidate is
prescribed or used.
Since enactment of the ACA, there have been and continue to be, numerous legal challenges and Congressional
actions to repeal and replace provisions of the law. For example, with enactment of the Tax Cuts for Jobs Act, or TCJA, in
2017, Congress repealed the “individual mandate.” The repeal of this provision, which requires most Americans to carry a
minimal level of health insurance, became effective in 2019. Further, on December 14, 2018, a U.S. District Court judge in
the Northern District of Texas ruled that the individual mandate portion of the ACA is an essential and inseverable feature
of the ACA and therefore because the mandate was repealed as part of the TCJA, the remaining provisions of the ACA are
invalid as well. The U.S. Supreme Court heard this case on November 10, 2020 and on June 17, 2021, dismissed this action
after finding that the plaintiffs do not have standing to challenge the constitutionality of the ACA. Litigation and legislation
over the ACA are likely to continue, with unpredictable and uncertain results.
The Trump Administration also took executive actions to undermine or delay implementation of the ACA,
including directing federal agencies with authorities and responsibilities under the ACA to waive, defer, grant exemptions
from, or delay the implementation of any provision of the ACA that would impose a fiscal or regulatory burden on states,
individuals, healthcare providers, health insurers, or manufacturers of pharmaceuticals or medical
108
Table of Contents
devices. On January 28, 2021, however, President Biden rescinded those orders and issued a new Executive Order which
directs federal agencies to reconsider rules and other policies that limit Americans’ access to health care, and consider
actions that will protect and strengthen that access. Under this Order, federal agencies are directed to re-examine: policies
that undermine protections for people with pre-existing conditions, including complications related to COVID-19;
demonstrations and waivers under Medicaid and the ACA that may reduce coverage or undermine the programs, including
work requirements; policies that undermine the Health Insurance Marketplace or other markets for health insurance;
policies that make it more difficult to enroll in Medicaid and the ACA; and policies that reduce affordability of coverage or
financial assistance, including for dependents. This Executive Order also directs the U.S. Department of Health and Human
Services to create a special enrollment period for the Health Insurance Marketplace in response to the COVID-19
pandemic.
In addition, the Centers for Medicare & Medicaid Services, or CMS, has proposed regulations that would give
states greater flexibility in setting benchmarks for insurers in the individual and small group marketplaces, which may have
the effect of relaxing the essential health benefits required under the ACA for plans sold through such marketplaces. On
November 30, 2018, CMS announced a proposed rule that would amend the Medicare Advantage and Medicare Part D
prescription drug benefit regulations to reduce out of pocket costs for plan enrollees and allow Medicare plans to negotiate
lower rates for certain drugs. Among other things, the proposed rule changes would allow Medicare Advantage plans to use
pre authorization, or PA, and step therapy, or ST, for six protected classes of drugs, with certain exceptions, permit plans to
implement PA and ST in Medicare Part B drugs; and change the definition of “negotiated prices” in the regulations. It is
unclear whether these proposed changes will be accepted, and if so, what effect such changes will have on our business.
We expect that these healthcare reforms, as well as other healthcare reform measures that may be adopted in the
future, may result in additional reductions in Medicare and other healthcare funding, more rigorous coverage criteria, new
payment methodologies and additional downward pressure on the price that we receive for any approved product and/or
the level of reimbursement physicians receive for administering any approved product we might bring to market.
Reductions in reimbursement levels may negatively impact the prices we receive or the frequency with which our products
are prescribed or administered. Any reduction in reimbursement from Medicare or other government programs may result
in a similar reduction in payments from private payors.
The prices of prescription pharmaceuticals in the United States and foreign jurisdictions are subject to considerable
legislative and executive actions and could impact the prices we obtain for our products.
The prices of prescription pharmaceuticals have also been the subject of considerable discussion in the United
States. There have been several recent U.S. congressional inquiries, as well as proposed and enacted state and federal
legislation designed to, among other things, bring more transparency to pharmaceutical pricing, review the relationship
between pricing and manufacturer patient programs, and reduce the costs of pharmaceuticals under Medicare and
Medicaid. In 2020, President Trump issued several executive orders intended to lower the costs of prescription products
and certain provisions in these orders have been incorporated into regulations. These regulations include an interim final
rule implementing a most favored nation model for prices that would tie Medicare Part B payments for certain physician-
administered pharmaceuticals to the lowest price paid in other economically advanced countries, effective January 1, 2021.
That rule, however, has been subject to a nationwide preliminary injunction and, on December 29, 2021, CMS issued a
final rule to rescind it. With issuance of this rule, CMS stated that it will explore all options to incorporate value into
payments for Medicare Part B pharmaceuticals and improve beneficiaries' access to evidence-based care.
In addition, in October 2020, HHS and the FDA published a final rule allowing states and other entities to develop
a Section 804 Importation Program, or SIP, to import certain prescription drugs from Canada into the United States. The
final rule is currently the subject of ongoing litigation, but at least six states (Vermont, Colorado, Florida, Maine, New
Mexico, and New Hampshire) have passed laws allowing for the importation of drugs from Canada with the intent of
developing SIPs for review and approval by the FDA. Further, on November 20, 2020, HHS finalized a regulation
removing safe harbor protection for price reductions from pharmaceutical manufacturers to plan sponsors under Part D,
either directly or through pharmacy benefit managers, unless the price reduction is required by law. The implementation of
the rule has been delayed by the Biden administration from January 1, 2022 to January 1, 2023 in
109
Table of Contents
response to ongoing litigation. The rule also creates a new safe harbor for price reductions reflected at the point-of-sale, as
well as a new safe harbor for certain fixed fee arrangements between pharmacy benefit managers and manufacturers, the
implementation of which have also been delayed by the Biden administration until January 1, 2023.
On July 9, 2021, President Biden signed Executive Order 14063, which focuses on, among other things, the price
of pharmaceuticals. The Order directs HHS to create a plan within 45 days to combat “excessive pricing of prescription
pharmaceuticals and enhance domestic pharmaceutical supply chains, to reduce the prices paid by the federal government
for such pharmaceuticals, and to address the recurrent problem of price gouging.” On September 9, 2021, HHS released its
plan to reduce pharmaceutical prices. The key features of that plan are to: (a) make pharmaceutical prices more affordable
and equitable for all consumers and throughout the health care system by supporting pharmaceutical price negotiations
with manufacturers; (b) improve and promote competition throughout the prescription pharmaceutical industry by
supporting market changes that strengthen supply chains, promote biosimilars and generic drugs, and increase
transparency; and (c) foster scientific innovation to promote better healthcare and improve health by supporting public and
private research and making sure that market incentives promote discovery of valuable and accessible new treatments.
At the state level, individual states are increasingly aggressive in passing legislation and implementing regulations
designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints,
discounts, restrictions on certain product access and marketing cost disclosure and transparency measures, and, in some
cases, designed to encourage importation from other countries and bulk purchasing. In addition, regional health care
organizations and individual hospitals are increasingly using bidding procedures to determine what pharmaceutical
products and which suppliers will be included in their prescription drug and other health care programs. These measures
could reduce the ultimate demand for our products, once approved, or put pressure on our product pricing. We expect that
additional state and federal healthcare reform measures will be adopted in the future, any of which could limit the amounts
that federal and state governments will pay for healthcare products and services, which could result in reduced demand for
our product candidates or additional pricing pressures.
In other countries, particularly the member states of the European Union, the pricing of prescription
pharmaceuticals is subject to governmental control. In these countries, pricing negotiations with governmental authorities
can take considerable time after the receipt of marketing approval for a product. Also, there can be considerable pressure
by governments and other stakeholders on prices and reimbursement levels, including as part of cost containment
measures. Political, economic and regulatory developments may further complicate pricing negotiations, and pricing
negotiations may continue after reimbursement has been obtained. Reference pricing used by various European Union
member states and parallel distribution, or arbitrage between low-priced and high-priced member states, can further reduce
prices. In some countries, we may be required to conduct a clinical trial or other studies that compare the cost-effectiveness
of our product candidate to other available therapies to obtain or maintain reimbursement or pricing approval. Publication
of discounts by third-party payors or authorities may lead to further pressure on prices or reimbursement levels within the
country of publication and other countries. If reimbursement of our products is unavailable or limited in scope or amount,
or if pricing is set at unsatisfactory levels, our business could be adversely affected.
Compliance with global privacy and data security requirements could result in additional costs and liabilities to us or
inhibit our ability to collect and process data globally, and the failure to comply with such requirements could subject us
to significant fines and penalties, which may have a material adverse effect on our business, financial condition or
results of operations.
The regulatory framework for the collection, use, safeguarding, sharing, transfer and other processing of information
worldwide is rapidly evolving and is likely to remain uncertain for the foreseeable future. Globally, virtually every
jurisdiction in which we operate has established its own data security and privacy frameworks with which we must comply.
For example, the collection, use, disclosure, transfer or other processing of personal data regarding individuals in the
European Union, including personal health data, is subject to the GDPR, which took effect across all member states of the
European Economic Area, or EEA, in May 2018. The GDPR is wide-ranging in scope and imposes numerous requirements
on companies that process personal data, including requirements relating to processing health and other sensitive data,
obtaining consent of the individuals to whom the personal data relates, providing information to
110
Table of Contents
individuals regarding data processing activities, implementing safeguards to protect the security and confidentiality of
personal data, providing notification of data breaches, and taking certain measures when engaging third-party processors.
The GDPR increases our obligations with respect to clinical trials conducted in the EEA by expanding the definition of
personal data to include coded data and requiring changes to informed consent practices and more detailed notices for
clinical trial subjects and investigators. In addition, the GDPR also imposes strict rules on the transfer of personal data to
countries outside the European Union, including the United States and, as a result, increases the scrutiny that clinical trial
sites located in the EEA should apply to transfers of personal data from such sites to countries that are considered to lack
an adequate level of data protection, such as the United States. The GDPR also permits data protection authorities to
require destruction of improperly gathered or used personal information and/or impose substantial fines for violations of
the GDPR, which can be up to 4% of global revenues or 20 million Euros, whichever is greater, and it also confers a
private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek
judicial remedies and obtain compensation for damages resulting from violations of the GDPR. In addition, the GDPR
provides that European Union member states may make their own further laws and regulations limiting the processing of
personal data, including genetic, biometric or health data.
Similar actions are either in place or under way in the United States. There are a broad variety of data protection laws
that are applicable to our activities, and a wide range of enforcement agencies at both the state and federal levels that can
review companies for privacy and data security concerns based on general consumer protection laws. The Federal Trade
Commission and state Attorneys General are aggressive in reviewing privacy and data security protections for consumers.
New laws also are being considered at both the state and federal levels. For example, the California Consumer Privacy Act,
which went into effect on January 1, 2020, is creating similar risks and obligations as those created by the GDPR, though
the act does exempt certain information collected as part of a clinical trial subject to the Federal Policy for the Protection of
Human Subjects (i.e. “the Common Rule”). Many other states are considering similar legislation. A broad range of
legislative measures also have been introduced at the federal level. Accordingly, failure to comply with federal and state
laws (both those currently in effect and future legislation) regarding privacy and security of personal information could
expose us to fines and penalties under such laws. There also is the threat of consumer class actions related to these laws
and the overall protection of personal data. Even if we are not determined to have violated these laws, government
investigations into these issues typically require the expenditure of significant resources and generate negative publicity,
which could harm our reputation and our business.
Given the breadth and depth of changes in data protection obligations, preparing for and complying with these
requirements is rigorous and time intensive and requires significant resources and a review of our technologies, systems
and practices, as well as those of any third-party collaborators, service providers, contractors or consultants that process or
transfer personal data collected in the European Union. The GDPR and other changes in laws or regulations associated
with the enhanced protection of certain types of sensitive data, such as healthcare data or other personal information from
our clinical trials, could require us to change our business practices and put in place additional compliance mechanisms,
may interrupt or delay our development, regulatory and commercialization activities and increase our cost of doing
business, and could lead to government enforcement actions, private litigation and significant fines and penalties against us
and could have a material adverse effect on our business, financial condition or results of operations.
We cannot assure stockholders that our third-party service providers with access to our or our customers’,
suppliers’, trial patients’ and employees’ personally identifiable and other sensitive or confidential information in relation
to which we are responsible will not breach contractual obligations imposed by us, or that they will not experience data
security breaches or attempts thereof, which could have a corresponding effect on our business, including putting us in
breach of our obligations under privacy laws and regulations and/or which could in turn adversely affect our business,
results of operations and financial condition. We cannot assure shareholders that our contractual measures and our own
privacy and security-related safeguards will protect us from the risks associated with the third-party processing, storage and
transmission of such information.
111
Table of Contents
We are subject to anti-corruption laws, as well as export control laws, customs laws, sanctions laws and other laws
governing our operations. If we fail to comply with these laws, we could be subject to civil or criminal penalties, other
remedial measures and legal expenses, which could adversely affect our business, results of operations and financial
condition.
Our operations are subject to anti-corruption laws, including the U.S. Foreign Corrupt Practices Act, or FCPA, the
Irish Criminal Justice (Corruption Offenses) Act, and other anti-corruption laws that apply in countries where we do
business and may do business in the future. The FCPA and these other laws generally prohibit us, our officers, and our
employees and intermediaries from bribing, being bribed or making other prohibited payments to government officials or
other persons to obtain or retain business or gain some other business advantage. We may in the future operate in
jurisdictions that pose a high risk of potential FCPA violations, and we may participate in collaborations and relationships
with third parties whose actions could potentially subject us to liability under the FCPA or local anti-corruption laws. In
addition, we cannot predict the nature, scope or effect of future regulatory requirements to which our international
operations might be subject or the manner in that existing laws might be administered or interpreted.
Compliance with the FCPA and other anti-corruption laws is expensive and difficult, particularly in countries in
which corruption is a recognized problem. In addition, the FCPA presents particular challenges in the pharmaceutical
industry, because, in many countries, hospitals are operated by the government, and doctors and other hospital employees
are considered foreign officials. Certain payments to hospitals in connection with clinical trials and other work have been
deemed to be improper payments to government officials and have led to FCPA enforcement actions.
We are also subject to other laws and regulations governing our international operations, including regulations
administered by the governments of the United States, and authorities in the European Union, including applicable export
control regulations, economic sanctions on countries and persons, customs requirements and currency exchange
regulations, collectively referred to as the trade control laws. For example, the provision of benefits or advantages to
physicians to induce or encourage the prescription, recommendation, endorsement, purchase, supply, order, or use of
medicinal products is prohibited in the European Union. The provision of benefits or advantages to physicians is also
governed by the national anti-bribery laws of European Union Member States, such as the UK Bribery Act 2010.
Infringement of these laws could result in substantial fines and imprisonment. Payments made to physicians in certain
European Union Member States must be publicly disclosed. Moreover, agreements with physicians often must be the
subject of prior notification and approval by the physician’s employer, his or her competent professional organization,
and/or the regulatory authorities of the individual European Union Member States. These requirements are provided in the
national laws, industry codes or professional codes of conduct applicable in the European Union Member States. Failure to
comply with these requirements could result in reputational risk, public reprimands, administrative penalties, fines, or
imprisonment.
There is no assurance that we will be effective in ensuring our compliance with all applicable anti-corruption
laws, including the FCPA or other legal requirements, including trade control laws. If we are not in compliance with the
FCPA and other anti-corruption laws or trade control laws, we may be subject to criminal and civil penalties, disgorgement
and other sanctions and remedial measures, and legal expenses, which could have an adverse impact on our business,
financial condition, results of operations and liquidity. Likewise, any investigation of any potential violations of the FCPA,
other anti-corruption laws or trade control laws by U.S. or other authorities could also have an adverse impact on our
reputation, our business, results of operations and financial condition.
If we fail to comply with environmental, health and safety laws and regulations, we could become subject to fines or
penalties or incur costs that could have a material adverse effect on the success of our business.
We are subject to numerous environmental, health and safety laws and regulations, including those governing
laboratory procedures and the handling, use, storage, treatment and disposal of hazardous materials and wastes. Our
operations currently, and may in the future, involve the use of hazardous and flammable materials, including chemicals and
medical and biological materials, and produce hazardous waste products. Even if we contract with third parties for the
disposal of these materials and wastes, we cannot eliminate the risk of contamination or injury from these materials. In the
event of contamination or injury resulting from our use of hazardous materials or disposal of hazardous wastes, we could
be held liable for any resulting damages, and any liability could exceed our resources.
112
Table of Contents
Although we maintain workers’ compensation insurance to cover us for costs and expenses, we may incur due to
injuries to our employees resulting from the use of hazardous materials, this insurance may not provide adequate coverage
against potential liabilities. We also maintain a general liability program for some of the risks, but our insurance program
includes limited environmental damage coverage, which has an annual aggregate coverage limit of $2.0 million. Although
we maintain an umbrella policy with an annual aggregate coverage limit of $10.0 million, which may provide some
environmental coverage, we do not maintain a separate policy covering environmental damages.
In addition, we may incur substantial costs to comply with current or future environmental, health and safety laws
and regulations. These current or future laws and regulations may impair our development or production efforts. Failure to
comply with these laws and regulations also may result in substantial fines, penalties or other sanctions.
Our employees may engage in misconduct or other improper activities, including non-compliance with regulatory
standards and requirements, which could cause significant liability for us and harm our reputation.
We are exposed to the risk of employee fraud or other misconduct, including intentional failures to comply with
FDA regulations or similar regulations of comparable non-U.S. regulatory authorities, provide accurate information to the
FDA or comparable non-U.S. regulatory authorities, comply with manufacturing standards we have established, comply
with federal and state healthcare fraud and abuse laws and regulations and similar laws and regulations established and
enforced by comparable non-U.S. regulatory authorities, report financial information or data accurately or disclose
unauthorized activities to us. In particular, sales, marketing and business arrangements in the healthcare industry are
subject to extensive laws and regulations intended to prevent fraud, kickbacks, self-dealing and other abusive practices.
These laws and regulations may restrict or prohibit a wide range of pricing, discounting, marketing and promotion, sales
commission, customer incentive programs and other business arrangements.
Employee misconduct could also involve the improper use of information obtained during clinical trials, which
could result in regulatory sanctions and serious harm to our reputation. It is not always possible to identify and deter
employee misconduct, and the precautions we take to detect and prevent this activity may not be effective in controlling
unknown or unmanaged risks or losses or in protecting us from governmental investigations or other actions or lawsuits
stemming from a failure to be in compliance with such laws, standards or regulations. If any such actions are instituted
against us, and we are not successful in defending ourselves or asserting our rights, those actions could have a significant
impact on our business and results of operations, including the imposition of significant fines or other sanctions.
We rely significantly on information technology and any failure, inadequacy, interruption or security lapse of that
technology, including any cyber security incidents, could harm our ability to operate our business effectively.
We are increasingly dependent upon technology systems and data to operate our business. In particular, the
COVID-19 pandemic has caused us to modify our business practices, including the requirement that our office-based
employees work from home. As a result, we are increasingly dependent upon our technology systems to operate our
business and our ability to effectively manage our business depends on the security, reliability and adequacy of our
technology systems and data.
Despite the implementation of security measures, our internal computer systems and those of third parties with
which we contract are vulnerable to damage from computer viruses, unauthorized access, natural disasters, terrorism, war
and telecommunication and electrical failures. Such systems are also vulnerable to service interruptions or to security
breaches from inadvertent or intentional actions by our employees, third-party vendors and/or business partners, or from
cyber-attacks by malicious third parties. Cyber-attacks are increasing in their frequency, sophistication and intensity, and
have become increasingly difficult to detect. Cyber-attacks could include the deployment of harmful malware, ransomware,
denial-of-service attacks, unauthorized access to or deletion of files, social engineering and other means to affect the
service reliability and threaten the confidentially, integrity and availability of information. Cyber-attacks also could include
phishing attempts or e-mail fraud to cause payments or information to be transmitted to an unintended recipient.
System failures, accidents or security breaches could cause interruptions in our operations, and could result in a
material disruption of our drug development programs and commercialization activities and business operations, in
113
Table of Contents
addition to possibly requiring substantial expenditures of resources to remedy. The loss of clinical trial data could result in
delays in our regulatory approval efforts and significantly increase our costs to recover or reproduce the data. To the extent
that any disruption or security breach were to result in a loss of, or damage to, our data or applications, or inappropriate
disclosure of confidential or proprietary information, we could incur liability and our product research, development and
commercialization efforts could be delayed.
We are subject to various laws protecting the confidentiality of certain patient health information, and our failure to
comply could result in penalties and reputational damage.
Certain countries in which we operate have, or are developing, laws protecting the confidentiality of certain
patient health information. European Union member states and other jurisdictions have adopted data protection laws and
regulations, which impose significant compliance obligations.
For example, the European Union General Data Protection Regulation, or the GDPR, which came into force on
May 25, 2018, introduced new data protection requirements in the European Union and substantial fines for breaches of the
data protection rules. The GDPR imposes strict obligations and restrictions on controllers and processors of personal data
including, for example, expanded disclosures about how personal data is to be used, increased requirements pertaining to
health data and pseudonymised (i.e., key-coded) data, mandatory data breach notification requirements and expanded rights
for individuals over their personal data. This could affect our ability to collect, analyze and transfer personal data, including
health data from clinical trials and adverse event reporting, or could cause our costs to increase, and harm our business and
financial condition.
While the GDPR, as a directly effective regulation, was designed to harmonize data protection law across the
European Union, it does permit member states to legislate in many areas (particularly with regard to the processing of
genetic, biometric or health data), meaning that inconsistencies between different member states will still arise. European
Union member states have their own regimes on medical confidentiality and national and European Union-level guidance
on implementation and compliance practices is often updated or otherwise revised, which adds to the complexity of
processing personal data in the European Union.
Risks Related to Our Acquisition of Zavante
We may fail to realize the anticipated benefits of our Acquisition of Zavante, those benefits may take longer to realize
than expected, and we may encounter significant integration difficulties.
On July 24, 2018, we completed the acquisition of Zavante pursuant to the Merger Agreement. Our ability to
realize the anticipated benefits of the Acquisition is expected to entail numerous material potential difficulties, including,
among others:
● any delay or failure in obtaining marketing approvals for CONTEPO, or any delay or failure to
commercialize CONTEPO in the United States thereafter;
● increased scrutiny from third parties, including regulators, legislative bodies and enforcement agencies,
including with respect to product pricing and commercialization matters;
● changes in laws or regulations that adversely impact the anticipated benefits of the Acquisition;
● challenges related to the perception by patients, the medical community and third-party payors of CONTEPO
for the treatment of cUTIs;
● disruptions to our manufacturing arrangements with third-party manufacturers, including our manufacturing
and supply arrangements with respect to CONTEPO and disruptions to our third-party distribution channel;
114
Table of Contents
● difficulties in managing the expanded operations of a larger and more complex company following the
Acquisition;
● difficulties in achieving the anticipated business opportunities and growth prospects from the Acquisition;
● the size of the treatable patient population for CONTEPO may be smaller than we believe it is;
● difficulties in attracting and retaining key personnel; and
● potential unknown liabilities, adverse consequences, unforeseen increased expenses or other unanticipated
problems associated with the Acquisition.
Many of these factors are outside of our control, and any one of them could result in increased costs, decreased
expected revenues and further diversion of management time and energy, which could materially adversely impact our
business, financial condition and results of operations.
The upfront consideration for the Acquisition was comprised of 815,209 of our ordinary shares, including the
81,518 ordinary shares that were initially held back but which were issued in July 2019 upon release of the Holdback
Shares pursuant to the terms of the Merger Agreement. Pursuant to the Merger Agreement, former Zavante stockholders
are also entitled to receive from us, subject to the terms and conditions of the Merger Agreement, up to $97.5 million in
contingent consideration, of which $25.0 million would become payable upon the first approval of a new drug application
from the FDA, for CONTEPO for any indication, or the Approval Milestone Payment, and an aggregate of up to
$72.5 million would become payable upon the achievement of specified net sales milestones, or the Net Sales Milestone
Payments, with the first commercial milestone becoming payable when CONTEPO exceeds $125.0 million in net sales in a
calendar year. At our Extraordinary General Meeting of Shareholders held in October 2018, our shareholders approved the
issuance of ordinary shares in settlement of potential milestone payment obligations that may become payable in the future
to former Zavante stockholders, including the Approval Milestone Payment which will be settled in our ordinary shares.
We also now have the right to settle the Net Sales Milestone Payments in ordinary shares, except as otherwise provided in
the Merger Agreement. The issuance of our ordinary shares in connection with the closing of the Acquisition was dilutive
to our existing shareholders, and the future issuance of our ordinary shares to satisfy our milestone payment obligations
would be further dilutive to our then existing shareholders.
Also, following the Acquisition, we now possess certain liabilities and obligations, including contractual liabilities
and obligations, that were assumed by us upon closing of the Acquisition. Prior to the Acquisition, former Zavante
stockholders and SG Pharmaceuticals, Inc. entered into a stock purchase agreement, dated as of May 5, 2015, or the Stock
Purchase Agreement, pursuant to which SG Pharmaceuticals, Inc. acquired all of the outstanding capital stock of Zavante
from the Zavante selling stockholders and SG Pharmaceuticals, Inc., subsequently merged with and into Zavante, with
Zavante as the surviving entity. Pursuant to the Stock Purchase Agreement, Zavante (as successor to SG
Pharmaceuticals, Inc.) is obligated to make milestone payments payable in cash to the selling stockholders of $3.0 million
upon marketing approval by the FDA with respect to any oral, intravenous or other form of fosfomycin, or the Zavante
Products, and milestone payments that may be settled in ordinary shares of up to $26.0 million in the aggregate upon the
occurrence of various specified levels of net sales with respect to the Zavante Products. In addition, Zavante is obligated to
make annual royalty payments to the selling stockholders of a mid-single-digit percentage of net sales of Zavante Products,
subject to adjustment based on net sales thresholds and with such percentage reduced to low single-digits if generic
fosfomycin products account for half of the applicable market on a product-by-product and country-by-country basis. The
Stock Purchase Agreement also provides that Zavante will pay to the selling stockholders a mid-single-digit percentage of
transaction revenue in connection with the consummation of the grant, sale, license or transfer of market exclusivity rights
for a qualified infectious disease product (within the meaning of the Cures Act) related to a Zavante Product.
In addition, we expect to incur expenses related to the continued development, regulatory approval process and
commercialization with respect to CONTEPO. Zavante has entered into a manufacturing and supply agreement with
Fisiopharma, pursuant to which Zavante has an obligation to purchase a minimum percentage of its commercial
requirements of CONTEPO in the United States. Zavante has also entered into a manufacturing and exclusive supply
115
Table of Contents
agreement with Laboratorios ERN, S.A., pursuant to which Laboratorios ERN, S.A. has agreed to supply Zavante with
certain technical documentation and data as required for submission of an NDA, or an abbreviated new drug application for
CONTEPO and certain regulatory support in connection with the commercial sale and use of CONTEPO in the
United States, and which provides for payments to Laboratorios ERN, S.A. of a one-time cash payment upon the first
commercial sale of CONTEPO and subsequent quarterly payments thereafter based on the number of vials of CONTEPO
sold in the United States during each quarter. Zavante has also entered into a manufacturing and supply agreement with
Ercros, S.A., pursuant to which Ercros, S.A. supplies to Zavante, on an exclusive basis, a blend of fosfomycin disodium
and succinic acid, or API Mixture, for CONTEPO and, if CONTEPO is approved, will supply the commercial API Mixture
for CONTEPO in the United States.
Because we have limited financial resources, by investing in the Acquisition, we may forgo or delay pursuit of
other opportunities that may have proven to have greater commercial potential. Further, it is possible that undisclosed,
contingent, or other liabilities or problems may arise in the future of which we were previously unaware. These undisclosed
liabilities could have an adverse effect on our business, financial condition and results of operations.
All of these factors could decrease or delay the expected accretive effect of the Acquisition and negatively impact
our share price. As a result, it cannot be assured that the Acquisition will result in the full realization of the benefits
anticipated from the Acquisition or in the anticipated time frames or at all.
Risks Related to Employee Matters
Our future success depends on our ability to attract, retain and motivate key executives and qualified personnel.
We are highly dependent on the principal members of our management team. Although we have formal
employment agreements with each of our executive officers, these agreements do not prevent our executives from
terminating their employment with us at any time. We do not maintain “key person” insurance on any of our executive
officers. The unplanned loss of the services of any of these persons might impede the achievement of our research,
development and commercialization objectives.
Recruiting and retaining qualified personnel, including in the United States and Ireland where we have key
business processes, will also be critical to our success. We may not be able to attract and retain these personnel on
acceptable terms given the competition among numerous pharmaceutical and biotechnology companies for similar
personnel. Our functional teams are small and therefore attrition can lead to gaps in institutional knowledge and risks to
running the business. In addition, we rely on consultants and advisors, including scientific and clinical advisors, to assist us
in formulating our research and development and commercialization strategy. Our consultants and advisors may be
employed by companies other than us and may have commitments under consulting or advisory contracts with other
entities that may limit their availability to us. If we cannot recruit and retain qualified personnel, we may be unable to
successfully develop our product candidates, conduct our clinical trials and commercialize our product candidates.
In 2020, we reduced the size of our organization, and we may encounter difficulties in managing our business as a
result of this reduction, or the attrition that may occur following this reduction, which could disrupt our operations. In
addition, we may not achieve anticipated benefits and savings from the reduction.
In April 2020, we announced a plan to restructure our hospital-based commercial sales force and transition to a
community-based sales effort. Additional reductions in headcount occurred in the third quarter including the restructuring
of the commercial organization, which led to the elimination of the role of the Chief Commercial Officer. Our commercial
operations now report directly to our Chief Executive Officer. The restructuring was intended to reduce costs and to align
the capabilities of our sales efforts with our strategic re-focus on making sales of XENLETA to community health care
professionals, as well as our business development strategy to in-license additional community products, such as
SIVEXTRO and additional community products. The restructuring resulted in the termination of long-term employees, the
loss of institutional knowledge and expertise and the reallocation and combination of certain roles and responsibilities
across the organization, all of which could adversely affect our operations. Given the complexity and nature of our
business, we must continue to implement and improve our managerial, operational and financial systems, manage our
facilities and continue to recruit and retain qualified personnel. This will be made more challenging given
116
Table of Contents
the restructuring described above and additional measures we may take to reduce costs. As a result, our management may
need to divert a disproportionate amount of its attention away from our day-to-day strategic and operational activities and
devote a substantial amount of time to managing these organizational changes. Further, the restructuring and possible
additional cost containment measures may yield unintended consequences, such as attrition beyond our intended reduction
in headcount and reduced employee morale. In addition, the restructuring may result in employees who were not affected
by the reduction in headcount seeking alternate employment, which would result in us seeking contract support at
unplanned additional expense. In addition, we may not achieve anticipated benefits from the restructuring. Due to our
limited resources, we may not be able to effectively manage our operations or recruit and retain qualified personnel, which
may result in weaknesses in our infrastructure and operations, risks that we may not be able to comply with legal and
regulatory requirements, loss of business opportunities, loss of employees and reduced productivity among remaining
employees. We may also determine to take additional measures to reduce costs, which could result in further disruptions to
our operations and present additional challenges to the effective management of our company. If our management is unable
to effectively manage this transition and restructuring and additional cost containment measures, our expenses may be
more than expected, and we may not be able to implement our business strategy.
Risks Related to Ownership of Our Ordinary Shares
The price of our ordinary shares may be volatile and fluctuate substantially.
The trading price of our ordinary shares has been and is likely to continue to be volatile. The stock market in
general and the market for smaller biopharmaceutical companies in particular have experienced significant volatility that
has often been unrelated to the operating performance of particular companies. The market price for our ordinary shares
may be influenced by many factors, including:
● our ability to successfully commercialize the oral and IV formulations of XENLETA for the treatment of
CABP and the IV formulation of CONTEPO, if approved;
● our ability to promote and distribute SIVEXTRO;
● our ability to obtain FDA approval of CONTEPO for the treatment of cUTIs, including AP;
● our ability to successfully implement our proposed business strategy;
● the success of competitive products or technologies;
● results of clinical trials of our product candidates or those of our competitors;
● regulatory delays and greater government regulation of potential products due to adverse events;
● regulatory or legal developments in the United States, the European Union and other countries or regions;
● developments or disputes concerning patent applications, issued patents or other proprietary rights;
● the recruitment or departure of key personnel;
● the level of expenses related to any of our product candidates or clinical development programs;
● the results of our efforts to discover, develop, acquire or in-license additional product candidates or products,
including additional community products;
● one or more of our manufacturers or suppliers could have an event which causes an unforeseen disruption of
the manufacture or supply of our product candidates;
117
Table of Contents
● our ability to comply with the restrictive covenants under our Loan Agreement and avoid an event of default
that may lead to an acceleration of the amounts due under the Loan Agreement;
● actual or anticipated changes in estimates as to financial results, development timelines or recommendations
by securities analysts;
● variations in our financial results or those of companies that are perceived to be similar to us;
● perception and market performance of companies that are perceived to be similar to us:
● changes in the structure of healthcare payment systems;
● market conditions in the pharmaceutical and biotechnology sectors;
● activism by any single large shareholder or combination of shareholders;
● our need to raise additional funds;
● the societal and economic impact of public health epidemics, such as the ongoing COVID-19 pandemic;
● general economic, industry and market conditions; and
● the other factors described in this “Risk Factors” section.
In the past, following periods of volatility in the market price of a company’s securities, securities class-action
litigation has often been instituted against that company. We also may face securities class-action litigation if we cannot
obtain regulatory approvals for or if we otherwise fail to successfully commercialize SIVEXTRO, XENLETA or, if
approved, CONTEPO or any of our other product candidates or if our securities experience volatility for any reason. Such
litigation, if instituted against us, could cause us to incur substantial costs to defend such claims and divert management’s
attention and resources. For example, we and our Chief Executive Officer, our former Chief Medical Officer and former
Chief Financial Officer were named as defendants in a purported class action lawsuit following our announcement in April
2019 that the FDA issued a CRL in connection with our NDA for CONTEPO for the treatment of cUTIs, including AP,
stating that it was unable to approve the application in its current form.
The number of ordinary shares underlying our outstanding warrants is significant in relation to our currently
outstanding ordinary shares, which could have a negative effect on the market price of our ordinary shares and make it
more difficult for us to raise funds through future equity offerings.
As part of our March 2021 registered direct offering we issued warrants to purchase up to an aggregate of
5,180,505 ordinary shares at an exercise price of $2.39 per share. As part of our May 2020 registered direct offering, we
issued warrants to purchase an aggregate of up to 4,144,537 ordinary shares at an exercise price of $7.92 per share. As part
of our December 2019 registered direct offering, we issued warrants to purchase an aggregate of up to 1,379,310 ordinary
shares at an exercise price of $19.00 per share. As of the date of this Annual Report on Form 10-K, there were 10,619,347
warrants outstanding from the three offerings and, upon exercise in full of these warrants, the shares issuable upon exercise
would represent a significant portion of our outstanding ordinary shares. Each of the December 2019 warrants was initially
exercisable six months following the date of issuance, which was December 24, 2019, and will expire on the three-year
anniversary of the date on which such warrants became initially exercisable. Each of the May 2020 warrants was
immediately exercisable and will expire on the two-year anniversary of the date of issuance. Each of the March 2021
warrants was immediately exercisable and will expire on the five-year anniversary of the date of issuance. We have
registered the issuance of shares upon exercise of these warrants under a registration statement under the Securities Act of
1933, as amended, and, accordingly, such shares can be freely sold into the public market upon issuance, subject to volume
limitations applicable to affiliates. Sales of these shares could cause the market price of our ordinary shares to decline
significantly. Furthermore, if our share price rises, the holders of these warrants may be more
118
Table of Contents
likely to exercise their warrants and sell a large number of shares, which could negatively impact the market price of our
ordinary shares and reduce or eliminate any appreciation in our share price that might otherwise occur.
We may also find it more difficult to raise additional equity capital while these warrants are outstanding. At any
time during which these warrants are likely to be exercised, we may be unable to obtain additional equity capital on more
favorable terms from other sources. In addition, the exercise of these warrants would result in a significant increase in the
number of our outstanding ordinary shares, which could have the effect of significantly diluting the interest of our current
shareholders, and following such exercise the former holders of such warrants could have significant influence over our
company as a result of the ordinary shares they acquire upon such exercise.
If we fail to meet the requirements for continued listing on The Nasdaq Global Select Market, our ordinary shares could
be delisted from trading, which would decrease the liquidity of our ordinary shares and our ability to raise additional
capital.
Our ordinary shares are currently listed for quotation on The Nasdaq Global Select Market. We are required to
meet specified requirements in order to maintain our listing on The Nasdaq Global Select Market, including, among other
things, a minimum bid price of $1.00 per share.
On April 29, 2020, we received written notice from The Nasdaq Stock Market LLC, or Nasdaq, indicating that,
based on the closing bid for the last 30 consecutive business days, we were not in compliance with the $1.00 minimum bid
price requirement for continued listing on The Nasdaq Global Select Market, as set forth in Listing Rule 5450(a)(1), or the
Bid Price Rule. On December 2, 2020, our board of directors effected a one-for-ten reverse stock split of our ordinary
shares for the purpose of regaining compliance with the Bid Price Rule. On December 17, 2020, we received notification
from Nasdaq that for 10 consecutive business days, the closing bid price of our ordinary shares had been at $1.00 per share
or greater, confirming that we had regained compliance with the Bid Price Rule.
On January 4, 2022, we again received written notice from Nasdaq indicating that, based on the closing bid for
the last 30 consecutive business days, we were not in compliance with the Bid Price Rule. The Notice does not result in the
immediate delisting of our ordinary shares from The Nasdaq Global Select Market. In accordance with Listing Rule
5810(c)(3)(A), we have a period of 180 calendar days to regain compliance with the Bid Price Rule. As a result, we will
have until July 5, 2022, or the Compliance Date, to regain compliance with the Bid Price Rule. To regain compliance, the
closing bid price of our ordinary shares must be at least $1.00 per share for a minimum of ten consecutive business days on
or before the Compliance Date. If we do not regain compliance with the Bid Price Rule by the Compliance Date, we may
be eligible for an additional 180 calendar day compliance period. To qualify, we would need to transfer the listing of our
ordinary shares to the Nasdaq Capital Market, provided that we meet the continued listing requirement for market value of
publicly held shares and all other initial listing standards, with the exception of the Bid Price Rule. To effect such a
transfer, we would also need to pay an application fee to Nasdaq and provide written notice to Nasdaq of our intention to
cure the deficiency during the additional compliance period. If we do not qualify for the additional compliance period or
fail to regain compliance during the additional 180-day period, then Nasdaq will notify us of its determination to delist our
ordinary shares, at which point we would have an opportunity to appeal the delisting determination to a Nasdaq hearing
panel. In addition to continuing to monitor the closing bid price of our ordinary shares, we expect to consider available
options to regain compliance with the Bid Price Rule. However, there can be no assurance that we will be able to regain
compliance with the Bid Price Rule.
If we do not regain compliance with the Bid Price Rule by the Compliance Date or if in the future we fail to
satisfy The Nasdaq Global Select Market’s other continued listing requirements, we may transfer to The Nasdaq Capital
Market, which generally has lower financial requirements for initial listing, to avoid delisting, or, if we fail to meet its
listing requirements, the OTC Bulletin Board. A transfer of our listing to The Nasdaq Capital Market or having our
ordinary shares trade on the OTC Bulletin Board could adversely affect the liquidity of our ordinary shares. Any such event
could make it more difficult to dispose of, or obtain accurate quotations for the price of, our ordinary shares, and there also
would likely be a reduction in our coverage by securities analysts and the news media, which could cause the price of our
ordinary shares to decline further. We may also face other material adverse consequences in such event, such as negative
publicity, a decreased ability to obtain additional financing, diminished investor and/or employee
119
Table of Contents
confidence, and the loss of business development opportunities, some or all of which may contribute to a further decline in
our share price.
There are many factors that may adversely affect our minimum bid price, including those described throughout
this section titled “Risk Factors”. Many of these factors are outside our control. As a result, we may not be able to comply
with the Bid Price Rule in the long term. Any potential delisting of our ordinary shares from The Nasdaq Global Select
Market would likely result in decreased liquidity and increased volatility for our ordinary shares and would adversely affect
our ability to raise additional capital or enter into strategic transactions. Any potential delisting of our ordinary shares from
The Nasdaq Global Select Market would also make it more difficult for our shareholders to sell their ordinary shares in the
public market.
Our ordinary shares do not trade on any exchange outside of the United States.
Our ordinary shares are listed only in the United States on The Nasdaq Global Select Market, and we have no
plans to list our ordinary shares in any other jurisdiction. As a result, a holder of ordinary shares outside of the
United States may not be able to effect transactions in our ordinary shares as readily as the holder may if our ordinary
shares were listed on an exchange in that holder’s home jurisdiction.
Substantial future sales of our ordinary shares in the public market, or the perception that these sales could occur,
could cause the price of our ordinary shares to decline significantly, even if our business is doing well.
Sales of a substantial number of our ordinary shares, or the perception in the market that these sales could occur,
could reduce the market price of our ordinary shares. We had 56,715,306 ordinary shares outstanding as of December 31,
2021. To the extent any of these shares are sold into the market, particularly in substantial quantities, the market price of
our ordinary shares could decline.
Future issuances of ordinary shares pursuant to our equity incentive plans could also result in a reduction in the
market price of our ordinary shares. We have filed registration statements on Form S-8 registering all of the ordinary shares
that we may issue under our equity compensation plans. These shares can be freely sold in the public market upon issuance
and once vested, subject to volume, notice and manner of sale limitations applicable to affiliates. The majority of ordinary
shares that may be issued under our equity compensation plans remain subject to vesting in tranches over a four-year
period. As of December 31, 2021, an aggregate of 533,564 options to purchase our ordinary shares had vested and become
exercisable although these options all have an exercise price that is higher than the recent market trading prices of our
ordinary shares.
In addition, on June 25, 2019, we entered into the Jefferies ATM Agreement with Jefferies, pursuant to which,
from time to time, we may offer and sell ordinary shares, for aggregate gross sale proceeds of up to $50.0 million through
Jefferies by any method permitted that is deemed an “at the market offering” as defined in Rule 415(a)(4) promulgated
under the Securities Act of 1933, as amended.
On May 6, 2021, we entered into the New Sale Agreement with Jefferies, as agent, pursuant to which we may
offer and sell ordinary shares, nominal value $0.01 per share for aggregate gross sale proceeds of up to $50.0 million, from
time to time through Jefferies, by any method permitted that is deemed an “at the market offering” as defined in Rule
415(a)(4) promulgated under the Securities Act of 1933, as amended. Upon entry into the New Sale Agreement, our
existing Jefferies ATM Agreement was terminated. We did not incur any termination penalties as a result of the
replacement of the Jefferies ATM Agreement. As of the effective date of the termination of the Jefferies ATM Agreement,
we had sold an aggregate of 5,925,699 of our ordinary shares pursuant to the Jefferies ATM Agreement for aggregate gross
proceeds of $33.7 million and net proceeds to us of $31.9 million, after deducting commissions and offering expenses
payable by us. The approximately $16.3 million of ordinary shares that had been available for sale pursuant to the Jefferies
ATM Agreement remained unsold at the time of its replacement. The replacement of the Jefferies ATM Agreement
terminated any future sales of ordinary shares through the Jefferies ATM Agreement.
