UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM 10-K
☒
ANNUAL REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
☐
TRANSITION REPORT PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
For the Transition Period from to .
For the Fiscal Year Ended December 31, 2020
or
Commission File Number 001-38114
AVENUE THERAPEUTICS, INC.
(Exact name of registrant as specified in its charter)
Delaware
(State or other jurisdiction of incorporation or organization)
47