As of December 31, 2021, we have issued and sold an aggregate of 18,232,689 ordinary shares pursuant to the
New Sale Agreement and received gross proceeds of $30.5 million and net proceeds of $29.3 million, after deducting
120
Table of Contents
commissions to Jefferies and other offering expenses. From January 1, 2022 and through the date of this filing, we have
issued and sold an aggregate of 1,338,282 ordinary shares pursuant to the New Sale Agreement and received gross
proceeds of $595,000 and net proceeds of $580,000, after deducting commissions to Jefferies and other offering expenses.
As of the date of this filing, we may issue and sell ordinary shares for gross proceeds of up to $19.0 million under the New
Sale Agreement.
On September 24, 2021, we entered into a purchase agreement, or Purchase Agreement, with Lincoln Park Capital
Fund, LLC, or Lincoln Park, which, subject to the terms and conditions, provides that we have the right to sell to Lincoln
Park and Lincoln Park is obligated to purchase up to $23.0 million of our Ordinary Shares. In addition, under the Purchase
Agreement, we agreed to issue a commitment fee of 632,474 Ordinary Shares, or the Commitment Shares, as consideration
for Lincoln Park entering into the Purchase Agreement and for the payment of $0.01 per Commitment Share. Under the
Purchase Agreement, we may from time to time, at our discretion, direct Lincoln Park to purchase on any single business
day, or a Regular Purchase up to (i) 400,000 Ordinary Shares if the closing sale price of our Ordinary Shares is not below
$0.25 per share on Nasdaq, (ii) 600,000 Ordinary Shares if the closing sale price of our Ordinary Shares is not below $2.00
per share on Nasdaq or (iii) 800,000 Ordinary Shares if the closing sale price of our Ordinary Shares is not below $3.00 per
share on Nasdaq. In any case, Lincoln Park’s commitment in any single Regular Purchase may not exceed $2,500,000
absent a mutual agreement to increase such amount. As of December 31, 2021, we have issued and sold an aggregate of
2,400,000 ordinary shares pursuant to the Purchase Agreement and received net proceeds of $2.4 million. From January 1,
2022 and through the date of this filing, we have issued and sold an aggregate of 3,600,000 ordinary shares pursuant to the
Purchase Agreement and received net proceeds of $1.6 million. As of the date of this filing, we may issue and sell ordinary
shares for gross proceeds of up to $19.0 million under the Purchase Agreement, subject to the Nasdaq rules which may
limit our ability to make sales of our ordinary shares to Lincoln Park in excess of a specified amount without prior
shareholder approval.
As part of our March 2021 registered direct offering we issued warrants to purchase up to an aggregate of
5,180,505 ordinary shares at an exercise price of $2.39 per share. As part of our May 2020 registered direct offering, we
issued warrants to purchase an aggregate of up to 4,144,537 ordinary shares at an exercise price of $7.92 per share. As part
of our December 2019 registered direct offering, we issued warrants to purchase an aggregate of up to 1,379,310 shares of
ordinary shares at an exercise price of $19.00 per share. As of the date of this Annual Report on Form 10-K, there were
10,619,347 warrants outstanding from the three offerings and, upon exercise in full of these warrants, the shares issuable
upon exercise would represent a significant portion of our outstanding ordinary shares. Each of the December 2019
warrants was initially exercisable six months following the date of issuance, which was December 24, 2019, and will
expire on the three-year anniversary of the date on which such warrants became initially exercisable. Each of the May 2020
warrants was immediately exercisable and will expire on the two-year anniversary of the date of issuance. Each of the
March 2021 warrants was immediately exercisable and will expire on the five-year anniversary of the date of issuance. We
have registered the issuance of shares upon exercise of these warrants under a registration statements under the Securities
Act of 1933, as amended, and, accordingly, such shares can be freely sold into the public market upon issuance, subject to
volume limitations applicable to affiliates. The exercise of these warrants or sale of the shares issuable upon exercise of
these warrants, or the perception that sales of these shares could occur, could cause the market price of our ordinary shares
to decline significantly.
Furthermore, if our share price rises, the holders of these warrants may be more likely to exercise their warrants
and sell a large number of shares, which could negatively impact the market price of our ordinary shares and reduce or
eliminate any appreciation in our share price that might have otherwise occurred.
If a large number of our ordinary shares are sold in the public market after they become eligible for sale, the sales
could reduce the trading price of our ordinary shares and impede our ability to raise future capital.
The upfront consideration for the Acquisition was comprised of 815,209 of our ordinary shares, including 81,518
ordinary shares that were initially held back but which were issued in July 2019 upon release of the Holdback Shares
pursuant to the terms of the Merger Agreement. Such shares are able to be freely sold in the public market, subject to any
requirements and restrictions, including any applicable volume limitations, imposed by Rule 144 under the Securities Act.
In addition, the Merger Agreement provides that we may issue up to an additional $97.5 million in our ordinary shares to
former Zavante stockholders upon the achievement of specified regulatory and commercial
121
Table of Contents
milestones in the future, and obligates us to provide registration rights with respect to the registration for resale of such
additional ordinary shares that may become issuable upon the achievement of such milestones.
The sale or resale of these shares in the public market, or the market’s expectation of such sales, may result in an
immediate and substantial decline in our share price. Such a decline will adversely affect our investors and also might
make it difficult for us to sell equity securities in the future at a time and at a price that we deem appropriate.
We are a “smaller reporting company”, and the reduced disclosure requirements applicable to smaller reporting
companies may make our ordinary shares less attractive to investors.
We are a “smaller reporting company” as defined in Rule 12b-2 promulgated under the Exchange Act. We may
remain a smaller reporting company until we have a non-affiliate public float in excess of $250 million and annual
revenues in excess of $100 million, or a non-affiliate public float in excess of $700 million, each as determined on an
annual basis. For so long as we remain a smaller reporting company, we are permitted and may take advantage of specified
reduced reporting and other burdens that are otherwise applicable generally to public companies. These provisions include:
● an exemption from compliance with the auditor attestation requirement of Section 404 of the Sarbanes-Oxley
Act of 2002, or the Sarbanes-Oxley Act, on the design and effectiveness of our internal controls over
financial reporting;
● an exemption from compliance with any requirement that the Public Company Accounting Oversight Board
may adopt regarding mandatory audit firm rotation; and
● reduced disclosure about our executive compensation arrangements.
We cannot predict whether investors will find our ordinary shares less attractive if we rely on such exemptions. If
some investors find our ordinary shares less attractive as a result, there may be a less active trading market for our ordinary
shares and the market price of our ordinary shares may be more volatile.
If we fail to maintain an effective system of internal control over financial reporting, we may not be able to accurately
report our financial results or prevent fraud. As a result, security holders could lose confidence in our financial and
other public reporting, which would harm our business and the trading price of our ordinary shares.
Effective internal control over financial reporting is necessary for us to provide reliable financial reports and,
together with adequate disclosure controls and procedures, is designed to prevent fraud. Any failure to implement required
new or improved controls, or difficulties encountered in their implementation could cause us to fail to meet our reporting
obligations. In addition, any testing by us, conducted in connection with Section 404 of the Sarbanes-Oxley Act, or
Section 404, or any subsequent testing by our independent registered public accounting firm, as and when required, may
reveal deficiencies in our internal control over financial reporting that are deemed to be material weaknesses or that may
require prospective or retroactive changes to our financial statements or identify other areas for further attention or
improvement. As a growing company, implementing and maintaining effective controls may require more resources, and
we may encounter internal control integration difficulties. Inferior internal controls could also cause investors to lose
confidence in our reported financial information, which could have a negative effect on the trading price of our ordinary
shares.
Pursuant to Section 404, we are required to furnish a report by our management on our internal control over
financial reporting. However, as a smaller reporting company, we are not required to include an attestation report on
internal control over financial reporting issued by our independent registered public accounting firm until we are no longer
a smaller reporting company. To achieve compliance with Section 404 within the prescribed period, we document and
evaluate our internal control over financial reporting, which is both costly and challenging. In this regard, we will need to
continue to dedicate internal resources, potentially engage outside consultants and adopt a detailed work plan to assess and
document the adequacy of internal control over financial reporting, continue steps to improve control processes as
appropriate, validate through testing that controls are functioning as documented and implement a
122
Table of Contents
continuous reporting and improvement process for internal control over financial reporting. Despite our efforts, there is a
risk that we will not be able to conclude within the prescribed timeframe that our internal control over financial reporting is
effective as required by Section 404. This could result in an adverse reaction in the financial markets due to a loss of
confidence in the reliability of our financial statements.
United States investors may have difficulty enforcing judgments against us, our directors and executive officers.
We are incorporated under the laws of Ireland, and our registered offices and a substantial portion of our assets are
located outside of the United States. As a result, it may not be possible to effect service of process on our directors,
executive officers, or us in the United States or to enforce judgments obtained in courts in the United States against such
persons or us based on civil liability provisions of the securities laws of the United States.
There is no treaty between Ireland and the United States providing for the reciprocal enforcement of judgments
obtained in the other jurisdiction and Irish common law rules govern the process by which a U.S. judgment may be
enforced in Ireland. The following requirements must be met as a precondition before a U.S. judgment will be eligible for
enforcement in Ireland:
● the judgment must be for a definite sum;
● the judgment must be final and conclusive, and the decree must be final and enforceable in the court which
pronounces it;
● the judgment must be provided by a court of competent jurisdiction, and the procedural rules of the court
giving the foreign judgment must have been observed;
● the U.S. court must have had jurisdiction in relation to the particular defendant according to Irish conflict of
law rules; and
● jurisdiction must be obtained by the Irish courts over judgment debtors in enforcement proceedings by
service in Ireland or outside Ireland in accordance with the applicable court rules in Ireland.
Even if the above requirements have been met, an Irish court may exercise its right to refuse to enforce the
U.S. judgment if the Irish court is satisfied that the judgment (1) was obtained by fraud; (2) is in contravention of Irish
public policy; (3) is in breach of natural justice; or (4) is irreconcilable with an earlier judgment. By way of example, a
judgment of a U.S. court of liabilities predicated upon U.S. federal securities laws may not be enforced by Irish courts on
the grounds of public policy if that U.S. judgment includes an award of punitive damages. Further, an Irish court may stay
proceedings if concurrent proceedings are being brought elsewhere.
We do not expect to pay dividends in the foreseeable future.
We have not paid any dividends on our ordinary shares since our incorporation. Even if future operations lead to
significant levels of distributable profits, we currently intend that earnings, if any, will be reinvested in our business and
that dividends will not be paid until we have an established revenue stream to support continuing dividends. If we propose
to pay dividends in the future, we must do so in accordance with Irish law, which provides that distributions including
dividend payments, share repurchases and redemptions be funded from “distributable reserves”. In addition, the terms of
the Loan Agreement with Hercules currently, and the terms of any future debt agreements may in the future, preclude us
from paying dividends. As a result, capital appreciation, if any, of our ordinary shares will be the sole source of gain for
holders of our ordinary shares for the foreseeable future.
We are exposed to risks related to currency exchange rates.
A portion of our expenses are denominated in currencies other than the U.S. dollar. Because our consolidated
financial statements are presented in U.S. dollars, changes in currency exchange rates have had and could have a
123
Table of Contents
significant effect on our operating results. Exchange rate fluctuations between foreign currencies and the U.S. dollar create
risk in several ways, including the following:
● weakening of the U.S. dollar may increase the U.S. dollar cost of overseas research and development
expenses;
● strengthening of the U.S. dollar may decrease the value of our revenues denominated in other currencies; and
● the exchange rates on non-U.S. dollar transactions and cash deposits can distort our financial results.
As a holding company, our operating results, financial condition and ability to pay dividends or other distributions are
entirely dependent on funding, dividends and other distributions received from our subsidiaries, which may be subject to
restrictions.
Our ability to pay dividends or other distributions and to pay our obligations in the future will depend on the level
of funding, dividends and other distributions, if any, received from our subsidiaries and any new subsidiaries we establish
in the future. The ability of our subsidiaries to make loans or distributions (directly or indirectly) to us may be restricted as
a result of several factors, including restrictions in financing agreements and the requirements of applicable law and
regulatory and fiscal or other restrictions. In particular, our subsidiaries and any new subsidiaries may be subject to laws
that restrict dividend payments, authorize regulatory bodies to block or reduce the flow of funds from those subsidiaries to
us, or limit or prohibit transactions with affiliates. Restrictions and regulatory action of this kind could impede access to
funds that we may need to make dividend payments or to fund our own obligations.
Furthermore, we may guarantee some of the payment obligations of certain of our subsidiaries from time to time.
These guarantees may require us to provide substantial funds or assets to our subsidiaries or their creditors or
counterparties at a time when we are in need of liquidity to fund our own obligations.
The ownership percentage of our shareholders may be diluted in the future which could dilute the voting power or
reduce the value our outstanding ordinary shares.
As with any publicly traded company, the ownership percentage of our shareholders may be diluted in the future
because of equity issuances for acquisitions, capital market transactions or otherwise, including equity awards that we
intend to continue to grant to our directors, officers and employees. From time to time, we may issue additional options or
other share awards to our directors, officers and employees under our benefits plans.
In addition, our articles of association authorize us to issue, without the approval of our shareholders, one or more
classes or series of preferred shares having such designation, powers, preferences and relative, participating, optional and
other special rights, including preferences over our ordinary shares respecting dividends and distributions, as our board of
directors generally may determine. The terms of one or more classes or series of preferred shares could dilute the voting
power or reduce the value of our ordinary shares. Similarly, the repurchase or redemption rights or liquidation preferences
we could assign to holders of preferred shares could affect the residual value of the ordinary shares. Additionally, we may
issue and sell our ordinary shares under our Jefferies ATM Agreement or the Purchase Agreement with Lincoln Park from
time to time, and we may issue additional ordinary shares as contingent consideration upon the achievement of certain
regulatory and commercialization milestones, subject to the terms and conditions of the Merger Agreement. See “—Risks
Related to Ownership of our Ordinary Shares—Substantial future sales of our ordinary shares in the public market, or the
perception that these sales could occur, could cause the price of our ordinary shares to decline significantly, even if our
business is doing well. ”
The rights of our shareholders may differ from the rights typically offered to shareholders of a U.S. corporation. We are
incorporated as a public limited company under Irish law.
The rights of our shareholders are governed by our memorandum and articles of association and Irish law. The
rights associated with our ordinary shares are different to the rights generally associated with shares held in a
124
Table of Contents
U.S. corporation. Material differences between the rights of shareholders of a U.S. corporation and the rights of our
shareholders include differences with respect to, among other things, distributions, dividends, repurchases and
redemptions, bonus issues, the election of directors, the removal of directors, the fiduciary and statutory duties of directors,
conflicts of interests of directors, the indemnification of directors and officers, limitations on director liability, the
convening of annual meetings of shareholders and special shareholder meetings, notice provisions for meetings, the
quorum for shareholder meetings, the adjournment of shareholder meetings, the exercise of voting rights, shareholder suits,
rights of dissenting shareholders, anti-takeover measures and provisions relating to the ability to amend the articles of
association.
As an Irish public limited company, certain capital structure decisions require shareholder approval, which may limit
our flexibility to manage our capital structure.
Under Irish law, our board of directors may issue new ordinary or preferred shares up to a maximum amount equal
to the authorized but unissued share capital, without shareholder approval, once authorized to do so by our articles of
association or by an ordinary resolution of our shareholders. Additionally, subject to specified exceptions, Irish law grants
statutory preemption rights to existing shareholders where shares are being issued for cash consideration but allows
shareholders to disapply such statutory preemption rights either in our articles of association or by way of special
resolution. Such disapplication can either be generally applicable or be in respect of a particular allotment of shares.
Accordingly, our articles of association contain, as permitted by Irish company law, provisions authorizing our board of
directors to issue new shares, and to disapply statutory preemption rights. The authorization of our board of directors to
issue shares and the disapplication of statutory preemption rights must both be renewed by the shareholders at least every
five years.
We asked our shareholders to renew the authorization of our board of directors to issue shares and the
disapplication of statutory preemption rights at our 2021 Annual General Meeting of Shareholders, or the 2021 Annual
Meeting, and to extend that authorization to the increase in authorized share capital that was approved by our shareholders
at the 2021 Annual Meeting. Our shareholders renewed the authorization of our board of directors to issue shares; however,
although we received over 67% support of the votes cast on renewing the pre-emption rights opt-out authority, we did not
receive the affirmative vote of at least 75% of the votes cast as required under Irish law for the passing of special
resolutions. We originally convened an Extraordinary General Meeting of Shareholders, or EGM, on December 22, 2021
but was ultimately adjourned to March 24, 2022 to allow us to solicit from our shareholders the additional proxies
necessary to obtain approval of the sole proposal to grant the board of directors authority under Irish law to allot and issue
ordinary shares (including rights to acquire ordinary shares) for cash without first offering those ordinary shares to our
existing shareholders pursuant to the statutory pre-emption right that would otherwise apply. On March 24, 2022, our
shareholders approved the dis-application of statutory pre-emption rights for an additional five year term.
The authorization of our board of directors to issue shares and the disapplication of statutory preemption rights
must both be renewed by the shareholders at least every five years, or at the time our shareholders approve an increase in
our authorized share capital. We cannot provide any assurance that these authorizations will always be approved, which
could limit our ability to issue equity and thereby adversely affect the holders of our ordinary shares. As a result of this
limitation, we may be limited in the amount of ordinary shares we may sell in any capital raising transaction, and where we
propose to issue shares for cash consideration, we may be required to first offer those shares to all of our existing
shareholders in a time-consuming pro-rata rights offering. In the event we are not able to obtain such shareholder approval
of the disapplication of pre-emption rights, when needed, we will be limited in the amount of ordinary shares we may sell
in any capital raising transaction without first offering those shares to all of our existing shareholders.
Irish law differs from the laws in effect in the U.S. with respect to defending unwanted takeover proposals and may give
our board less ability to control negotiations with hostile offerors.
We are subject to the Irish Takeover Panel Act, 1997, Takeover Rules, 2013. Under those Irish Takeover Rules,
the board is not permitted to take any action that might frustrate an offer for our ordinary shares once the board has
received an approach that may lead to an offer or has reason to believe that such an offer is or may be imminent, subject to
certain exceptions. Potentially frustrating actions such as (i) the issue of ordinary shares, options or convertible
125
Table of Contents
securities, (ii) material acquisitions or disposals, (iii) entering into contracts other than in the ordinary course of business or
(iv) any action, other than seeking alternative offers, which may result in frustration of an offer, are prohibited during the
course of an offer or at any earlier time during which the board has reason to believe an offer is or may be imminent. These
provisions may give the board less ability to control negotiations with hostile offerors and protect the interests of holders of
ordinary shares than would be the case for a corporation incorporated in a jurisdiction of the United States.
The operation of the Irish Takeover Rules may affect the ability of certain parties to acquire our ordinary shares.
Under the Irish Takeover Rules, if an acquisition of ordinary shares were to increase the aggregate holding of the
acquirer and its concert parties to ordinary shares that represent 30% or more of the voting rights of a company, the
acquirer and, in certain circumstances, its concert parties would be required (except with the consent of the Irish Takeover
Panel) to make an offer for our outstanding ordinary shares at a price not less than the highest price paid for the ordinary
shares by the acquirer or its concert parties during the previous 12 months. This requirement would also be triggered by an
acquisition of ordinary shares by a person holding (together with its concert parties) ordinary shares that represent between
30% and 50% of the voting rights in the company if the effect of such acquisition were to increase that person’s percentage
of the voting rights by 0.05% within a 12-month period. The Irish Takeover Rules could therefore discourage an investor
from acquiring 30% or more of our outstanding ordinary shares, unless such investor was prepared to make a bid to acquire
all outstanding ordinary shares.
Certain separate concert parties will also be presumed to be acting in concert. Our board of directors and their
relevant family members, related trusts and “controlled companies” are presumed to be acting in concert with any
corporate shareholder who holds 20% or more of the company. The application of these presumptions may result in
restrictions upon the ability of any of the concert parties and members of our board of directors to acquire more of our
securities, including under the terms of any executive incentive arrangements. We may consult with the Irish Takeover
Panel with respect to the application of this presumption and the restrictions on the ability to acquire further securities if
necessary, although we are unable to provide any assurance as to whether the Irish Takeover Panel would overrule this
presumption.
We will be exposed to the risk of future changes in law, which could materially adversely affect us.
We are subject to Irish law. As a result, we are subject to the risk of future adverse changes in Irish law (including
Irish corporate and tax law). In addition, we and our subsidiaries are also subject to the risk of future adverse changes in
Austrian and U.S. law, as well as changes of law in other countries in which we and our subsidiaries operate.
Future adverse changes in law could result in our not being able to maintain a worldwide effective corporate tax rate
that is competitive in our industry.
While we believe that being incorporated in Ireland should not affect our ability to maintain a worldwide effective
corporate tax rate that is competitive in our industry, we cannot give any assurance as to what our effective tax rate will be
because of, among other things, uncertainty regarding the tax policies of the jurisdictions where we will operate. The tax
laws of Ireland, Austria, the United States, and other jurisdictions could change in the future, and such changes could cause
a material change in our worldwide effective corporate tax rate. In particular, legislative action could be taken by Ireland,
Austria, the United States or other jurisdictions which could override tax treaties upon which we expect to rely and
adversely affect our effective tax rate. As a result, our actual effective tax rate may be materially different from our
expectation.
The IRS may not agree with the conclusion that we should be treated as a foreign corporation for U.S. federal tax
purposes.
Although we are incorporated in Ireland, the IRS may assert that we should be treated as a U.S. corporation (and,
therefore, a U.S. tax resident) for U.S. federal tax purposes pursuant to Section 7874 of the Code. For U.S. federal tax
purposes, a corporation generally is considered a tax resident in the jurisdiction of its organization or incorporation.
Because we are an Irish incorporated entity, we would be classified as a foreign corporation (and, therefore, a non-U.S. tax
resident) under these rules. Section 7874 of the Code provides an exception under which a foreign incorporated
126
Table of Contents
entity may, in certain circumstances, be treated as a U.S. corporation for U.S. federal tax purposes. New statutory and/or
regulatory provisions under Section 7874 of the Code or otherwise could be enacted that adversely affect our status as a
foreign corporation for U.S. federal tax purposes, and any such provisions could have prospective or retroactive application
to us and our shareholders.
Our ability to utilize our net operating loss carryforwards and certain other tax attributes may be limited.
Under Sections 382 and 383 of the Code, if a corporation undergoes an “ownership change” (generally defined as
a greater than 50 percentage point change (by value) in the ownership of its equity by certain significant shareholders over
a rolling three year period), the corporation’s ability to use its pre-change net operating loss carryforwards and certain other
pre-change tax attributes to offset its post-change income and taxes may be limited. We may have experienced such
ownership changes in the past, and we may experience ownership changes in the future as a result of shifts in our share
ownership, some of which would be outside our control. If our ability to use our net operating losses and other tax
attributes is limited by ownership changes, we may be unable to utilize a material portion of our net operating losses and
other tax attributes to offset our future taxable income. In addition, there is also a risk that due to changes in laws and
regulations, such as suspensions on the use of net operating losses, or other unforeseen reasons, our existing net operating
losses could expire or otherwise become unavailable to offset future income tax liabilities.
U.S. persons who own 10 percent or more of our shares may be subject to U.S. federal income taxation on certain of our
foreign subsidiaries’ income even if such income is not distributed to such U.S. persons.
A foreign corporation is treated as a “controlled foreign corporation”, or CFC, for U.S. federal income tax
purposes if, on any day during a taxable year, “United States shareholders” (as defined below) own (directly, indirectly or
constructively within the meaning of Section 958 of the Code) more than 50% of the total combined voting power of all
classes of our voting shares or more than 50% of the total value of all of our shares. A “United States shareholder” of a
foreign corporation is a U.S. person who owns (directly, indirectly or constructively within the meaning of Section 958 of
the Code) at least 10% of the total combined voting power of voting shares of such non-U.S. corporation or at least 10% of
the total value of shares of all classes of stock of such non-U.S. corporation.
As a result of the Tax Act, all of our non-U.S. subsidiaries will be treated as CFCs.
Any United States shareholder who owns our shares (directly or indirectly within the meaning of Section 958(a)
of the Code) on the last day in such taxable year must include in its gross income for U.S. federal income tax purposes its
pro rata share (based on direct or indirect ownership of value) of the non-U.S. subsidiaries’ “subpart F income”, regardless
of whether that income was actually distributed to such U.S. person (with certain adjustments). “Subpart F income” of a
CFC generally includes among other items passive income, such as dividends, interest, royalties, rents, annuities and net
gains from commodities, foreign currency and securities transactions and from sales of property that produced, or was held
for the production of, passive income (or no income).
United States shareholders must also include in their gross income for U.S. federal income tax purposes their pro
rata share of a CFC’s “global intangible low tax income”, or GILTI. In general terms, GILTI is the net income of the CFCs
(other than income already included in United States shareholders’ taxable income) that exceeds 10% of the CFCs’ bases in
depreciable tangible assets. GILTI is treated in a manner similar to subpart F income.
In addition, if a U.S. person disposes of shares in a non-U.S. corporation and the U.S. person was a United States
shareholder at any time when the corporation was a CFC during the five-year period ending on the date of disposition, any
gain from the disposition will generally be treated as a dividend to the extent of the U.S. person’s share of the corporation’s
undistributed earnings and profits that were accumulated during the period or periods that the U.S. person owned the shares
while the corporation was a CFC (with certain adjustments). Also, a U.S. person may be required to comply with specified
reporting requirements, regardless of the number of shares owned.
127
Table of Contents
A transfer of our ordinary shares, other than a transfer effected by means of the transfer of book-entry interests in the
Depository Trust Company, may be subject to Irish stamp duty.
Transfers of our ordinary shares effected by means of the transfer of book entry interests in the Depository Trust
Company, or DTC, will not be subject to Irish stamp duty. However, if you hold our ordinary shares directly rather than
beneficially through DTC, any transfer of your ordinary shares could be subject to Irish stamp duty (currently at the rate of
1% of the higher of the price paid or the market value of the shares acquired). Payment of Irish stamp duty is generally a
legal obligation of the transferee. The potential for stamp duty could adversely affect the price of our ordinary shares.
Our ordinary shares received by means of a gift or inheritance could be subject to Irish capital acquisitions tax.
Irish capital acquisitions tax, or CAT, could apply to a gift or inheritance of our ordinary shares irrespective of the
place of residence, ordinary residence or domicile of the parties. This is because our ordinary shares will be regarded as
property situated in Ireland. The person who receives the gift or inheritance has primary liability for CAT. Gifts and
inheritances passing between spouses are exempt from CAT. Children have a tax-free threshold of €335,000 in respect of
taxable gifts or inheritances received from their parents.
Our business and operations could be negatively affected if we become subject to shareholder activism, which could
cause us to incur significant expense, hinder execution of our business strategy and impact our share price.
Shareholder activism, which takes many forms and arises in a variety of situations, has been increasingly
prevalent. If we become the subject of certain forms of shareholder activism, such as proxy contests, the attention of our
management and our board of directors may be diverted from execution of our business strategy. Such shareholder activism
could give rise to perceived uncertainties as to our future strategy, adversely affect our relationships with business partners
and make it more difficult to attract and retain qualified personnel. Also, we may incur substantial costs, including
significant legal fees and other expenses, related to activist shareholder matters. Our share price could be subject to
significant fluctuation or otherwise be adversely affected by the events, risks and uncertainties of any shareholder activism.
We may be classified as a passive foreign investment company for one or more of our taxable years, which may result in
adverse U.S. federal income tax consequence to U.S. holders.
A corporation organized outside the United States generally will be classified as a “passive foreign investment
company”, or PFIC, for U.S. federal income tax purposes (1) in any taxable year in which (A) at least 75% of its gross
income is passive income or (B) on average at least 50% of the gross value of its assets is attributable to assets that produce
passive income or are held for the production of passive income, and (2) as to a given holder who was a holder in such
taxable year and regardless of such corporation’s income or asset composition, in any subsequent taxable year, unless
certain elections are made by that holder that allow the holder to discontinue that classification as to that holder, generally
at a substantial tax cost to that holder. Passive income for this purpose generally includes dividends, interest, royalties,
rents, annuities and net gains from commodities, foreign currency and securities transactions and from sales of property
that produced, or was held for the production of, passive income (or no income).
Based on our gross income and average value of our gross assets for each relevant taxable year, and given the
nature of our business, we do not believe that we were a PFIC for any such taxable year from our initial public offering
through the year ended December 31, 2021, although there is no assurance that the IRS will agree with this conclusion. Our
status in any taxable year (determined without regard to our status in any prior taxable year) will depend on our assets and
activities in that year, and because this is a factual determination made annually after the end of the year, there can be no
assurance that we will not be considered a PFIC for the current taxable year or any other taxable year. In particular, in
many cases the gross value of our assets may be inferred from the market price of our ordinary shares, which may fluctuate
considerably given that market prices of biotechnology companies can be especially volatile. In other cases, factors
external to our specific circumstances may make the presumptive relationship between the gross value of our assets and our
market capitalization unreliable, in which case the gross value of our individual assets, based upon valuation methods
suitable for use in U.S. federal tax matters (the choice of which may vary from taxable year to
128
Table of Contents
taxable year), will govern the determination of our status. While, based on the market price of our ordinary shares, we
would be treated as a PFIC in 2021, we believe that the market price renders an unreliable valuation of our gross assets.
Based on our valuation of our gross assets taking into account our specific circumstances, we believe that we were not a
PFIC in 2021. There is no assurance, however, that the IRS will agree with our valuation.
If we are treated as a PFIC for the taxable year ending December 31, 2022, or any other taxable year during which
a U.S. holder held or holds our ordinary shares, certain adverse U.S. federal income tax consequences generally will apply
to the U.S. holder. We currently intend to make available, upon request, the information necessary to permit a U.S. holder
to make a valid qualified electing fund, or QEF, election, which may mitigate some of the adverse U.S. federal income tax
consequences applicable to a U.S. holder of ordinary shares if we are a PFIC for a given taxable year. However, we may
choose not to provide such information at a future date.
General Risk Factors
We may become involved in lawsuits to protect or enforce our patents or other intellectual property, which could be
expensive, time consuming and unsuccessful.
Competitors may infringe our patents, trademarks, copyrights or other intellectual property. To counter such
infringement or unauthorized use, we may be required to file claims, which can be expensive, time consuming and a
distraction to management. Any claims we assert against perceived infringers could provoke these parties to assert
counterclaims against us alleging our patents, trademarks, copyrights or other intellectual property are invalid or
unenforceable or that we infringe their intellectual property. In addition, in a patent infringement proceeding, a court may
decide that a patent of ours is invalid or unenforceable, in whole or in part, construe the patent’s claims narrowly or may
refuse to stop the other party from using the technology at issue on the grounds that our patents do not cover the technology
in question.
We have broad discretion in the use of our funds and may not use them effectively.
We have broad discretion in the application of our available funds and could spend the funds in ways that do not
improve our results of operations or enhance the value of our ordinary shares. Our failure to apply these funds effectively
could result in financial losses that could have a material adverse effect on our business, cause the price of our ordinary
shares to decline and delay the development of our product candidates. Pending their use, we may invest funds in a manner
that does not produce income or that loses value.
We incur increased costs as a result of operating as a public company, and our management is required to devote
substantial time to new compliance initiatives and corporate governance practices.
As a public company we incur, and particularly after we are no longer a smaller reporting company, we will incur
significant legal, accounting and other expenses that we did not incur as a private company. In addition, the Sarbanes-
Oxley Act, the Dodd-Frank Wall Street Reform and Consumer Protection Act, the listing requirements of The Nasdaq
Global Select Market and other applicable securities rules and regulations impose various requirements on public
companies, including establishment and maintenance of effective disclosure and financial controls and corporate
governance practices. Our management and other personnel need to devote a substantial amount of time to these
compliance initiatives. Moreover, these rules and regulations have increased our legal and financial compliance costs and
make some activities more time-consuming and costly. For example, these rules and regulations have made it more
expensive for us to obtain director and officer liability insurance, and if such insurance becomes prohibitively expensive,
this could make it more difficult for us to attract and retain qualified members of our board.
ITEM 1B. UNRESOLVED STAFF COMMENTS
None.
129
Table of Contents
ITEM 2. PROPERTIES
Facilities
Our facilities consist of approximately 2,900 square meters of leased laboratory and office space in Vienna,
Austria, approximately 8,000 square feet of subleased office space in Fort Washington, Pennsylvania and we also lease
office space in Dublin, Ireland and San Diego, California. We believe that suitable additional or alternative space will be
available in the future on commercially reasonable terms.
ITEM 3. LEGAL PROCEEDINGS
We are not currently subject to any material legal proceedings.
ITEM 4. MINE SAFETY DISCLOSURES
Not applicable.
130
Table of Contents
PART II
ITEM 5. MARKET FOR REGISTRANT’S COMMON EQUITY, RELATED STOCKHOLDER MATTERS AND
ISSUER PURCHASES OF EQUITY SECURITIES
Market Information
Our ordinary shares have been listed on the Nasdaq Global Select Market since June 26, 2017 and trade under the
symbol “NBRV”.
Stockholders
As of January 31, 2022, there were 25 holders of record of our ordinary shares. The number of record holders may
not be representative of the number of beneficial owners because many of our ordinary shares are held by depositories,
brokers or other nominees.
Securities Authorized for Issuance Under Equity Compensation Plans
Information regarding securities authorized for issuance under our equity compensation plans is contained in
Part III, Item 12 of this Annual Report on Form 10-K.
Dividend Policy
We have never declared or paid any cash dividends on our capital stock. We currently intend to retain all available
funds and any future earnings to support our operations and finance the growth and development of our business. In
addition, the terms of the Loan Agreement with Hercules preclude us from paying dividends. We do not intend to pay cash
dividends on our ordinary shares for the foreseeable future.
Recent Sales of Unregistered Securities
We did not sell any of our equity securities or any options, warrants, or rights to purchase our equity securities
during the year ended December 31, 2021 that were not registered under the Securities Act of 1933, as amended, or the
Securities Act, and that have not otherwise been described in a Current Report on Form 8-K or a Quarterly Report on Form
10-Q.
Purchase of Equity Securities
We did not purchase any of our registered equity securities during the period covered by this Annual Report on
Form 10-K.
ITEM 6. [Reserved]
131
Table of Contents
ITEM 7. MANAGEMENT’S DISCUSSION AND ANALYSIS OF FINANCIAL CONDITION AND RESULTS OF
OPERATIONS
You should read the following discussion and analysis of our financial condition and results of operations together
with our historical consolidated financial statements and the related notes thereto appearing elsewhere in this Annual
Report. The objective of the following discussion and analysis is to provide material information relevant to your
assessment of the financial condition and results of operations of our company, including an evaluation of the amounts and
certainty of cash flows from operations and from outside sources, and to better allow you to view our company from
management’s perspective. Some of the information contained in this discussion and analysis or set forth elsewhere in this
Annual Report, including information with respect to our plans and strategy for our business and related financing,
includes forward-looking statements that involve risks and uncertainties. As a result of many factors, including those
factors set forth in “Risk Factor Summary and“Risk Factors” in Part I, Item 1A of this Annual Report, our actual results
could differ materially from the results described in or implied by the forward-looking statements contained in the
following discussion and analysis.
Overview
We are a biopharmaceutical company engaged in the commercialization and research and development of novel
anti-infective agents to treat serious infections. We have the commercial rights to two approved products, SIVEXTRO and
XENLETA, as well as one development product candidate, CONTEPO. In August 2019, our first product was approved by
the U.S. Food and Drug Administration, or FDA, and we made it available in the United States in September 2019 under
the brand name XENLETA. XENLETA (lefamulin) is a first-in-class semi-synthetic pleuromutilin antibiotic for systematic
administration in humans discovered and developed by our team. XENLETA is designed to inhibit the synthesis of
bacterial protein, that is required for bacteria to grow, by binding with high affinity, high specificity and at molecular
targets that are different than other antibiotic classes. Based on results from two global, Phase 3 clinical trials, we believe
that XENLETA is well-positioned for use as a first-line monotherapy for the treatment of community-acquired bacterial
pneumonia, or CABP, due to its novel mechanism of action, targeted spectrum of activity, resistance profile, achievement
of substantial drug concentration in lung tissue and fluid, availability of oral and intravenous, or IV, formulations and a
generally well-tolerated safety profile. We believe XENLETA represents a potentially important new treatment option for
the five million adults in the United States diagnosed with CABP each year.
Since inception, we have incurred significant operating losses. As of December 31, 2021, we had an accumulated
deficit of $595.7 million. To date, we have financed our operations primarily through equity offerings, convertible and term
debt financings and research and development support from governmental grants and proceeds from our licensing
agreements. We have devoted substantially all of our efforts to research and development, including clinical trials, as well
as commercializing SIVEXTRO and XENLETA. Our ability to generate profits from operations and become and remain
profitable depends on our ability to successfully develop and commercialize drugs that generate significant revenue.
We expect to continue to incur significant expenses and have negative cash flows for at least the next several
years. Our expenses will increase if we suffer any regulatory delays or are required to conduct additional clinical trials to
satisfy regulatory requirements. If we obtain marketing approval for CONTEPO or any other product candidate that we
develop, in-license or acquire, we expect to incur significant commercialization expenses related to product sales,
marketing, distribution and manufacturing. In light of the COVID-19 pandemic, a substantial decrease of non-COVID-19
respiratory infections, the associated disruption to the healthcare delivery and the uncertainty of resuming full direct
physician promotion, the timing and amount of sales of SIVEXTRO, XENLETA or any product candidates are uncertain.
Based on our current forecasts and plans, we will need to obtain substantial additional funding in connection with our
continuing operations. Adequate additional capital may not be available to us on acceptable terms, or at all. If we are
unable to raise capital when needed or on attractive terms, we could be forced to delay, reduce or eliminate our research
and development programs and commercialization efforts.
132
Table of Contents
Business Update Regarding COVID-19
On March 11, 2020, the World Health Organization declared the outbreak of COVID-19 as a pandemic. The
outbreak had an impact on the global economy, resulting in rapidly changing market and economic conditions. National
and local governments around the world instituted certain measures, including travel bans, prohibitions on group events
and gatherings, shutdowns of certain non-essential businesses, curfews, shelter-in-place orders and recommendations to
practice social distancing. The COVID-19 pandemic has presented a substantial public health and economic challenge
around the world and is affecting our employees, communities and business operations, as well as the U.S. economy and
financial markets.
The extent of the impact of COVID-19 on our business will depend on the length and severity of the pandemic,
including the extent there is any resurgence of the COVID-19 virus or any variant strains of the virus, the availability and
effectiveness of vaccines and the impact of the foregoing on our business. The full extent to which the COVID-19
pandemic will continue to directly or indirectly impact our business, results of operations and financial condition will
depend on future developments that are highly uncertain and cannot be accurately predicted. The full impact of COVID-19
is unknown and may continue as the rates of infection have increased in many states in the U.S., thus additional restrictive
measures may be necessary. Federal, state and local governmental policies and initiatives designed to reduce the
transmission of COVID-19 have resulted in, among other things, a significant reduction in physician office visits, the
cancellation of elective medical procedures, and the adoption of hybrid-remote-working policies, all of which have had,
and we believe will continue to have, an impact on our consolidated results of operations, financial position and cash flows.
In response to the COVID-19 pandemic, we closed our administrative offices and shifted to a remote working
business model. We have implemented a hybrid-remote-working policy for all of our employees, and we may take further
actions that alter our operations as may be required by federal, state, or local authorities, or which we determine are in our
best interests. The commercial and medical organizations suspended in-person interactions with physicians and customers
and were restricted to conducting educational and promotional activities virtually. The impact of the COVID-19 pandemic
could continue to have a material adverse effect on our business, results of operations, financial condition, liquidity and
prospects in the near-term and beyond 2022. While we have used all currently available information in our forecasts, the
ultimate impact of the COVID-19 pandemic and our product sales for SIVEXTRO and XENLETA, on our results of
operations, financial condition and cash flows is highly uncertain, and cannot currently be accurately predicted. According
to the Centers for Disease Control and Prevention, or CDC, there have been lower incidences of influenza-like illness cases
within the United States from a median of 49,696 per week during the period of September 2019 through February 2020, to
19,537 during the period of March through May 2020, which are largely responsible for the seasonality observed with
community-acquired bacterial pneumonia and which lead to the decrease in bacterial respiratory tract infection rates,
indicated by the decrease in the number of physician office visits, hospitalizations and antibiotic prescriptions. Data from
clinical laboratories in the United States indicated a 61% decrease in the number of specimens submitted and a 98%
decrease in influenza activity as measured by percentage of submitted specimens testing positive. Our results of operations,
financial condition and cash flows are dependent on future developments, including the duration of the pandemic and the
related length of its impact on the global economy or any other negative trend in the U.S. or global economy and any new
information that may emerge concerning the COVID-19 pandemic and the actions to contain it or treat its impact, which at
the present time are highly uncertain and cannot be predicted with any accuracy.
SIVEXTRO is approved for the treatment of ABSSSIs caused by certain susceptible Gram-positive
microorganisms. Before we were permitted to sell SIVEXTRO under the Distribution Agreement, we were required to
secure a sales force of a certain size and the restrictions related to COVID-19 needed to be eased in a sufficient manner to
permit us to promote and distribute SIVEXTRO. Re-securing a sales force of a certain size for the promotion and
distribution of SIVEXTRO has resulted in significant additional expense and our efforts to maintain a sales force may not
be successful. We have secured a virtual and in-person sales effort with community-based expertise with Amplity Health,
which is a contract sales organization, to replace our hospital-based sale force and began a small and focused sales effort
for SIVEXTRO and XENLETA in September 2020. We expanded this effort to 60 sales representatives in 2021 and may
expand it further. We also piloted a virtual promotion effort with incremental sales representatives in the third quarter of
2021.
133
Table of Contents
XENLETA is approved for the treatment of CABP in adults in the United States. The National Institute for
Allergy and Infectious Diseases, or NIAID, has identified that secondary bacterial pneumonia caused by common upper
respiratory tract bacteria plays a predominant role in the cause of death in pandemic influenza. NIAID recommends that the
prevention, diagnosis, prophylaxis, and treatment of secondary bacterial pneumonia, as well as the stockpiling of
antibiotics and bacterial vaccines, be high priorities for pandemic planning. We believe there is a potential for XENLETA
to be considered for U.S. government stockpiling for pandemic preparedness.
Two ongoing pediatric Phase 1 clinical trials for lefamulin and IV fosfomycin were temporarily closed for
enrollment as hospitals suspended access and non-essential clinical research to focus on health care delivery to COVID-19
patients. As of July 2020, both trials started to re-open, where allowed by the institution, and initiated screening of
potential subjects at sites.
Financial Operations Overview
Revenue
In September 2019 we launched XENLETA and in April 2021 we began exclusive distribution of SIVEXTRO in
the United States and certain of its territories. For the year ended December 31, 2021, we recorded $23.8 million of
SIVEXTRO product revenue, net of gross-to-net accruals and adjustments for returns, and $(0.4) million of XENLETA
product revenue, net of gross-to-net accruals and adjustments for returns. Our distribution partners had primarily utilized
their existing inventory from the initial launch to satisfy product demand for XENLETA, which in turn impacted sales
during the year ended December 31, 2021. Given the fact that the launch lot inventory had 36 month dating, and has a near
term shelf life expiration, we recorded a $1.3 million returns reserve adjustment during 2021. We launched a new 10-count
blister pack of XENLETA in the fourth quarter of 2021, which has four year dating for expiry. Future product revenues will
be subject to the amount and frequency of reorders from our wholesale customers based on the ultimate consumption
patterns from the end users of SIVEXTRO and XENLETA.
Collaboration revenues for the year ended December 31, 2021 included $2.6 million related to the restructured
China Region License Agreement, a portion of which is recognized over the estimated period the manufacturing
collaboration and regulatory support will be provided to Sumitomo Pharmaceuticals (Suzhou), as well as $1.2 million of
our share of revenues through April 11, 2021 associated with the SIVEXTRO distribution agreement with Merck & Co.,
Inc. which commenced at the end of September 2020.
Our revenues for the year ended December 31, 2021 included governmental research premiums, non-refundable
government grants, collaboration revenues and the benefit of government loans at below-market interest rates.
Cost of Revenues
Cost of revenues represented 17.0%, 1.1% and 0.1% of our total operating expenses for the years ended December
31, 2021, 2020 and 2019, respectively. Cost of revenues primarily represent the cost of the product itself, labor and
overhead, and any reserve for excess or obsolete inventory. Other cost of revenues include costs associated with the
manufacturing collaboration and regulatory support under our licensing agreements. The increase in cost of revenue for the
year ended December 31, 2021 was primarily due to the launch of SIVEXTRO under our own National Drug Code, or
NDC, on April 12, 2021.
Research and Development Expenses
Research and development expenses represented 16.3%, 21.2% and 29.7% of our total operating expenses for the
years ended December 31, 2021, 2020 and 2019, respectively.
For each of our research and development programs, we incur both direct and indirect expenses. Direct expenses
include third-party expenses related to these programs such as expenses for manufacturing services (prior to our products
receiving FDA approval, after which time these costs are capitalized in inventory until product is sold),
134
Table of Contents
non-clinical and clinical studies and other third party development services. Indirect expenses include salaries and related
costs, including stock-based compensation, for personnel in research and development functions, infrastructure costs
allocated to research and development operations, costs associated with obtaining and maintaining intellectual property
associated with our research and development operations, laboratory consumables, consulting fees related to research and
development activities and other overhead costs. We utilize our research and development staff and infrastructure resources
across multiple programs, and many of our indirect costs historically have not been specifically attributable to a single
program. Accordingly, we cannot state precisely our total indirect costs incurred on a program-by-program basis.
The following table summarizes our direct research and development expenses by program and our indirect costs.
(in thousands)
Direct Costs
XENLETA
CONTEPO
FDA filing fee refund
Other programs and initiatives
Indirect Costs
Total research and development
expenses
Year Ended Ended December 31,
2020
2019
2021
$
$
2,891
340
—
1,383
8,016
$
2,119
450
—
1,347
11,186
7,765
2,977
(2,589)
1,412
16,850
$
12,630
$
15,102
$
26,415
We expect to continue to incur research and development expenses in connection with required regulatory
activities, our activities related to our ongoing pediatric studies of lefamulin for the treatment of CABP and of CONTEPO
for the treatment of cUTI, and may incur costs related to the pursuit of the clinical development of lefamulin and
CONTEPO for additional indications including the treatment of resistant bacterial infections in patients with cystic fibrosis,
or CF and engagement in earlier stage research and development activities. We initiated screening of our Phase 1 clinical
trial of XENLETA for the treatment of resistant bacterial infections in patients with CF in March 2022, and are on track to
begin dosing in April 2022. Given the ongoing COVID-19 pandemic and the high risk it puts CF patients under, it is
difficult to estimate recruitment timelines at this time. It is difficult to estimate the duration and completion costs of our
research and development programs.
The successful development and commercialization of our product candidates is highly uncertain. This is due to
the numerous risks and uncertainties associated with product development and commercialization, including the
uncertainty of:
● the efficacy and potential advantages of our product candidates compared to alternative treatments, including
any standard of care, and our ability to achieve market acceptance for any of our product candidates that
receive marketing approval;
● the costs and timing of commercialization activities, including product sales, marketing, distribution and
manufacturing, for any of our product candidates that receive marketing approval;
● the costs, timing and outcome of regulatory review of our product candidates;
● the scope, progress, costs and results of clinical trials and other research and development activities; and
● the costs and timing of preparing, filing and prosecuting patent applications, maintaining, enforcing and
protecting our intellectual property rights and defending against any intellectual property-related claims.
A change in the outcome of any of these variables with respect to the development of our product candidates
could result in a significant change in the costs and timing associated with the development of that product candidate.
135
Table of Contents
For example, if the FDA or another regulatory authority were to require us to conduct clinical trials or other testing beyond
those that we have completed or currently contemplate will be required for the completion of clinical development of any
product candidate, we could be required to expend significant additional resources and time on the completion of clinical
development of that product candidate.
Selling, General and Administrative Expenses
Selling, general and administrative expenses represented 66.7%, 77.7%, and 70.2% of our total operating
expenses for the years ended December 31, 2021, 2020 and 2019, respectively.
Selling, general and administrative expenses consist primarily of salaries and related costs, including stock-based
compensation not related to research and development activities for personnel in our commercial, medical affairs, finance,
information technology and administrative functions, as well as costs related to our contract commercial organization, to
provide community-based commercial and sales services. Selling, general and administrative expenses also include costs
related to professional fees for auditors, lawyers and tax advisors and consulting fees not related to research and
development operations, as well as functions that are partly or fully outsourced by us, such as accounting, payroll
processing and information technology.
We expect selling, general and administrative expenses in 2022 to be comparable to 2021.
Critical Accounting Policies and Estimates
Our management’s discussion and analysis of our financial condition and results of operations is based on our
consolidated financial statements, which we have prepared in accordance with generally accepted accounting principles in
the United States, or U.S. GAAP. The preparation of our consolidated financial statements requires us to make estimates
and assumptions that affect the reported amounts of assets and liabilities and the disclosure of contingent assets and
liabilities at the end of the reporting period, as well as the reported revenues and expenses during the reporting periods and
how our estimates and assumptions have changed over each relevant reporting period. However, these estimates and
assumptions are subject to uncertainty, due to unknown trends and events and various other factors that we believe to be
reasonably likely under the circumstances, the results of which form the basis for making judgments about the carrying
values of assets and liabilities that are not readily apparent from other sources. Actual results may differ from these
estimates under different assumptions or conditions.
Our significant accounting policies and estimates are described in more detail in the notes to our consolidated
financial statements appearing at the end of this filing. However, we believe that the following accounting policies and
estimates are the most critical to aid you in fully understanding and evaluating our financial condition and results of
operations.
Revenue Recognition
Under Accounting Standards Codification, or ASC, 606, an entity recognizes revenue when its customer obtains
control of promised goods or services, in an amount that reflects the consideration that the entity expects to receive in
exchange for those goods or services. We then recognize as revenue the amount of the transaction price that is allocated to
the respective performance obligation when (or as) the performance obligation is satisfied as services are rendered.
The transaction price that we recognize as revenue reflects the amount we expect with the sale and transfer of
control of the product to our customers. Once the customer takes control of the product, our performance obligation under
the sale contract is complete and revenue is recorded net of applicable reserves for various types of variable consideration.
The types of variable consideration are as follows and are further described in Note 2 in our Consolidated Financial
Statements.
● Fees-for-service
136
Table of Contents
● Product returns
● Chargebacks and rebates
● Government rebates
● Commercial payer and other rebates
● Group Purchasing Organizations, or GPO, administration fees
● Voluntary patient assistance programs
In determining the amounts of variable consideration, we must make significant judgments and estimates. In
assessing the amount of net revenue to record, we consider both the likelihood and the magnitude of the revenue reversal.
Actual amounts of consideration ultimately received may differ significantly from our estimates. If actual results in the
future vary from our estimates, we adjust our estimates which would affect net product revenue and earnings in the period
such variances become known.
XENLETA Inventory and Purchase Commitments
Our XENLETA inventory is stated at the lower of cost or net realizable value, with cost determined on a first-in,
first-out basis, and consists primarily of material costs, third-party manufacturing costs, and related transportation costs in
our supply chain. Our inventory is subject to expiration dating, which can be extended in certain circumstances. We also
have non-cancellable purchase commitments for XENLETA active pharmaceutical ingredient, or API. We continually
evaluate forecasted product sales for XENLETA which is used in estimating the need to reserve for estimated excess, slow-
moving and obsolete inventory on hand and potential accrued losses on firm purchase committments. During the years
ended December 31, 2021 and 2020, we recorded $0.3 million and $0.7 million, respectively, of non-cash reserves for
excess and obsolete inventory due to timing of expiry dating of expiring inventory.
137
Table of Contents
Results of Operations
Comparison of Years Ended December 31, 2021 and 2020
(in thousands)
Consolidated operations data:
Product revenue, net
Collaboration revenue
Research premium and grant revenue
Total revenue
Costs and expenses:
Cost of revenues
Research and development expenses
Selling, general and administrative expenses
Total operating expenses
Loss from operations
Other income (expense):
Other income (expense), net
Interest income (expense), net
Loss on extinguishment of debt
Loss before income taxes
Income tax expense
Net loss
Year Ended December 31,
2020
2021
Change
$
$
23,386
3,830
1,679
28,895
(13,148)
(12,630)
(51,645)
(77,423)
(48,528)
469
(901)
—
(48,960)
(490)
(49,450)
$
$
$
108
2,756
2,163
5,027
(766)
(15,102)
(55,285)
(71,153)
(66,126)
1,187
(1,649)
(2,757)
(69,345)
(139)
(69,484)
$
23,278
1,074
(484)
23,868
(12,382)
2,472
3,640
(6,270)
17,598
(718)
748
2,757
20,385
(351)
20,034
Revenues
Revenues for the year ended December 31, 2021 were $28.9 million compared to $5.0 million for the year ended
December 31, 2020. The $23.9 million increase was primarily due to $23.8 million in SIVEXTRO product revenue, net
since the launch of SIVEXTRO under our own NDC on April 12, 2021.
Cost of Revenues
Cost of revenues for the year ended December 31, 2021 was $13.1 million compared to $0.8 million for the year
ended December 31, 2020. The $12.4 million increase was primarily due to the launch of SIVEXTRO under our own NDC
on April 12, 2021. Cost of revenues for XENLETA primarily represents direct and indirect manufacturing costs, while cost
of revenues for SIVEXTRO represent the actual purchase cost for the finished product from Merck. Prior to the FDA
approval of XENLETA on August 19, 2019, the inventory costs for XENLETA were expensed as research and
development expenses since the approval was outside of our control and therefore not considered probable. As such, the
majority of the expenses incurred for our initial inventories of XENLETA has been previously expensed. For the years
ended December 31, 2021 and 2020, cost of revenues include $0.3 million and $0.7 million, respectively, of a non-cash
reserve adjustment for excess and obsolete inventory due to timing of expiring inventory.
Research and Development Expenses
Research and development expenses for the year ended December 31, 2021 were $12.6 million compared to $15.1
million for the year ended December 31, 2020. The $2.5 million decrease was primarily due to a $0.7 million decrease in
stock-based compensation expense, a $1.0 million decrease in staff costs, and a $0.7 million decrease in study costs.
Selling, General and Administrative Expenses
Selling, general and administrative expense for the year ended December 31, 2021 were $51.6 million compared
to $55.3 million for the year ended December 31, 2020. The $3.6 million decrease was primarily due to a $5.9
138
Table of Contents
million decrease in staff costs due to the reduction of headcount, a $1.2 million decrease in stock-based compensation
expense, a $0.7 million decrease in travel costs, a $0.6 million decrease in infrastructure costs, and a $2.5 million decrease
in professional fees, partly offset by a $7.4 million increase in advisory and external consultancy expenses primarily related
to commercialization activities and professional service fees for the relaunch of SIVEXTRO and XENLETA.
Other Income (Expense), net
Other income (expense), net, decreased by $0.7 million for the year ended December 31, 2021 primarily due to
remeasurements of our foreign currency account balances.
Interest Income (Expense), net
Interest income (expense), net decreased by $0.7 million due the repayment of indebtedness under our Loan
Agreement with Hercules in March 2020. See Note 7 to our consolidated financial statements included elsewhere in this
Form 10-K for further information.
Loss on Extinguishment of Debt
In connection with the third amendment to our Loan Agreement with Hercules, we recognized a non-cash $2.8
million loss on the extinguishment of debt during the year ended December 31, 2020, which represents the excess of the
reacquisition price of the $30.0 million debt repaid over the net carrying amount of the extinguished debt. We did not have
a loss on the extinguishment of debt during the year ended December 31, 2021.
Income Tax Expense
Our income tax expense was $0.5 million for the year ended December 31, 2021 compared to $139,000 for the
year ended December 31, 2020.
Comparison of Years Ended December 31, 2020 and 2019
(in thousands)
Consolidated operations data:
Product revenue, net
Collaboration revenue
Research premium and grant revenue
Total revenue
Costs and expenses:
Cost of revenues
Research and development expenses
Selling, general and administrative expenses
Total operating expenses
Loss from operations
Other income (expense):
Other income (expense), net
Interest income (expense), net
Loss on extinguishment of debt
Loss before income taxes
Income tax expense
Net loss
Year Ended December 31,
2019
2020
Change
$
$
108
2,756
2,163
5,027
$
1,538
6,210
1,733
9,481
(766)
(15,102)
(55,285)
(71,153)
(66,126)
1,187
(1,649)
(2,757)
(69,345)
(139)
(69,484)
$
(70)
(26,415)
(62,485)
(88,970)
(79,489)
215
(3,389)
—
(82,663)
(101)
(82,764)
$
$
139
(1,430)
(3,454)
430
(4,454)
(696)
11,313
7,200
17,817
13,363
972
1,740
(2,757)
13,318
(38)
13,280
Table of Contents
Revenues
Revenues for the year ended December 31, 2020 were $5.0 million compared to $9.5 million for the year ended
December 31, 2019. The $4.5 million decrease was primarily due to a $3.5 million decrease in collaboration revenue and a
$1.4 million decrease in product revenue, net, partially offset by a $0.4 million increase in research premiums and
government grants provided to us by the Austrian government. The decrease in collaboration revenues was primarily due to
the $5.0 million recognized in 2019 under our China Region License Agreement, partially offset by $1.8 million
recognized in 2020 under our SIVEXTRO distribution agreement with Merck & Co., Inc.
Cost of Revenues
Cost of revenues primarily represents direct and indirect manufacturing costs of our XENLETA product. Prior to
the FDA approval of XENLETA on August 19, 2019, the inventory costs for the product were expensed as research and
development expenses since the approval was outside of our control and therefore not considered probable. As such, the
majority of the expenses incurred for our initial inventories of XENLETA has been previously expensed. As a result, we
anticipate that our cost of revenues for XENLETA will remain at relatively low levels for a period of time until our initial
pre-launch inventory stock has been distributed by our customers based on end user consumption demand. For the year
ended December 31, 2020, cost of revenues include a $0.7 million non-cash reserve for excess and obsolete inventory due
to timing of expiring inventory.
Research and Development Expenses
Research and development expenses for the year ended December 31, 2020 were $15.1 million compared to $26.4
million for the year ended December 31, 2019. The $11.3 million decrease was primarily due to a $7.2 million decrease in
research materials and purchased services related to the development of lefamulin, a $2.9 million decrease in staff costs
due to the reduction of employees, a $2.0 million decrease in research consulting fees, a $0.9 million decrease in stock-
based compensation expense and $0.4 million decrease in travel expenses, partly offset by a $2.0 million increase in other
fees due to a $2.6 million NDA filing fee refund for CONTEPO in 2019.
Selling, General and Administrative Expenses
Selling, general and administrative expense for the year ended December 31, 2020 were $55.3 million compared
to $62.5 million for the year ended December 31, 2019. The $7.2 million decrease was primarily due to a $4.2 million
decrease in staffing expense related to the termination of our sales force in early 2020, $3.7 million decrease in stock-based
compensation expense, a $1.6 million decrease in travel expenses, a $0.7 million decrease in advisory and external
consultancy expenses primarily related to commercialization activities and professional service fees, and a $0.1 million
decrease in other corporate costs, partly offset by a $1.2 million increase in insurance costs, a $1.5 million increase in
professional fees.
Other Income (Expense), net
Other income (expense), net was $1.2 million for the year ended December 31, 2020 compared to a $0.2 million
for the year ended December 31, 2019. The $1.0 million increase was primarily from $0.6 million income from the
sublease of our laboratory and office space in Vienna, Austria.
Interest Income (Expense), net
Interest income (expense), net decreased by $1.7 million due to the repayment of $30.0 million of indebtedness
under our Loan Agreement with Hercules in March 2020. See Note 7 to our consolidated financial statements included
elsewhere in this Form 10-K for further information.
140
Table of Contents
Loss on Extinguishment of Debt
In connection with the repayment of our Loan Agreement with Hercules, we recognized a non-cash $2.8 million
loss on the extinguishment of debt during the year ended December 31, 2020, which represents the excess of the
reacquisition price of the $30.0 million debt repaid over the net carrying amount of the extinguished debt.
Income Tax Expense
Our income tax expense was $139,000 for the year ended December 31, 2020 compared to $101,000 for the year
ended December 31, 2019.
Liquidity and Capital Resources
Since our inception, we have incurred net losses and generated negative cash flows from our operations. To date,
we have financed our operations through the sale of equity securities, convertible and term debt financings, research and
development support from governmental grants and loans and proceeds from licensing agreements. As of December 31,
2021, we had cash and cash equivalents, restricted cash and short-term investments of $47.9 million. We will need to
obtain substantial additional funding to achieve our business objectives during the next 12 months and beyond. If we are
unable to raise additional funds when needed, including through the sale of our ordinary shares for cash, we may be unable
to pursue our business plans and strategy, and we may be required to delay, limit, reduce or terminate our product
development or commercialization efforts or grant rights to develop and market product candidates that we would
otherwise prefer to develop and market ourselves. Additionally, our inability to raise funds when needed may cause
investors to lose confidence in us and raise substantial doubt about our ability to continue as a going concern, which may
cause our share price to decline.
In September 2021, we entered into a purchase agreement, or Purchase Agreement, with Lincoln Park Capital
Fund, LLC, or Lincoln Park, which, subject to the terms and conditions, provides that we have the right to sell to Lincoln
Park and Lincoln Park is obligated to purchase up to $23.0 million of our ordinary shares. In addition, under the Purchase
Agreement, we agreed to issue a commitment fee of 632,474 ordinary shares, or the Commitment Shares, as consideration
for Lincoln Park entering into the Purchase Agreement and for the payment of $0.01 per Commitment Share. Under the
Purchase Agreement, we may from time to time, at our discretion, direct Lincoln Park to purchase on any single business
day, or a Regular Purchase, up to (i) 400,000 ordinary shares if the closing sale price of our ordinary shares is not below
$0.25 per share on Nasdaq, (ii) 600,000 ordinary shares if the closing sale price of our ordinary shares is not below $2.00
per share on Nasdaq or (iii) 800,000 ordinary shares if the closing sale price of our ordinary shares is not below $3.00 per
share on Nasdaq. In addition to Regular Purchases, we may also direct Lincoln Park to purchase other amounts as
accelerated purchases or as additional accelerated purchases on the terms and subject to the conditions set forth in the
Purchase Agreement. In any case, Lincoln Park’s commitment in any single Regular Purchase may not exceed $2.5 million
absent a mutual agreement to increase such amount. As of December 31, 2021, we have issued and sold an aggregate of
2,400,000 ordinary shares pursuant to the Purchase Agreement and received net proceeds of $2.4 million. From January 1,
2022 and through the date of this filing, we have issued and sold an aggregate of 3,600,000 ordinary shares pursuant to the
Purchase Agreement and received net proceeds of $1.6 million. As of the date of this filing, we may issue and sell ordinary
shares for gross proceeds of up to $19.0 million under the Purchase Agreement, subject to the Nasdaq rules which may
limit our ability to make sales of our ordinary shares to Lincoln Park in excess of a specified amount without prior
shareholder approval.
In May 2021, we entered into an Open Market Sale AgreementSM, or the New Sale Agreement, with Jefferies, as
agent, pursuant to which we may offer and sell ordinary shares for aggregate gross sale proceeds of up to $50.0 million,
from time to time through Jefferies, by any method permitted that is deemed an “at the market offering” as defined in Rule
415(a)(4) promulgated under the Securities Act of 1933, as amended. Upon entry into the New Sale Agreement, our
existing Jefferies ATM Agreement entered into in June 2019 was terminated. We did not incur any termination penalties as
a result of the replacement of the Jefferies ATM Agreement. As of December 31, 2021, we have issued and sold an
aggregate of 18,232,689 ordinary shares pursuant to the New Sale Agreement and received gross proceeds of $30.5 million
and net proceeds of $29.3 million, after deducting commissions to Jefferies and other offering expenses. From January 1,
2022 and through the date of this filing, we have issued and sold an aggregate of 1,338,282
141
Table of Contents
ordinary shares pursuant to the New Sale Agreement and received gross proceeds of $595,000 and net proceeds of
$580,000, after deducting commissions to Jefferies and other offering expenses.
In March 2021, we entered into a securities purchase agreement with certain institutional investors pursuant to
which we agreed to issue and sell in a registered direct offering (1) an aggregate of 9,761,010 ordinary shares, $0.01
nominal value per share, and accompanying warrants to purchase up to an aggregate of 4,880,505 ordinary shares and (2)
pre-funded warrants to purchase up to an aggregate of 600,000 ordinary shares and accompanying ordinary share warrants
to purchase up to an aggregate of 300,000 ordinary shares. Each share was issued and sold together with an accompanying
ordinary share warrant at a combined price of $2.4525, and each pre-funded warrant was issued and sold together with an
accompanying ordinary share warrant at a combined price of $2.4425. The proceeds to us from the offering were $25.4
million gross and $23.4 million net after deducting the placement agent’s fees and estimated offering expenses. Each pre-
funded warrant had an exercise price per ordinary share equal to $0.01 and each pre-funded warrant was exercised in full
on the issuance date. Each ordinary share warrant has an exercise price per ordinary share equal to $2.39, was exercisable
on the date of issuance and will expire on the five-year anniversary of the date of issuance.
In December 2020, we completed a registered public offering in which we sold 6,000,000 ordinary shares at a
public offering price of $2.50. The proceeds to us from the offering were $15.0 million gross and $13.3 million net, after
deducting the placement agent’s fees and offering expenses. In December 2018, we announced the closing of up to a $75.0
million term loan with Hercules, or the Loan Agreement, $25.0 million of which was funded on the day of closing. Under
the terms of the loan, in addition to the $25.0 million received at closing, we borrowed an additional $10.0 million in
connection with the approval by the FDA of the NDA for XENLETA. In March 2020, we repaid Hercules $30.0 million of
the $35.0 million in aggregate principal amount of debt outstanding under the Loan Agreement. See Note 7 to the
consolidated financial statements included elsewhere in this Form 10-K for additional information on the terms associated
with the remaining term loans potentially available to us and the costs and other conditions associated with this funding
source.
Cash Flows
Comparison of Years Ended December 31, 2021 and 2020
The following table summarizes our cash flows for the years ended December 31, 2021 and 2020:
(in thousands)
Net cash (used in) provided by:
Operating activities
Investing activities
Financing activities
Effects of foreign currency translation on cash
Net increase/(decrease) in cash, cash equivalents and
restricted cash
Year Ended December 31,
2020
2021
$
$
$
(59,557)
(81)
66,366
(484)
(71,331)
(274)
26,924
(140)
6,244
$
(44,821)
Operating Activities
Cash flow used in operating activities decreased by $11.8 million from $71.3 million for the year ended
December 31, 2020 to $59.6 million for the year ended December 31, 2021 primarily due to a $15.2 million decrease in net
loss, after adjustments for non-cash amounts included in net loss, offset by a higher working capital of $3.5 million
primarily due to increases in inventory and accounts receivable driven by the launch of SIVEXTRO under our own NDC in
April 2021.
142
Table of Contents
Investing Activities
Cash flow used in investing activities decreased by $0.2 million from $0.3 million cash used for the year ended
December 31, 2020 to $0.1 million cash used for the year ended December 31, 2021 primarily due to changes in restricted
cash and lower investments in property, plant and equipment.
Financing Activities
Cash flow generated from financing activities for the year ended December 31, 2021 was $66.4 million from our
March 2021 financing, our Purchase Agreement with Lincoln Park, as well as our New Sale Agreement. Cash flow
generated from financing activities for the year ended December 31, 2020 was $26.9 million, primarily from total net
proceeds of approximately $56.9 million from the securities purchase agreements entered into in May 2020 and December
2020, warrant exercises, as well as our Jefferies ATM Agreement, partly offset by the repayment of $30.0 million of long-
term borrowings on our debt facility in the year ended December 31, 2020.
Comparison of Years Ended December 31, 2020 and 2019
The following table summarizes our cash flows for the years ended December 31, 2020 and 2019:
(in thousands)
Net cash (used in) provided by:
Operating activities
Investing activities
Financing activities
Effect of foreign currency translation on cash
Net decrease in cash, cash equivalents and restricted cash
Year Ended December 31,
2019
2020
$
$
(71,331)
(274)
26,924
(140)
(44,821)
$
$
(71,892)
331
56,075
(106)
(15,592)
Operating Activities
Cash flow used in operating activities decreased by $0.6 million from $71.9 million for the year ended
December 31, 2019 to $71.3 million for the year ended December 31, 2020 primarily due to a $11.8 million decrease in net
loss, after adjustments for non-cash amounts included in net loss and higher working capital of $11.2 million primarily due
to a decrease in accrued expenses and other current liabilities and an increase in inventory.
Investing Activities
Cash flow provided by investing activities decreased by $0.6 million from $0.3 million cash provided for the year
ended December 31, 2019 to $0.3 million cash used for the year ended December 31, 2020 primarily due to changes in
restricted cash.
Financing Activities
Cash flow provided by financing activities decreased by $29.2 million from $56.1 million for the year ended
December 31, 2019 to $26.9 million for the year ended December 31, 2020 primarily due to the repayment of $30.0 million
of long-term borrowings on our debt facility and lower net proceeds of $20.4 million related to sales of our ordinary shares
under our ATM Agreements , partly offset by higher net proceeds of $33.3 million from our May 2020 and December 2020
equity offerings of ordinary shares, as well as the exercise of warrants.
Material Cash Requirements
We anticipate that our expenses will increase as we expect to incur significant additional commercialization
expenses related to product sales, marketing, distribution and manufacturing. In addition, our expenses will increase if we
suffer any regulatory delays or are required to conduct additional clinical trials to satisfy regulatory requirements.
143
Table of Contents
In addition, our expenses will increase if and as we:
● initiate or continue the research and development of XENLETA and CONTEPO for additional indications
and of our other product candidates;
● seek to develop additional product candidates;
● seek marketing approval for any product candidates that successfully complete clinical development;
● are required by the FDA, EMA or other regulators to conduct additional clinical trials prior to or after
approval;
● continue to build or re-build a medical affairs, sales, marketing and distribution infrastructure and scale up
manufacturing capabilities to commercialize SIVEXTRO, XENLETA and any other product candidates for
which we receive marketing approval;
● in-license or acquire other products, product candidates or technologies, including additional community
products;
● maintain, expand and protect our intellectual property portfolio;
● expand our physical presence in the United States and Ireland;
● incur additional debt;
● establish and expand manufacturing arrangements with third parties; and
● add operational, financial and management information systems and personnel, including personnel to
support our product development and our operations as a public company in addition to our
commercialization efforts.
As described above, on March 11, 2020, we entered into a Third Amendment to our Loan Agreement with
Hercules. Pursuant to the Third Amendment, we repaid to Hercules in March 2020, $30.0 million of the $35.0 million in
aggregate principal amount of debt outstanding under the Loan Agreement, which we refer to as the Prepayment. Under the
Third Amendment, we and Hercules agreed to defer the end of term loan charge payment in the amount of approximately
$2.1 million that would have otherwise become payable on the date of the Prepayment and to reduce the prepayment
charge with respect to the Prepayment from $600,000 to $300,000 and to defer its payment, in each case, until June 1, 2023
or such earlier date on which all loans under the Loan Agreement are repaid or become due and payable. The Third
Amendment also reset the revenue performance covenant to 70% of targeted revenue based on a revised net product
revenue forecast and lowered our minimum liquidity requirement to $3.0 million in cash and cash equivalents, in each
case, following the Prepayment. The new minimum liquidity requirement will not apply if CONTEPO receives regulatory
approval from the U.S. Food and Drug Administration and we achieve at least 70% of our revised net product revenue
targets under the Loan Agreement. On June 2, 2021, we entered into a further amendment, or the Fourth Amendment, to
our Loan Agreement with Hercules. Pursuant to the Fourth Amendment, the date on which we must commence repaying
principal under the Loan Agreement was extended to April 1, 2022, which date may be extended until July 1, 2022, subject
to our receipt of a specified amount of additional net financing proceeds and the achievement of a specified product
revenue milestone. Additionally, the time during which the Tranche Advance (as defined in Note 7 to our consolidated
financial statements) may be requested by us under the Loan Agreement was extended until the Amortization Date. In
addition, pursuant to the Fourth Amendment, the minimum liquidity requirement of $3.0 million in cash and cash
equivalents will be waived at any time we have recognized $15.0 million of net product revenue during the applicable
trailing three months. Based on our current operating plans, we expect that our existing cash resources as of the date of this
Annual Report on Form 10-K will be sufficient to enable us to fund our operations, debt service obligations and capital
expenditure requirements well into the fourth quarter of 2022. We have
144
Table of Contents
based this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we
currently expect. This estimate assumes, among other things, that we do not obtain any additional funding through grants
and clinical trial support, collaboration agreements, or equity or debt financings. This estimate also assumes that we remain
in compliance with the covenants and no event of default occurs under the Loan Agreement.
We expect to continue to invest in critical commercial promotion and distribution, medical affairs and other
commercialization activities, as well as investing in our supply chain for the commercialization of SIVEXTRO, XENLETA
and, if approved, CONTEPO. We expect to seek additional funding in future periods to support these activities.
Our future capital requirements will depend on many factors, including:
● the costs and timing of process development and manufacturing scale-up activities associated with
XENLETA and CONTEPO;
● the costs to secure supply of SIVEXTRO and costs to sell and market the product in the U.S.;
● the costs, timing and outcome of regulatory review of lefamulin in Europe and for any other indications and
CONTEPO;
● the costs of commercialization activities for SIVEXTRO, XENLETA and potentially CONTEPO if we
receive marketing approval, including the costs and timing of establishing product sales, marketing,
distribution and outsourced manufacturing capabilities, including the costs of building finished product
inventory and its components in preparation of initial marketing of CONTEPO, if approved;
● the commercial success of SIVEXTRO and XENLETA and the amount and frequency of reorders or product
returns by our wholesale customers;
● subject to the resubmission of our NDA for CONTEPO and potential receipt of marketing approval, revenue
received from commercial sales of CONTEPO;
● the costs of developing XENLETA and CONTEPO for the treatment of additional indications;
● the impact of the COVID-19 pandemic;
● our ability to establish collaborations on favorable terms, if at all;
● the scope, progress, results and costs of product development of any other product candidates that we may
develop;
● the extent to which we in-license or acquire rights to other products, product candidates or technologies,
including additional community products;
● the costs related to the promotion, sale and distribution of the products under our Distribution Agreement
with Merck & Co., Inc.;
● the costs of preparing, filing and prosecuting patent applications, maintaining and protecting our intellectual
property rights and defending against intellectual property-related claims;
● the continued availability of Austrian governmental grants;
● the need to satisfy interest and principal obligations under our Loan Agreement with Hercules as well as the
covenants contained in our Loan Agreement;
145
Table of Contents
● the rate of the expansion of our physical presence in the United States and Ireland; and
● the costs of operating as a public company in the United States.
Our commercial revenues, if any, will be derived from sales of SIVEXTRO, XENLETA, and if approved,
CONTEPO or any other products that we successfully develop, in-license or acquire. In addition, SIVEXTRO, XENLETA
and, if approved, CONTEPO or any other product candidate that we develop, in-license or acquire may not achieve
commercial success. Accordingly, we will need to obtain substantial additional financing to achieve our business
objectives. Adequate additional financing may not be available to us on acceptable terms, or at all. In addition, we may
seek additional capital due to favorable market conditions or strategic considerations, even if we believe that we have
sufficient funds for our current or future operating plans.
Until such time, if ever, as we can generate substantial product revenues, we expect to finance our cash needs
through a combination of equity offerings, debt financings, collaborations, and funding from local and international
government entities and non-government organizations in the disease areas addressed by our product candidates and
marketing, distribution or licensing arrangements. To the extent that we raise additional capital through the sale of equity,
warrants or convertible debt securities, the ownership interest of our shareholders will be diluted, and the terms of these
securities may include liquidation or other preferences that adversely affect the rights of our existing shareholders.
Additional debt financing, if available, may involve agreements that include covenants limiting or restricting our ability to
take specific actions, such as incurring additional debt, making capital expenditures or declaring dividends.
If we raise additional funds through collaborations, strategic alliances or marketing, distribution or licensing
arrangements with third parties, we may have to relinquish valuable rights to our technologies, future revenue streams,
research programs or product candidates or to grant licenses on terms that may not be favorable to us. If we are unable to
raise additional funds through equity or debt financings when needed, we may be required to delay, limit, reduce or
terminate our product development or future commercialization efforts or grant rights to develop and market product
candidates that we would otherwise prefer to develop and market ourselves.
In addition, as part of our corporate strategy, we continue to evaluate business development opportunities and
potential collaborations. We may further expand our product pipeline through opportunistically in licensing or acquiring
the rights to complementary products, product candidates and technologies for the treatment of a range of infectious
diseases or other products that we would market with our commercial infrastructure, including additional community
products, which could involve an acquisition of or combination or other strategic transaction with another operating
business. To the extent any additional business development opportunity is consummated, our capital expenditures may
increase significantly.
We have contractual commitments related primarily to contracts entered into with contract manufacturing
organizations and contract research organizations in connection with the commercial manufacturing of XENLETA, the
purchase of SIVEXTRO finished product and other research and development activities. The contractual commitments are
further described in Note 15 to our consolidated financial statements included elsewhere in this Form 10-K.
Capital Expenditures
Capital expenditures were $25,000 and $0.1 million for the year ended December 31, 2021 and 2020, respectively.
Currently, there are no material capital projects planned in 2022.
ITEM 7A. QUANTITATIVE AND QUALITATIVE DISCLOSURES ABOUT MARKET
We are exposed to a variety of financial risks in the ordinary course of our business: market risk, credit risk and
liquidity risk. Our overall risk management program focuses on preservation of capital given the unpredictability of
financial markets. These market risks are principally limited to interest rate and foreign currency fluctuations.
146
Table of Contents
Market Risk
We do not have any significant credit risk exposure to any single counterparty or any group of counterparties
having similar characteristics. The credit risk on liquid funds (bank accounts, cash balances, marketable securities and term
deposits) is limited because the counterparties are banks with high credit ratings from international credit rating agencies.
The primary objective of our investment activities is to preserve principal and liquidity while maximizing income without
significantly increasing risk. We do not enter into investments for trading or speculative purposes.
We are exposed to foreign exchange risk arising from various currency exposures, primarily with respect to the
euro and the British pound. Our functional currency is the U.S. dollar, but we receive payments and acquire materials, in
each of these other currencies. We have not established any formal practice to manage the foreign exchange risk against
our functional currency. However, we attempt to minimize our net exposure by buying or selling foreign currencies at spot
rates upon receipt of new funds to facilitate committed or anticipated foreign currency transactions.
Interest rate risk may arise from short-term or long-term debt. Our outstanding indebtedness with Hercules bears
interest at the greater of 9.80% and 9.80% plus the prime rate of interest minus 5.50%. Based on the current prime rate, our
outstanding indebtedness with Hercules bears interest at 9.80%. If the prime rate increases to over 5.50%, the interest on
our loan with Hercules will increase.
Inflation generally affects us by increasing our cost of labor and research, manufacturing and development costs.
We believe that inflation has not had a material effect on our financial statements included elsewhere in this Annual Report
on Form 10-K. However, our operations may be adversely affected by inflation in the future.
Liquidity Risk
Since our inception, we have incurred net losses and generated negative cash flows from our operations. We
anticipate based on our current operating plans, that our existing cash, cash equivalents, restricted cash and short-term
investments as of the date of this Annual Report on Form 10-K will be sufficient to enable us to fund our operating
expenses, debt service obligations and capital expenditure requirements well into the fourth quarter of 2022. We have based
this estimate on assumptions that may prove to be wrong, and we could use our capital resources sooner than we currently
expect. This estimate assumes, among other things, that we do not obtain any additional funding through grants and clinical
trial support, collaboration agreements or equity or debt financings.
We expect to continue to invest in critical commercial and medical affairs activities, as well as investing in our
supply chain for the commercialization of SIVEXTRO, XENLETA and the potential launch of CONTEPO. We expect to
seek additional funding in future periods to support these activities.
If we obtain marketing approval for CONTEPO or any other product candidate that we develop, in-license or
acquire, we expect to incur significant additional commercialization expenses related to distribution and manufacturing.
Our expenses will increase if we suffer any delays in our clinical programs, including regulatory delays, or are required to
conduct additional clinical trials to satisfy regulatory requirements.
There can be no assurance that we will be successful in acquiring additional capital at a level sufficient to fund our
operations or on terms favorable to us. If we are unable to raise capital when needed or on attractive terms, we could be
forced to delay, reduce or eliminate our research and development programs or our commercialization efforts.
ITEM 8. FINANCIAL STATEMENTS AND SUPPLEMENTARY DATA
Our consolidated financial statements, together with the report of our independent registered public accounting
firm, appear on pages F-1 through F-33 of this Annual Report on Form 10-K.
147
Table of Contents
ITEM 9. CHANGES IN AND DISAGREEMENTS WITH ACCOUNTANTS ON ACCOUNTING AND
FINANCIAL DISCLOSURE
None.
ITEM 9A. CONTROLS AND PROCEDURES
Conclusions Regarding the Effectiveness of Disclosure Controls and Procedures
We have carried out an evaluation of the effectiveness of the design and operation of our disclosure controls and
procedures (as such term is defined in Rules 13a-15(e) and 15d-15(e) under the Exchange Act) under the supervision and
the participation of the company’s management, which is responsible for the management of the internal controls, and
which includes our Chief Executive Officer and Chief Financial Officer (our principal executive officer and principal
financial officer, respectively). The term “disclosure controls and procedures”, as defined in Rules 13a-15(e) and 15d-15(e)
under the Securities Exchange Act of 1934, means controls and other procedures of a company that are designed to ensure
that information required to be disclosed by a company in the reports that it files or submits under the Securities Exchange
Act of 1934 is recorded, processed, summarized and reported within the time periods specified in the Securities and
Exchange Commission’s rules and forms.
Disclosure controls and procedures include, without limitation, controls and procedures designed to ensure that
information required to be disclosed by a company in the reports that it files or submits under the Securities Exchange Act
of 1934 is accumulated and communicated to the company’s management, including its principal executive and principal
financial officers, as appropriate to allow timely decisions regarding required disclosure. There are inherent limitations to
the effectiveness of any system of disclosure controls and procedures, including the possibility of human error and the
circumvention or overriding of the controls and procedures. Accordingly, even effective disclosure controls and procedures
can only provide reasonable assurance of achieving their control objectives. Based upon our evaluation of our disclosure
controls and procedures as of December 31, 2021, our Chief Executive Officer and Chief Financial Officer concluded that,
as of such date, our disclosure controls and procedures were effective at a reasonable level of assurance.
Management’s Annual Report on Internal Control Over Financial Reporting
Internal control over financial reporting refers to the process designed by, or under the supervision of, our Chief
Executive Officer and Chief Financial Officer, and effected by our board of directors, management and other personnel, 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, and includes those policies and procedures
that: (1) pertain to the maintenance of records that in reasonable detail accurately and fairly reflect the transactions and
dispositions of our assets; (2) provide reasonable assurance that transactions are recorded as necessary to permit
preparation of financial statements in accordance with generally accepted accounting principles, and that our receipts and
expenditures are being made only in accordance with authorizations of our management and board of directors; and
(3) 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.
Internal control over financial reporting cannot provide absolute assurance of achieving financial reporting
objectives because of its inherent limitations. Internal control over financial reporting is a process that involves human
diligence and compliance and is subject to lapses in judgment and breakdowns resulting from human failures. Internal
control over financial reporting also can be circumvented by collusion or improper management override. Because of such
limitations, there is a risk that material misstatements may not be prevented or detected on a timely basis by internal
control over financial reporting. However, these inherent limitations are known features of the financial reporting process.
Therefore, it is possible to design into the process safeguards to reduce, though not eliminate, this risk.
Management is responsible for establishing and maintaining adequate internal control over our financial reporting,
as such term is defined in Rules 13a-15(f) and 15d-15(e) under the Exchange Act. Under the supervision and with the
participation of our management, including our Chief Executive Officer and Chief Financial Officer, we
148
Table of Contents
conducted an evaluation of the effectiveness of our internal control over financial reporting. Management has used the
framework set forth in the report entitled “Internal Control—Integrated Framework (2013)” published by the Committee
of Sponsoring Organizations of the Treadway Commission to evaluate the effectiveness of our internal control over
financial reporting. Based on its evaluation, management has concluded that our internal control over financial reporting
was effective as of December 31, 2021, the end of our most recent fiscal year.
Our independent registered public accounting firm has not performed an evaluation of our internal control over
financial reporting during any period in accordance with the provisions of the Sarbanes-Oxley Act. For as long as we
remain a “smaller reporting company” as defined in Rule 12b-2 under the Exchange Act, we intend to take advantage of
the exemption permitting us not to comply with the requirement that our independent registered public accounting firm
provide an attestation on the effectiveness of our internal control over financial reporting.
Changes in Internal Control over Financial Reporting
There were no changes in our internal control over financial reporting (as defined in Exchange Act Rule 13a-
15(f)) that occurred during the three months ended December 31, 2021 that have materially affected, or are reasonably
likely to materially affect, our internal control over financial reporting.
ITEM 9B. OTHER INFORMATION
None.
ITEM 9C. DISCLOSURE REGARDING FOREIGN JURISDICTIONS THAT PREVENT INSPECTIONS
Not applicable.
149
Table of Contents
ITEM 10. DIRECTORS, EXECUTIVE OFFICERS AND CORPORATE GOVERNANCE
Board of Directors
PART III
Set forth below are the names and certain biographical information about each member of our board of directors,
including their ages as of March 1, 2022. The information presented includes each director’s principal occupation and
business experience for at least the past five years and the names of other public companies of which he or she has served
as a director during the past five years.
Name
Daniel Burgess(1)(3)
Theodore Schroeder
Colin Broom, MD
Carrie Bourdow(2)(3)
Mark Corrigan(1)
Lisa Dalton(2)
Charles Rowland, Jr.(2)
Stephen Webster(1)(3)
Steven Gelone
Age
60
66
66
59
64
49
63
61
54
Position
Director, Chairman of the Board
Director, Chief Executive Officer
Director
Director
Director
Director
Director
Director
Director, President and Chief Operating Officer
(1) Member of the audit committee.
(2) Member of the compensation committee.
(3) Member of the nominating and corporate governance committee.
Daniel Burgess has served on our board of directors since June 23, 2017. Mr. Burgess was a member of the
supervisory board of Nabriva Austria and served as its chairman from October 2016 until the redomiciliation to Ireland.
Mr. Burgess has been a venture partner at SV Health Investors (SV) since 2014. Mr. Burgess is currently the chairman of
the board and chief executive officer of Pulmocide Ltd., a private biopharmaceutical company, a position he has held since
May 2021. Mr. Burgess served as the part-time president and chief executive officer of Therini Bio, Inc., a private
therapeutics company, from May 2019 to December 2021. He was previously president and chief executive officer of
Rempex Pharmaceuticals, an antibiotics company he co-founded in 2011 and that was subsequently sold to The Medicines
Company (now Novartis AG) in 2013. Prior to this, Mr. Burgess was president and chief executive officer of Mpex
Pharmaceuticals from 2007 until its acquisition by Aptalis Inc. (now AbbVie Inc.) in 2011. Prior to his time at Mpex, Mr.
Burgess served in various senior operating roles for other biotechnology companies. In addition, he serves as a member of
the boards of directors of Cidara Therapeutics, Inc., a public biotechnology company; Arbutus Biopharma Corp., a public
biotechnology company; and several private healthcare companies. Mr. Burgess was a member of the board of directors of
Santarus, Inc., from 2004 until its acquisition in 2014 by Salix Pharmaceuticals Inc., a publicly traded pharmaceutical
company. He received his B.A. in economics from Stanford University and an M.B.A. from Harvard University. We
believe Mr. Burgess is qualified to serve as a director because of his expertise and experience as an executive in the
pharmaceutical industry, his service on other boards of directors and his educational background.
Theodore Schroeder has served on our board of directors and as chief executive officer since July 24, 2018.
During the last 30 years, Mr. Schroeder has been focused on drug development and commercialization in both large and
small pharmaceutical companies. Most recently, he served as president, chief executive officer and director of Zavante
Therapeutics from June 2015 until its acquisition by Nabriva Therapeutics in July 2018. Mr. Schroeder co-founded
Cadence Pharmaceuticals in 2004 and previously held leadership roles at Elan Pharmaceuticals, Dura Pharmaceuticals and
earlier in his career, Bristol-Myers Squibb. He currently serves on the board of Cidara Therapeutics, and Otonomy, Inc. and
formerly was a member of the board of Collegium Pharmaceutical. He is a former chair of BIOCOM, the California life
sciences trade association and in 2014, he was named the EY Entrepreneur of the Year for the San Diego region and was
listed as a national finalist. He received a bachelor’s degree in management from Rutgers University. We
150
Table of Contents
believe Mr. Schroeder is qualified to serve as a director because of his expertise and experience as an executive in the
pharmaceutical industry, his service on other boards of directors and his educational background.
Colin Broom has served on our board of directors since June 23, 2017. Dr. Broom has served as the chief
executive officer and a member of the board of directors of Pulmotect, Inc., a private biotechnology company, since
September 2019. Dr. Broom was previously our chief executive officer from April 12, 2017 until July 24, 2018, and the
chief executive officer of Nabriva Austria from August 2014 until the redomiciliation to Ireland. Prior to joining Nabriva
Austria, he served as chief scientific officer at ViroPharma Incorporated from 2004 until it was acquired by Shire plc in
2014. Dr. Broom served as vice president of clinical development and medical affairs in Europe for Amgen Inc. from 2000
to 2003 and previously held several leadership positions with Hoechst Marion Roussel (now Sanofi), SmithKline Beecham
and Glaxo (now GlaxoSmithKline) . Dr. Broom served as a member of the board of directors of NPS Pharmaceuticals, Inc.
from 2009 until its acquisition by Shire in 2015. He is a member of the U.K. Royal College of Physicians and a fellow of
the Faculty of Pharmaceutical Medicine. Dr. Broom received his B.Sc. from University College, London and M.B.B.S.
from St. George’s Hospital Medical School, London. We believe that Dr. Broom is qualified to serve as a director due to
his extensive experience in all stages of drug development and commercialization.
Carrie Bourdow has served on our board of directors since June 23, 2017. Ms. Bourdow has been the president,
the chief executive officer, and member of the board of directors of Trevena, Inc., a publicly-traded biopharmaceutical
company, since October 2018. She has served in various senior positions at Trevena since May 2015. She joined Trevena
as chief commercial officer and was appointed executive vice president and chief operating officer in January 2018. Prior
to joining Trevena, Ms. Bourdow was vice president of marketing at Cubist Pharmaceuticals, Inc., from 2013 until its
acquisition by Merck & Co., Inc. in January 2015. At Cubist, Ms. Bourdow led launch strategy, marketing, reimbursement,
and operations for acute care hospital pharmaceuticals. Prior to Cubist, Ms. Bourdow served for more than 20 years at
Merck & Co., Inc., where she held positions of increasing responsibility across multiple therapeutic areas. Ms. Bourdow
also serves as a director of Sesen Bio, Inc., a publicly traded pharmaceutical company. Ms. Bourdow holds a B.A. degree
from Hendrix College and an M.B.A. from Southern Illinois University. We believe Ms. Bourdow is qualified to serve as a
director due to her extensive experience in the biopharmaceutical industry, including her experience with anti-infectives
and with the commercialization of new drugs.
Mark Corrigan has served on our board of directors since June 2, 2021. Dr. Corrigan previously served on our
board of directors from June 23, 2017 to May 26, 2020, and prior to the redomiciliation to Ireland, Dr. Corrigan served on
the supervisory board of Nabriva Austria from October 2016 until the redomiciliation to Ireland. Dr. Corrigan was most
recently the chief executive officer of Correvio Pharma Corporation (formerly Cardiome Pharma), a public
biopharmaceutical company, from March 2019 until May 2021. From April 2016 until March 2019, Dr. Corrigan was
founder and president of research and development of Tremeau Pharmaceuticals. Dr. Corrigan served as president and chief
executive officer of Zalicus, Inc. from January 2010 until July 2014. Previously, Dr. Corrigan was executive vice president
of research and development at the specialty pharmaceutical company Sepracor Inc., and prior to this, he spent 10 years
with Pharmacia & Upjohn, most recently as group vice president of Global Clinical Research and Experimental Medicine.
Dr. Corrigan currently serves on the boards of directors of Wave Biosciences, a public biopharmaceutical company,
Tremeau Pharmaceuticals, a private company, and Exacis BioTherapeutics, a private biopharmaceutical company. He
previously served on the boards of directors of Correvio Pharma Corporation, Novelin Therapeutics, Inc., BlackThorn
Therapeutics, Inc., Cubist Pharmaceuticals, Inc., CoLucid Pharmaceuticals, Inc., Avanair Pharmaceuticals, Inc., and
EPIRUS Biopharmaceuticals, Inc., where he served as chairman of the board of directors. Dr. Corrigan holds an M.D. from
the University of Virginia and received specialty training in psychiatry at Maine Medical Center and Cornell University.
We believe Dr. Corrigan is qualified to serve as a director due to his extensive experience in the biopharmaceutical industry
as both an executive and a board member and because of his education and training.
Lisa Dalton has served on our board of directors since June 2, 2021. Ms. Dalton has served as the chief people
officer at Spark Therapeutics, a member of the Roche Group, since July 2014. She previously served as vice president,
human resources at Shire. Ms. Dalton received her M.B.A. from Rutgers University School of Business and B.A. from
Pennsylvania State University. We believe Ms. Dalton is qualified to serve as a director because of her expertise and
experience as an executive in the pharmaceutical industry.
151
Table of Contents
Steven Gelone has served on our board of directors since March 10, 2021 and as our president and chief operating
officer since July 24, 2018. Dr. Gelone previously served as Nabriva Austria’s chief development officer and head of
business development from 2014 until the redomiciliation to Ireland, our chief development officer from the
redomiciliation to Ireland until June 30, 2017 and our chief scientific officer from June 30, 2017 until July 24, 2018. Prior
to joining Nabriva Austria, he served as head of clinical research and development at Spark Therapeutics, Inc. in 2014 and
vice president of clinical and preclinical development at ViroPharma Incorporated from 2005 to 2014. Dr. Gelone also
served as director of medical affairs at Vicuron Pharmaceuticals from 2002 to 2003 and director of clinical pharmacology
and experimental medicine at GlaxoSmithKline Pharmaceuticals from 2000 to 2002. Dr. Gelone received his B.S. Pharm.
and Pharm.D. from Temple University. We believe Dr. Gelone is qualified to serve as a director due to his extensive
experience in the biopharmaceutical industry as an executive and because of his education and training.
Charles A. Rowland, Jr. has served on our board of directors since June 23, 2017. Mr. Rowland previously
served on the supervisory board of Nabriva Austria from January 2015 until the redomiciliation to Ireland. Mr. Rowland
served as chief executive officer of Aurinia Pharmaceuticals Inc. from April 2016 to January 2017. Mr. Rowland
previously served as vice president and chief financial officer of ViroPharma Incorporated from 2008 until it was acquired
by Shire plc in 2014. Prior to joining ViroPharma, Mr. Rowland served as executive vice president and chief financial
officer, as well as interim co-chief executive officer, for Endo Pharmaceuticals Inc. from 2006 to 2008 and chief financial
officer at Biovail Corporation from 2004 to 2006. He previously held finance and operational positions of increasing
responsibility at Breakaway Technologies, Inc., Pharmacia, Novartis International AG and Bristol-Myers Squibb Company.
Mr. Rowland currently serves as a member of the board of directors for Blueprint Medicines Corporation, a public
biopharmaceutical company, Viking Therapeutics, a public, clinical-stage biopharmaceutical company, and Orchard
Therapeutics, a public, clinical-stage biopharmaceutical company. In addition, Mr. Rowland serves as a member of the
board of directors for Generation Bio, a public biopharmaceutical company. Previously, he served on the board of directors
at Idenix Pharmaceuticals, Inc., Vitae Pharmaceuticals, Inc., Bind Therapeutics Inc. and Aurinia Pharmaceuticals Inc. Mr.
Rowland received his B.S. from Saint Joseph’s University and M.B.A. from Rutgers University. We believe that Mr.
Rowland is qualified to serve as a director due to his extensive experience in pharmaceutical operations and all areas of
finance and accounting.
Stephen Webster has served on our board of directors since June 23, 2017. Mr. Webster previously served on the
supervisory board of Nabriva Austria from October 2016 until the redomiciliation to Ireland. Mr. Webster served as the
chief financial officer of Spark Therapeutics from July 2014 until its acquisition by Roche Holdings, Inc. in December
2019. He was previously senior vice president and chief financial officer of Optimer Pharmaceuticals, Inc. from June 2012
until its acquisition by Cubist Pharmaceuticals in November 2013. Prior to this, Mr. Webster served as senior vice president
and chief financial officer of Adolor Corporation, also acquired by Cubist, from 2008 to 2011. Previously, Mr. Webster
served as managing director, Investment Banking Division, Health Care Group for Broadpoint Capital Inc. (formerly First
Albany Capital) . He also was a co-founder and served as president and chief executive officer of Neuronyx, Inc. Prior to
this, Mr. Webster held positions of increasing responsibility, including as director, Investment Banking Division, Health
Care Group, for PaineWebber Incorporated. Mr. Webster is currently a member of the board of directors of TCR2
Therapeutics, Inc., Cullinan Oncology, Inc., and NextCure, Inc. He was a member of the board of directors of Viking
Therapeutics, Inc., a public biopharmaceutical company, from 2014 to 2020. Mr. Webster holds an A.B. in economics from
Dartmouth College and an M.B.A. from the University of Pennsylvania. We believe that Mr. Webster is qualified to serve
as a director due to his extensive experience in the biopharmaceutical industry, particularly his service as a chief financial
officer and in other executive management roles.
Board Committees
Our board of directors has established an audit committee, a compensation committee and a nominating and
corporate governance committee, each of which operates under a charter that has been approved by our board. Copies of
the committee charters are posted under the heading “Corporate Governance” on the Investor section of our website, which
is located at http://investors.nabriva.com.
152
Table of Contents
Audit Committee
Our audit committee consists of Mark Corrigan, Daniel Burgess and Stephen Webster. Stephen Webster is the
chair of the audit committee. The audit committee oversees our accounting and financial reporting processes and the audits
of our consolidated financial statements. The audit committee is responsible for, among other things:
● making recommendations to our board regarding the ratification by the annual general meeting of
shareholders of our independent auditors;
● overseeing the work of the independent auditors, including resolving disagreements between management
and the independent auditors relating to financial reporting;
● pre-approving all audit and non-audit services permitted to be performed by the independent auditors;
● reviewing the independence and quality control procedures of the independent auditors;
● reviewing and approving all proposed related-party transactions;
● discussing the annual audited consolidated and statutory financial statements with management;
● annually reviewing and reassessing the adequacy of our audit committee charter;
● meeting separately with the independent auditors to discuss critical accounting policies, recommendations on
internal controls, the auditor’s engagement letter and independence letter and other material written
communications between the independent auditors and the management; and
● attending to such other matters as are specifically delegated to our audit committee by our board from time to
time.
Our Board has determined that Stephen Webster is an “audit committee financial expert” as defined in the
applicable SEC rules.
Compensation Committee
Our compensation committee consists of Charles A. Rowland, Jr., Lisa Dalton and Carrie Bourdow. Charles A.
Rowland, Jr. is the chair of the compensation committee. The compensation committee assists the board in reviewing and
approving or recommending our compensation structure, including all forms of compensation relating to our directors and
management. The compensation committee is responsible for, among other things:
● reviewing and making recommendations to the board with respect to compensation of our board of directors
and management;
● reviewing and approving the compensation, including equity compensation, change-of-control benefits and
severance arrangements, of our chief executive officer, chief financial officer and such other members of our
management as it deems appropriate;
● overseeing the evaluation of our management;
● reviewing periodically and making recommendations to our board with respect to any incentive
compensation and equity plans, programs or similar arrangements;
● exercising the rights of our board under any equity plans, except for the right to amend any such plans unless
otherwise expressly authorized to do so; and
153
Table of Contents
● attending to such other matters as are specifically delegated to our compensation committee by our board
from time to time.
Nominating and Corporate Governance Committee
Our nominating and corporate governance committee consists of Daniel Burgess, Carrie Bourdow and Stephen
Webster. Daniel Burgess is the chair of the nominating and corporate governance committee. The nominating and corporate
governance committee assists the board in selecting individuals qualified to become our directors and in determining the
composition of the board and its committees. The nominating and corporate governance committee is responsible for,
among other things:
● recommending to the board persons to be nominated for election or re-election to the board at any meeting of
shareholders;
● overseeing the board’s annual review of its own performance and the performance of its committees; and
● developing and recommending to the board a set of corporate governance guidelines.
Executive Officers
The following table sets forth certain information regarding our executive officers, including their ages as of
March 1, 2022:
Name
Theodore Schroeder
J. Christopher Naftzger
Steven Gelone
Christine Guico-Pabia
Daniel Dolan
Age
66
54
54
59
45
Position
Chief Executive Officer
General Counsel and Secretary
President and Chief Operating Officer
Chief Medical Officer
Chief Financial Officer
In addition to the biographical information for Mr. Schroeder and Dr. Gelone, which is set forth above under
“Board of Directors”, set forth below is certain biographical information about Dr. Guico-Pabia, and Messrs. Naftzger and
Dolan:
J. Christopher Naftzger has served as our general counsel and secretary since September 1, 2021. Previously,
Mr. Naftzger served as General Counsel and Corporate Secretary of Krystal Biotech, an emerging-stage, gene therapy
company, from February 2020 to May 2021. Before joining Krystal, he was Vice President, Deputy General Counsel and
Assistant Secretary of Nabriva Therapeutics from January 2017 to January 2020. Prior to Nabriva, Mr. Naftzger served as
Vice President, General Counsel, Chief Compliance Officer, and Secretary of Unilife Medical Solutions, a developer and
manufacturer of innovative drug delivery systems. Mr. Naftzger also held senior in-house counsel positions with
Chesapeake Corporation and Koch Industries, and was a corporate partner with Blank Rome LLP in Washington, DC. Mr.
Naftzger obtained his undergraduate degree from Hampden-Sydney College and his law degree from the Willamette
University College of Law.
Christine Guico-Pabia has served as our chief medical officer since October 1, 2021. Dr. Guico-Pabia brings
over 30 years of global biopharmaceutical experience and extensive expertise in every stage of drug development,
pharmacoeconomics and outcomes research, and medical affairs. Most recently, she was Vice President, Head of Clinical
Development and Medical Affairs of Metagenics from 2014 to 2021. Dr. Guico-Pabia previously held leadership positions
at small startups and large multinational companies including McKesson, Merck, Wyeth, and Pfizer. Dr. Guico-Pabia
completed her MD at the University of Santo Tomas Medical School in Manila, Philippines, obtained her MBA from
Temple University Fox School of Business, and her MPH from Johns Hopkins University Bloomberg School of Public
Health.
154
Table of Contents
Daniel Dolan has served as our chief financial officer since March 2021. Mr. Dolan previously served as Vice
President of Finance at Radius Health, Inc., or Radius, a commercial-stage biopharmaceutical company, from July 2017 to
January 2021. He also acted as principal financial officer and principal accounting officer of Radius from September 2020
to December 2020. Prior to joining Radius, Mr. Dolan worked at Shire plc from September 2005 to July 2017, where he
held financial management positions of increasing responsibility, including Vice President of Finance, Global Product
Strategy from May 2016 to July 2017 and Senior Finance Director, GI/Internal Medicine from May 2013 to May 2016. Mr.
Dolan received his M.B.A. and B.S. from Widener University.
Code of Business Conduct and Ethics
Our Code of Business Conduct and Ethics is applicable to all of our directors, officers and employees and is
available on our website at http://investors.nabriva.com/corporate-governance/governance-overview. Our Code of Business
Conduct and Ethics provides that our directors, officers and employees are expected to avoid any action, position or
interest that conflicts with the interests of our company or gives the appearance of a conflict. We expect that any
amendment to this code, or any waivers of its requirements, will be disclosed on our website. Information contained on, or
that can be accessed through, our website is not incorporated by reference into this document, and you should not consider
information on our website to be part of this document.
Delinquent Section 16(a) Reports
Section 16(a) of the Exchange Act requires our directors, executive officers and persons who own more than 10%
of our ordinary shares to file an initial report of ownership on Form 3 and changes in ownership on Form 4 or Form 5 with
the SEC. Such officers, directors and 10% shareholders are also required by SEC rules to furnish us with copies of any
Forms 3, 4 or 5 that they file. The SEC rules require us to disclose late filings of initial reports of stock ownership and
changes in share ownership by our directors, executive officers and 10% shareholders.
Based solely on a review of copies of Forms 3, 4 and 5 furnished to us by reporting persons and any written
representations furnished by certain reporting persons, we believe that during the fiscal year ended December 31, 2021, all
Section 16(a) filing requirements applicable to our directors, executive officers and 10% shareholders were completed in a
timely manner other than (1) Forms 4 for each of Theodore Schroeder, Steven Gelone and Robert Crotty, in each case filed
on April 8, 2021 and relating to the withholding of securities for tax purposes on February 6, 2021 and March 6, 2021 in
connection with the vesting of restricted stock units and (2) a Form 3 for J. Christopher Naftzger, filed on September 15,
2021.
ITEM 11. EXECUTIVE COMPENSATION
The following discussion provides the amount of compensation paid, and benefits in-kind granted, by us and our
subsidiaries to the members of our board of directors and certain executives for services provided in all capacities to us and
our subsidiaries for the year ended December 31, 2021.
Executive and Director Compensation Processes
Our executive compensation program is administered by the compensation committee of our board of directors,
subject to the oversight and approval of our full board of directors. Our compensation committee reviews our executive
compensation practices on an annual basis and based on this review approves, or, as appropriate, makes recommendations
to our board of directors for approval of our executive compensation program.
In designing our executive compensation program, our compensation committee considers publicly available
compensation data for national and regional companies in the biotechnology/pharmaceutical industry to help guide its
executive compensation decisions at the time of hiring and for subsequent adjustments in compensation. Since 2016, our
compensation committee has retained Radford, a part of Aon Hewitt, a business unit of Aon plc, as its independent
compensation consultant, to provide comparative data on executive compensation practices in our industry and to advise on
our executive compensation program generally. The committee also has retained Radford for guidelines and review
155
Table of Contents
of non-employee director compensation. Although our compensation committee considers the advice and guidelines of
Radford as to our executive compensation program, our compensation committee ultimately makes its own decisions about
these matters. In the future, we expect that our compensation committee will continue to engage independent compensation
consultants to provide additional guidance on our executive compensation programs and to conduct further competitive
benchmarking against a peer group of publicly traded companies.
Our director compensation program is administered by our board of directors with the assistance of the
compensation committee. The compensation committee conducts an annual review of director compensation and makes
recommendations to the board of directors with respect thereto.
Summary Compensation Table
Our “named executive officers” for the year ended December 31, 2021 were as follows: Mr. Schroeder, our chief
executive officer, Dr. Gelone, our president and chief operating officer and Mr. Dolan, our chief financial officer. The
following table sets forth information regarding compensation awarded to, earned by or paid to our named executive
officers for the periods presented.
Salary($) Bonus ($)(1)
Name and principal position Year
2021
Theodore Schroeder(5)
2020
Chief Executive Officer
Steven Gelone
President and Chief
Operating Officer
2021
2020
594,170
576,800
500,947
486,300
Share
Awards
($)(2)
307,850
464,130
—
—
225,000
—
611,349
270,863
Option
Awards
($)(2)
—
339,625
—
231,493
Non-Equity
Incentive Plan
Compensation Compensation
All Other
($) (3)
302,993
242,256
191,590
153,185
($)(4)
Total ($)
1,237,300
1,654,570
32,287
31,759
14,138
12,675
1,543,024
1,154,516
Daniel Dolan(6)
Chief Financial Officer
2021
271,250
—
—
110,000
93,500
26,690
501,440
(1) The amount reported in the “Bonus” column represents a $225,000 retention bonus awarded to Dr. Gelone in 2021,
which shall be paid in March 2022.
(2) The amounts reported in the “Share Awards” and “Option Awards” columns reflect the aggregate grant-date fair value
of share-based compensation awarded during the year computed in accordance with the provisions of ASC Topic 718.
See Note 10 to the consolidated financial statements regarding assumptions underlying the valuation of equity awards.
(3) The amounts reported in the “Non-Equity Incentive Plan Compensation” column represent awards to our named
executive officers under our annual cash bonus program.
(4) The compensation included in the “All Other Compensation” column consists of amounts we contributed to our
401(k) plan and medical insurance premiums paid by us on behalf of such individual.
(5) Mr. Schroeder declined to accept his bonus payout for 2021.
(6) Mr. Dolan commenced employment with us in March 2021.
Narrative Disclosure to Summary Compensation Table
Base Salary
In 2021, we paid annualized base salaries of $594,104 to Mr. Schroeder, $500,889 to Dr. Gelone and $330,000 to
Mr. Dolan. In 2020, we paid annualized base salaries of $576,800 to Mr. Schroeder and $486,300 to Dr. Gelone.
156
Table of Contents
In January 2022, our board of directors, following approval and recommendation from the compensation
committee and consistent with the recommendations of the compensation committee’s independent compensation
consultant, approved an increase to the base salaries of our named executive officers for 2022 as follows: $515,916 for
Dr. Gelone and $363,000 for Mr. Dolan. Our board of directors also approved of an increase in base salary for Mr.
Schroeder, who declined to accept an increase to his base salary. The board also approved the 2022 base salary for
Mr. Naftzger, our general counsel and secretary, of $367,500, and Dr. Guico-Pabia, our chief medical officer, of $428,480,
which was also consistent with the recommendation of the compensation committee’s independent consultant.
None of our named executive officers is currently party to an employment agreement or other agreement or
arrangement that provides for automatic or scheduled increases in base salary.
Annual Performance-Based Compensation
Our executive officers, which include the named executive officers, participate in our performance-based bonus
program. All annual cash bonuses for our executives under the performance-based bonus program are tied to the
achievement of strategic and operational corporate goals for the company, which are set by the compensation committee
and approved by the board. There are no discretionary individual goals under the bonus program. The 2021 strategic and
operational goals for Nabriva related to the following objectives:
● commercialization of our products;
● finance, specifically fundraising;
● regulatory approvals;
● business development; and
● chemistry, manufacturing, and control (CMC).
Under their respective employment agreements, the annual target bonus for Mr. Schroeder is 60% of his current
base salary, the annual target bonus for Dr. Gelone is 45% of his current base salary and the annual target bonus for each of
Dr. Guico-Pabia, Mr. Naftzger and Mr. Dolan is 40% of their respective current base salaries.
At a meeting held in January 2022, our compensation committee reviewed the accomplishments of the named
executive officers as measured against the aforementioned 2021 goals. The compensation committee reviewed whether
each goal had been obtained and the weight such goals should be given in determining the bonus payout for 2021
performance. Based on its review, the compensation committee recommended a 85% payout of the target bonuses for 2021
for Mr. Schroeder, Dr. Gelone and Mr. Dolan. Mr. Schroeder declined to accept his bonus payout for 2021. Accordingly,
the 2021 bonus payouts which were paid in February 2022, were $191,590 for Dr. Gelone and $93,500 for Mr. Dolan.
Equity Incentive Awards
We believe that equity grants provide our executive officers with a strong link to our long-term performance,
create an ownership culture and help to align the interests of our executive officers and our shareholders. In addition, we
believe that equity grants with a time-based vesting feature promote executive retention because this feature incents our
executive officers to remain in our employment during the vesting period. Accordingly, our board of directors periodically
reviews the equity incentive compensation of our executive officers, which includes the named executive officers, and from
time to time may grant equity incentive awards to them in the form of stock options or restricted stock units, or RSUs. We
also generally make stock option grants to new executive officers in connection with the commencement of their
employment.
157
Table of Contents
Since our initial public offering, we have granted stock options with exercise prices that are set at no less than the
fair market value of the underlying award on the date of grant, as determined by reference to the trading price of our
ordinary shares on Nasdaq, and approved by our compensation committee or our board.
The following table sets forth the number of our ordinary shares issuable upon vesting of the share awards granted
to our named executive officers in 2022:
Name
Theodore Schroeder
Steven Gelone
Daniel Dolan
Option Award
(#)
239,800
93,400
83,200
RSU Award
(#)
119,900
46,700
41,600
On January 28, 2021, our board of directors granted share option awards, as well as restricted share share units, or
RSUs, under the 2020 Share Incentive Plan to Mr. Schroeder, Dr. Gelone and Mr. Dolan, in each case, subject to
shareholder approval of an amendment to increase the number of ordinary shares authorized for issuance under our 2020
Share Incentive Plan. The share option awards and RSUs vest over a four year period beginning on January 28, 2022, with
25% of the option vesting upon the first anniversary of the grant date and on a monthly pro rata basis thereafter over the
remaining three years. Twenty five percent (25%) of the RSUs vest annually over the four year vesting period. If
shareholder approval of the amendment to the 2020 Share Incentive Plan is not obtained, the options will remain
outstanding and will convert into cash-settled share appreciation rights. If shareholder approval of the amendment to the
2020 Share Incentive Plan is not obtained, each of the RSUs will represent the right to receive the economic equivalent of
one ordinary share in cash on the applicable vesting date.
The following table sets forth the number of our ordinary shares issuable upon exercise or vesting of the share
awards granted to our named executive officers in 2021:
Name
Theodore Schroeder
Steven Gelone
Daniel Dolan
Option Award
(#)
—
—
100,000
RSU Award
(#)
117,500
333,197
—
On January 29, 2021, our board of directors granted RSUs under the 2020 Share Incentive Plan to Mr. Schroeder
and Dr. Gelone. The RSUs vest over a four year period beginning on January 29, 2021. Twenty five percent (25%) of the
RSUs vest annually over the four year vesting period. Mr. Dolan´s option to purchase 100,000 of our ordinary shares vests
over four years, with 25% of the options vesting on March 31, 2022, and the remaining 75% of the option vesting on a
monthly pro rata basis over the remaining three years of the vesting period. The option was awarded to Mr. Dolan in
connection with the commencement of his employment.
As previously disclosed, our board of directors in 2020 awarded Dr. Gelone 23,250 options and 11,625 RSUs that
were subject to performance conditions related to the commercial performance of the company and life cycle management
of our product and product candidate portfolio. The vesting of these awards continues to be subject to the achievement of
performance conditions, which, due to business disruption caused by the COVID-19 global pandemic, were extended and
modified in March 2022.
158
Table of Contents
Outstanding Equity Awards as of December 31, 2021
The following table sets forth information regarding outstanding stock options and RSUs held by our named
executive officers as of December 31, 2021:
Option Awards
Number of
securities
underlying
unexercised
options
(#)
Number of
securities
underlying
unexercised
options
(#)
exercisable unexercisable
Option
exercise
price
($)
Option
expiration
date
Equity incentive
plan awards:
Number of
unearned shares,
units or other
rights that have
not vested
(#)
Equity incentive
plan awards:
Market or
payout value of
unearned shares,
units or other
rights that have
not vested
($)
72,603
31,339
24,348
8,879
5,590
11,300
9,791
6,619
624
20,299
10,979
—
—
12,397 (1)
11,641 (2)
44,402 (3)
35.30 07/25/2028
19.00
13.50
01/31/2029
02/06/2030
— (4)
— (5)
— (6)
209 (7)
1,131 (8)
126 (9)
7,541 (2)
20,021 (3)
23,250 (10)
100,000 (11)
72.05 07/05/2025
83.40 02/05/2026
85.00 02/07/2027
64.70 01/31/2028
35.30 07/25/2028
24.90 08/02/2028
19.00 01/31/2029
13.50
5.30
1.66
02/06/2030
09/25/2030
03/31/2031
4,761 (12)
18,623 (13)
117,500 (14)
3,084 (12)
8,396 (13)
42,500 (14)
11,625 (15)
290,697 (16)
—
—
—
—
—
2,852
11,155
70,383
1,847
5,029
25,458
6,963
174,128
—
—
—
—
—
Name
Theodore
Schroeder
Steven
Gelone
Daniel Dolan
(1) Mr. Schroeder’s option to purchase 85,000 of our ordinary shares vests over four years, with 25% of the options
vesting on July 25, 2019, and the remaining 75% of the option vesting on a monthly pro rata basis over the remaining
three years of the vesting period.
(2) Mr. Schroeder’s and Dr. Gelone’s option to purchase ordinary shares vests over four years, with 25% of the options
vesting on January 31, 2020, and the remaining 75% of the option vesting on a monthly pro rata basis over the
remaining three years of the vesting period.
(3) Mr. Schroeder’s and Dr. Gelone’s option to purchase ordinary shares vests over four years, with 25% of the options
vesting on February 6, 2021, and the remaining 75% of the option vesting on a monthly pro rata basis over the
remaining three years of the vesting period.
(4) Dr. Gelone’s option to purchase 8,879 of our ordinary shares vests over four years, with 25% of the options vesting on
May 31, 2016, and the remaining 75% of the option vesting on a monthly pro-rata basis over the remaining three years
of the vesting period.
(5) Dr. Gelone’s option to purchase 5,590 of our ordinary shares vests over four years, with 25% of the options vesting on
February 28, 2017, and the remaining 75% of the option vesting on a monthly pro-rata basis over the remaining three
years of the vesting period.
(6) Dr. Gelone’s option to purchase 11,300 of our ordinary shares vests over four years, with 25% of the options vesting
on February 28, 2018, and the remaining 75% of the option vesting on a monthly pro rata basis over the remaining
three years of the vesting period.
159
Table of Contents
(7) Dr. Gelone’s option to purchase 10,000 of our ordinary shares vests over four years, with 25% of the options vesting
on January 31, 2019, and the remaining 75% of the option vesting on a monthly pro rata basis over the remaining three
years of the vesting period.
(8) Dr. Gelone’s option to purchase 7,750 of our ordinary shares vests over four years, with 25% of the options vesting on
July 25, 2019, and the remaining 75% of the option vesting on a monthly pro-rata basis over the remaining three years
of the vesting period.
(9) Dr. Gelone’s option to purchase 750 of our ordinary shares vests over four years, with 25% of the options vesting on
August 2, 2019, and the remaining 75% of the option vesting on a monthly pro-rata basis over the remaining three
years of the vesting period.
(10) Dr. Gelone’s option to purchase ordinary shares is subject to the commercial performance and life cycle management
of the product and product candidate portfolio.
(11) Mr. Dolan´s option to purchase 100,000 of our ordinary shares vests over four years, with 25% of the options vesting
on March 31, 2022, and the remaining 75% of the option vesting on a monthly pro rata basis over the remaining three
years of the vesting period.
(12) Mr. Schroeder’s and Dr. Gelone’s RSUs vest over four years, with 25% of the RSUs vesting on January 31, 2020, and
the remaining 75% of the RSUs vesting on a monthly pro-rata basis over the remaining three years of the vesting
period.
(13) Mr. Schroeder’s and Dr. Gelone’s RSUs vest over four years, with 25% of the RSUs vesting on February 6, 2021, and
the remaining 75% of the RSUs vesting on a monthly pro-rata basis over the remaining three years of the vesting
period.
(14) Mr. Schroeder’s and Dr. Gelone’s RSUs vest over four years, with 25% of the RSUs vesting on January 29, 2022 and
25% of the RSUs vesting annually over the remainder of the vesting period.
(15) Dr. Gelone’s vesting of the RSUs is subject to the commercial performance and life cycle management of the product
and product candidate portfolio.
(16) Dr. Gelone’s RSUs vest over two years, with 100% of the RSUs vesting on April 28, 2023.
160
Table of Contents
Employment Agreements with Executive Officers
Agreement with Theodore Schroeder, Chief Executive Officer and Director
Mr. Schroeder was appointed our chief executive officer and entered into an employment agreement dated and
effective as of July 23, 2018. He was appointed to our board on August 1, 2018. On March 10, 2021, we entered into an
amended and restated employment agreement with Mr. Schroeder, or the Schroeder Employment Agreement. The
Schroeder Employment Agreement continues until terminated in accordance with its terms, as described below.
Pursuant to the Schroeder Employment Agreement, Mr. Schroeder receives an annual base salary of $594,104 and
is eligible to receive an annual performance bonus targeted at 60% of his annual base salary, with the actual amount of such
bonus, if any, to be determined by the Board. Mr. Schroeder is also (1) eligible to receive equity awards at such times and
on such terms and conditions as the Board may determine and (2) entitled to participate in any and all benefit programs that
we make available to our executive officers, for which he may be eligible, under the plan documents governing such
programs.
The employment agreement, and Mr. Schroeder’s employment, may be terminated as follows: (1) upon Mr.
Schroeder’s death or “disability” (as disability is defined in his employment agreement); (2) at our election, with or without
“cause” (as cause is defined in his employment agreement); and (3) at Mr. Schroeder’s election, with or without “good
reason” (as good reason is defined in his employment agreement).
In the event of the termination of Mr. Schroeder’s employment by us without cause, including as a result of a
termination of his employment for good reason prior to, or more than twelve months following, a “change in control” (as
change in control is defined in the Schroeder Employment Agreement), Mr. Schroeder will be entitled to his base salary
that has accrued and to which he is entitled as of the termination date. In addition, subject to his execution and
nonrevocation of a release of claims in our favor and his continued compliance with his proprietary rights, non‑disclosure
and developments agreement with us, he is entitled to (1) continued payment of his base salary, in accordance with our
regular payroll procedures, for a period of 18 months (2) provided he is eligible for and timely elects to continue receiving
group medical insurance under COBRA and the payments would not result in the violation of nondiscrimination
requirements of applicable law, payment by us of the portion of health coverage premiums we pay for similarly‑situated,
active employees who receive the same type of coverage, for a period of up to 18 months following his date of termination,
(3) a lump sum payment equal to any earned but unpaid annual bonus for a previously completed calendar year, (4) a lump
sum payment equal to a prorated annual bonus for the year in which Mr. Schroeder’s employment is terminated based on
the number of days he provided services to us during the year in which his employment is terminated and (5) accelerated
vesting of his then‑unvested equity awards that are subject to time-based vesting and that would have vested within twelve
months of the termination date, whether granted under the 2017 Share Incentive Plan, 2020 Share Incentive Plan or any
successor equity incentive plan or as an inducement to his employment.
In the event of the termination of Mr. Schroeder’s employment by us without cause, including as a result of a
termination of his employment for good reason prior to, or by him for good reason within twelve months following a
change in control, subject (as described above with respect to certain payments), to his execution and nonrevocation of a
release of claims in our favor and his continued compliance with his proprietary rights, non‑disclosure and developments
agreement with us, Mr. Schroeder would be entitled to the same payments and benefits as described in the preceding
paragraph, except that, in lieu of a pro‑rated annual bonus payment, he would be entitled to receive a lump sum payment
equal to 100% of his target bonus for the year in which his employment is terminated and he shall also be entitled to full
vesting acceleration of his then‑unvested equity awards, whether granted under the 2017 Share Incentive Plan, 2020 Share
Incentive Plan or any successor equity incentive plan or as an inducement to his employment, such that his equity awards
become fully exercisable and non‑forfeitable as of the termination date, except as otherwise determined by the Board in the
case of awards subject to performance conditions.
161
Table of Contents
If Mr. Schroeder’s employment is terminated for any other reason, including as a result of his death or disability,
for cause, or voluntarily by Mr. Schroeder without good reason, our obligations under the Schroeder Employment
Agreement cease immediately, and Mr. Schroeder is only entitled to his base salary that has accrued and to which he is
entitled as of the termination date and solely if his employment is terminated as a result of his death or disability, subject to
his execution and nonrevocation of a release of claims in our favor and his continued compliance with his proprietary
rights, non‑disclosure and developments agreement with us, he or his estate, as applicable, is entitled to any earned but
unpaid annual bonus from a previously completed calendar year.
As a condition of his employment, Mr. Schroeder signed a proprietary rights, non‑disclosure and developments
agreement.
Agreements with Daniel Dolan, Chief Financial Officer, Steven Gelone, President, Chief Operating Officer and Director,
Christine Guico-Pabia, Chief Medical Officer and Christopher Naftzger, General Counsel and Secretary
Mr. Dolan was appointed our chief financial officer effective as of March 12, 2021, and entered into an
employment agreement dated and effective as of March 10, 2021, or the Dolan Employment Agreement. Dr. Gelone was
appointed our chief development officer and entered into an employment agreement dated and effective as of December 1,
2014, which was amended and restated as of May 26, 2016 and further amended on restated on July 24, 2018. Dr. Gelone
was subsequently appointed our chief scientific officer on June 30, 2017 and our president and chief operating officer on
July 24, 2018. Dr. Gelone was appointed to our board on March 10, 2021. On March 10, 2021, we entered into an amended
and restated employment agreement with Dr. Gelone, or the Gelone Employment Agreement. Dr. Guico-Pabia was
appointed as our chief medical officer and entered into an employment agreement dated and effective as of October 1,
2021, or the Guico-Pabia Employment Agreement. Mr. Naftzger was appointed as our general counsel and secretary and
entered into an employment agreement dated and effective as of September 1, 2021, or the Naftzger Employment
Agreement. Each of the Dolan Employment Agreement, Gelone Employment Agreement, Guico-Pabia Employment
Agreement and Naftzger Employment Agreement, or the Executive Employment Agreements, provides that such executive
officer is an at will employee, and his employment with us can be terminated by the respective executive officer or us at
any time and for any reason.
Pursuant to the Dolan Employment Agreement, Mr. Dolan receives an annual base salary of $330,000 and is
eligible to receive an annual performance bonus targeted at 40% of his annual base salary, with the actual amount of such
bonus, if any, to be determined by the Board. Pursuant to the Gelone Employment Agreement, Dr. Gelone receives an
annual base salary of $509,888 and is eligible to receive an annual performance bonus targeted at 45% of his annual base
salary, with the actual amount of such bonus, if any, to be determined by the Board. Pursuant to the Guico-Pabia
Employment Agreement, Dr. Guico-Pabia receives an annual base salary of $416,000 and is eligible to receive an annual
performance bonus targeted at 40% of her annual base salary, with the actual amount of such bonus, if any, to be
determined by the Board. Pursuant to the Naftzger Employment Agreement, Mr. Naftzger receives an annual base salary of
$350,000 and is eligible to receive an annual performance bonus targeted at 40% of his annual base salary, with the actual
amount of such bonus, if any, to be determined by the Board. Each of Mr. Dolan, Dr. Gelone, Dr. Guico-Pabia and Mr.
Naftzger are also (1) eligible to receive equity awards at such times and on such terms and conditions as the Board may
determine and (2) entitled to participate in any and all benefit programs that we make available to our executive officers,
for which he may be eligible, under the plan documents governing such programs.
In addition, pursuant to the Dolan Employment Agreement, subject to approval by the compensation committee of
the Board or a majority of our independent directors as defined in Nasdaq Listing Rule 5605(a)(2), Mr. Dolan shall receive
a nonqualified share option to purchase 100,000 ordinary shares at an exercise price per share equal to the closing price per
share of the ordinary shares on the Nasdaq Global Select Market on the date of grant, to vest over a period of four (4)
years, subject to the terms and conditions of our 2021 Inducement Share Incentive Plan and a nonqualified share option
agreement between us and Mr. Dolan, and awarded outside of our equity incentive plans as an “inducement grant” within
the meaning of Nasdaq Listing Rule 5635(e)(4).
Each Executive Employment Agreement and the employment of each of Mr. Dolan, Dr. Gelone, Dr. Guico-Pabia
and Mr. Naftzger may be terminated in one of three ways: (1) upon the death or “disability” (as disability is defined in the
applicable Executive Employment Agreement) of such executive officer; (2) at our election, with or
162
Table of Contents
without “cause” (as cause is defined in the applicable Executive Employment Agreement); and (3) at such executive
officer’s election, with or without “good reason” (as good reason is defined in the applicable Executive Employment
Agreement).
In the event of the termination of such executive officer’s employment by us without cause or by him for good
reason prior to, or more than twelve months following, a “change in control” (as change in control is defined in the
applicable Executive Employment Agreement), such executive officer will be entitled to his or her base salary that has
accrued and to which he is entitled as of the termination date. In addition, subject to such executive officer’s execution and
nonrevocation of a release of claims in our favor and his or her continued compliance with his or her proprietary rights,
non-disclosure and developments agreement with us, such executive officer is entitled to (1) continued payment of such
executive officer’s base salary, in accordance with our regular payroll procedures, for, in the case of Mr. Dolan, Dr. Guico-
Pabia and Mr. Naftzger, a period of 12 months, and in the case of Dr. Gelone, a period of 15 months, (2) provided he or she
is eligible for and timely elects to continue receiving group medical insurance under COBRA and the payments would not
result in the violation of nondiscrimination requirements of applicable law, payment by us of the portion of health coverage
premiums we pay for similarly-situated, active employees, who receive the same type of coverage, for, in the case of Mr.
Dolan, Dr. Guico-Pabia and Mr. Naftzger, a period of up to 12 months and, in the case of Dr. Gelone, a period of 15
months, following the date of termination, (3) a lump sum payment equal to any earned but unpaid annual bonus for a
previously completed calendar year and (4) a lump sum payment equal to a prorated annual bonus for the year in which
such executive officer’s employment is terminated based on the number of days such executive officer provided services to
us during the year in which such executive officer’s employment is terminated.
In the event of the termination of the executive officer’s employment by us without cause or by him or by her for
good reason within twelve months following a change in control, subject (as described above with respect to certain
payments) to such executive officer’s execution and nonrevocation of a release of claims in our favor and his or her
continued compliance with his or her proprietary rights, non-disclosure and developments agreement with us, such
executive officer will be entitled to the same payments and benefits as described in the preceding paragraph, except that, in
lieu of a pro-rated annual bonus payment, such executive officer will be entitled to receive a lump sum payment equal to
100% of such executive officer’s target bonus for the year in which his or her employment is terminated, and such
executive officer shall also be entitled to full vesting acceleration of his or her then-unvested equity awards, whether
granted under the 2017 Share Incentive Plan, 2020 Share Incentive Plan or any successor equity incentive plan, such that
his or her equity awards become fully exercisable and non-forfeitable as of the termination date, except as otherwise
determined by the Board in the case of awards subject to performance conditions.
If such executive officer’s employment is terminated for any other reason, including as a result of his or her death
or disability, for cause, or voluntarily by such executive officer without good reason, our obligations under the applicable
Executive Employment Agreements cease immediately, and such executive officer is only entitled to his or her base salary
that has accrued and to which he is entitled as of the termination date and, solely if such executive officer’s employment is
terminated as a result of his or her death or disability and subject to his or her execution and nonrevocation of a release of
claims in our favor and his or her continued compliance with his or her proprietary rights, non-disclosure and
developments agreement with us, such executive officer or the estate of such executive officer, as applicable, is entitled to
any earned but unpaid annual bonus from a previously completed calendar year.
As a condition to their employment, each of Mr. Dolan, Dr. Gelone, Dr. Guico-Pabia and Mr. Naftzger signed a
proprietary rights, non‑disclosure and developments agreement.
Equity Incentive Plans
In this section, we describe our 2020 Share Incentive Plan, 2017 Share Incentive Plan and Stock Option Plan
2015. Prior to the redomiciliation to Ireland, or Redomiciliation, Nabriva Austria granted awards to eligible recipients
under the Stock Option Plan 2015. In connection with the Redomiciliation, both plans were amended to take account of
certain requirements under Irish law and assumed by us, with each option to acquire one Nabriva Austria common share
becoming an option to acquire ten of our ordinary shares on the same terms and conditions. We currently make share
awards to eligible recipients solely under our 2020 Share Incentive Plan.
163
Table of Contents
2020 Share Incentive Plan
On March 4, 2020, our board of directors adopted the 2020 Share Incentive Plan, or the 2020 Plan, which was
approved by our shareholders at the 2020 Annual General Meeting of Shareholders in July 2020, or the AGM. As of the
date of the 2020 AGM, the total number of ordinary shares reserved for issuance under the 2020 Plan was for the sum of
9,300,000 ordinary shares, plus the number of our ordinary shares that remained available for grant under the 2017 Plan as
of immediately prior to the AGM and the number of ordinary shares subject to awards granted under the 2017 Plan and our
Amended and Restated Stock Option Plan 2015, that expire, terminate or are otherwise surrendered, cancelled, forfeited or
repurchased by us at their original issuance price pursuant to a contractual repurchase right. Following shareholder
approval of the 2020 Plan, no further awards will be made under the 2017 Plan.
The 2020 Plan provides for the grant of incentive share options, nonstatutory share options, share appreciation
rights, restricted share awards, restricted share units, other share-based and cash-based awards and performance awards.
As of January 31, 2022, under our 2020 Share Incentive Plan, there were options to purchase an aggregate of
418,730 of our ordinary shares at a weighted average exercise price of $4.72 per share, 734,938 restricted stock units
outstanding with a weighted average grant date fair value of $2.10 per share, and 271,080 ordinary shares available for
future issuance under the plan.
The 2020 Plan is administered by the board of directors. The exercise or measurement prices, vesting periods,
performance goals and other award restrictions are determined at the discretion of the board of directors, except that the
exercise price or measurement price per share of options or share appreciation rights may not be less than 100% of the fair
market value of the ordinary shares on the date of grant, provided that if the board of directors approves the grant of an
option or a share appreciation right with an exercise or measurement price to be determined on a future date, the exercise or
measurement price may not be less than 100% of the fair market value of the ordinary shares on such future date. No share
option or share appreciation right will be granted under the 2020 Plan with a term in excess of ten years.
If, during the term of the 2020 Plan, there is a change in our share capital or a restructuring measure which has an
effect on our share capital, such as a share split or reverse share split, the board of directors will make equitable
adjustments to the price or the amount of outstanding awards.
The 2020 Plan also contains provisions addressing the consequences of any reorganization event. A reorganization
event is defined as (a) any merger or consolidation of ours with or into another entity as a result of which all of our
ordinary shares are converted into or exchanged for the right to receive cash, securities or other property, or are canceled,
(b) any transfer or disposition of all of our ordinary shares for cash, securities or other property pursuant to a share
exchange or other transaction or (c) any liquidation or dissolution of ours; any one of which, (a), (b) or (c), may be effected
pursuant to the laws of the Republic of Ireland.
The 2020 Plan provides that, if a reorganization event occurs, the board of directors may take one or more of the
following actions with respect to all or any outstanding awards other than restricted shares on such terms as the board of
directors determines: (1) provide that such awards will be assumed, or substantially equivalent awards will be substituted,
by the acquiring or succeeding corporation (or an affiliate thereof), (2) upon written notice to a participant, provide that all
of the participant’s unvested awards will be forfeited immediately prior to the consummation of such reorganization event
and/or that all of the participant’s unexercised awards will terminate immediately prior to the consummation of such
reorganization event unless exercised by the participant (to the extent then exercisable) within a specified period following
the date of such notice, (3) provide that outstanding awards will become exercisable, realizable, or deliverable, or
restrictions applicable to an award will lapse, in whole or in part prior to or upon such reorganization event, (4) in the event
of a reorganization event under the terms of which holders of our ordinary shares will receive, upon consummation thereof,
a cash payment for each share surrendered in the reorganization event, or the Acquisition Price, make or provide for a cash
payment to participants with respect to each award held by a participant equal to (A) the number of ordinary shares subject
to the vested portion of the award (after giving effect to any acceleration of vesting that occurs upon or immediately prior
to such reorganization event) multiplied by (B) the excess, if any, of (I) the Acquisition Price over (II) the exercise,
measurement or purchase price of such award and any applicable tax withholdings, in exchange for the termination of such
award, (5) provided that, in connection with our
164
Table of Contents
liquidation or dissolution, awards will convert into the right to receive liquidation proceeds (if applicable, net of the
exercise, measurement or purchase price thereof and any applicable tax withholdings) and (6) any combination of the
foregoing. Our board of directors is not obligated to treat all awards, all awards held by a participant, or all awards of the
same type, identically.
No award may be granted under the 2020 Plan after the date that is ten years from the date the 2020 Plan is
approved by our shareholders. Our board of directors may, at any time, amend, suspend or terminate the 2020 Plan or any
portion thereof. However, if shareholder approval is required, including by application of Irish law or the terms of the 2020
Plan, the board of directors may not effect such modification or amendment without such approval.
2017 Share Incentive Plan
The 2017 Share Incentive Plan permits the award of share options, share appreciation rights, or SARs, restricted
shares, restricted share units or RSUs, and other share-based awards to our employees, officers, directors, consultants and
advisers. With the approval of the 2020 Share Incentive Plan, there were no further shares available for issuance under the
2017 Plan. However, all outstanding awards under 2017 Plan will remain in effect and continue to be governed by the
terms of the 2017 Plan. As of January 31, 2022, under our 2017 Share Incentive Plan, there were options to purchase an
aggregate of 389,497 of our ordinary shares at a weighted average exercise price of $31.04 per share and 54,800 restricted
stock units outstanding with a weighted average grant date fair value of $13.85 per share. Unless the context specifically
indicates otherwise, references to our 2017 Share Incentive Plan in this Annual Report on Form 10-K refer to the 2017
Share Incentive Plan, as amended and adopted by us.
If, during the term of the 2017 Share Incentive Plan, there is a change in our capital or a restructuring measure
which has an effect on our capital, such as a share split or reverse share split, which change or measure results in a change
in the value of the share-based awards outstanding under the 2017 Share Incentive Plan, the board will make appropriate
adjustments to the price or the amount of such outstanding awards.
The 2017 Share Incentive Plan also contains provisions addressing the consequences of any reorganization event.
A reorganization event is defined as (a) any merger or consolidation of us with or into another entity as a result of which all
of our ordinary shares are converted into or exchanged for the right to receive cash, securities or other property, or are
cancelled, (b) any transfer or disposition of all of our ordinary shares for cash, securities or other property pursuant to a
share exchange or other transaction or (c) our liquidation or dissolution; any one of which, (a), (b) or (c), may be effected
pursuant to the laws of the Republic of Ireland.
The 2017 Share Incentive Plan provides that, if a reorganization event occurs, the board of directors may take one
or more of the following actions to all or any outstanding awards other than restricted shares on such terms as the board of
directors determines: (1) provide that such awards will be assumed, or substantially equivalent awards will be substituted,
by the acquiring or succeeding corporation (or an affiliate thereof), (2) upon written notice to a participant, provide that all
of the participant’s unvested awards will be forfeited immediately prior to the consummation of such reorganization event
and/or that all of the participant’s unexercised awards will terminate immediately prior to the consummation of such
reorganization event unless exercised by the participant (to the extent then exercisable) within a specified period following
the date of such notice, (3) provide that outstanding awards will become exercisable, realizable, or deliverable, or
restrictions applicable to an award will lapse, in whole or in part prior to or upon such reorganization event, (4) in the event
of a reorganization event under the terms of which holders of our ordinary shares will receive, upon consummation thereof,
a cash payment for each share surrendered in the reorganization event, which we refer to as the Acquisition Price, make or
provide for a cash payment to participants with respect to each award held by a participant equal to (A) the number of
ordinary shares subject to the vested portion of the award (after giving effect to any acceleration of vesting that occurs
upon or immediately prior to such reorganization event) multiplied by (B) the excess, if any, of (I) the Acquisition Price
over (II) the exercise, measurement or purchase price of such award and any applicable tax withholdings, in exchange for
the termination of such award, (5) provide that, in connection with our liquidation or dissolution, awards will convert into
the right to receive liquidation proceeds (if applicable, net of the exercise, measurement or purchase price thereof and any
applicable tax withholdings) and (6) any combination of the foregoing. Our board is not obligated to treat all awards, all
awards held by a participant, or all awards of the same type, identically.
165
Table of Contents
No additional awards may be granted under the 2017 Share Incentive Plan. The board of directors may, at any
time, amend, suspend or terminate the 2017 Share Incentive Plan or any portion thereof. However, if shareholder approval
is required, including by application of Irish law, the board may not effect such modification or amendment without such
approval.
Stock Option Plan 2015
The Stock Option Plan 2015 provided for the grant of options to purchase our ordinary shares to our employees,
including executive officers, and to directors. With the approval of the 2017 Share Incentive Plan, there were no further
shares available for issuance under the Stock Option Plan 2015. However, all outstanding awards under Stock Option Plan
2015 will remain in effect and continue to be governed by the terms of the Stock Option Plan 2015. As of January 31,
2021, under our Stock Option Plan 2015, there were options to purchase an aggregate of 160,205 of our ordinary shares at
a weighted average exercise price of $80.17 per share and no ordinary shares are available for issuance under the plan.
Unless the context specifically indicates otherwise, references to our Stock Option Plan 2015 in this Annual Report on
Form 10-K refer to the Stock Option Plan 2015, as amended and adopted by us.
Options granted under the Stock Option Plan 2015 entitle beneficiaries thereof to purchase our ordinary shares at
an exercise price equal to 100% of the fair market value per share on the beneficiary’s date of participation, which
following the Redomiciliation was derived from the closing sale price of our ordinary shares on the Nasdaq Global Select
Market. Options granted under the Stock Option Plan 2015 generally vest over four years from the beneficiary’s date of
participation. Typically, 25% of the options subject to a particular grant vest on the last day of the last calendar month of
the first year of the vesting period, and the remaining 75% vests on a monthly pro-rata basis over the second, third and
fourth years of the vesting period (i.e., 2.083% per month). Any alternative vesting period determined by us is subject to
approval by our executive officers, board of directors or shareholders, in accordance with any applicable voting
requirements.
The Stock Option Plan 2015 provides that, if a liquidity event (as defined below) occurs, all options outstanding
under the Stock Option Plan 2015 will be assumed (or substantially equivalent awards will be substituted by an acquiring
or succeeding corporation (or an affiliate of the acquiring or succeeding corporation)), and any then-unvested options shall
continue to vest in accordance with the beneficiary’s original vesting schedule. If a beneficiary is terminated due to a good
leaver event (within the meaning of the Stock Option Plan 2015), on or prior to the first anniversary of the date of the
liquidity event, the beneficiary’s options will be immediately exercisable in full as of the date of such termination. If the
acquiring or succeeding corporation (or an affiliate of the acquiring or succeeding corporation) refuses to assume the
options outstanding under the Stock Option Plan 2015 or to substitute substantially equivalent options therefor, all then-
unvested options under the Stock Option Plan 2015 will automatically vest in full upon the liquidity event. For purposes of
the Stock Option Plan 2015, a liquidity event generally refers to an exclusive license of or the sale, lease or other disposal
of all or substantially all of our assets, a sale or other disposal (but not a pledge) of 50% or more of our shares, a merger or
consolidation of us with or into any third party, or our liquidation, winding up or other form of dissolution of us.
Unless otherwise specifically permitted in an option agreement or resolved upon by the board of directors, the
exercise of vested options is permitted under the Stock Option Plan 2015 only during specified periods and on specified
terms in the case of a liquidity event or following an initial public offering occurring during the term of the option. A
beneficiary is entitled to exercise vested options at any time during the remaining term of the option while the beneficiary
is providing services to us, and within the three-month period following a termination of the beneficiary’s services due to a
good leaver event. Options granted under the Stock Option Plan 2015 will have a term of no more than ten years from the
beneficiary’s date of participation.
If, during the term of the Stock Option Plan 2015, there is a change in our capital or a restructuring measure which
has an effect on our capital, such as a stock split or reverse stock split, which change or measure results in a change in the
value of the options outstanding under the Stock Option Plan 2015, the board may make appropriate adjustments to the
price or the amount of such outstanding options.
166
Table of Contents
The board of directors may, at any time, amend, suspend or terminate the Stock Option Plan 2015 in whole or in
part. However, if shareholder approval is required, including by application of Irish law, the board may not effect such
modification or amendment without such approval.
401(k) Plan
We maintain a defined contribution employee retirement plan for our U.S.-based employees. Our 401(k) plan is
intended to qualify as a tax-qualified plan under Section 401 of the Internal Revenue Code, so that contributions to our
401(k) plan, and income earned on such contributions, are not taxable to participants until withdrawn or distributed from
the 401(k) plan. Our 401(k) plan provides that each participant may contribute up to 100% of his or her pre-tax
compensation, up to a statutory limit, which is $19,500 for 2021. Participants who are at least 50 years old can also make
“catch-up” contributions, which in 2021 may be up to an additional $6,500 above the statutory limit. Under our 401(k)
plan, each employee is fully vested in his or her deferred salary contributions. Employee contributions are held and
invested by the plan’s trustee, subject to participants’ ability to give investment directions by following certain procedures.
We generally match 100.0% of the first 3.0% of the employee’s voluntary contribution to the 401(k) plan and 50.0% of the
next 2.0% contributed by the employee. Our 401(k) matching policy was temporarily suspended during a portion of 2020.
Risk Considerations in Our Compensation Program
Our compensation committee has reviewed and evaluated the philosophy and standards on which our
compensation plans have been developed and implemented across our company. It is our belief that our compensation
programs do not encourage inappropriate actions or risk taking by our executive officers. We do not believe that any risks
arising from our employee compensation policies and practices are reasonably likely to have a material adverse effect on
our company. In addition, we do not believe that the mix and design of the components of our executive compensation
program encourage management to assume excessive risks.
167
Table of Contents
Summary Compensation Table
DIRECTOR COMPENSATION
The following table sets forth a summary of the compensation earned by the non-employee members of the board
of directors for the year ended December 31, 2021.
Name
Daniel Burgess
Colin Broom
Lisa Dalton(6)
Charles Rowland, Jr.
Stephen Webster
Carrie Bourdow
Mark Corrigan(6)
George Talbot(7)
Fees Earned or
Paid in Cash
($)(1)
89,509
39,781
26,309
60,396
68,917
49,364
27,370
25,644
Option Awards
($)(2)
24,185 (3)
24,185 (3)
33,635 (4)
24,185 (3)
24,185 (3)
24,185 (3)
33,635 (4)
—
Share Awards
Total ($)
($)(2)
18,900 (5) 132,594
82,866
18,900 (5)
18,900 (5)
78,844
18,900 (5) 103,481
18,900 (5) 112,002
92,449
18,900 (5)
79,905
18,900 (5)
25,644
—
(1) Fees earned consist of gross director retainer fees which were subject to income tax withholdings in Ireland.
(2) The amounts reported in the “Option Awards” and “Share Awards” columns reflect the aggregate fair value of share-
based compensation awarded during 2021 computed in accordance with the provisions of ASC Topic 718. See Note 10
to the consolidated financial statements regarding assumptions underlying the valuation of equity awards.
(3) Represents the grant of an option to purchase 35,000 of our ordinary shares vesting with respect to all of the shares on
the last date of the month of the first anniversary of the grant date.
(4) Represents the grant of an option to purchase 35,000 of our ordinary shares vesting with respect to all of the shares on
the last date of the month of the first anniversary of the grant date, as well as the grant of an option to purchase 10,500
shares vesting on a monthly pro-rata basis over three years of the vesting period.
(5) Represents the grant of 17,500 RSUs vesting with respect to all of the shares on the last date of the month of the first
anniversary of the grant date.
(6) Lisa Dalton and Mark Corrigan joined as directors on June 2, 2021.
(7) George Talbot resigned as a director on July 28, 2021.
Director Compensation Arrangements
Effective as of October 31, 2018, our board of directors adopted a non-employee director compensation policy,
which provided for the following:
● each new non-employee director receives an initial grant of an option to purchase 7,000 of our ordinary
shares upon his or her initial election to the board of directors;
● each non-employee director receives an annual grant of an option to purchase 3,500 of our ordinary shares on
the date of our annual general meeting of shareholders;
● each non-employee director receives an annual cash fee of $40,000;
● the chairman of our board of directors receives an additional annual cash fee of $30,000;
168
Table of Contents
● each non-employee director who is a member of the audit committee receives an additional annual cash fee
of $10,000 ($20,000 for the audit committee chair);
● each non-employee director who is a member of the compensation committee receives an additional annual
cash fee of $7,500 ($15,000 for the compensation committee chair); and
● each non-employee director who is a member of the nominating and corporate governance committee
receives an additional annual cash fee of $5,000 ($10,000 for the nominating and corporate governance
committee chair).
On December 16, 2019, our board of directors approved an amendment to our non-employee director
compensation policy. Effective as of December 16, 2019, the amendment increased the initial grant of an option to
purchase our ordinary shares to new non-employee directors upon their initial election to the board of directors to 10,500
ordinary shares and increased the annual grant of an option to purchase our ordinary shares to 3,500 ordinary shares and
1,750 restricted stock units. Effective as of July 29, 2021, a subsequent amendment increased the initial grant of an option
to purchase our ordinary shares to new non-employee directors upon their initial election to the board of directors to
105,000 ordinary shares and increased the annual grant of an option to purchase our ordinary shares to 35,00 ordinary
shares and 17,500 restricted stock units.
The stock options to be granted to our non-employee directors under our non-employee director compensation
policy have an exercise price equal to the fair market value of our ordinary shares on the date of grant and will expire ten
years after the date of grant. The initial stock options granted to newly elected director vest, subject to such director’s
continued service on the board, over a three-year period on a monthly pro-rata basis at the end of each successive month
following the date of the initial grant. The annual stock options granted to directors will vest, subject to such director’s
continued service on the board, fully on the last date of the month of the first anniversary of the grant date. The annual
restricted stock units awarded to directors will vest, subject to such director’s continued service on the board, fully on the
last date of the month of the first anniversary of the grant date.
Under our non-employee director compensation policy, the annual cash fees are payable in arrears in four equal
quarterly installments payable the week following the end of each quarter. Each non-employee director is also entitled to
reimbursement for reasonable travel and other expenses incurred in connection with attending meetings of the board of
directors and any committee on which he or she serves or otherwise in direct service of the company.
ITEM 12. SECURITY OWNERSHIP OF CERTAIN BENEFICIAL OWNERS AND MANAGEMENT AND
RELATED STOCKHOLDER MATTERS
The following table sets forth information with respect to the beneficial ownership of our ordinary shares as of
January 31, 2022 by:
● each of our directors and director nominees;
● each of our “named executive officers”;
● all of our directors and executive officers as a group; and
● each person, or group of affiliated persons, who is known by us to beneficially own more than 5% of our
ordinary shares.
The percentages in the columns entitled “Percentage of Shares Beneficially Owned” are based on a total of
56,715,965 ordinary shares outstanding as of January 31, 2022.
169
Table of Contents
Beneficial ownership is determined in accordance with the rules and regulations of the SEC and includes voting or
investment power with respect to our ordinary shares. Our ordinary shares subject to options that are currently exercisable
or exercisable within 60 days of January 31, 2022 are considered outstanding and beneficially owned by the person holding
the options for the purpose of calculating the percentage ownership of that person but not for the purpose of calculating the
percentage ownership of any other person. Except as otherwise noted, the persons and entities in this table have sole voting
and investing power with respect to all of the ordinary shares beneficially owned by them, subject to community property
laws, where applicable. Except as otherwise set forth below, the address of the beneficial owner is c/o Nabriva
Therapeutics plc, 25-28 North Wall Quay, Dublin 1, Ireland.
Name and Address of Beneficial Owner
Directors and Named Executive Officers:
Daniel Burgess(1)
Stephen Webster(2)
Charles A. Rowland, Jr.(3)
Carrie Bourdow(4)
Colin Broom(5)
Lisa Dalton(6)
Mark Corrigan(6)
Steven Gelone(7)
Theodore Schroeder(8)
Daniel Dolan(9)
All current directors and executive officers as a group (12 individuals)(10)
5% Shareholders:
Lincoln Park Capital Fund, LLC (11)
*
Less than one percent.
Number of
Shares
Beneficially
Owned
Percentage of
Shares
Beneficially
Owned
19,665
15,713
20,793
13,903
100,359
2,336
2,336
107,069
343,002
25,000
657,176
* %
* %
* %
* %
* %
* %
* %
* %
* %
* %
1.16 %
4,512,589
7.96 %
(1) Consists of (i) 4,225 ordinary shares and (ii) 15,440 ordinary shares issuable upon exercise of stock options
exercisable within 60 days of January 31, 2022.
(2) Consists of (i) 1,773 ordinary shares and (ii) 13,940 ordinary shares issuable upon exercise of stock options
exercisable within 60 days of January 31, 2022.
(3) Consists of (i) 6,273 ordinary shares and (ii) 14,520 ordinary shares issuable upon exercise of stock options
exercisable within 60 days of January 31, 2022.
(4) Consists of (i) 973 ordinary shares and (ii) 12,930 ordinary shares issuable upon exercise of stock options exercisable
within 60 days of January 31, 2022.
(5) Consists of (i) 22,094 ordinary shares directly owned by Dr. Broom and (ii) 78,265 ordinary shares issuable upon
exercise of stock options exercisable within 60 days of January 31, 2022.
(6) Consists of 2,336 ordinary shares issuable upon exercise of stock options exercisable within 60 days of January 31,
2022.
(7) Consists of (i) 29,097 ordinary shares, (ii) 76,887 ordinary shares issuable upon exercise of stock options exercisable
within 60 days of January 31, 2022 and (iii) 1,085 ordinary shares issuable upon the vesting of restricted stock units
within 60 days of January 31, 2022.
170
Table of Contents
(8) Consists of (i) 204,403 ordinary shares, (ii) 136,486 ordinary shares issuable upon exercise of stock options
exercisable within 60 days of January 31, 2022 and (iii) 2,113 ordinary shares issuable upon the vesting of restricted
stock units within 60 days of January 31, 2022.
(9) Consists of (i) 275,838 ordinary shares and (ii) 378,140 ordinary shares issuable upon exercise of stock options within
60 days of January 31, 2022 and (iii) 3,198 ordinary shares issuable upon the vesting of restricted stock units within 60
days of January 31, 2022.
(10) Consists of 25,000 ordinary shares issuable upon exercise of stock options exercisable within 60 days of January 31,
2022.
(11) Based solely upon a Schedule 13G filed on November 19, 2021, which sets forth beneficial ownership as of November
18, 2021. Consists of 4,512,589 ordinary shares held by Lincoln Park Capital Fund, LLC, or LPC Fund. Lincoln Park
Capital, LLC, or LPC, is the Managing Member of LPC Fund. Rockledge Capital Corporation, or RCC, and Alex
Noah Investors, Inc., or Alex Noah are the Managing Members of LPC. Josh Scheinfeld is the president and sole
shareholder of RCC, as well as a principal of LPC. Jonathan Cope is the president and sole shareholder of Alex Noah,
as well as a principal of LPC. As a result of the foregoing, each of LPC, RCC LPC, RCC, Mr. Scheinfeld, Alex Noah,
and Mr. Cope (i) may be deemed to beneficially own and (ii) have shared voting and shared dispositive power over the
4,512,589 ordinary shares directly held by LPC Fund. Each of LPC, RCC, Mr. Scheinfeld, Alex Noah and Mr. Cope
disclaims beneficial ownership of the ordinary shares directly held by LPC Fund, except to the extent of its or his
pecuniary interest therein, if any. LPC Funds' address is 440 N. Wells Street, Suite 410, Chicago, Illinois 60654.
Securities Authorized for Issuance under Equity Compensation Plans
The following table contains information about our equity compensation plans as of December 31, 2021. As of
December 31, 2021, we had four equity compensation plans: the 2020 Share Incentive Plan, the 2017 Share Incentive Plan,
the Stock Option Plan 2015 and the 2018 Employee Share Purchase Plan, each of which were approved by our
shareholders. In addition, from time to time, the compensation committee grants inducement equity awards to individuals
as an inducement material to the individual’s entry into employment with us within the meaning of Nasdaq Listing Rules,
including pursuant to our 2021 Inducement Share Incentive Plan, or the Inducement Plan, that was adopted by our board of
directors without shareholder approval. We also previously made such inducement awards pursuant to our 2019
Inducement Share Incentive Plan.
Plan category
Number of
securities to be
issued upon
exercise
of outstanding
options, warrants
and rights
(a)
Weighted‑average
exercise price of
outstanding
options, warrants
and rights
(b)
Equity compensation plans approved by security holders
Equity compensation plans not approved by security holders
Total
1,673,170 (1) $
465,045 (2)
$
2,138,215
27.07 (3)
7.91 (3)
20.46 (4)
Number of
securities
remaining
available for future
issuance under
equity
compensation plans
(excluding
securities reflected
in column(a))
(c)
290,218 (5)
128,120
418,338
(1) Includes ordinary shares underlying awards outstanding under our 2020 Share Incentive Plan, 2017 Share Incentive
Plan and our Stock Option Plan 2015.
(2) Represents an option award and a performance-based restricted share unit award granted to Mr. Schroeder on July 25,
2018, as an inducement material to Mr. Schroeder’s acceptance of employment with the company in accordance with
Nasdaq Listing Rule 5635(c)(4) and other inducement awards made in accordance with Nasdaq
171
Table of Contents
Listing Rule 5635(c)(4) under our 2019 Inducement Share Incentive Plan and 2021 Inducement Share Incentive Plan.
(3) Only share option awards were used in computing the weighted-average exercise price.
(4) Only share option awards were used in computing the weighted-average exercise price.
(5) Includes ordinary shares available for issuance under our 2020 Share Incentive Plan and 2018 Employee Share
Purchase Plan.
2021 Inducement Share Incentive Plan
On December 9, 2020, our board of directors adopted without stockholder approval the 2021 Inducement Share
Incentive Plan, or the 2021 Inducement Plan and, subject to the adjustment provisions of the 2021 Inducement Plan,
reserved 200,000 oridnary shares for issuance purusant to equity awards granted under the 2021 Inducement Plan. In
accordance with Nasdaq Listing Rule 5635(c)(4), awards under the 2021 Inducement Plan may only be made to individuals
who were not previously employees or non-employee directors of the company (or following such individuals’ bona fide
period of non-employment with the company), as an inducement material to the individuals’ entry into employment with
the company. In September 2021, our board of directors adopted an amendment to the 2021 Inducement Plan that increased
the amount of shares reserved for issuance under the plan from 200,000 shares to 500,000 shares.
Options and SARs granted will be exercisable at such times and subject to such terms and conditions as the board
may specify in the applicable option agreement; provided, however, that no option or SAR will be granted with a term in
excess of ten years. The board will also determine the terms and conditions of restricted shares and RSUs, including the
conditions for vesting and repurchase (or forfeiture) and the issue price, if any.
172
Table of Contents
ITEM 13. CERTAIN RELATIONSHIPS AND RELATED TRANSACTIONS, AND DIRECTOR
INDEPENDENCE
Board Determination of Independence
Applicable Nasdaq rules require a majority of a listed company’s board of directors to be comprised of
independent directors within one year of listing. In addition, the Nasdaq rules require that, subject to specified exceptions,
each member of a listed company’s audit, compensation and nominating and corporate governance committees be
independent under the Securities Exchange Act of 1934, as amended, or the Exchange Act. Audit committee members
must also satisfy the independence criteria set forth in Rule 10A-3 under the Exchange Act, and compensation committee
members must also satisfy the independence criteria set forth in Rule 10C-1 under the Exchange Act. Under applicable
Nasdaq rules, a director will only qualify as an “independent director” if, in the opinion of the listed company’s board of
directors, that person does not have a relationship that would interfere with the exercise of independent judgment in
carrying out the responsibilities of a director. To be considered independent for purposes of Rule 10A-3, a member of an
audit committee of a listed company may not, other than in his or her capacity as a member of the audit committee, the
board of directors, or any other board committee, accept, directly or indirectly, any consulting, advisory, or other
compensatory fee from the listed company or any of its subsidiaries or otherwise be an affiliated person of the listed
company or any of its subsidiaries. In order to be considered independent for purposes of Rule 10C-1, the board must
consider, for each member of a compensation committee of a listed company, all factors specifically relevant to
determining whether a director has a relationship to such company which is material to that director’s ability to be
independent from management in connection with the duties of a compensation committee member, including, but not
limited to: (1) the source of compensation of the director, including any consulting, advisory or other compensatory fee
paid by such company to the director; and (2) whether the director is affiliated with the company or any of its subsidiaries
or affiliates.
In April 2021, our board of directors undertook a review of the independence of each director. Based upon
information requested from and provided by each director concerning his or her background, employment and affiliations,
including family relationships, our board determined that each of our directors, with the exception of Colin Broom,
Theodore Schroeder and Steven Gelone, is an “independent director” as defined under applicable Nasdaq rules, including,
in the case of all the members of our audit committee, the independence criteria set forth in Rule 10A-3 under the
Exchange Act, and in the case of all the members of our compensation committee, the independence criteria set forth in
Rule 10C-1 under the Exchange Act. In making such determination, our board considered the relationships that each such
director has with us, including each of the transactions described below in “—Board Policies—Related Person
Transactions—Certain Relationships and Related Transactions”, and all other facts and circumstances that our board
deemed relevant in make such independence determination. Mr. Schroeder is not an independent director because he is our
chief executive officer, and Dr. Broom is not an independent director because he was employed as our chief executive
officer during the past three years. In addition, Dr. Gelone is not an independent director because he is our president and
chief operating officer.
Board Policies
Related Person Transactions
Our board of directors has adopted written policies and procedures for the review of any transaction, arrangement
or relationship in which the company is a participant, the amount involved exceeds the lesser of $120,000 and one percent
of the average of the our total assets at year-end for the last two completed fiscal years and one of our executive officers,
directors, director nominees or 5% shareholders, or their immediate family members, each of whom we refer to as a
“related person”, has a direct or indirect material interest.
If a related person proposes to enter into such a transaction, arrangement or relationship, which we refer to as a
“related person transaction”, the related person must report the proposed related person transaction to our chief financial
officer or general counsel. The policy calls for the proposed related person transaction to be reviewed and, if deemed
appropriate, approved by our audit committee. Whenever practicable, the reporting, review and approval will occur prior to
entry into the transaction. If advance review and approval is not practicable, the committee will review, and, in its
173
Table of Contents
discretion, may ratify the related person transaction. The policy also permits the chair of the audit committee to review and,
if deemed appropriate, approve proposed related person transactions that arise between committee meetings, subject to
ratification by the committee at its next meeting. Any related person transactions that are ongoing in nature will be
reviewed annually.
A related person transaction reviewed under the policy will be considered approved or ratified if it is authorized
by the audit committee after full disclosure of the related person’s interest in the transaction. As appropriate for the
circumstances, the audit committee will review and consider:
● the related person’s interest in the related person transaction;
● the approximate dollar value of the amount involved in the related person transaction;
● the approximate dollar value of the amount of the related person’s interest in the transaction without regard to
the amount of any profit or loss;
● whether the transaction was undertaken in the ordinary course of our business;
● whether the terms of the transaction are no less favorable to us than terms that could have been reached with
an unrelated third party;
● the purpose of, and the potential benefits to us of, the transaction; and
● any other information regarding the related person transaction or the related person in the context of the
proposed transaction that would be material to investors in light of the circumstances of such transaction.
Our audit committee may approve or ratify the transaction only if it determines that, under all of the
circumstances, the transaction is in our best interests. Our audit committee may impose any conditions on the related
person transaction that it deems appropriate.
In addition to the transactions that are excluded by the instructions to the SEC’s related person transaction
disclosure rule, our board of directors has determined that the following transactions do not create a material direct or
indirect interest on behalf of related persons and, therefore, are not related person transactions for purposes of this policy:
● interests arising solely from the related person’s position as an executive officer of another entity, whether or
not the person is also a director of the entity, that is a participant in the transaction where the related person
and all other related persons own in the aggregate less than a 10% equity interest in such entity, the related
person and his or her immediate family members are not involved in the negotiation of the terms of the
transaction and do not receive any special benefits as a result of the transaction and the amount involved in
the transaction is less than the greater of $200,000 or 5% of the annual gross revenues of the company
receiving payment under the transaction; and
● a transaction that is specifically contemplated by provisions of our memorandum and articles of association.
The policy provides that transactions involving compensation of our executive officers shall be reviewed and
approved by our compensation committee in the manner specified in the compensation committee’s charter.
In addition, under our Code of Business Conduct and Ethics, our directors, executive officers and employees have
an affirmative responsibility to disclose any transaction or relationship that reasonably could be expected to give rise to a
conflict of interest.
174
Table of Contents
Certain Relationships and Related Transactions
Since January 1, 2020, we have engaged in the following transactions with our executive officers, directors and
holders of more than 5% of our voting securities, and affiliates of our executive officers, directors and 5% shareholders. We
believe that all of the transactions described below were made on terms no less favorable to us than could have been
obtained from unaffiliated third parties:
Consulting Agreement with Sender Consulting LLC
On March 9, 2021, Sender Consulting LLC, a single-member limited liability company of which Gary Sender is
the principal, entered into a two-year consulting agreement with us, effective March 15, 2021, to provide financially related
advice and actively manage projects as requested. In addition to an hourly service fee, Mr. Sender is entitled to receive an
award of 7,000 RSUs as of the effective date of the consulting agreement, which vests as to 50% of the shares underlying
the RSUs each year over the term of the consulting agreement.
Consulting Agreement with Jennifer Schranz
On May 3, 2021, we entered into a two-year consulting agreement with Jennifer Schranz, our former chief
medical officer. Pursuant to the consulting agreement, Dr. Schranz has agreed to provide expert scientific advisory services
to us in connection with the advancement of our pipeline programs and product candidates in consideration for our
agreement to forego the repayment of any and all amounts owed by Dr. Schranz to us pursuant her retention agreement
following her resignation from the company on March 19, 2021. In addition, Dr. Schranz received an award of 7,000 RSUs
as of the date of the consulting agreement, which vests as to 50% of the shares underlying the RSUs on each annual
anniversary of the consulting agreement over two years.
June 2020 Financing
In June 2020, we entered into a securities purchase agreement with certain institutional investors pursuant to which we
agreed to issue and sell in a registered direct offering an aggregate of 4,144,537 ordinary shares and accompanying
warrants to purchase up to an aggregate of 4,144,537 ordinary shares. Each share in the offering was issued and sold
together with an accompanying warrant at a combined price of $9.1686. Each warrant has an exercise price of $7.92 per
share, was immediately exercisable following the date of issuance and expires on the two-year anniversary of the date of
issuance. In connection with such offering, entities affiliated with FMR LLC, a beneficial owner of more than 5% of our
voting securities, purchased an aggregate of 872,498 ordinary shares and accompanying warrants to purchase up to
872,498 ordinary shares at a purchase price of $9.1686 per ordinary share and accompanying warrant for an aggregate
purchase price of $7,999,601.
ITEM 14. PRINCIPAL ACCOUNTANT FEES AND SERVICES
The following table sets forth, for each of the years indicated, the aggregate fees billed or expected to be billed to
us for services rendered by KPMG LLP, or KPMG.
(in thousands)
Audit Fees(1)
Tax Fees(2)
All Other Fees
Total
Year Ended
December 31,
2021
2020
$
$
813
9
—
822
$
$
724
9
—
733
(1) This category includes fees related to services associated with our at-the-market facility and December 2020 public
offering.
175
Table of Contents
(2) This category includes fees related to services rendered on tax compliance, tax advice and tax planning.
Pre-Approval Policies and Procedures
Our audit committee has adopted policies and procedures relating to the approval of all audit and non-audit
services that are to be performed by our independent registered public accounting firm. This policy generally provides that
we will not engage our independent registered public accounting firm to render audit or non-audit services unless the
service is specifically approved in advance by our audit committee or the engagement is entered into pursuant to a de
minimis exception in accordance with applicable SEC rules.
All of the services provided to us by KPMG during the last two fiscal years were approved by the audit
committee.
ITEM 15. EXHIBITS AND FINANCIAL STATEMENT SCHEDULES
PART IV
(a)
(1)
(2)
(3)
Financial Statements: See Index to Consolidated Financial Statements on page F-1 of this Annual Report
on Form 10-K.
No financial statement schedules have been filed as part of this Annual Report on Form 10-K because they
are not applicable, not required or because the information is otherwise included in our financial
statements or notes thereto.
The exhibits listed on the Exhibit Index set forth immediately following Item 16 are filed or furnished as
part of this Annual Report. The Exhibit Index is incorporated herein by reference.
ITEM 16. FORM 10-K SUMMARY
None
176
Table of Contents
Exhibit
Number
Description of Exhibit
Form
File Number
Date of
Filing
Exhibit
Number
Filed
Herewith
EXHIBIT INDEX
Incorporated by Reference
2.1* Agreement and Plan of Merger dated as of
July 23, 2018, by and among Nabriva
Therapeutics plc, Zuperbug Merger Sub
I, Inc., Zuperbug Merger Sub II, Inc.,
Zavante Therapeutics, Inc. and Cam
Gallagher, solely in his capacity as
Stockholder Representative
3.1 Amended and Restated Memorandum and
Articles of Association of Nabriva
Therapeutics plc
4.1 Description of the Registrant’s Securities
Registered under Section 12 of the
Exchange Act
4.2 Form of December 2019 Warrant
4.3 Form of May 2020 Warrant
4.4 Form of March 2021 Warrant
4.5 Registration Rights Agreement dated
September 24, 2021 between Nabriva
Therapeutics plc and Lincoln Park Capital
Fund, LLC
10.1 Form of Indemnification Agreement
10.2# 2017 Share Incentive Plan, as Amended
10.3# Stock Option Plan 2007, as Amended
10.4# Stock Option Plan 2015, as Amended
10.5 Lease Agreement, dated March 16, 2007,
by and between Nabriva Therapeutics AG
and CONTRA
Liegenschaftsverwaltung GmbH
10.6# Form of Restricted Share Unit Agreement
under the 2017 Share Incentive Plan (Share
Withholding)
10.7# Form of Restricted Share Unit Agreement
under the 2017 Share Incentive Plan
(Automatic Sale)
10.8# Form of Share Option Agreement under
the 2017 Share Incentive Plan
10.9** Manufacturing Services Agreement, dated
May 8, 2017, by and between Patheon UK
Limited and Nabriva Therapeutics AG
8-K
001-37558
07/25/2018
2.1
10-Q
001-37558
8/5/2021
3.1
10-K
001-37558
03/11/2021
8-K
8-K
8-K
8-K
8-K
10-Q
8-K
8-K
001-37558
12/20/2019
001-37558
06/01/2020
001-37558
03/01/2021
001-37558
09/27/2021
001-38132
06/26/2017
001-37558
11/09/2017
001-38132
06/26/2017
001-38132
6/26/2017
4.1
4.1
4.1
4.1
4.1
10.1
10.2
10.2
10.3
F-1
333-205073
06/18/15
10.4
10-K
001-37558
03/12/2019
10.10
8-K
001-37558
02/02/2018
10.1
8-K
001-37558
02/02/2018
10.2
10-K
03/16/2018
03/16/2018
10.16
177
Table of Contents
10.10** Master Agreement for the Manufacture,
Packaging and Supply of Products, dated
August 7, 2017, by and between ALMAC
Pharma Services Limited and Nabriva
Therapeutics Ireland DAC
10.11** Key Intermediate Supply Agreement,
dated of August 28, 2017 by and among
Nabriva Therapeutics Ireland DAC, and
SEL Biochem Xinjiang Co., Ltd, and
Fountain International Development
Holding Limited
10.12** License Agreement, dated March 26, 2018,
by and among Nabriva Therapeutics
Ireland DAC, Sinovant Sciences, Ltd.,
Nabriva Therapeutics GmbH and Roivant
Sciences, Ltd.
10.13 Transition, Separation and Release of
Claims Agreement, by and between
Nabriva Therapeutics US, Inc. and Colin
Broom, dated as of July 23, 2018
10.14# Amended and Restated Employment
Agreement, by and between Nabriva
Therapeutics US, Inc. and Theodore
Schroeder, dated as of March 10, 2021
10.15 Consulting Agreement, by and between
Nabriva Therapeutics US, Inc. and Colin
Broom, dated as of July 24, 2018 (included
as Attachment A to Exhibit 10.1)
10.16 Form of Inducement Option Award
10-K
03/16/2018
03/16/2018
10.17
10-K
03/16/2018
03/16/2018
10.18
10-Q
001-37558
05/08/2018
10.2
8-K
001-37558
07/25/2018
10.1
10-K
001-37558
03/11/2021
10.18
8-K
001-37558
07/25/2018
10.1
Agreement.
S-8
333-226330
07/25/2018
99.2
10.17 Form of Inducement Performance-Based
Share Award Agreement.
S-8
333-226330
07/25/2018
99.3
10.18 Stock Purchase Agreement by and among
SG Pharmaceuticals, Inc., the Sellers
named on Annex A, and Julia Feliciano, as
Sellers’ Representative, dated as of May 5,
2015
10.19** License Agreement by and between ICPD
Holdings, LLC and Evelyn J. Ellis-Grosse
and Zavante Therapeutics, Inc., dated as of
March 1, 2014
10.20** Manufacturing and Supply Agreement by
and between Zavante Therapeutics, Inc.
and Ercros, S.A., dated as of July 28, 2016
10-Q
001-37558
11/06/2018
10.4
10-Q
001-37558
11/06/2018
10.5
10-Q
001-37558
11/06/2018
10.7
178
Table of Contents
10.21** Amended and Restated Three-Way
Agreement by and between Laboratorios
ERN, S.A, Ercros, S.A., and Zavante
Therapeutics, Inc., dated as of July 28,
2016
10.22** Amended and Restated Pharmaceutical
Manufacturing and Exclusive Supply
Agreement by and between Laboratorios
ERN, S.A. and Zavante Therapeutics, Inc.
dated as of July 28, 2016, as amended
10.23** Manufacturing and Supply Agreement by
and between Zavante Therapeutics, Inc.
and Fisiopharma, S.r.l., dated as of
April 25, 2017
10.24** Commercial Packaging Agreement by and
between Zavante Therapeutics, Inc. and
AndersonBrecon Inc., d/b/a PCI of Illinois,
dated as of December 26, 2017
10.25** Packaging and Supply Agreement by and
between Sharp Corporation and Nabriva
Therapeutics US, Inc., dated as of
August 30, 2018
10.26# Third Amended and Restated Employment
Agreement by and between Nabriva
Therapeutics US, Inc. and Steven Gelone,
dated as of March 10, 2021
10-Q
001-37558
11/06/2018
10.8
10-Q
001-37558
11/06/2018
10.9
10-Q
001-37558
11/06/2018
10.10
10-Q
001-37558
11/06/2018
10.11
10-Q
001-37558
11/06/2018
10.12
10-K
001-37558
03/11/2021
10.31
99.1
10.27# 2018 Employee Share Purchase Plan
DEF 14A
001-37558
06/19/2018
10.28** Loan and Security Agreement, dated as of
December 20, 2018, by and among
Nabriva Therapeutics plc, Nabriva
Therapeutics Ireland DAC, certain other
subsidiaries of Nabriva Therapeutics plc
from time to time party thereto, any bank
and other financial institution or entity
from time to time party thereto and
Hercules Capital, Inc, as
administrativeagent and collateral agent.
10.29** Agreement for the Commercial Supply of
Products by and between Arran Chemical
Company Limited and Nabriva
Therapeutics Ireland DAC, dated as of
November 12, 2018
10.30** Active Pharmaceutical Ingredient Supply
Agreement by and between Nabriva
Therapeutics Ireland DAC and Hovione
Limited, dated as of November 23, 2018.
10-K
001-37558
3/12/2019
10.35
10-K
001-37558
3/12/2019
10.37
10-K
001-37558
3/12/2019
10.38
179
Table of Contents
10.31 2019 Inducement Share Incentive Plan
S-8
333-230216
3/12/2019
99.1
10.32 First Amendment to Loan and Security
Agreement, dated as of September 26,
2019, by and among Nabriva Therapeutics
Public Limited Company, Nabriva
Therapeutics Ireland Designated Activity
Company, Nabriva Therapeutics GmbH,
Nabriva Therapeutics US, Inc., Zavante
Therapeutics, Inc., and Hercules Capital,
Inc.
10.33 Second Amendment to Loan and Security
Agreement, dated as of January 8, 2020, by
and among Nabriva Therapeutics Public
Limited Company, Nabriva Therapeutics
Ireland Designated Activity Company,
Nabriva Therapeutics GmbH, Nabriva
Therapeutics US, Inc., Zavante
Therapeutics, Inc., and Hercules Capital,
Inc.
10.34 Third Amendment to Loan and Security
Agreement, dated as of March 11, 2020, by
and among Nabriva Therapeutics Public
Limited Company, Nabriva Therapeutics
Ireland Designated Activity Company,
Nabriva Therapeutics GmbH, Nabriva
Therapeutics US, Inc., Zavante
Therapeutics, Inc., and Hercules Capital,
Inc.
10.35# Form of Share Option / Cash Settled Share
Appreciation Right Agreement under the
2020 Share Incentive Plan
10.36# 2020 Share Incentive Plan, as amended
10.37 Sales Promotion and Distribution
Agreement, dated as of July 15, 2020, by
and among Nabriva Therapeutics Ireland
Designated Activity Company, MSD
International GmbH and Merck Sharp &
Dohme Corp.
10.38 Sublease Agreement, dated as of February
8, 2021, by and between Professional
Payroll Solutions, LLC and Nabriva
Therapeutics US, Inc.
10.39# 2021 Inducement Share Incentive Plan, as
10-Q
001-37558
11/12/2019
10.1
10-K
001-37558
03/12/2020
10.40
10-K
001-37558
03/12/2020
10.41
10-K
8-K
001-37558
03/12/2020
001-37558
07/29/2020
10.43
99.1
10-Q
001-37558
08/6/2020
10.2
8-K
001-37558
02/12/2021
10.1
amended
S-1
333-260146
10/08/2021
10.43
10.40# Employment Agreement, by and between
Nabriva Therapeutics US, Inc. and Daniel
Dolan, dated as of March 10, 2021
10-K
001-37558
03/11/2021
10.47
180
Table of Contents
10.41*** First Amendment to License Agreement,
dated October 29, 2021, by and among
Nabriva Therapeutics Ireland DAC,
Sinovant Sciences, Ltd., Nabriva
Therapeutics GmbH and Roivant Sciences,
Ltd.
10.42 Consulting Agreement, by and between
Nabriva Therapeutics US, Inc. and Sender
Consulting LLC, dated as of March 9,
2021.
10.43# Employment Agreement dated August 24,
2021 by and between Nabriva
Therapeutics US, Inc. and J. Christopher
Naftzger
10.44# Employment Agreement dated August 23,
2021 by and between Nabriva
Therapeutics US, Inc. and Christine Guico-
Pabia
10.45 Purchase Agreement dated September 24,
2021 between Nabriva Therapeutics plc
and Lincoln Park Capital Fund, LLC
10.46 Fourth Amendment to Loan and Security
Agreement, dated as of June 2, 2021, by
and among Nabriva Therapeutics Public
Limited Company, Nabriva Therapeutics
Ireland Designated Activity Company,
Nabriva Therapeutics GmbH, Nabriva
Therapeutics US, Inc., Zavante
Therapeutics, Inc., and Hercules Capital,
Inc.
10.47 Assignment, Assumption and Novation
agreement, by and among Nabriva
Therapeutics Ireland Designated Activity
Company, Nabriva Therapeutics GmbH,
Roivant Sciences Ltd., Roivant China
Holdings Ltd., Sinovant Sciences HK
Limited, Sinovant Sciences Co., Ltd.,
Sumitomo Dainippon Pharma Co., Ltd.
and Sumitomo Pharmaceuticals (Suzhou)
Co., Ltd.
10.48 First Amendment to Sales Promotion and
Distribution Agreement, dated as of July
15, 2020, by and among Nabriva
Therapeutics Ireland Designated Activity
Company, MSD International GmbH and
Merck Sharp & Dohme Corp.
10-K
001-37558
03/11/2021
10.48
10-K
001-37558
03/11/2021
10.49
10-Q
001-37558
11/09/2021
10.1
10-Q
8-K
001-37558
001-37558
11/09/2021
9/24/2021
10.2
10.1
10-Q
001-37558
08/05/2021
10.1
10-Q
001-37558
08/05/2021
10.2
10-Q
001-37558
08/05/2021
10.3
181
Table of Contents
10.49 Second Amendment to Sales Promotion
and Distribution Agreement, dated as of
April 12, 2021, by and among Nabriva
Therapeutics Ireland Designated Activity
Company, MSD International GmbH and
Merck Sharp & Dohme Corp.
10.50 First Amendment to API Supply
Agreement, dated August 4, 2021, by and
between Nabriva Therapeutics Ireland
Designated Activity Company and
Hovione Limited
10.51 Consulting Agreement, dated May 3, 2021,
by and between Nabriva Therapeutics US,
Inc. and Jennifer Schranz
10.52 Open Market Sale AgreementSM, dated May
6, 2021, by and between Nabriva
Therapeutics plc and Jefferies LLC
10.53 Form of Share Option Agreement under
10-Q
001-37558
08/05/2021
10.4
10-Q
001-37558
08/05/2021
10.5
10-Q
001-37558
05/06/2021
10.1
10-Q
001-37558
05/06/2021
10.2
the 2020 Share Incentive Plan, as amended
10-Q
001-37558
05/06/2021
10.3
10.54 Form of Restricted Share Unit Agreement
under the 2020 Share Incentive Plan, as
amended (Share Withholding)
10.55 Form of Restricted Share Unit Agreement
under the 2020 Share Incentive Plan, as
amended (Automatic Sale)
10.56 Form of Share Option Agreement under
10-Q
001-37558
05/06/2021
10.4
10-Q
0001-37558
05/06/2021
10.5
the 2021 Inducement Share Incentive Plan
10-Q
001-37558
05/06/2021
10.6
10.57# Form of Contingent RSU Award
Agreement under the 2020 Share Incentive
Plan, as amended
10.58*** Side Agreement to Manufacturing Services
Agreement, dated November 19, 2021, by
and among Nabriva Therapeutics Ireland
DAC and Patheon UK Ltd.
21.1 Subsidiaries of Nabriva Therapeutics plc
23.1 Consent of KPMG LLP
31.1 Certification of principal executive officer
pursuant to Rule 13a-14(a) or 15d-14(a) of
the Securities Exchange Act of 1934, as
adopted pursuant to Section 302 of the
Sarbanes-Oxley Act of 2002.
182
X
X
X
X
X
Table of Contents
31.2 Certification of principal financial officer
pursuant to Rule 13a-14(a) or 15d-14(a) of
the Securities Exchange Act of 1934, as
adopted pursuant to Section 302 of the
Sarbanes-Oxley Act of 2002.
32.1 Certification of principal executive officer
pursuant to 18 U.S.C. §1350, as adopted
pursuant to Section 906 of the Sarbanes-
Oxley Act of 2002.
32.2 Certification of principal financial officer
pursuant to 18 U.S.C. §1350, as adopted
pursuant to Section 906 of the Sarbanes-
Oxley Act of 2002.
101.INS Inline XBRL Instance Document
101.SCH Inline XBRL Taxonomy Extension
Schema Document
101.CAL Inline XBRL Taxonomy Calculation
Linkbase Document
101.DEF Inline XBRL Taxonomy Extension
Definition Linkbase Document
101.LAB Inline XBRL Taxonomy Label Linkbase
Document
101.PRE Inline XBRL Taxonomy Presentation
Linkbase Document
104 Cover Page Interactive Data File
(formatted as Inline XBRL and contained
in Exhibit 101)
X
X
X
X
X
X
X
X
X
X
# Management contract or compensatory plan or arrangement filed in response to Item 15(a)(3) of the Instructions to the
Annual Report on Form 10-K.
* Confidential treatment was granted for certain portions that are omitted from this exhibit. The omitted information has
been filed separately with the U.S. Securities and Exchange Commission (the “SEC”) pursuant to the registrant’s
application for confidential treatment. In addition, schedules have been omitted from this exhibit pursuant to Item 601(b)
(2) of Regulation S-K. A copy of any omitted schedule will be furnished supplementally to the SEC upon request;
provided, however, that the registrant may request confidential treatment for any document so furnished.
** Confidential treatment has been granted as to certain portions, which portions have been omitted and separately filed
with the Securities and Exchange Commission.
*** Portions of this exhibit have been omitted pursuant to Item 601(b)(10)(iv) of Regulation S-K.
183
Table of Contents
SIGNATURES
Pursuant to the requirements of Section 13 or 15(d) of the Securities Exchange Act of 1934, the registrant has duly
caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.
Date: March 29, 2022
NABRIVA THERAPEUTICS PLC
By:
/s/ THEODORE SCHROEDER
Theodore Schroeder
Chief Executive Officer
Pursuant to the requirements of the Securities Exchange Act of 1934, this report has been signed below by the
following persons on behalf of the registrant and in the capacities and on the dates indicated:
Signature
Title
Date
/s/ THEODORE SCHROEDER
Theodore Schroeder
Director, Chief Executive Officer (Principal
Executive Officer)
/s/ DANIEL DOLAN
Daniel Dolan
Chief Financial Officer (Principal Financial and
Accounting Officer)
March 29, 2022
March 29, 2022
/s/ DANIEL BURGESS
Daniel Burgess
/s/ COLIN BROOM
Colin Broom
/s/ CARRIE BOURDOW
Carrie Bourdow
/s/ LISA DALTON
Lisa Dalton
/s/ CHARLES A. ROWLAND JR.
Charles A. Rowland Jr.
/s/ STEPHEN WEBSTER
Stephen Webster
/s/ STEVEN GELONE
Steven Gelone
/s/ MARK CORRIGAN
Mark Corrigan
Chairman of the Board
March 29, 2022
Director
Director
Director
Director
Director
March 29, 2022
March 29, 2022
March 29, 2022
March 29, 2022
March 29, 2022
Director, President and Chief Operating Officer
March 29, 2022
Director
March 29, 2022
184
Table of Contents
INDEX TO FINANCIAL STATEMENTS
Nabriva Therapeutics plc
Audited Consolidated Financial Statements
Report of Independent Registered Public Accounting Firm (KPMG LLP, Philadelphia, PA, Auditor Firm ID:
185)
Consolidated balance sheets as of December 31, 2021 and 2020
Consolidated statements of operations for the years ended December 31, 2021, 2020 and 2019
Consolidated statements of changes in stockholders’ equity for the years ended December 31, 2021, 2020 and
2019
Consolidated statements of cash flows for the years ended December 31, 2021, 2020 and 2019
Notes to the consolidated financial statements
F-2
F-4
F-5
F-6
F-7
F-8
F-1
Table of Contents
REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
To the Stockholders and Board of Directors
Nabriva Therapeutics plc:
Opinion on the Consolidated Financial Statements
We have audited the accompanying consolidated balance sheets of Nabriva Therapeutics plc and subsidiaries (the
Company) as of December 31, 2021 and 2020, the related consolidated statements of operations, changes in stockholders’
equity, and cash flows for each of the years in the three-year period ended December 31, 2021, and the related notes
(collectively, the consolidated financial statements). In our opinion, the consolidated financial statements present fairly, in
all material respects, the financial position of the Company as of December 31, 2021 and 2020, and the results of its
operations and its cash flows for each of the years in the three-year period ended December 31, 2021, in conformity with
U.S. generally accepted accounting principles.
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 to the consolidated financial statements, the Company has incurred recurring losses
and negative cash flows from operations that raise substantial doubt about its ability to continue as a going concern.
Management’s plans in regard to these matters are also described in Note 1. The consolidated financial statements do not
include any adjustments that might result from the outcome of this uncertainty.
Basis for Opinion
These consolidated financial statements are the responsibility of the Company’s management. Our responsibility is to
express an opinion on these consolidated financial statements based on our audits. We are a public accounting firm
registered with the Public Company Accounting Oversight Board (United States) (PCAOB) and are required to be
independent with respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and
regulations of the Securities and Exchange Commission and the PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and
perform the audit to obtain reasonable assurance about whether the consolidated financial statements are free of material
misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an
audit of its internal control over financial reporting. As part of our audits, we are required to obtain an understanding of
internal control over financial reporting but not for the purpose of expressing an opinion on the effectiveness of the
Company’s internal control over financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the 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. We believe that our audits provide a reasonable
basis for our opinion.
Critical Audit Matter
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: (1) relates to accounts
or disclosures that are material to the consolidated financial statements and (2) involved our especially challenging,
subjective, or complex judgments. The communication of a critical audit matter 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.
F-2
Table of Contents
Evaluation of the net realizable value of XENLETA inventory and potential loss on firm purchase commitments
As discussed in Notes 2 and 15 to the consolidated financial statements, the Company had XENLETA inventory
with a carrying value of $10.7 million and had firm purchase commitments of $54.0 million for XENLETA active
pharmaceutical ingredient (API) as of December 31, 2021. Inventory is stated at the lower of cost or net realizable
value, and valued on a first-in, first-out basis. The Company reviews inventories for realization and records a
provision for estimated excess, slow-moving and obsolete inventory, as well as inventory with a carrying value in
excess of net realizable value and accrues potential losses on firm purchase commitments.
We identified the evaluation of the net realizable value of excess or obsolete XENLETA inventory and potential
loss on firm purchase commitments of XENLETA API as a critical audit matter. A high degree of auditor
judgment was required to evaluate XENLETA forecasted sales and the resulting inventory consumption prior to
inventory expiration dates and in comparison to firm purchase commitments of XENLETA API.
The following are the primary procedures we performed to address this critical audit matter. To evaluate the
XENLENTA forecasted sales, we inquired of operational personnel of the Company and compared them to
analyst reports. To evaluate inventory consumption prior to inventory expiration dates and the potential loss on
firm purchase commitments of XENLETA API, we compared the forecasted sales quantities to inventory
expiration date by manufacturing lot and to firm purchase commitments of XENLETA API. We also performed a
sensitivity analysis of XENLENTA forecasted sales used in the Company’s analysis.
/s/ KPMG LLP
We have served as the Company’s auditor since 2017.
Philadelphia, Pennsylvania
March 29, 2022
F-3
Table of Contents
NABRIVA THERAPEUTICS plc
Consolidated Balance Sheets
(in thousands, except share data)
Assets
Current assets:
Cash and cash equivalents
Restricted cash
Short-term investments
Accounts receivable, net and other receivables
Inventory
Prepaid expenses
Total current assets
Property, plant and equipment, net
Intangible assets, net
Other non-current assets
Total assets
Liabilities and stockholders´ equity
Current liabilities:
Current portion of long-term debt
Accounts payable
Accrued expense and other current liabilities
Deferred revenue
Total current liabilities
Non-current liabilities:
Long-term debt
Other non-current liabilities
Total non-current liabilities
Total liabilities
Commitments and contingencies (Note 15)
Stockholders’ equity:
Ordinary shares, nominal value $0.01, 100,000,000 ordinary shares authorized
at December 31, 2021; 56,715,306 and 21,078,781 issued and outstanding at
December 31, 2021 and December 31, 2020, respectively
Preferred shares, nominal value $0.01, 100,000,000 shares authorized at
December 31, 2021; None issued and outstanding
Additional paid in capital
Accumulated other comprehensive income
Accumulated deficit
Total stockholders’ equity
Total liabilities and stockholders’ equity
As of
December 31, 2021
As of
December 31, 2020
$
$
$
$
$
$
$
47,659
175
16
12,751
14,509
5,155
80,265
233
31
380
80,909
3,765
4,372
13,829
374
22,340
4,265
954
5,219
27,559
41,359
231
16
3,909
5,823
5,880
57,218
768
80
370
58,436
2,041
2,889
12,844
750
18,524
5,686
1,091
6,777
25,301
567
211
—
648,432
27
(595,676)
53,350
80,909
$
—
579,123
27
(546,226)
33,135
58,436
The accompanying notes form an integral part of these consolidated financial statements.
F-4
Table of Contents
NABRIVA THERAPEUTICS plc
Consolidated Statements of Operations
(in thousands, except share and per share data)
Revenues:
Product revenue, net
Collaboration revenue
Research premium and grant revenue
Total revenue
Operating expenses:
Cost of revenues
Research and development expenses
Selling, general and administrative expenses
Total operating expenses
Loss from operations
Other income (expense):
Other income (expense), net
Interest income (expense), net
Loss on extinguishment of debt
Loss before income taxes
Income tax expense
Net loss
Loss per share
Basic and diluted ($ per share)
Weighted average number of shares:
Basic and diluted
$
$
$
2021
Year ended December 31,
2020
2019
23,386
3,830
1,679
28,895
(13,148)
(12,630)
(51,645)
(77,423)
(48,528)
469
(901)
—
(48,960)
(490)
(49,450)
(1.14)
$
$
$
108
2,756
2,163
5,027
(766)
(15,102)
(55,285)
(71,153)
(66,126)
1,187
(1,649)
(2,757)
(69,345)
(139)
(69,484)
(5.41)
$
$
$
1,538
6,210
1,733
9,481
(70)
(26,415)
(62,485)
(88,970)
(79,489)
215
(3,389)
—
(82,663)
(101)
(82,764)
(11.15)
43,349,461
12,845,089
7,419,948
The accompanying notes form an integral part of these consolidated financial statements.
F-5
Table of Contents
NABRIVA THERAPEUTICS plc
Consolidated Statements of Changes in Stockholders’ Equity
Ordinary shares
Additional
paid in
Accumulated
other
Total
comprehensive Accumulated stockholders'
Number
of shares Amount
$
$
(in thousands)
January 1, 2019
Issuance of ordinary shares and warrants
Equity transaction costs
Stock-based compensation expense
Shares issued in connection with the vesting of restricted stock units
Shares issued in connection with the employee stock purchase plan
Shares issued in connection with the acquisition of Zavante Therapeutics, Inc.
Net loss
December 31, 2019
Issuance of ordinary shares
Shares issued in connection with the employee stock purchase plan
Shares issued in connection with the vesting of restricted stock units
Equity transaction costs
Stock-based compensation expense
Net loss
December 31, 2020
Issuance of ordinary shares
Shares issued in connection with the vesting of restricted stock units
Equity transaction costs
Stock-based compensation expense
Net loss
December 31, 2021
6,702
2,584
—
—
66
21
82
—
9,455
11,571
9
44
—
—
—
21,079
34,922
82
632
—
—
56,715
$
capital
income
deficit
equity
462,514
48,056
(2,794)
9,748
(1)
372
(1)
—
517,894
60,944
43
—
(4,977)
5,219
—
579,123
69,790
—
(3,772)
3,291
—
648,432
$
$
27
$
—
—
—
—
—
27
—
—
—
—
—
—
27
—
—
—
—
—
27
$
(393,978)
$
—
—
—
—
—
—
(82,764)
(476,742)
—
—
—
—
—
(69,484)
(546,226)
—
—
—
—
(49,450)
(595,676)
$
68,630
48,082
(2,794)
9,748
—
372
—
(82,764)
41,274
61,060
43
—
(4,977)
5,219
(69,484)
33,135
70,138
2
(3,766)
3,291
(49,450)
53,350
67
26
—
—
1
—
1
—
95
116
—
—
—
—
—
211
348
2
6
—
—
567
$
The accompanying notes form an integral part of these consolidated financial statements.
F-6
Table of Contents
NABRIVA THERAPEUTICS plc
Consolidated Statements of Cash Flows
(in thousands)
Cash flows from operating activities
Net loss
Adjustments to reconcile net loss to net cash used in operating activities:
2021
Year Ended December 31,
2020
2019
$
(49,450)
$
(69,484)
$
(82,764)
Non-cash other income/expense, net
Non-cash interest income
Non-cash interest expense
Loss on extinguishment of debt
Depreciation and amortization expense
Decrease in right-of-use assets
Stock-based compensation
Other, net
Changes in operating assets and liabilities:
(Increase)/decrease in other non-current assets
(Increase)/decrease in accounts receivable, net and other receivables and
prepaid expenses
Increase in inventory
Increase/(decrease) in accounts payable
Increase/(decrease) in accrued expenses and other liabilities
Increase/(decrease) in deferred revenue
Decrease in other non-current liabilities
Decrease in income tax liabilities
Net cash used in operating activities
Cash flows from investing activities
Purchases of plant and equipment and intangible assets
Other
Net cash (used in) provided by investing activities
Cash flows from financing activities
Proceeds from exercise of warrants
Proceeds from issuance of ordinary shares and warrants
Proceeds from at-the-market facility
Proceeds from long-term debt, net of issuance costs
Proceeds from employee stock purchase plan
Repayments of long-term borrowings
Equity transaction costs
Net cash provided by financing activities
Effects of exchange rate changes on the balance of cash held in foreign
currencies
Net increase/(decrease) in cash, cash equivalents and restricted cash
Cash, cash equivalents, and restricted cash at beginning of year
Cash, cash equivalents and restricted cash at end of year
Supplemental disclosure of cash flow information:
Interest paid
Taxes paid
Equity transaction costs included in accounts payable and accrued expenses
$
424
—
404
—
356
281
3,291
(6)
(10)
(8,117)
(8,686)
1,581
946
(376)
(189)
(6)
(59,557)
(25)
(56)
(81)
—
27,911
42,280
—
—
—
(3,825)
66,366
(484)
6,244
41,590
47,834
497
513
712
50
—
636
2,757
417
403
5,219
62
8
(5,887)
(5,141)
(1,813)
714
750
(2)
(20)
(71,331)
(113)
(161)
(274)
665
53,460
7,520
—
43
(30,000)
(4,764)
26,924
(140)
(44,821)
86,411
41,590
$
1,396
4
765
(40)
22
519
—
396
374
9,748
48
50
2,582
(682)
1,310
(3,209)
—
(172)
(74)
(71,892)
(61)
392
331
—
20,138
27,945
9,980
372
—
(2,360)
56,075
(106)
(15,592)
102,003
86,411
2,560
11
552
The accompanying notes form an integral part of these consolidated financial statements.
F-7
Table of Contents
NABRIVA THERAPEUTICS plc
Notes to the Consolidated Financial Statements
(in thousands, except per share data)
1. Organization and Business Activities
Nabriva Therapeutics plc, or Nabriva Ireland, together with its wholly owned and consolidated subsidiaries,
Nabriva Therapeutics GmbH, or Nabriva Austria, Nabriva Therapeutics US, Inc., Zavante Therapeutics, Inc., or Zavante,
and Nabriva Therapeutics Ireland DAC, collectively, Nabriva, or the Company, is a biopharmaceutical company engaged in
the commercialization and development of novel anti-infective agents to treat serious infections. The Company’s
headquarters are located at 25-28 North Wall Quay, Dublin, Ireland.
In September 2021, Sumitomo Pharmaceuticals (Suzhou) and the Company announced the approval received by
Sumitomo Pharmaceuticals (Suzhou) to market oral and intravenous formulations of XENLETA for the treatment of
community-acquired pneumonia in adults in Taiwan.
In September 2020, the Centers for Medicare & Medicaid Services, or CMS, granted a new technology add-on
payment, or NTAP, for XENLETA® (lefamulin) for injection, when administered in the hospital inpatient setting. Both the
intravenous, or IV and oral formulations of XENLETA were granted Qualified Infectious Disease Product, or QIDP, and
Fast Track designation by the U.S. Food and Drug Administration, or FDA. NTAP was also granted for CONTEPO™
(fosfomycin for injection, previously referred to as ZTI-01 and ZOLYD), making it the first QIDP antibiotic to be granted
conditional NTAP approval prior to receiving FDA approval. CONTEPO was granted QIDP and Fast Track Designation by
the FDA for the treatment of complicated urinary tract infections, or cUTIs, including acute pyelonephritis.
In July 2020, the Company announced that the European Commission, or EC, issued a legally binding decision for
approval of the marketing authorization application for XENLETA™ (lefamulin) for the treatment of community-acquired
pneumonia, or CAP, in adults following a review by the European Medicines Agency, or EMA. The EMA approval of
XENLETA in CAP patients when it is considered inappropriate to use antibacterial agents that are commonly
recommended for initial treatment or when these agents have failed paves the way for the launch of XENLETA across the
European Economic Area, or EEA, and United Kingdom, or U.K. The EC approved XENLETA for all countries of the
European Economic Area, or EEA, and United Kingdom, or U.K. Nabriva intends to work with a commercial partner to
make XENLETA available to patients in the European Economic Area, or EEA, and United Kingdom, or U.K.
In July 2020, the Company announced that Sunovion Pharmaceuticals Canada Inc., or Sunovion, received approval
from Health Canada to market oral and IV formulations of XENLETA® (lefamulin) for the treatment of CAP in adults,
with the Notice of Compliance from Health Canada dated July 10, 2020. Nabriva entered into a license and
commercialization agreement in March 2019 with Sunovion Pharmaceuticals Canada Inc. for XENLETA in Canada.
In July 2020, the Company announced that it entered into a Sales Promotion and Distribution Agreement, or the
Distribution Agreement, with MSD International GmbH, or MSD, and Merck Sharp & Dohme Corp., or Supplier, each a
subsidiary of Merck & Co. Under the Distribution Agreement, MSD appointed the Company as its sole and exclusive
distributor of certain products containing tedizolid phosphate as the active ingredient previously marketed and sold by
Supplier and MSD under the trademark SIVEXTRO® for injection, intravenous use and oral use in the United States and
its territories. SIVEXTRO is an oxazolidinone-class antibacterial indicated in adults and patients 12 years of age and older
for the treatment of acute bacterial skin and skin structure infections caused by certain susceptible Gram-positive
microorganisms. Nabriva has also engaged Amplity Health, a leading pharmaceutical contract commercial organization, to
provide community-based commercial and sales services for SIVEXTRO and XENLETA® in the United States.
In June 2020 the Company announced that WE Pharma Ltd., or WEP Clinical, a specialist pharmaceutical services
company, had signed an exclusive agreement with the Company to supply XENLETA® (lefamulin) on a named
F-8
Table of Contents
patient or expanded access basis in certain countries outside of the US, China and Canada. The Named Patient Program, or
NPP, is designed to ensure that physicians, contingent on meeting the necessary eligibility criteria and receiving approval,
can request IV or oral XENLETA on behalf of patients who live in certain countries where it is not yet available and have
an unmet medical need.
In September 2019, the Company announced that the oral and IV formulations of XENLETA (lefamulin) are
available in the United States for the treatment of community-acquired bacterial pneumonia, or CABP, through major
specialty distributors. This followed the approval by the FDA of the Company’s New Drug Application, or NDA, for
XENLETA on August 19, 2019 for the treatment of adults with CABP. XENLETA is the first oral and IV treatment in the
pleuromutilin class of antibiotics available for the systematic administration in humans.
Liquidity
Since its inception, the Company has incurred net losses and generated negative cash flows from its operations
which has resulted in a significant accumulated deficit to date. The Company has financed its operations through the sale of
equity securities, convertible and term debt financings and research and development support from governmental grants
and proceeds from its licensing agreements. As of December 31, 2021, the Company had cash and cash equivalents,
restricted cash and short-term investments of $47.9 million.
The Company follows the provisions of Financial Accounting Standards Board, or FASB, Accounting Standards
Codification, or ASC, Topic 205-40, Presentation of Financial Statements — Going Concern, or ASC 205-40, which
requires management to assess the Company’s ability to continue as a going concern for one year after the date the
consolidated financial statements are issued.
The Company expects to continue to invest in critical commercial and medical affairs activities, its commitments
per the agreement with Merck & Co., Inc., as well as investing in its supply chain for the commercialization of
SIVEXTRO, XENLETA and the potential launch of CONTEPO, if approved. The Company expects to seek additional
funding in future periods to support these activities. While the Company has raised capital in the past, the ability to raise
capital in future periods is not considered probable, as defined under the accounting standards. As such, under the
requirements of ASC 205-40, management may not consider the potential for future capital raises in their assessment of the
Company’s ability to meet its obligations for the next twelve months.
In April 2020, the Company announced a restructuring of its hospital-based commercial sales force and transition
to a community-based sales effort. The restructuring reduced costs to align with the capabilities of the Company’s sales
effort with its strategic re-focus on making sales of XENLETA to community health care professionals. The termination of
the sales force was timed, in part, to coincide with operational changes that were implemented by the Company in response
to the outbreak of the novel coronavirus, SARS-CoV-2, causing the disease referred to as “COVID-19”. In response to the
COVID-19 pandemic, the Company closed its administrative offices and shifted to a remote working business model. The
Company implemented a hybrid-remote-working policy for all of its employees, all of which have had, and we believe will
continue to have, an impact on our consolidated results of operations, financial position and cash flows. The commercial
and medical organizations suspended in-person interactions with physicians and customers and were restricted to
conducting educational and promotional activities virtually. The Company has secured a virtual and in-person sales effort
with community-based expertise with Amplity Health, which is a contract sales organization, to replace its hospital-based
sale force and began a small and focused sales effort for SIVEXTRO and XENLETA in September 2020. The Company
expanded this effort to 60 sales representatives and may expand it further. The Company also piloted a virtual promotion
effort with incremental sales representatives in the third quarter of 2021.
F-9
Table of Contents
The Company’s expenses will increase if it suffers any regulatory delays or is required to conduct additional
clinical trials to satisfy regulatory requirements. The Company has incurred and expects to continue to incur significant
commercialization expenses related to its commitments per the agreement with Merck & Co., Inc., product sales,
marketing, distribution and manufacturing for SIVEXTRO, XENLETA and CONTEPO, if approved. It is also uncertain
when, if ever, the Company will generate sufficient revenues from product sales to achieve profitability.
As a result, based on the Company’s available cash resources, the minimum cash required under the Loan and
Security Agreement (the “Loan Agreement”) with Hercules Capital, Inc., and in accordance with the requirements of ASC
205-40, management has concluded that substantial doubt exists about the Company’s ability to continue as a going
concern for one year from the date these consolidated financial statements are issued. A failure to raise the additional
funding or to effectively implement cost reductions could harm the Company’s business, results of operations and future
prospects. If the Company is not able to secure adequate additional funding in future periods, the Company may make
additional reductions in certain expenditures. This may include liquidating assets and suspending or curtailing planned
programs. The Company may also have to delay, reduce the scope of, suspend or eliminate one or more research and
development programs or its commercialization efforts.
In May 2021, the Company entered into an Open Market Sale AgreementSM, or the New Sale Agreement, with
Jefferies, as agent, pursuant to which the Company may offer and sell ordinary shares, for aggregate gross sale proceeds of
up to $50.0 million, from time to time through Jefferies, by any method permitted that is deemed an “at the market
offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as amended. As of December 31,
2021, the Company has issued and sold an aggregate of 18,232,689 ordinary shares pursuant to the New Sale Agreement
and received gross proceeds of $30.5 million and net proceeds of $29.3 million, after deducting commissions to Jefferies
and other offering expenses. From January 1, 2022 and through the date of this filing, the Company has issued and sold an
aggregate of 1,338,282 ordinary shares pursuant to the New Sale Agreement and received gross proceeds of $595,000 and
net proceeds of $580,000, after deducting commissions to Jefferies and other offering expenses. As of the date of this
filing, the Company may issue and sell ordinary shares for gross proceeds of up to $19.0 million under the New Sale
Agreement.
In September 2021, the Company entered into a purchase agreement, or Purchase Agreement, with Lincoln Park
Capital Fund, LLC, or Lincoln Park, which, subject to the terms and conditions, provides that the Company has the right to
sell to Lincoln Park and Lincoln Park is obligated to purchase up to $23.0 million of its ordinary shares. In addition, under
the Purchase Agreement, the Company agreed to issue a commitment fee of 632,474 ordinary shares, or the Commitment
Shares, as consideration for Lincoln Park entering into the Purchase Agreement and for the payment of $0.01 per
Commitment Share. Under the Purchase Agreement, the Company may from time to time, at its discretion, direct Lincoln
Park to purchase on any single business day, or a Regular Purchase, up to (i) 400,000 ordinary shares if the closing sale
price of its ordinary shares is not below $0.25 per share on Nasdaq, (ii) 600,000 ordinary shares if the closing sale price of
its ordinary shares is not below $2.00 per share on Nasdaq or (iii) 800,000 ordinary shares if the closing sale price of its
ordinary shares is not below $3.00 per share on Nasdaq. In addition to Regular Purchases, the Company may also direct
Lincoln Park to purchase other amounts as accelerated purchases or as additional accelerated purchases on the terms and
subject to the conditions set forth in the Purchase Agreement. In any case, Lincoln Park’s commitment in any single
Regular Purchase may not exceed $2.5 million absent a mutual agreement to increase such amount. As of December 31,
2021, the Company has issued and sold an aggregate of 2,400,000 ordinary shares pursuant to the Purchase Agreement and
received net proceeds of $2.4 million. From January 1, 2022 and through the date of this filing, the Company has issued
and sold an aggregate of 3,600,000 ordinary shares pursuant to the Purchase Agreement and received net proceeds of $1.6
million. As of the date of this filing, the Company may issue and sell ordinary shares for gross proceeds of up to $19.0
million under the Purchase Agreement.
Based on its current operating plans, the Company expects that its existing cash, cash equivalents, restricted cash
and short-term investments as of the date of this filing will be sufficient to enable the Company to fund its operating
expenses, debt service obligations and capital expenditure requirements well into the fourth quarter of 2022. The Company
has based this estimate on assumptions that may prove to be wrong, and the Company could use its capital resources
sooner than expected. This estimate assumes, among other things, that the Company does not obtain any additional funding
through grants and clinical trial support, collaboration agreements or equity or debt financings. This estimate also assumes
that the Company remains in compliance with the covenants and no event of default occurs under
F-10
Table of Contents
the Loan Agreement. The consolidated financial statements have been prepared assuming the Company will continue as a
going concern, which contemplates the continuity of operations, the realization of assets and the satisfaction of liabilities
and commitments in the normal course of business.
2. Summary of Significant Accounting Policies
Basis of Preparation
The consolidated financial statements have been prepared in accordance with generally accepted accounting
principles in the United States of America, or US GAAP, and US Securities and Exchange Commission, or SEC,
regulations for annual reporting. The consolidated financial statements include the accounts of Nabriva Therapeutics plc
and its wholly-owned subsidiaries. All intercompany accounts and transactions have been eliminated in consolidation.
Functional Currency Transactions and Balances
In preparing the consolidated financial statements, transactions in currencies other than the U.S. dollar are
recognized at the exchange rates prevailing at the dates of the transactions. Foreign currency exchange gains and losses
resulting from the settlement of such transactions and from the translation at year-end exchange rates of monetary assets
and liabilities denominated in foreign currencies are recognized in the consolidated statements of operations.
Use of Estimates
The preparation of consolidated financial statements in conformity with US GAAP requires management to make
estimates and assumptions that affect the amount of assets and liabilities and disclosure of contingent assets and liabilities
at the date of the consolidated financial statements and the reported amounts of revenues and expenses during the reporting
period. Actual results could differ from those estimates.
Cash and Cash Equivalents
The Company considers highly liquid investments with original maturities of three months or less to be cash
equivalents.
Short-term Investments
The Company has designated its investments in securities as available-for-sale securities and measures these
securities at their respective fair values. Investments that mature in one year or less are classified as short-term available-
for-sale securities. Investments that are not considered available for use in current operations are classified as long-term
available-for-sale securities. Changes in the fair value of available-for-sale investments are recognized in other
comprehensive income (loss).
Inventory
Inventory is stated at the lower of cost or net realizable value. Inventory is valued on a first-in, first-out basis and
consists primarily of material costs, third-party manufacturing costs, and related transportation costs along the Company's
supply chain. The Company capitalizes inventory upon regulatory approval when, based on management’s judgment,
future commercialization is considered probable and the future economic benefit is expected to be realized; otherwise, such
costs are recorded as research and development expense. Costs of drug product to be consumed in any current or future
clinical trials will continue to be recognized as research and development expense and costs of sample inventory is
recorded as selling, general and administrative expense. The Company reviews inventories for realization on a quarterly
basis and would record provisions for estimated excess, slow-moving and obsolete inventory, as well as inventory with a
carrying value in excess of net realizable value when necessary. As of December 31, 2021, the Company had a $1.0 million
non-cash reserve for excess and obsolete inventory due to timing of expiring inventory.
F-11
Table of Contents
The components of our inventory at December 31, 2021 and 2020 are as follows:
(in thousands)
XENLETA raw materials
XENLETA work in process
XENLETA finished goods
Total XENLETA
SIVEXTRO finished goods
Total inventory
Property, Plant and Equipment
As of
December 31,
2021
As of
December 31,
2020
$
$
1,528
9,142
18
10,688
3,821
14,509
$
$
952
4,608
263
5,823
—
5,823
Property, plant and equipment are stated at cost less accumulated depreciation. Depreciation is calculated using
the straight-line method over the estimated useful lives of the assets. The estimated useful lives of property, plant and
equipment are as follows: 3-5 years for IT equipment, 5-10 years for laboratory equipment and 3-10 years for other plant
and office equipment. The assets’ residual values and useful lives are reviewed, and adjusted if appropriate, at each
reporting date. When assets are sold or otherwise disposed of, the difference between the net proceeds, if any, and the net
carrying amount of the asset is recognized as a gain or a loss in other operating income or expenses.
Intangible Assets and Other Long-lived Assets
Intangible assets, such as acquired computer software licenses, are capitalized on the basis of the costs incurred to
acquire the software and bring it into use. These costs are amortized on a straight-line basis over their estimated useful
lives (3-10 years).
Long-lived assets are assessed for potential impairment when there is evidence that events or changes in
circumstances indicate that the carrying amount of an asset may not be recovered. An impairment loss would be recognized
when undiscounted cash flows expected to be generated by an asset, is less than its carrying amount. The impairment loss
would be measured as the amount by which the asset’s carrying value exceeds its fair value and recognized in these
financial statements.
Segment Information
Operating segments are defined as components of an enterprise about which separate discrete information is
available for evaluation by the chief operating decision maker, or decision-making group, in deciding how to allocate
resources and in assessing performance. The Company views its operations and manages its business as one operating
segment, which is the commercialization and development of novel anti-infective agents to treat serious and life-
threatening infections.
Revenue Recognition—The Company recognizes revenue from sales of its commercial products in accordance with ASC
606, Revenue from Contracts with Customers, or ASC 606.
Net Product Revenue
In September 2019, the Company launched XENLETA and in April 2021 the Company began exclusive
distribution of SIVEXTRO in the United States and certain of its territories. The Company sells its products principally to a
limited number of specialty distributors and wholesalers. The Company recognizes revenue once it has transferred physical
possession of the goods and the customer obtains legal title to the product. Payment terms between Nabriva and its
customers are generally approximately 60 days from the invoice date. In addition to distribution agreements with
customers, the Company enters into arrangements with health care providers and payers that provide for government
mandated and/or privately negotiated rebates, chargebacks and discounts with respect to the purchase of its product.
F-12
Table of Contents
The transaction price that the Company recognizes as revenue reflects the amount it expects to be entitled to in
connection with the sale and transfer of control of product to its customers. At the time that the Company’s customers take
control of the product, which is when the Company’s performance obligation under the sales contracts is complete, the
Company records product revenues net of applicable reserves for various types of variable consideration. The types of
variable consideration are as follows:
● Fees-for-service
● Product returns
● Chargebacks and rebates
● Government rebates
● Commercial payer and other rebates
● Group Purchasing Organizations, or GPO, administration fees
● Voluntary patient assistance programs
In determining the amounts of certain allowances and accruals, the Company must make significant judgments
and estimates. For example, in determining these amounts, the Company estimates prescription demand from retail
pharmacies, specialty pharmacies, hospital demand, buying patterns by hospitals, hospital systems and/or group purchasing
organizations and the levels of inventory held by distributors and customers. The Company also analyzes third party end
usage product consumption patterns to gauge demand for its products. Making these determinations involves analyzing
third party industry data to determine whether trends in historical channel distribution patterns will predict future product
sales. The Company receives data periodically from its customers on inventory levels and historical channel sales mix, and
the Company considers this data when determining the amount of the allowances and accruals for variable consideration.
In assessing the amount of net revenue to record, the Company considers both the likelihood and the magnitude of
the revenue reversal. Actual amounts of consideration ultimately received may differ from the Company’s estimates. If
actual results in the future vary from the Company’s estimates, the Company adjusts these estimates, which would affect
net product revenue and earnings in the period such variances become known. The specific considerations the Company
uses in estimating these amounts related to variable consideration associated with the Company’s products are as follows:
Fees-for-service – The Company offers discounts and pays certain distributor service fees which are recorded as a
reduction of revenue in the period the related product revenue is recognized. The Company does not consider the fees
separate from the distributors’ purchase of the product. The Company records its fee-for-service accruals based on
distributors’ purchases and the applicable discount rate.
Product returns – Generally, the Company’s customers have the right to return products during the 18-month
period beginning six months prior to the labeled expiration date and ending twelve months after the labeled expiration date.
Since the Company has a limited history of SIVEXTRO and XENLETA returns, the Company estimated returns based on
industry data for comparable products in the market. As the Company distributes its product and establishes historical sales
over a longer period of time (i.e., two to three years), the Company will be able to place more reliance on historical
purchasing, demand and return patterns of its customers when evaluating its reserves for product returns. The Company’s
XENLETA product has a forty-eight month shelf life and SIVEXTRO has a thirty-six month shelf life.
The Company’s customers also have the right to return excess inventory on new products that do not yield
forecasted sales. To the extent the Company’s customers determine that the quantities they purchased are in excess of
F-13
Table of Contents
their customers demand, product returns could increase in excess of what the Company has currently reserved which would
result in a reduction to net revenues in future periods.
At the end of each reporting period for any of its products, the Company may decide to constrain revenue for
product returns based on information from various sources, including channel inventory levels and dating and sell-through
data, the expiration dates of product currently being shipped, price changes of competitive products and introductions of
generic products.
Chargebacks and rebates – Chargebacks are discounts that occur when certain contracted customers, which
currently consist primarily of group purchasing organizations, public health service institutions, and Federal government
entities purchasing via the Federal Supply Schedule, purchase directly from our wholesalers or specialty distributors.
Contracted customers generally purchase the product at a discounted price. The Company provides a credit to its
wholesaler or specialty distributor customers (i.e., chargeback), representing the difference between the customer’s
acquisition list price and the discounted price. The calculation of the accrual for chargebacks and rebates is based on
estimates of claims and their associated cost that the Company expects to receive associated with product sales that have
been recognized as revenue but remain in the distribution channel as inventory at the end of each reporting period.
Government rebates –The Company is subject to discount obligations primarily under state Medicaid and
Medicare programs. The Company estimates its Medicaid and Medicare rebates based upon a range of possible outcomes
that are probability-weighted for the estimated payer mix. These reserves are recorded in the same period the related
product revenue is recognized, resulting in a reduction of product revenue and the establishment of a current liability that is
included in accrued expenses on the consolidated balance sheet. For Medicare, the Company also estimates the number of
patients in the prescription drug coverage gap for whom the Company will owe an additional liability under the Medicare
Part D program. The calculation of the accrual for government rebates is based on estimates of claims and their associated
cost that the Company expects to receive associated with product sales that have been recognized as revenue but remain in
the distribution channel as inventory at the end of each reporting period.
Commercial payer and other rebates – The Company contracts with certain private payer organizations, primarily
insurance companies and pharmacy benefit managers, for the payment of rebates with respect to utilization of SIVEXTRO
and XENLETA and contracted formulary status. The Company estimates these rebates and records reserves for such
estimates in the same period the related revenue is recognized. Currently, the reserve for customer payer rebates considers
future utilization based on third party studies of payer prescription data; the utilization is applied to product that remains in
the distribution and retail pharmacy channel inventories at the end of each reporting period. The calculation of the accrual
for commercial payer and other rebates is based on estimates of claims and their associated cost that the Company expects
to receive associated with product sales that have been recognized as revenue but remain in the distribution channel as
inventory at the end of each reporting period.
GPO administration fees – The Company contracts with GPOs and pays administration fees related to contacting
and membership management services provided. In assessing if the consideration paid to the GPO should be recorded as a
reduction in the transaction price, the Company determines whether the payment is for a distinct good or service or a
combination of both. Since GPO fees are not specifically identifiable, the Company does not consider the fees separate
from the purchase of the product. Additionally, the GPO services generally cannot be provided by a third party. Because of
these factors, the consideration paid is considered a reduction of revenue.
Patient assistance – The Company offers certain voluntary patient assistance programs for prescriptions, such as
co-pay assistance programs, which are intended to provide financial assistance to qualified commercially insured patients
with prescription drug co-payments required by payers. The calculation of the accrual for co-pay assistance is based on an
estimate of claims and the cost per claim that the Company expects to receive associated with product sales that have been
recognized as revenue but remains in the distribution channel as inventory at the end of each reporting period.
At the end of each reporting period, the Company will adjust its variable consideration estimates for product
returns, chargebacks, and rebates when the Company believes actual experience may differ from current estimates.
F-14
Table of Contents
Cost of Revenues
Cost of revenues for XENLETA primarily represents direct and indirect manufacturing costs, while cost of
revenues for SIVEXTRO represent the actual purchase cost for the finished product from Merck. Prior to the FDA
approval of XENLETA on August 19, 2019, the inventory costs for XENLETA were expensed as research and
development expenses since the approval was outside of our control and therefore not considered probable. As such, the
majority of the expenses incurred for our initial inventories of XENLETA has been previously expensed. For the years
ended December 31, 2021 and 2020, cost of revenues include a $0.3 million and $0.7 million non-cash reserve adjustment
for excess and obsolete inventory due to timing of expiry dating of inventory.
Research Premium and Grant Revenue
Grant revenue comprises (a) the research premium from the Austrian government, (b) grants received from the
Austrian Research Promotion Agency (Österreichische Forschungsförderungsgesellschaft, or FFG), and (c) the benefit of
government loans at below-market interest rates.
The research premium the Company receives from the Austrian government is calculated at a specified percent of
specified research and development cost base. The Company recognizes the research premium as long as it has incurred
research and development expenses. All grants are non-refundable as long as the conditions of the grant are met. Nabriva is
and has been in full compliance with the conditions of the grants and all related regulations.
Research and Development Expenses
All research and development costs are expensed as incurred. Research and development costs included direct
personnel and material costs, related overheads, depreciation of equipment used for research or development purposes;
costs for clinical research; costs for the utilization of third parties’ patents for research and development purposes and other
taxes related to research facilities.
Share-based Payments
The Company measures the cost of employee services received in exchange for an award of equity instruments
based on the grant-date fair value of the award in accordance with ASC 718, Compensation—Stock Compensation. The fair
value of stock options is estimated using the Black-Scholes option pricing model. All grants under share-based payment
programs are accounted for at fair value and that cost is recognized over the period during which an employee is required
to provide service in exchange for the award—the requisite service period (vesting period). The Company accounts for
forfeitures as incurred. Compensation expense for options granted to non-employees is determined as the fair value of the
consideration received or the fair value of the equity instruments issued, whichever is more reliably measured.
Leases
The Company follows ASC Topic 842, Leases, which sets out the principles for the recognition, measurement,
presentation and disclosure of leases for both lessees and lessors.
The Company determines if an arrangement is a lease at inception. Operating lease right-of-use, or ROU, assets
and operating lease liabilities are recognized based on the present value of the future minimum lease payments over the
remaining lease term. ROU assets are included in property, plant and equipment, and operating lease liabilities are included
in accrued expenses on the Company’s consolidated balance sheet. The Company has elected not to recognize ROU assets
or lease liabilities for short-term leases. Since none of the Company’s lease agreements provide an implicit rate, the
Company estimates an incremental borrowing rate over the lease term in determining the present value of lease payments.
Operating lease expense is recognized on a straight-line basis over the lease term, subject to any changes in the lease or
expectations regarding the terms. Variable lease costs such as operating costs and property taxes are expensed as incurred.
F-15
Table of Contents
Income Taxes
The Company accounts for income taxes under the asset and liability method, which requires the recognition of
deferred tax assets and liabilities for the expected future tax consequences of events that have been included in the financial
statements. Under this method, the Company determines deferred tax assets and liabilities on the basis of the differences
between the financial statement and tax bases of assets and liabilities by using enacted tax rates in effect for the year in
which the differences are expected to reverse. The effect of a change in tax rates on deferred tax assets and liabilities is
recognized in income in the period that includes the enactment date.
The Company recognizes deferred tax assets to the extent that it believes that these assets are more likely than not
to be realized. In making such a determination, the Company considers all available positive and negative evidence,
including future reversals of existing taxable temporary differences, projected future taxable income, tax-planning
strategies, and results of recent operations. If the Company determines that it would be able to realize its deferred tax assets
in the future in excess of their net recorded amount, the Company would make an adjustment to the deferred tax asset
valuation allowance, which would reduce the provision for income taxes.
In recognizing the benefit of tax positions, the Company has taken or expects to take, the Company determines
whether it is more likely than not that the tax positions will be sustained on the basis of the technical merits of the position
and for those tax positions that meet the more-likely-than-not recognition threshold, the Company recognizes the largest
amount of tax benefit that is more than 50 percent likely to be realized upon ultimate settlement with the related tax
authority.
The Company’s policy is to record interest and penalties related to tax matters in income tax expense.
Recent Accounting Pronouncements
From time to time, new accounting pronouncements are issued by the FASB or other standard setting bodies that
the Company adopts as of the specified effective date. The Company has not adopted any new accounting pronouncements
for the year ended December 31, 2021, nor are there any recently issued accounting pronouncements that are expected to
have a material impact on the Company´s consolidated financial statements in future periods.
Click or tap here to enter text.
3. Fair Value Measurement
US GAAP establishes a valuation hierarchy for disclosure of the inputs to valuation used to measure fair value.
This hierarchy prioritizes the inputs into three broad levels 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 (as exchange rates).
● Level 3: Valuation techniques that include inputs for the asset or liability that are not based on observable
market data (those are unobservable inputs) and significant to the overall fair value measurement.
F-16
Table of Contents
The following table presents the financial instruments measured at fair value and classified by level according to
the fair value measurement hierarchy:
(in thousands)
December 31, 2021
Assets:
Cash equivalent:
Money market fund
Short-term investments:
Term deposits
Total assets
(in thousands)
December 31, 2020
Assets:
Cash equivalent:
Money market fund
Short-term investments:
Term deposits
Total assets
Level 1 Level 2 Level 3 Total
$ 8,050
$ — $ — $ 8,050
16
$ 8,066
16
— —
$ — $ — $ 8,066
Level 1 Level 2 Level 3 Total
$ 8,050
$ — $ — $ 8,050
16
$ 8,066
16
— —
$ — $ — $ 8,066
There were no transfers between Level 1 and 2 in the years ended December 31, 2021 and 2020. There were no
changes in valuation techniques during the years ended December 31, 2021 and 2020.
As of December 31, 2021 and 2020, the Company did not hold any financial instruments as liabilities that were
held at fair value. The Company believes that the carrying value of its long-term debt approximates fair value based on
current interest rates. Receivables and accounts payable are carried at their historical cost which approximates fair value
due to their short-term nature.
4. Accounts Receivable, net and Other Receivables
Accounts receivable, net and other receivables include the following:
(in thousands)
Receivables from customers, net
Receivables from collaborative arrangments
Research premium
Other receivables
Total accounts receivable, net and other receivables
As of December 31
2021
2020
$
$
8,778
2,193
1,237
543
12,751
$
$
56
2,426
1,308
119
3,909
The following table summarizes balances and activity of product revenue allowances and reserves:
Receivables from customers, gross
Less: fee for service
Less: chargeback reserve
Less: cash discount
Receivables from customers, net
As of December 31,
2021
2020
$
$
10,149
(924)
(249)
(198)
8,778
$
$
75
—
(17)
(2)
56
F-17
Table of Contents
5. Property, Plant and Equipment
Property, plant and equipment was comprised of the following:
(in thousands)
IT equipment
Laboratory equipment
ROU asset
Other equipment
Less: Accumulated depreciation
Property, plant and equipment, net
6. Accrued Expenses and Other Current Liabilities
As of December 31
2021
2020
$
$
1,083
3,404
—
101
4,588
(4,355)
233
$
$
1,077
3,392
226
204
4,899
(4,131)
768
Accrued expenses and other current liabilities include the following:
(in thousands)
Research and development related costs
Payroll and related costs
Accounting, tax and audit services
Manufacturing and inventory
Product returns
Government rebates
Other accrued gross to net
Other
Total other current liabilities
As of December 31,
2021
2020
$
$
789
5,085
736
592
2,282
1,751
1,090
1,504
13,829
$
$
1,055
4,049
470
4,779
349
135
178
1,829
12,844
33
431
(115)
349
Product return activity during the years ended December 31, 2021 and 2020 was as follows:
Balance at January 1
Provision recorded during the period
Credits issued during the period
Balance at December 31
2021
2020
$
$
349
2,043
(110)
2,282
$
$
7. Debt
In December 2018, the Company entered into the Loan Agreement by and among the Company, Nabriva
Therapeutics Ireland DAC, and certain other subsidiaries of the Company and Hercules Capital, Inc., or Hercules, pursuant
to which a term loan of up to an aggregate principal amount of $75.0 million was available to the Company. The Loan
Agreement initially provided for an initial term loan advance of $25.0 million, which was funded in December 2018, and,
at the Company’s option and subject to the occurrence of certain funding conditions, several additional tranches of which
$5.0 million became available upon the approval by the FDA of the NDA for XENLETA, which was drawn down. The
other tranches are no longer available as their contingencies were not achieved. The Company may request a term loan
advance of $5.0 million, or the Tranche Advance, through the Amortization Date discussed below subject to Hercules’s
sole discretion.
The term loan bears interest at an annual rate equal to the greater of 9.80% or 9.80% plus the prime rate of interest
minus 5.50%. The Loan Agreement provided for interest-only payments through July 1, 2021 and repayment of the
outstanding principal balance of the term loan thereafter in monthly installments through June 1, 2023, or the Maturity
Date. In addition, the Company is required to pay a fee of 6.95% of the aggregate amount of advances under
F-18
Table of Contents
the Loan Agreement at the Maturity Date, or the End of Term Fee. At the Company’s option, the Company may elect to
prepay any portion of the outstanding term loan that is greater than or equal to $5.0 million by paying such portion of the
principal balance and all accrued and unpaid interest thereon plus a prepayment charge equal to the following percentage of
the principal amount being prepaid, or the Prepayment Fee: (i) 3.0% if the term loan is prepaid during the first 12 months
following the initial closing, (ii) 2.0% if the term loan is prepaid after 12 months following the initial closing but before 24
months following the initial closing and (iii) 1.0% if the term loan is prepaid any time thereafter but prior to the Maturity
Date.
On March 11, 2020, the Company entered into an amendment, or the Third Amendment, to its Loan Agreement
with Hercules. Pursuant to the Third Amendment, the Company repaid $30.0 million of the $35.0 million in aggregate
principal amount of debt outstanding under the Loan Agreement, or the Prepayment. The Company determined to enter
into the Third Amendment following the effectiveness of a performance covenant in February 2020 under which it became
obligated to either (1) achieve 80% of its net product revenue sales target over a trailing six-month period, or (2) maintain
an amount of cash and cash equivalents in accounts pledged to Hercules plus a specified amount of eligible accounts
receivables equal to the greater of the amount outstanding under the Loan Agreement or $40.0 million, or the Liquidity
Requirement. Under the Third Amendment, the Company and Hercules agreed to defer the end of term loan charge
payment of $2.1 million that would have otherwise become payable on the date of the Prepayment and to reduce the
Prepayment Fee with respect to the Prepayment from $600,000 to $300,000 and to defer its payment, in each case, until
June 1, 2023 or such earlier date on which all loans under the Loan Agreement are repaid or become due and payable. The
Third Amendment also reset the revenue performance covenant to 70% of targeted revenue based on a revised net product
revenue forecast and lowered the minimum liquidity requirement to $3.0 million in cash and cash equivalents, in each case,
following the Prepayment. The new minimum liquidity requirement will not apply if CONTEPO receives regulatory
approval from the U.S. Food and Drug Administration and the Company achieves at least 70% of its revised net product
revenue targets under the Loan Agreement.
On June 2, 2021, the Company entered into a further amendment, or the Fourth Amendment, to its Loan and
Security Agreement with Hercules. Pursuant to the Fourth Amendment, the date on which the Company must commence
repaying principal under the Loan Agreement was extended to April 1, 2022, or the Amortization Date, which date may be
extended until July 1, 2022, subject to the receipt by the Company of a specified amount of additional net financing
proceeds and the achievement of a specified product revenue milestone. Additionally, the time during which the Tranche
Advance may be requested by the Company under the Loan Agreement, was extended until the Amortization Date. In
addition, pursuant to the Fourth Amendment, the minimum liquidity requirement of $3.0 million in cash and cash
equivalents will be waived at any time the Company has recognized $15.0 million of net product revenue during the
applicable trailing three months.
The Company’s obligations under the Loan Agreement are guaranteed by all current and future subsidiaries of the
Company, and each of the Company and its subsidiaries has granted Hercules a security interest in all of their respective
personal property, intellectual property and other assets owned or later acquired. The Loan Agreement also contains certain
events of default, representations, warranties and covenants of the Company and its subsidiaries. For example, the Loan
Agreement contains representations and covenants that, subject to exceptions, restrict the Company’s and its subsidiaries’
ability to do the following, among other things: declare dividends or redeem or repurchase equity interests; incur additional
indebtedness and liens; make loans and investments; engage in mergers, acquisitions and asset sales; certain transactions
with affiliates; undergo a change in control; and add or change business locations or settle in cash potential milestone
payment obligations that may become payable by the Company in the future to former security holders of Zavante. The
Company was in compliance with all of its Loan Agreement covenants at December 31, 2021.
The Loan Agreement also grants Hercules or its nominee an option to purchase up to an aggregate of $2.0 million
of the Company’s equity securities, or instruments exercisable for or convertible into equity securities, sold to investors in
any private financing upon the same terms and conditions afforded to such other investors for as long as there are amounts
outstanding under the Loan Agreement.
The Company incurred $1.3 million of costs in connection with the Loan Agreement which along with the initial
fee of $0.7 million paid to Hercules were recorded as debt issuance cost and are being amortized as interest expense using
the effective interest method over the term of the loan. In connection with the Third Amendment, the
F-19
Table of Contents
Company recognized a non-cash $2.7 million loss on the extinguishment of debt during the three months ended March 31,
2020 which represented the excess of the reacquisition price of the $30.0 million debt repaid over the net carrying amount
of the extinguished debt. The carrying value of the term loan payable at December 31, 2021 includes the present value of
the End of Term Fee and the Prepayment Fee. The End of Term Fee on the remaining $5.0 million principal balance is
being accrued as additional interest expense using the effective interest method over the term of the loan.
Long-term debt as December 31, 2021 and 2020 consisted of the following:
(in thousands)
Term loan payable
End of term fee
Unamortized debt issuance costs
Carrying value of term loan
Other long-term debt
Less: Amounts due within one year
Total long-term debt
As of December 31,
2021
2020
$
$
5,000
2,331
(145)
7,186
844
(3,765)
4,265
$
$
As of December 31, 2021, the maturities of our long-term debt were as follows:
(in thousands)
2022
2023
8. Stockholders’ Equity
$
$
5,000
2,048
(206)
6,842
885
(2,041)
5,686
3,765
4,811
In September 2021, the Company entered into a purchase agreement, or Purchase Agreement, with Lincoln Park
Capital Fund, LLC, or Lincoln Park, which, subject to the terms and conditions, provides that the Company has the right to
sell to Lincoln Park and Lincoln Park is obligated to purchase up to $23.0 million of its ordinary shares. In addition, under
the Purchase Agreement, the Company agreed to issue a commitment fee of 632,474 ordinary shares, or the Commitment
Shares, as consideration for Lincoln Park entering into the Purchase Agreement and for the payment of $0.01 per
Commitment Share. Under the Purchase Agreement, the Company may from time to time, at its discretion, direct Lincoln
Park to purchase on any single business day, or a Regular Purchase, up to (i) 400,000 ordinary shares if the closing sale
price of our ordinary shares is not below $0.25 per share on Nasdaq, (ii) 600,000 ordinary shares if the closing sale price of
our ordinary shares is not below $2.00 per share on Nasdaq or (iii) 800,000 ordinary shares if the closing sale price of our
ordinary shares is not below $3.00 per share on Nasdaq. In addition to Regular Purchases, the Company may also direct
Lincoln Park to purchase other amounts as accelerated purchases or as additional accelerated purchases on the terms and
subject to the conditions set forth in the Purchase Agreement. In any case, Lincoln Park’s commitment in any single
Regular Purchase may not exceed $2.5 million absent a mutual agreement to increase such amount. As of December 31,
2021, the Company has issued and sold an aggregate of 2,400,000 ordinary shares pursuant to the Purchase Agreement and
received net proceeds of $2.4 million. From January 1, 2022 and through the date of this filing, the Company has issued
and sold an aggregate of 3,600,000 ordinary shares pursuant to the Purchase Agreement and received net proceeds of $1.6
million. As of the date of this filing, the Company may issue and sell ordinary shares for gross proceeds of up to $19.0
million under the Purchase Agreement.
In May 2021, the Company entered into an Open Market Sale AgreementSM, or the New Sale Agreement, with
Jefferies, as agent, pursuant to which the Company may offer and sell ordinary shares, nominal value $0.01 per share for
aggregate gross sale proceeds of up to $50.0 million, from time to time through Jefferies, by any method permitted that is
deemed an “at the market offering” as defined in Rule 415(a)(4) promulgated under the Securities Act of 1933, as
amended. Upon entry into the New Sale Agreement, the Company´s existing Jefferies ATM Agreement entered into in June
2019 was terminated. The Company did not incur any termination penalties as a result of the replacement of the Jefferies
ATM Agreement. As of the effective date of the termination of the Jefferies ATM Agreement, the Company has sold an
aggregate of 5,925,699 of our ordinary shares pursuant to the Jefferies ATM Agreement for aggregate gross
F-20
Table of Contents
proceeds of $33.7 million and net proceeds to the Company of $31.9 million, after deducting commissions and offering
expenses payable by the Compamy. The approximately $16.3 million of ordinary shares that had been available for sale
pursuant to the Jefferies ATM Agreement remained unsold at the time of its replacement. The replacement of the Jefferies
ATM Agreement terminated any future sales of ordinary shares through the Jefferies ATM Agreement. As of December 31,
2021, the Company has issued and sold an aggregate of 18,232,689 ordinary shares pursuant to the New Sale Agreement
and received gross proceeds of $30.5 million and net proceeds of $29.3 million, after deducting commissions to Jefferies
and other offering expenses. From January 1, 2022 and through the date of this filing, the Company has issued and sold an
aggregate of 1,338,282 ordinary shares pursuant to the New Sale Agreement and received gross proceeds of $595,000 and
net proceeds of $580,000, after deducting commissions to Jefferies and other offering expenses.
In March 2021, the Company entered into a securities purchase agreement with certain institutional investors
pursuant to which the Company issued and sold in a registered direct offering (1) an aggregate of 9,761,010 ordinary
shares, $0.01 nominal value per share, and accompanying warrants to purchase up to an aggregate of 4,880,505 ordinary
shares and (2) pre-funded warrants to purchase up to an aggregate of 600,000 ordinary shares and accompanying ordinary
share warrants to purchase up to an aggregate of 300,000 ordinary shares. Each share was issued and sold together with an
accompanying ordinary share warrant at a combined price of $2.4525, and each pre-funded warrant was issued and sold
together with an accompanying ordinary share warrant at a combined price of $2.4425. The proceeds to the Company from
the offering were $25.4 million gross and $23.4 million net after deducting the placement agent’s fees and estimated
offering expenses. Each pre-funded warrant had an exercise price per ordinary share equal to $0.01 and each pre-funded
warrant was exercised in full on the issuance date. Each ordinary share warrant has an exercise price per ordinary share
equal to $2.39, is exercisable on the date of issuance and will expire on the five-year anniversary of the date of issuance.
As of December 31, 2021, there were 5,180,505 warrants outstanding from the offering at an exercise price of $2.39 per
share.
In December 2020, the Company completed a registered public offering in which it sold 6,000,000 ordinary shares
at a public offering price of $2.50. The proceeds to the Company from the offering were $15.0 million gross and $13.3
million net, after deducting the placement agent’s fees and other offering expenses.
In May 2020, the Company entered into a securities purchase agreement with certain institutional investors,
including Fidelity Management & Research Company, LLC pursuant to which the Company issued and sold in a registered
direct offering an aggregate of 4,144,537 ordinary shares and accompanying warrants to purchase up to an aggregate of
4,144,537 ordinary shares. Each share the Company issued and sold together with an accompanying warrant at a combined
price of $9.1686. The proceeds to the Company from the offering were $38.0 million gross and $35.2 million net, after
deducting the placement agent’s fees and other offering expenses. Each warrant was immediately exercisable and will
expire on the two-year anniversary of the issuance date. As of December 31, 2021, there were 4,059,532 warrants
outstanding from the offering at an exercise price of $7.92 per share.
In December 2019, the Company sold to certain institutional investors in a registered direct offering an aggregate
of 1,379,310 ordinary shares, and accompanying warrants to purchase up to an aggregate of 1,379,310 ordinary shares.
Each share was issued and sold together with an accompanying warrant at a combined price of $14.50 per security. The
proceeds to the Company from the offering were $20.0 million gross and $18.3 million net, after deducting the placement
agent’s fees and other offering expenses. As of December 31, 2021, there were 1,379,310 warrants outstanding from the
offering, where each warrant has an exercise price of $19.00 per share and will expire on the date that is three years and six
months after the initial issuance date.
9. Revenue
(in thousands)
Product revenue, net
Collaboration revenues
Research premium and grant revenue
Total revenue
2021
Year Ended December 31,
2020
2019
$
$
23,386
3,830
1,679
28,895
$
$
108
2,756
2,163
5,027
$
$
1,538
6,210
1,733
9,481
F-21
Table of Contents
Collaboration revenues for the year ended December 31, 2021 include $2.6 million related to the restructured
China Region License Agreement, a portion of which is recognized over the estimated period the manufacturing
collaboration and regulatory support will be provided to Sumitomo Pharmaceuticals (Suzhou), as well as $1.2 million of
the Company’s share of revenues associated with the SIVEXTRO distribution agreement with Merck & Co., Inc. through
April 11, 2021 (see Note 14). Collaboration revenues for the year ended December 31, 2020 includes a $0.5 million
regulatory milestone payment from Sunovion, $1.8 million for the Company´s share of revenues associated with the
SIVEXTRO distribution agreement with Merck & Co., Inc., as well as collaboration revenues associated with the
restructuring of the China Region License Agreement. Collaboration revenues for the year ended December 31, 2019
includes a $1.0 million upfront payment under the Sunovion License Agreement received in April 2019, and a $5.0 million
milestone payment under the China Region License Agreement.
The Company sells its products to pharmaceutical wholesalers/distributors (i.e., the Company’s customers). The
Company’s wholesalers/distributors in turn sell the Company’s products directly to clinics, hospitals, and private practices.
Revenue from the Company’s product sales is recognized as physical delivery of product occurs (when the Company’s
customer obtains control of the product), in return for agreed-upon consideration.
SIVEXTRO product revenues, net of gross-to-net accruals and adjustments for returns were $23.8 million since
the Company began exclusive distribution of SIVEXTRO under its own National Drug Code, or NDC, on April 12, 2021.
For the years ended December 31, 2021, 2020 and 2019 XENLETA product revenues, net of gross-to-net accruals and
adjustments for returns, were $(0.4) million, $0.1 million and $1.5 million, respectively, including revenues from the
Company´s Named Patient Program of $17,000 for the year ended December 31, 2021. The Company´s gross-to-net, or
GTN, estimates are based upon information received from external sources (such as written or oral information obtained
from the Company´s customers with respect to their period-end inventory levels and sales to end-users during the period),
in combination with management’s informed judgments. Due to the inherent uncertainty of these estimates, the actual
amount incurred may be materially above or below the amount initially estimated when product revenues are originally
recorded, then requiring prospective adjustments to the Company’s reported product revenues, net.
For the year ended December 31, 2021, the Company recorded a $1.3 million returns reserve adjustment for shelf
life expiration of certain XENLETA products. For the year ended December 31, 2020, the Company recorded a returns
reserve adjustment of $0.4 million for slow-moving inventory, representing 50% of XENLETA IV inventory held at its
Specialty Distributors, as well as an adjustment for returns from a single mail order specialty pharmacy.
10. Share Based Payments
Stock Plan Activity
On April 2, 2015, the Company’s shareholders, management board and supervisory board adopted the Stock
Option Plan 2015, or the SOP 2015, as amended. Each vested option grants the beneficiary the right to acquire one share in
the Company. The vesting period for the options is four years following the grant date. On the last day of the last
calendar month of the first year of the vesting period, 25% of the options attributable to each beneficiary are automatically
vested. During the second, third and fourth years of the vesting period, the remaining 75% of the options vest on a monthly
pro rata basis (i.e. 2.083% per month). Options granted under the SOP 2015 have a term of no more than ten years from the
beneficiary’s date of participation. With the approval of the 2017 Share Incentive Plan, there were no further shares
available for issuance under the SOP 2015. However, all outstanding awards under SOP 2015 will remain in effect and
continue to be governed by the terms of the SOP 2015.
On July 26, 2017, the Company’s board of directors adopted the 2017 Share Incentive Plan, or the 2017 Plan, and
the shareholders approved the 2017 Plan at the Company’s Extraordinary General Meeting of Shareholders on September
15, 2017. The 2017 Plan permitted the award of share options (both incentive and nonstatutory options), share appreciation
rights, or SARs, restricted shares, restricted share units, or RSUs, and other share-based awards to the Company’s
employees, officers, directors, consultants and advisers. The 2017 Plan is administered by the Company’s board of
directors. Under the 2017 Plan, the Company granted RSUs which vest over a period of four years with 25%
F-22
Table of Contents
vesting upon the first anniversary of the grant date and on a monthly pro rata basis thereafter over the remaining three
years. During 2018, the Company granted RSUs to certain employees where vesting of the RSUs was subject to FDA
approval of an NDA for XENLETA. Fifty percent (50%) of each RSU award vested upon FDA approval, and the
remaining fifty percent (50%) vested on the one-year anniversary of such approval. In connection with the FDA approval
that was received in August 2019, the Company started recognizing compensation expense, as there was no compensation
expense recognized on these awards prior to the FDA approval as it was determined that approval was not probable since it
was outside of the Company’s control. Also during 2018, the Company granted RSUs to certain employees that have
vested in three six-month increments beginning in May 2019 and ending in May 2020. Lastly, the Company granted RSUs
in 2018 to certain employees where vesting of the RSUs is subject to FDA approval of an NDA for CONTEPO. Fifty
percent (50%) of each RSU award will vest upon FDA approval, and the remaining fifty percent (50%) will vest on the
one-year anniversary of such approval. With the approval of the 2020 Share Incentive Plan, there were no further shares
available for issuance under the 2017 Plan. However, all outstanding awards under 2017 Plan will remain in effect and
continue to be governed by the terms of the 2017 Plan.
On March 12, 2019, the Company’s board of directors adopted the 2019 Inducement Share Incentive Plan, or the
2019 Inducement Plan and, subject to the adjustment provisions of the 2019 Inducement Plan, reserved 200,000 ordinary
shares for issuance pursuant to equity awards granted under the 2019 Inducement Plan. In accordance with Nasdaq Listing
Rule 5635(c)(4), awards under the 2019 Inducement Plan may only be made to individuals who were not previously
employees or non-employee directors of the Company (or following such individuals’ bona fide period of non-employment
with the Company), as an inducement material to the individuals’ entry into employment with the Company. On April 28,
2020, the board of directors resolved not to make any further awards under the 2019 Inducement Plan.
In July 2018, the Company granted a non-statutory option to purchase 85,000 of its ordinary shares and 15,000
performance-based RSUs to the Company’s newly appointed Chief Executive Officer, or the CEO. These equity awards
were granted outside of the 2017 Plan and the 2019 Inducement Plan, were approved by the Company’s compensation
committee and board of directors and were made as an inducement material to the CEO entering into employment with the
Company in accordance with Nasdaq Listing Rule 5635(c)(4). The exercise price per share for the share option is $35.30
per share, and the option award has a ten-year term and will vest over a four-year period, with 25% of the shares
underlying the award vesting on the first anniversary of the grant date and the remaining 75% of the shares underlying the
option award to vest monthly over the subsequent 36-month period. The performance-based RSUs are subject to vesting as
follows: 50% will vest upon certification by the board of directors of the receipt of approval by the FDA of an NDA for
each of lefamulin and CONTEPO for any indication, and 50% will vest on the first anniversary of such certification by the
board of directors, provided, in each case, the CEO is performing services to the Company on the applicable vesting dates.
If the FDA does not approve an NDA for both lefamulin and CONTEPO by January 31, 2020, the performance-based
RSUs will terminate in full. Since CONTEPO was not approved by this date the award was forfeited. The Company also
issues non-statutory options to new employees upon the commencement of their employment.
On March 4, 2020, the Company´s board of directors adopted the 2020 Share Incentive Plan, or the 2020 Plan,
which was approved by the Company´s shareholders at the 2020 Annual General Meeting of Shareholders in July 2020, or
2020 AGM. As of the date of the 2020 AGM, the total number of ordinary shares reserved for issuance under the 2020
Plan was for the sum of 930,000 ordinary shares, plus the number of the Company´s ordinary shares that remained
available for grant under the 2017 Plan as of immediately prior to the AGM and the number of ordinary shares subject to
awards granted under the 2017 Plan and the Company´s Amended and Restated Stock Option Plan 2015, that expire,
terminate or are otherwise surrendered, cancelled, forfeited or repurchased by us at their original issuance price pursuant to
a contractual repurchase right. The 2020 Plan provides for the grant of incentive share options, non-statutory share options,
share appreciation rights, restricted share awards, restricted share units, other share-based and cash-based awards and
performance awards. Under the 2020 Plan the Company granted RSUs to certain employees that vest in three six-month
increments beginning in January 2021 and ending in January 2022. The Company also granted RSUs to certain employees,
where vesting of the RSUs was subject to individual performance goals. During the year ended December 31, 2021, the
Company granted RSUs to certain employees that vest in annual increments beginning January 2022 and ending in January
2025. Additionally, the Company granted 7,000 RSUs to its former Chief Medical Officer
F-23
Table of Contents
and to its former Chief Financial Officer, which vest as to 50% of the shares underlying the RSUs each year over the term
of their respective consulting agreements.
At December 31, 2021, 271,080 ordinary shares were available for future issuance under the 2020 Plan.
On December 9, 2020, the Company´s board of directors adopted without stockholder approval the 2021
Inducement Share Incentive Plan, or the 2021 Inducement Plan and, subject to the adjustment provisions of the 2021
Inducement Plan, reserved 200,000 ordinary shares for issuance pursuant to equity awards granted under the 2021
Inducement Plan. In accordance with Nasdaq Listing Rule 5635(c)(4), awards under the 2021 Inducement Plan may only
be made to individuals who were not previously employees or non-employee directors of the Company (or following such
individuals’ bona fide period of non-employment with the company), as an inducement material to the individuals’ entry
into employment with the Company. In September 2021, the Company’s board of directors adopted an amendment to the
2021 Inducement Plan that increased the amount of shares reserved for issuance under the plan from 200,000 shares to
500,000 shares. Options and SARs granted will be exercisable at such times and subject to such terms and conditions as the
board may specify in the applicable option agreement; provided, however, that no option or SAR will be granted with a
term in excess of ten years. The board will also determine the terms and conditions of restricted shares and RSUs,
including the conditions for vesting and repurchase (or forfeiture) and the issue price, if any.
Stock Options
The following table summarizes information regarding the Company´s stock option awards:
Outstanding as of January 1, 2019
Granted
Exercised
Cancelled and forfeited
Outstanding as of December 31, 2019
Granted
Exercised
Cancelled and forfeited
Outstanding as of December 31, 2020
Granted
Exercised
Cancelled and forfeited
Outstanding as of December 31, 2021
Vested and exercisable as of December 31, 2021
Weighted
average
exercise
price in
$ per share
65.17
20.11
—
64.33
47.82
11.27
—
31.92
35.08
1.23
—
16.90
20.46
45.05
Options
609,133
316,645
—
(108,887)
816,891
465,055
—
(229,108)
1,052,838
637,880
—
(342,241)
1,348,477
533,564
Weighted
Average
Remaining
Contractual
Term
(in years)
Aggregate
intrinsic
value
(in thousands)
—
—
—
—
—
—
—
—
—
—
—
—
8.0
6.7
$
$
—
—
—
—
—
—
—
—
—
—
—
—
—
—
The Company has 1,348,477 option grants outstanding at December 31, 2021 with exercise prices ranging from
$1.06 per share to $110.00 per share. As of December 31, 2021, there was $1.8 million of total unrecognized compensation
expense related to unvested stock options, which will be recognized over the weighted-average remaining vesting period of
0.9 years.
The weighted average fair value of the stock options granted during years ended December 31, 2021, 2020 and
2019 was $0.82, $5.99 and $11.95 per share, respectively, based on a Black Scholes option pricing model using the
following assumptions:
F-24
Table of Contents
Input parameters
Range of expected volatility
Expected term of options (in years)
Range of risk-free interest rate
Dividend yield
2021
2020
75.3% ‑ 77.3% 63.7% ‑ 74.4%
5.5 - 6.1
0.8% ‑ 1.3%
—
5.5 - 6.1
0.8% ‑ 1.5%
—
2019
59.8% - 63.1%
6.0 - 6.1
1.9% - 3.0%
–
The expected price volatility is based on historical trading volatility for the publicly traded peer companies under
consideration of the remaining life of the options. The risk-free interest rate is based on the average of five and seven-year
market yield on U.S. treasury securities in effect at the time of grant.
Restricted Stock Units (“RSUs”)
The following table summarizes information regarding the Company’s restricted share unit awards:
RSUs
Weighted average
grant date fair
value in $ per share
Outstanding as of January 1, 2019
Granted
Vested and issued
Forfeited
Outstanding as of December 31, 2019
Granted
Vested and issued
Forfeited
Outstanding as of December 31, 2020
Granted
Vested and issued
Forfeited
Outstanding as of December 31, 2021
137,210
47,900
(65,758)
(14,183)
105,169
244,832
(52,640)
(57,977)
239,384
769,132
(90,330)
(128,448)
789,738
33.34
19.00
31.80
27.87
28.50
10.99
31.15
21.74
11.60
2.02
12.04
6.93
2.92
As of December 31, 2021, there was unrecognized compensation costs of $1.1 million associated with RSUs
which are expected to be recognized over the awards average remaining vesting period of 1.7 years. The intrinsic value of
RSU’s that vested during the years ended December 31, 2021, 2020 and 2019 was $0.2 million, $0.4 million and $1.5
million, respectively.
Stock-based Compensation
The following table presents stock-based compensation expense included in the Company’s consolidated
statements of operations:
(in thousands)
Research and development expense
Selling, general and administrative expense
Total stock-based compensation expense
2021
565
2,726
3,291
$
$
Year Ended
December 31,
2020
1,280
3,939
5,219
$
$
2019
2,138
7,610
9,748
$
$
F-25
Table of Contents
Employee Stock Purchase Plan
The Company’s board of directors adopted, and in August 2018 Company’s stockholders approved, the 2018
employee stock purchase plan, or the 2018 ESPP. The maximum aggregate number of shares of ordinary shares that may
be purchased under the 2018 ESPP is 50,000 shares, or the ESPP Share Pool, subject to adjustment as provided for in the
2018 ESPP. The 2018 ESPP allowed eligible employees to purchase shares at a 15% discount to the lower of the closing
share price at the beginning and end of the six-month offering periods commencing November 1 and ending April 30 and
commencing May 1 and ending October 31 of each year. The Company suspended the 2018 ESPP in April 2020.
11. Post-employment Benefit Obligations
As required under Austrian labor law, the Company makes contributions to a state plan classified as defined
contribution plan (Mitarbeitervorsorgekasse) for its employees in Austria. Monthly contributions to the plan are 1.53% of
salary with respect to each employee and are recognized as expense in the period incurred. For the years ended
December 31, 2021, 2020 and 2019, contributions costs were $56,000, $57,000 and $68,000, respectively.
For employees of Nabriva Therapeutics US, Inc., the Company makes contributions to a defined contribution plan
as defined in subsection 401(k) of the Internal Revenue Code. The Company matches 100% of the first 3% of the
employee’s voluntary contribution to the plan and 50% of the next 2% contributed by the employee. Contributions are
recognized as expense in the period incurred. In the years ended December 31, 2021, 2020 and 2019, contributions were
$360,000, $396,000 and $710,000, respectively.
12. Income Tax Expense
Income (loss) before income taxes attributable to domestic and international operations, consists of the following:
(in thousands)
Domestic
Foreign
Loss before income taxes
$
$
Income tax expense consists of the following:
Year ended December 31
2020
(71,344)
1,999
(69,345)
$
$
$
$
2021
(40,540)
(8,420)
(48,960)
2019
(78,761)
(3,902)
(82,663)
(in thousands)
Current tax
Domestic
Foreign
Deferred tax
Domestic
Foreign
Total income tax expense
2021
Year ended December 31
2020
2019
— $
(490)
—
—
$
(490)
— $
(139)
—
—
$
(139)
—
(101)
—
—
(101)
$
$
F-26
Table of Contents
The reconciliation to our effective tax rate from the Irish statutory income tax rate of 12.5% for the years ended
December 31, 2021, 2020 and 2019 is as follows:
(% of pre-tax income)
Statutory income tax rate
Non-deductible expenses
Income not subject to tax
Tax credits
Foreign operations
Tax audit assessments
Other
Valuation allowance
Effective income tax rate
2021
Year ended December 31
2020
2019
12.5 %
—
0.4
—
(7.3)
—
(1.7)
(4.9)
(1.0)%
12.5 %
—
0.2
0.6
3.0
—
2.3
(18.8)
(0.2)%
12.5 %
(0.1)
0.3
0.4
0.6
(11.8)
0.8
(2.8)
(0.1)%
The following table summarizes the components of deferred income tax balances:
(in thousands)
Deferred tax assets:
Net operating loss carryforwards
Tax loss on liquidation of subsidiary
Equity compensation
Non-deductible reserves
Total deferred tax assets
Valuation allowance
Net deferred tax assets
Deferred tax liabilities:
Financial liabilities
Property, plant and equipment
Total deferred tax liability
Deferred tax, net
As of December 31,
2021
2020
$
$
$
111,220
2,501
4,067
905
118,693
(118,583)
110
100
10
110
— $
108,095
4,029
4,449
447
117,020
(116,200)
820
757
63
820
—
The table below summarizes changes in the deferred tax valuation allowance:
(in thousands)
Balance at beginning of year
Tax benefit
Balance at end of year
$
$
2021
(116,200)
(2,383)
(118,583)
Year ended December 31,
2020
(103,185)
(13,015)
(116,200)
$
$
2019
(100,832)
(2,353)
(103,185)
$
$
The following table summarizes carryforwards of net operating losses as of December 31, 2021.
(in thousands)
Ireland
Austria
United States
United States
Amount
297,453
239,510
10,403
35,516
$
$
$
$
Expiration
Indefinite
Indefinite
Indefinite
2033
Due to uncertainty regarding the ability to realize the benefit of deferred tax assets primarily relating to net
operating loss carryforwards and the fact that the Company is in a three year pretax cumulative loss position, a full
valuation allowance has been established.
F-27
Table of Contents
The Company’s U.S. subsidiary has net operating loss and tax credit carryforwards that may be subject to annual
limitations due to ownership changes as defined by Sections 382 and 383 of the Internal Revenue Code. These limitations
could restrict the amount of tax attributes that can be utilized annually to offset future U.S. taxable income or tax liabilities.
On the basis of this evaluation, as of December 31, 2021, 2020 and 2019, the Company has recorded a valuation
allowance of $118.6 million, $116.2 million and $103.2 million, respectively, to recognize only the portion of the deferred
tax asset that is more likely than not to be realized. The amount of the deferred tax asset considered realizable, however,
could be adjusted if estimates of future taxable income during the carryforward period are reduced or increased or if
objective negative evidence in the form of cumulative losses is no longer present and additional weight is given to
subjective evidence such as our projections for growth.
At December 31, 2021, the Company had no uncertain tax positions and did not expect any material increase or
decrease in income tax expense related to examinations or changes in uncertain tax positions. The Company’s U.S.
subsidiary, Nabriva Therapeutics US, Inc., resolved its examination for tax year 2018 with the Internal Revenue Service
with a decrease in a research and development tax credit carryforward of $0.1 million.
The Company files income tax returns in Ireland. In addition, the Company’s foreign subsidiaries file separate
income tax returns in Austria and the United States and state jurisdictions in which they are located. Tax years 2017 and
forward remain open for examination for Ireland tax purposes and 2016 and forward remain open for examination for
Austrian tax purposes and years 2018 and forward remain open for examination for United States tax purposes.
The Company’s policy is to record interest and penalties related to tax matters in income tax expense.
13. Earnings (Loss) per Share
Basic and Diluted Loss per Share
Basic and diluted loss per share is calculated by dividing the net loss attributable to shareholders by the weighted
average number of shares outstanding during the year. Diluted net loss per share is the same as basic net loss per share
during the periods presented as the effects of the Company’s common stock equivalents are antidilutive and thus not
included in the calculation.
(in thousands, except per share data)
Net loss for the period
Weighted average number of shares outstanding
Basic and diluted loss per share
2021
$
(49,450)
43,349,461
(1.14)
$
Year ended December 31,
2020
(69,484) $
$
12,845,089
$
(5.41) $
2019
(82,764)
7,419,948
(11.15)
The following ordinary share equivalents were excluded from the calculations of diluted loss per share as their
effect would be anti-dilutive:
Stock option awards
Restricted share units
Warrants
2021
1,348,477
789,738
10,619,347
Year ended December 31
2020
1,052,838
239,384
5,438,842
2019
816,891
105,169
1,379,310
F-28
Table of Contents
14. Significant Arrangements and License Agreements
Sales Promotion and Distribution Agreement with Merck & Co.
On July 15, 2020, the Company entered into a Sales Promotion and Distribution Agreement, or the Distribution
Agreement, with MSD International GmbH, or MSD, and Merck Sharp & Dohme Corp., or Supplier, each a subsidiary of
Merck & Co., Inc. Under the Distribution Agreement and subject to the satisfaction of certain conditions, MSD appointed
the Company as its sole and exclusive distributor of certain products containing tedizolid phosphate as the active ingredient
previously marketed and sold by Supplier and MSD under the trademark SIVEXTRO® for injection, intravenous use and
oral use, or the Products, in the United States and its territories, or the SIVEXTRO Territory. SIVEXTRO is an
oxazolidinone-class antibacterial indicated in adults and pediatric patients 12 years of age and older for the treatment of
acute bacterial skin and skin structure infections caused by certain susceptible Gram-positive microorganisms. On April 12,
2021, in accordance with the terms of the Distribution Agreement, the Company began exclusive distribution of
SIVEXTRO under its own National Drug Code, or NDC, and the Company recognizes 100% of net product sales of
SIVEXTRO in its results of operations.
Under the Distribution Agreement and subject to the fulfillment of certain conditions, including the Company
having engaged sufficient sales representatives, restrictions relating to travel and physician office access in the SIVEXTRO
Territory due to COVID-19 having continued to decrease in a sufficient portion of the SIVEXTRO Territory so as not to
hinder the successful detailing of SIVEXTRO, the Company has been granted the right by MSD initially to promote the
Products in the SIVEXTRO Territory and, upon satisfaction of additional conditions, including an increase in sales
representatives, the right to exclusively distribute the Products in the SIVEXTRO Territory, including the sole right and
responsibility to fill orders with respect to the Products in the SIVEXTRO Territory. The Company successfully satisfied
those conditions, including the increase in the number of sales representatives, and began filling orders of SIVEXTRO with
its own Nabriva NDC beginning April 12, 2021. Subject to applicable law, the Company is entitled to determine the final
selling prices of the Products charged by the Company to its customers at its sole discretion, subject to an overall annual
limit on price increases, and will be solely responsible for sales contracting and all market access activities, including
bidding, hospital listing and reimbursement. The Company is responsible for all costs related to the promotion, sale and
distribution of the Products by the Company, as well as all costs required to meet its staffing obligations under the
Distribution Agreement. The Company is obligated to use commercially reasonable efforts to promote and distribute the
Products and to maximize the sales of the Products throughout the SIVEXTRO Territory. The Company has agreed to
employ a sales force or retain the services of a contract sales organization to fulfill its obligations under the Distribution
Agreement. The Company has secured a virtual and in-person sales effort with community-based expertise with Amplity
Health, which is a contract sales organization, to replace its hospital-based sale force and began a small and focused sales
effort for SIVEXTRO and XENLETA in September 2020. The Company expanded this effort to 60 sales representatives
and may expand it further. The Company also piloted a virtual promotion effort with incremental sales representatives in
the third quarter of 2021.
Furthermore, a subsidiary of Merck will sell, and the Company has agreed to purchase, SIVEXTRO at specified
prices in such quantities as the Company may specify. Although the Company is entitled, subject to appliable law, to
determine the final selling prices of SIVEXTRO in its sole discretion, subject to an overall annual limit on price increases,
the Company may not be able to sell SIVEXTRO at prices high enough to recoup its investment in a sales force and other
commercialization activities.
China Region License Agreement
In March 2018, the Company entered into the China Region License Agreement, with Sinovant Sciences, Ltd., or
Sinovant, an affiliate of Roivant Sciences, Ltd., to develop and commercialize lefamulin in the greater China region. As
part of the China Region License Agreement, Nabriva Therapeutics Ireland DAC and Nabriva Therapeutics GmbH, the
Company’s wholly owned subsidiaries, granted Sinovant an exclusive license to develop and commercialize, and a non-
exclusive license to manufacture, certain products containing lefamulin, or the China Region Licensed Products, in the
People’s Republic of China, Hong Kong, Macau, and Taiwan, together the Extended China Territory. In May 2021, the
Company entered into an assignment, assumption and novation agreement, or the Assignment Agreement, pursuant to
which the Company consented to the assignment by Sinovant, an affiliate of Roivant Sciences, Ltd., of the China
F-29
Table of Contents
Region License Agreement to develop and commercialize lefamulin in the greater China region to Sumitomo
Pharmaceuticals (Suzhou), a wholly-owned subsidiary of Sumitomo Dainippon Pharma Co., Ltd. (“Sumitomo”). Pursuant
to the Assignment Agreement, the Company agreed to release Sinovant and its affiliates from their obligations under the
China Region License Agreement and consented to Sumitomo Pharmaceuticals (Suzhou)’s assumption of such obligations.
In addition, Sumitomo Dainippon Pharma Co., Ltd., or Sumitomo, has agreed to guarantee all of the obligations of
Sumitomo Pharmaceuticals (Suzhou) under the China Region License Agreement.
Under the China Region License Agreement, Sumitomo Pharmaceuticals (Suzhou) and the Company’s
subsidiaries have established a joint development committee, or the JDC, to review and oversee development and
commercialization plans in the Extended China Territory. The China Region License Agreement includes milestone events
consisting of a non-refundable $5.0 million upfront payment, an additional $91.5 million in milestone payments upon the
achievement of certain regulatory and commercial milestone events related to lefamulin for CABP, plus an additional $4.0
million in milestone payments if any China Region Licensed Product receives a second or any subsequent regulatory
approval in the People’s Republic of China. The Company has received the $5.0 million upfront payment, a $1.5 million
payment for the submission of a clinical trial application, or CTA, by Sinovant to the Chinese Food and Drug
Administration, which was received in the first quarter of 2019 and a $5.0 million milestone payment in the third quarter of
2019 in connection with the FDA approval for lefamulin. The Company will also be eligible to receive low double-digit
royalties on sales, if any, of China Region Licensed Products in the Extended China Territory. In December 2020, the
Company announced the restructuring of its China Region License Agreement. The restructured agreement provided for
additional manufacturing collaboration and regulatory support to be provided to the contract counterparty by the Company
that is expected to help expedite the delivery of XENLETA to patients in greater China. The restructured agreement also
accelerated $3.0 million of the $5.0 million milestone payment to the Company that was previously payable upon
regulatory approval of XENLETA in China, including a non-refundable upfront payment of $1.0 million which was
received in the fourth quarter of 2020 and a $1.0 million milestone achieved during the first quarter of 2021. During 2021,
management determined that the remaining $1.0 million milestone payment was probable of achievement and therefore the
Company is recognizing the $3.0 million of accelerated payments under the restructured agreement as collaboration
revenue in the consolidated statements of operations over the estimated period the manufacturing collaboration and
regulatory support will be provided to the contract counterparty, which was $2.4 million for the year ended December 31,
2021, based on the proportional performance of the underlying performance obligation. The remaining milestones of $86.0
million are tied to additional regulatory approvals and annual sales targets. The future regulatory and commercial milestone
payments under the China Region License Agreement will be recorded during the period the milestones become probable
of achievement.
Except for the manufacturing collaboration and regulatory support discussed above, Sumitomo Pharmaceuticals
(Suzhou) will be solely responsible for all costs related to developing, obtaining regulatory approval of and
commercializing China Region Licensed Products in the Extended China Territory and is obligated to use commercially
reasonable efforts to develop, obtain regulatory approval for and commercialize China Region Licensed Products in the
Extended China Territory. The Company is obligated to use commercially reasonable efforts to supply, pursuant to supply
agreements to be negotiated by the parties, to Sumitomo Pharmaceuticals (Suzhou) a sufficient supply of lefamulin for
Sumitomo Pharmaceuticals (Suzhou) to manufacture finished drug products for development and commercialization of the
China Region Licensed Products in the Extended China Territory.
Unless earlier terminated, the China Region License Agreement will expire upon the expiration of the last royalty
term for the last China Region Licensed Product in the Extended China Territory, which the Company expects will occur in
2033. Following the expiration of the last royalty term, the license granted to Sumitomo Pharmaceuticals (Suzhou) will
become non-exclusive, fully-paid, royalty-free and irrevocable. The China Region License Agreement may be terminated
in its entirety by Sumitomo Pharmaceuticals (Suzhou) upon 180 days’ prior written notice at any time. Either party may,
subject to specified cure periods, terminate the China Region License Agreement in the event of the other party’s uncured
material breach. Either party may also terminate the China Region License Agreement under specified circumstances
relating to the other party’s insolvency. The Company has the right to terminate the China Region License Agreement
immediately if Sumitomo Pharmaceuticals (Suzhou) does not reach certain development milestones by certain specified
dates (subject to specified cure periods). The China Region License Agreement contemplates that the Company will enter
into ancillary agreements with Sumitomo Pharmaceuticals (Suzhou), including clinical and commercial supply agreements
and a pharmacovigilance agreement.
F-30
Table of Contents
Sunovion License Agreement
In March 2019, the Company entered into the Sunovion License Agreement with Sunovion. As part of the
Sunovion License Agreement, Nabriva Therapeutics Ireland DAC, the Company’s wholly owned subsidiary, granted
Sunovion an exclusive license under certain patent rights, trademark rights and know-how to commercialize certain
products containing XENLETA in the forms clinically developed by us or any of our affiliates, or the Sunovion Licensed
Products, in Canada in all uses in humans in CABP and in any other indication for which the Sunovion Licensed Products
have received regulatory approval in Canada. Under the Sunovion License Agreement, Sunovion and DAC established a
joint development committee, or the Sunovion JDC, to review and oversee regulatory approval and commercialization
plans in Canada. Sunovion will be solely responsible for all costs related to obtaining regulatory approval of and
commercializing Sunovion Licensed Products in the Canada and is obligated to use commercially reasonable efforts to
develop, obtain regulatory approval for, and commercialize Licensed Product in the Canada.
On November 7, 2019, the Company, through Sunovion, submitted a New Drug Submission, or NDS. Health
Canada determined there was a screening deficiency in December 2019 and a response from the Company/Sunovion was
provided on December 18, 2019 and acknowledged by Health Canada on January 13, 2020. The NDS approval occurred on
July 10, 2020.
The Company identified two performance obligations at inception: (1) the delivery of the exclusive license to
Sunovion, which the Company has determined is a distinct license of functional intellectual property that Sunovion has
obtained control of; and, (2) the participation in the Sunovion JDC. The $1.0 million non-refundable upfront payment was
allocated entirely to the delivery of the license as the Sunovion JDC deliverable was deemed to be de minimis. With the
NDS approval that occurred on July 10, 2020, the Company received a regulatory milestone payment of $0.5 million. Any
future regulatory and commercial milestone payments under the Sunovion License Agreement will be recorded during the
period the milestones become probable of achievement.
Named Patient Program Agreement with WE Pharma Ltd.
On June 30, 2020 the Company announced that WE Pharma Ltd., or WEP Clinical, a specialist pharmaceutical
services company, had signed an exclusive agreement with the Company to supply XENLETA on a named patient or
expanded access basis in certain countries outside of the US, China and Canada. The Named Patient Program, or NPP, is
designed to ensure that physicians, contingent on meeting the necessary eligibility criteria and receiving approval, can
request IV or oral XENLETA on behalf of patients who live in certain countries where it is not yet available and have an
unmet medical need.
15. Commitments and Contingencies
Future minimum contractual obligations and commitments at December 31, 2021 are as follows:
(in thousands)
Operating lease obligations
XENLETA API purchase
Other contractual commitments
Total contractual commitments and
contingencies
Total
2022
$
785
53,985
10,913
702
4,691
5,072
Year ending December 31,
2023
2024
2025
83
4,691
3,983
—
4,691
929
—
6,652
929
2026
— $
Thereafter
—
26,608
—
—
6,652
$ 65,683
$ 10,465
$
8,757
$ 5,620
$ 7,581
$ 6,652
$ 26,608
The Company has contractual commitments related primarily to contracts entered into with contract
manufacturing organizations and contract research organizations in connection with the commercial manufacturing of
XENLETA, the purchase of SIVEXTRO finished product and other research and development activities. The estimated
payments to the service providers included in the table above are based on the achievement of milestones included within
the agreements. Also, some of these contracts are subject to early termination clauses exercisable at the discretion of the
Company.
F-31
Table of Contents
XENLETA API Supply
On August 4, 2021, our wholly-owned subsidiary, Nabriva Therapeutics Ireland DAC, entered into an
amendment, or the First Amendment, to its API Supply Agreement, or the Hovione Supply Agreement, with Hovione
Limited, or Hovione, which provides for the long-term commercial supply of the active pharmaceutical ingredients, or API,
for XENLETA. Under the First Amendment, Hovione agreed to cancel our May 2021 purchase order for XENLETA API,
which represented our minimum purchase requirement under the Hovione Supply Agreement. In addition, pursuant to the
First Amendment, Hovione agreed to reduce our annual minimum purchase requirements for XENLETA API to no
minimum purchase requirement in 2021, by 50% from 2022 to 2024 and by 25% in 2025, in consideration for cash
payments from us totaling €3.2 million and the right to a low single-digit royalty on total net sales of XENLETA in the
United States for a period commencing on August 4, 2021 and ending on November 22, 2030, or the Royalty Term, which
royalty payments shall be no greater than an aggregate of €10.0 million. If the aggregate amount of royalties payments
received by Hovione under the First Amendment is less than an aggregate of €4.0 million, we are obligated to pay Hovione
the difference in a lump sum payment at the end of the Royalty Term. In addition, pursuant to the First Amendment,
Hovione agreed to extend the duration of the Hovione Supply Agreement from November 22, 2025 to November 22, 2030
with annual minimum purchase requirements for 2026 to 2030 at the newly agreed annual minimum purchase amount for
2025. Pursuant to the First Amendment, upon the occurrence of certain events of insolvency for us, any unpaid minimum
annual commitment amounts and royalty amounts under the agreement will become immediately due and payable.
Zavante Obligations
In connection with the acquisition of Zavante in July 2018, the Company is obligated to pay up to $97.5 million in
contingent consideration to the former Zavante shareholders, of which $25.0 million would become payable upon the first
approval of a NDA from the FDA for CONTEPO for any indication, or the Approval Milestone Payment, and an aggregate
of up to $72.5 million would become payable upon the achievement of specified sales milestones, or the Net Sales
Milestone Payments. The Company’s shareholders have approved the issuance of the Company’s ordinary shares in
settlement of potential milestone payment obligations that may become payable in the future to former Zavante
stockholders, including the Approval Milestone Payment which will be settled in Company ordinary shares. The Company
also has the right to settle the Net Sales Milestone Payments in Company ordinary shares, except as otherwise provided in
the Merger Agreement.
The Company is obligated to pay $3.0 million in cash upon marketing approval by the FDA with respect to any
oral, intravenous or other form of fosfomycin, or the Zavante Products, and milestone payments of up to $26.0 million that
may be settled in ordinary shares in the aggregate upon the occurrence of various specified levels of net sales with respect
to the Zavante Products. In addition, Zavante is obligated to make annual royalty payments of a mid-single-digit
percentage of net sales of Zavante Products, subject to adjustment based on net sales thresholds and with such percentage
reduced to low single-digits if generic fosfomycin products account for half of the applicable market on a product-by-
product and country-by-country basis. Zavante will also pay a mid-single-digit percentage of transaction revenue in
connection with the consummation of the grant, sale, license or transfer of market exclusivity rights for a qualified
infectious disease product (within the meaning of the 21st Century Cures Act) related to a Zavante Product.
Litigation
The Company has no contingent liabilities in respect of legal claims arising in the ordinary course of business.
16. Subsequent Events
Nasdaq Deficiency Notice
On January 4, 2022, the Company received written notice, or the Notice, from The Nasdaq Stock Market LLC, or
Nasdaq, indicating that, based on the closing bid for the last 30 consecutive business days, the Company is not in
F-32
Table of Contents
compliance with the $1.00 minimum bid price requirement for continued listing on The Nasdaq Global Select Market, as
set forth in Listing Rule 5450(a)(1), or the Bid Price Rule. The Notice does not result in the immediate delisting of the
Company’s ordinary shares from The Nasdaq Global Select Market. In accordance with Listing Rule 5810(c)(3)(A), the
Company has a period of 180 calendar days to regain compliance with the Bid Price Rule. As a result, the Company will
have until July 5, 2022, or the Compliance Date, to regain compliance with the Bid Price Rule. To regain compliance, the
closing bid price of the Company’s ordinary shares must be at least $1.00 per share for a minimum of ten consecutive
business days on or before the Compliance Date. If the Company does not regain compliance with the Bid Price Rule by
the Compliance Date, the Company may be eligible for an additional 180 calendar day compliance period. To qualify, the
Company would need to transfer the listing of its ordinary shares to the Nasdaq Capital Market, provided it meets the
continued listing requirement for market value of publicly held shares and all other initial listing standards, with the
exception of the Bid Price Rule. To effect such a transfer, the Company would also need to pay an application fee to
Nasdaq and provide written notice to Nasdaq of its intention to cure the deficiency during the additional compliance
period. If the Company does not qualify for the additional compliance period or fails to regain compliance during the
additional 180-day period, then Nasdaq will notify the Company of its determination to delist the Company’s ordinary
shares, at which point the Company would have an opportunity to appeal the delisting determination to a Nasdaq hearing
panel. In addition to continuing to monitor the closing bid price of its ordinary shares, the Company expects to consider
available options to regain compliance with the Bid Price Rule. However, there can be no assurance that the Company will
be able to regain compliance with the Bid Price Rule.
EGM Vote
On March 24, 2022 the Company held an extraordinary general meeting of shareholders, at which time its
shareholders voted by a special resolution of over 75% of the votes cast at the meeting to grant the board of directors
authority under Irish law to allot and issue ordinary shares (including rights to acquire ordinary shares) for cash without
first offering those ordinary shares to existing shareholders pursuant to the statutory pre-emption right that would otherwise
apply through March 23, 2027.
CONTEPO NDA
Given the uncertainties of the timing of onsite inspection at its manufacturing partners in Europe, the Company
requested to be able to resubmit the CONTEPO NDA through June 2023, which the FDA granted on March 21, 2022. This
extension granted by the FDA provides the Company the flexibility to submit at any time up and through June 2023.
F-33
NABRIVA THERAPEUTICS PLC
RESTRICTED SHARE UNIT AGREEMENT
GRANTED UNDER 2020 SHARE INCENTIVE PLAN
Exhibit 10.57
This Restricted Share Unit Agreement (this “Agreement”) is made between Nabriva Therapeutics plc, a public limited
company organized under the laws of Ireland (the “Company”), and the Participant pursuant to the 2020 Share Incentive
Plan (as amended from time to time, the “Plan”).
NOTICE OF GRANT
I.
Participant Information
Participant:
Participant Address:
II.
Grant Information
Grant Date:
Number of Restricted Share Units:
III.
Vesting Table
Vesting Date
Number of Restricted Share
Units that Vest
This Agreement includes this Notice of Grant and the following Exhibits and Schedules, which are expressly incorporated
by reference in their entirety herein:
Exhibit A – General Terms and Conditions
Exhibit B – Nabriva Therapeutics plc 2020 Share Incentive Plan
Schedule 1 – Vesting Schedule
Schedule 2 – Additional Terms and Conditions
IN WITNESS WHEREOF, the parties hereto have executed this Agreement.
NABRIVA THERAPEUTICS PLC
PARTICIPANT
__________________________
Name:
Title:
__________________________
Name:
Restricted Share Unit Agreement
2020 Share Incentive Plan
EXHIBIT A
GENERAL TERMS AND CONDITIONS
For valuable consideration, receipt of which is acknowledged, the parties hereto agree as
follows:
1.
Grant of Restricted Share Units. This Agreement evidences the grant by the Company,
on the grant date (the “Grant Date”) set forth in the Notice of Grant that forms part of this Agreement
(the “Notice of Grant”), to the Participant, subject to the terms and conditions set forth in this
Agreement and in the Company’s 2020 Share Incentive Plan (as amended from time to time, the
“Plan”), of an award with respect to the number of restricted share units (the “RSUs”) set forth in the
Notice of Grant. Each RSU granted hereunder represents the right to receive one ordinary share of the
Company (an “Ordinary Share”) upon vesting of the RSU, subject to the terms and conditions set
forth herein; provided, however, that if the Company’s shareholders do not approve an increase to the
number of Ordinary Shares available for issuance under the Plan (the “Share Pool Increase”) at the
Company’s 2022 Annual General Meeting of Shareholders (the “2022 AGM”), then each RSU
represents the right to receive, upon vesting, cash in an amount equal to the fair market value of an
Ordinary Share as of the vesting date, subject to the terms and conditions set forth herein. For the
avoidance of doubt, in the event that the Share Pool Increase is not approved by Company
shareholders at the 2022 AGM, no Ordinary Shares shall be issued upon vesting of this award of RSUs
and if the Share Pool Increase is approved by Company shareholders at the 2022 AGM, then only
Ordinary Shares and not cash shall be issued upon vesting of this award of RSUs.
1.
Vesting.
(a)
The RSUs shall vest in accordance with the Vesting Table set forth in the Notice
of Grant.
(b)
Upon the vesting of the RSUs, the Company will deliver to the Participant, for
each RSU that becomes vested, one Ordinary Share, or, if the Company’s shareholders do not approve
the Share Pool Increase at the 2022 AGM, cash in an amount equal to the fair market value of an
Ordinary Share on the date of vesting, subject to the payment of any taxes pursuant to Section 4. Each
Ordinary Share, or, if applicable, the cash equivalent thereof, will be delivered to the Participant as
soon as practicable following each vesting date, but in any event within 30 days of such date.
2.
Forfeiture of Unvested RSUs Upon Cessation of Service.
In the event that the Participant ceases to perform services to the Company for any reason or no
reason, with or without cause, all of the RSUs that are unvested as of the time of such cessation shall
be forfeited immediately and automatically to the Company, without the payment of any consideration
to the Participant, effective as of such cessation. The Participant shall have no further rights with
respect to the unvested RSUs, any Ordinary Shares, or the cash equivalent thereof, as applicable, that
may have been issuable with respect thereto. If the Participant provides services to a
subsidiary of the Company, any references in this Agreement to provision of services to the Company
shall instead be deemed to refer to service with such subsidiary.
3.
Tax Matters.
(a)
Acknowledgments; No Section 83(b) Election. The Participant acknowledges
that he or she is responsible for obtaining the advice of the Participant’s own tax advisors with respect
to the award of RSUs and the Participant is relying solely on such advisors and not on any statements
or representations of the Company or any of its agents with respect to any or all income tax, social
insurance, payroll tax, payment on account or other tax-related items related to participation in the
Plan and legally applicable to the Participant (“Tax-Related Items”) relating to the RSUs. The
Participant understands that the Participant (and not the Company) shall be responsible for the
Participant’s Tax-Related Items that may arise in connection with the grant, vesting and/or settlement
of the RSUs and to the extent the RSUs are settled in Ordinary Shares, the subsequent sale of any
Ordinary Shares acquired pursuant to the settlement of the RSUs and the receipt of any dividends
thereon. The Participant acknowledges that no election under Section 83(b) of the Internal Revenue
Code, as amended, is available with respect to the RSUs and that the Company is under no obligation
to structure the terms of the grant or any aspect of the RSUs to reduce or eliminate the Participant’s
liability for Tax-Related Items or achieve any particular tax result. Further, if the Participant becomes
subject to tax in more than one jurisdiction between the Grant Date and the date of any relevant
taxable event, as applicable, the Participant acknowledges that the Company may be required to
withhold or account for Tax-Related Items in more than one jurisdiction.
(b) Withholding. The Participant acknowledges and agrees that the Company has
the right to deduct from payments of any kind otherwise due to the Participant any federal, state, local
or other Tax-Related Items of any kind (including Tax-Related Items of jurisdictions outside the
United States, as applicable) required by law to be withheld with respect to the RSUs. To the extent
the RSUs are to be settled with Ordinary Shares, the Participant may satisfy such Tax-Related Items by
instructing the Company to withhold a number of Ordinary Shares having a fair market value (valued
in the manner determined by (or in a manner approved by) the Board) on the applicable vesting date
equal to the Tax-Related Items, based on minimum statutory withholding rates for federal and state tax
purposes, including payroll taxes, that are applicable to such supplemental taxable income. If the
Participant does not instruct the Company to withhold Ordinary Shares to satisfy any applicable Tax-
Related Items, or if the RSUs are otherwise settleable in cash, then the Participant agrees that if under
applicable law the Participant will owe Tax-Related Items at such time on any portion of the RSUs the
Company shall be entitled to satisfy the obligations with regard to all Tax-Related Items by one or a
combination of the following:
(1)
(2)
immediate payment from the Participant of the amount to be withheld by the Company; or
withholding from wages or other cash compensation paid to the Participant by the Company.
To the extent the RSUs shall be settled upon vesting with Ordinary Shares, the Company shall not
deliver any Ordinary Shares to the Participant until it is satisfied that all required withholdings have
been made and the Participant has complied with the above and applicable obligations in connection
with Tax-Related Items.
4.
Transfer Restrictions; Clawback.
(a)
The Participant shall not sell, assign, transfer, pledge, hypothecate or otherwise
dispose of or encumber, by operation of law or otherwise (collectively “transfer”) any RSUs, or any
interest therein. The Company shall not be required to treat as the owner of any RSUs or issue any
Ordinary Shares or, if applicable, the cash equivalent thereof, to any transferee to whom the such
RSUs have been transferred in violation of any of the provisions of this Agreement.
(b)
In accepting this award of RSUs, the Participant agrees to be bound by any
clawback policy that the Company has adopted or may adopt in the future.
5.
Rights as a Shareholder. The Participant shall have no rights as a shareholder of the
Company with respect to any Ordinary Shares that may be issuable with respect to the RSUs unless
and until Ordinary Shares are issued to the Participant following the vesting of the RSUs.
6.
Provisions of the Plan. This Agreement is subject to the provisions of the Plan
(including the provisions relating to amendments to the Plan), a copy of which is attached hereto as
Exhibit B.
7.
Miscellaneous.
(a)
No Right to Continued Service/Compensation for Loss. The Participant
acknowledges and agrees that, notwithstanding the fact that the vesting of the RSUs is contingent upon
his or her continued service to the Company, this Agreement does not constitute an express or implied
promise of continued service relationship with the Participant or confer upon the Participant any rights
with respect to a continued service relationship with the Company. Under no circumstances will the
Participant ceasing to be an employee of the Company be entitled to compensation for any loss of any
right or benefit or prospective right or benefit under the Plan which the Participant might otherwise
have enjoyed whether such compensation is claimed by way of damages for wrongful dismissal or
other breach of contract or by way of compensation for loss of office or otherwise howsoever.
(b)
Section 409A. The RSUs awarded pursuant to this Agreement are intended to
be exempt from or comply with the requirements of Section 409A of the Internal Revenue Code and
the Treasury Regulations issued thereunder (“Section 409A”). The delivery of Ordinary Shares or the
cash equivalent thereof, as applicable, on the vesting of the RSUs may not be accelerated or deferred
unless permitted or required by Section 409A.
(c)
Participant’s Acknowledgements. The Participant acknowledges that he or she:
(i) has read this Agreement; (ii) has been represented in the preparation, negotiation and execution of
this Agreement by legal counsel of the Participant’s own choice or has voluntarily declined to seek
such counsel; (iii) understands the terms and consequences of this Agreement; and (iv) is fully aware
of the legal and binding effect of this Agreement.
(d)
Governing Law. This Agreement shall be governed by, except to the extent
preempted by other applicable laws (1) with respect to the corporate law requirements applicable to
the Company, the validity and authorization of the issuance of Ordinary Shares under the Plan and
similar matters, the laws of Ireland (without reference to conflict of law principles thereof) and (2)
with respect to all other matters relating to the Plan and Awards, the laws of the State of Delaware,
excluding choice-of-law principles of the law of that state.
EXHIBIT B
NABRIVA THERAPEUTICS PLC 2020 SHARE INCENTIVE PLAN
Schedule 1
Vesting Schedule
[N/A for Time-Based Awards]
Schedule 2
Additional terms to Restricted Share Unit Award Agreement
Terms and Conditions
This Schedule (the “Schedule”) includes additional terms and conditions that govern the RSUs
granted to you under the Plan if you reside in one of the countries listed below. Certain capitalized
terms used but not defined in this Schedule have the meanings set forth in the Plan and/or the
Agreement.
Notifications
This Schedule also includes country-specific information of which you should be aware with respect
to your participation in the Plan. The information is based on the securities, exchange control and
other laws in effect in the respective countries as of April [__], 2021. Such laws are often complex
and change frequently. As a result, the Company strongly recommends that you do not rely on the
information noted herein as the only source of information relating to the consequences of your
participation in the Plan because the information may be out of date at the time that you vest in the
RSUs and, Ordinary Shares, or the cash equivalent thereof, are issued to you or any shares issued upon
vesting are sold.
In addition, the information is general in nature and may not apply to your particular situation, and the
Company is not in a position to assure you of any particular result. Accordingly, you are advised to
seek appropriate professional advice as to how the relevant laws in your country may apply to your
particular situation. Finally, please note that if you are a citizen or resident of a country other than the
country in which you are currently working, or transfers employment after grant, the information
contained in the Schedule may not be applicable.
Ireland
Notifications
Director Notification Obligation. If you are a director, shadow director or secretary of the Company or
an Irish subsidiary or affiliate of the Company, and you acquire or dispose of an interest under this
Agreement comprising more than 1% of the share capital in the Company, you must notify the entity
in which you hold that office (whether the Company itself or an Irish subsidiary or affiliate of the
Company) in writing within five business days of receiving or disposing of an interest in the Company,
or within five business days of becoming aware of the event giving rise to the notification requirement
or within five days of becoming a director or secretary if such an interest exists at the time. This
notification requirement also applies with respect to the interests of a spouse or children under the age
of 18 (whose interests will be attributed to the director, shadow director or secretary).
Exhibit 10.58
Certain identified information has been excluded from the exhibit because it is both (i) not material
and (ii) is the type of information that the registrant treats as private or confidential. Double asterisks
denote omissions.
SIDE AGREEMENT
to the
Manufacturing Services Agreement
effective as of May 08th, 2017
This Side Agreement (the “Side Agreement”) to the above-mentioned Manufacturing Services
Agreement, as assigned by Nabriva Therapeutics GmbH (formerly Nabriva Therapeutics AG) to
Nabriva Therapeutics Ireland DAC (the “MSA”), is entered into by and between Patheon UK Ltd, a
corporation existing under the laws of United Kingdom, with registered offices at Kingfisher Drive,
Covingham, Swindon, SN3 5BZ, UK (“Patheon”) and Nabriva Therapeutics Ireland DAC, an Irish
designated activity company, having its registered office at Alexandra House, Office 225/227, The
Sweepstakes, Ballsbridge, Dublin 4, D04 C7H2, Ireland (“Customer” or “Nabriva”).
Each of Patheon and Customer is hereinafter referred as “Party” or together as “Parties”. This Side
Agreement is effective as of January 1st, 2021 (the “Effective Date”).
Capitalized terms shall have the meaning set forth in the MSA unless otherwise defined herein.
WHEREAS, pursuant to Schedule B to the MSA, Customer agreed to order and purchase an annual
binding minimum amount of Product following its approval in each relevant Territory so ensuring a
certain minimum conversion revenue (i.e: €[**] in Year 1, and €[**] in Year 2 for the amount of €
[**]) (the “Initial Minimum Conversion Revenue”) for Patheon, and that, if such Minimum
Conversion Revenue is not met in a given Year, then Customer will pay such an additional sum at the
end of that Year that ensures the Minimum Conversion Revenue is paid to Patheon;
WHEREAS, the Product was approved for the US market in August 2019, and in Europe in July 2020;
WHEREAS, in 2020, Nabriva did not order any volume of Product to Patheon and substantially
reduced its demand to [**] batches only in 2021;
WHEREAS, in consideration of the above recitals, Nabriva owes Patheon the amount of (i) €[**] for
Year 2020 and, (ii) provided that [**] batches of Product are ordered and paid by Nabriva in 2021, the
amount of €[**] for Year 2021, equal to the amount of €[**] less the conversion cost of the [**]
ordered batched (i.e. €[**]), for an aggregate amount of €[**] (“Amount Due”);
WHEREAS, Nabriva asked Patheon to discount the Amount Due of €[**] (“Discount”), to defer payment of the Amount
Due less the Discount, and to revise its Product volume requirements until 2025;
WHEREAS, Patheon has been available to support Customer with the above matter, at the following terms and conditions;
NOW, THEREFORE, in consideration of the premises contained herein, and other valuable
consideration, the receipt and sufficiency of which are hereby acknowledged, the Parties agree as
follows:
1.
The above recitals form an integral and substantial part of this Side Agreement.
2.
3.
4.
(i)
(ii)
The Parties hereby agree to amend Section 8.1 of the MSA to extend the Initial Term of
the MSA until 31st December 2025. All other provisions in Section 8.1 shall remain
unchanged.
Patheon agreed to discount the Amount Due of €[**] (“Discount”) and Nabriva agrees
to reimburse Patheon for the Amount Due less the Discount, for an aggregate amount
of €[**], according to the following milestones:
(a)
(b)
(c)
€[**] by 30th November 2021;
€[**] by 31st October 2022;
€[**] by 31st October 2023.
The Parties agree to revise the Price for the Manufacturing Services as follows:
each batch of Product manufactured by Patheon in 2021 will be invoiced to Nabriva at
the unit price (conversion cost plus components) of €[**];
each batch of Product manufactured by Patheon starting from the 1st January 2022 will
be charged by Patheon to Nabriva at the Price per vial set forth in the Schedule B
attached to this agreement as ‘Annex 1’ that entirely replaces the Schedule B of the
MSA.
Section 4.2(a) of the MSA shall apply to the Product Price starting from January 1st,
2022.
5.
Starting from Year 2021, the annual binding minimum amount of Product (“Binding
Volume”) that Nabriva is obliged to order and purchase during the Initial Term of the
MSA is the following:
Year
2021
2022
2023
2024
2025
Binding Volume/Vials
[**]
[**]
[**]
[**]
[**]
It is understood and agreed between the Parties that, should Nabriva (i) not pay in full and at
the agreed dates the amounts set forth in Section 3 above, or (ii) not order or purchase the
above Binding Volume each Year during the Initial Term, in addition to the provisions of
Section 4.2.1 of the MSA and save any other remedy that Patheon may have under the MSA,
Patheon shall be entitled to and Nabriva shall be obliged to immediately reimburse Patheon for
the amounts (if still due by Nabriva) as follows:
(i)
(ii)
(iii)
€[**] if the Binding Volume is not ordered and paid in full in Year 2021;
€[**] if the Binding Volume is not ordered and paid in full in Year 2022;
Any outstanding amount calculated as the difference between the Amount Due, and any
other instalment paid by Nabriva in accordance with Section 3 above.
For the sake of clarity, the Parties acknowledge that at the execution date of this Side
Agreement, Nabriva has already ordered a paid a batch of Product (#00009) as part of the its
2021 Binding Volume commitment, at the Price applicable in 2020, for a total amount of €[**]
instead of the Price agreed in Section 4 above (i.e. €[**]). Therefore, upon execution of this
Side Agreement, Patheon will be entitled to charge Nabriva for the batch Price difference equal
to €[**].
6.
7.
This Side Agreement constitutes a supplement to the MSA, forms an integral and
substantial part thereof and, unless otherwise expressly provided herein, shall be
subject to the same terms and conditions of the MSA and duly governed thereby.
Nothing contained in this Side Agreement shall be deemed to constitute a novation of
the terms of the MSA, nor affect any of the rights, powers or remedies of the Parties
under the MSA, nor constitute a waiver of any provision thereof, except as specifically
set forth in this Side Agreement.
This Side Agreement may be executed in one or more counterparts, each of which shall
be deemed an original but all of which together shall constitute one and the same
instrument.
IN WITNESS WHEREOF, the duly authorized representatives of each Party have executed this Side
Agreement on the date written above.
Nabriva Therapeutics Ireland DAC
Patheon UK Ltd.
Signature: /s/ Dan Dolan
Signature: /s/ Andrew Robinson
Name: Dan Dolan
Title: Director
Name: Andrew Robinson
Title: Director
ANNEX 1
SCHEDULE B
MINIMUM ORDER QUANTITY, ANNUAL VOLUME, AND PRICE
Long Term Forecast (binding minimum batches) (*)
Product
2021
2022
2023
2024
Annual Volume Forecast
Lefamulin Vials
[**]
[**]
[**]
[**]
2025
[**]
Manufacturing Prices
Bulk Prices:
Product
Lefamulin Vials
Lefamulin Vials
[**]
Minimum Order
Quantity: Batch Size
(Vials) x Campaign
Length (Batches)
[**]
[**]
Price Per Bulk Unlabelled Vial
Component
Price
[**]
[**]
Conversion
Price
[**]
[**]
Bulk
Price
[**]
[**]
SUBSIDIARIES OF NABRIVA THERAPEUTICS plc
Nabriva Therapeutics GmbH
Nabriva Therapeutics Ireland Designated Activity Company
Zavante Therapeutics, Inc.
Nabriva Therapeutics US, Inc.
Exhibit 21.1
Austria
Ireland
Delaware
Delaware
Consent of Independent Registered Public Accounting Firm
Exhibit 23.1
We consent to the incorporation by reference in the registration statements (Nos. 333-208097, 333-222003, 333-226330,
333-228094, 333-230216, 333-240178, 333-254157 and 333-260927) on Form S-8, (Nos. 333-219567, 333-223739 and
333-248530) on Form S-3 and (No. 333-260146) on Form S-1 of our report dated March 29, 2022, with respect to the
consolidated financial statements of Nabriva Therapeutics plc.
/s/ KPMG LLP
Philadelphia, Pennsylvania
March 29, 2022
EXHIBIT 31.1
CERTIFICATIONS
I, Theodore Schroeder, certify that:
1. I have reviewed this Annual Report on Form 10-K of Nabriva Therapeutics plc;
2. 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;
3. 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 registrant as of, and
for, the periods presented in this report;
4. The registrant’s other certifying officer 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 registrant and have:
(a) 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 registrant, 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;
(b) 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;
(c) Evaluated the effectiveness of the registrant’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
(d) Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred
during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual
report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control
over financial reporting; and
5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control
over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or
persons performing the equivalent functions):
(a) 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 registrant’s ability to record, process,
summarize and report financial information; and
(b) Any fraud, whether or not material, that involves management or other employees who have a significant role
in the registrant’s internal control over financial reporting.
/s/ Theodore Schroeder
Theodore Schroeder
Chief Executive Officer
(Principal Executive Officer)
Dated: March 29, 2022
EXHIBIT 31.2
CERTIFICATIONS
I, Daniel Dolan, certify that:
1. I have reviewed this Annual Report on Form 10-K of Nabriva Therapeutics plc;
2. 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;
3. 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 registrant as of, and
for, the periods presented in this report;
4. The registrant’s other certifying officer 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 registrant and have:
(a) 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 registrant, 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;
(b) 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;
(c) Evaluated the effectiveness of the registrant’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
(d) Disclosed in this report any change in the registrant’s internal control over financial reporting that occurred
during the registrant’s most recent fiscal quarter (the registrant’s fourth fiscal quarter in the case of an annual
report) that has materially affected, or is reasonably likely to materially affect, the registrant’s internal control
over financial reporting; and
5. The registrant’s other certifying officer and I have disclosed, based on our most recent evaluation of internal control
over financial reporting, to the registrant’s auditors and the audit committee of the registrant’s board of directors (or
persons performing the equivalent functions):
(a) 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 registrant’s ability to record, process,
summarize and report financial information; and
(b) Any fraud, whether or not material, that involves management or other employees who have a significant role
in the registrant’s internal control over financial reporting.
/s/ Daniel Dolan
Daniel Dolan
Chief Financial Officer
(Principal Financial Officer)
Dated: March 29, 2022
CERTIFICATION
PURSUANT TO 18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
EXHIBIT 32.1
In connection with the Annual Report on Form 10-K of Nabriva Therapeutics plc (the “Company”) for the year
ended December 31, 2021 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), the
undersigned, Theodore Schroeder, Chief Executive Officer of the Company, hereby certifies, pursuant to 18 U.S.C.
Section 1350, that:
(1) The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of
1934, as amended; and
(2) The information contained in the Report fairly presents, in all material respects, the financial condition and results
of operations of the Company.
/s/ Theodore Schroeder
Theodore Schroeder
Chief Executive Officer
(Principal Executive Officer)
Dated: March 29, 2022
CERTIFICATION
PURSUANT TO 18 U.S.C. SECTION 1350,
AS ADOPTED PURSUANT TO
SECTION 906 OF THE SARBANES-OXLEY ACT OF 2002
EXHIBIT 32.2
In connection with the Annual Report on Form 10-K of Nabriva Therapeutics plc (the “Company”) for the year
ended December 31, 2021 as filed with the Securities and Exchange Commission on the date hereof (the “Report”), the
undersigned, Daniel Dolan, Chief Financial Officer of the Company, hereby certifies, pursuant to 18 U.S.C. Section 1350,
that:
(1) The Report fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of
1934, as amended; and
(2) The information contained in the Report fairly presents, in all material respects, the financial condition and results
of operations of the Company.
/s/ Daniel Dolan
Daniel Dolan
Chief Financial Officer
(Principal Financial Officer)
Dated: March 29, 2022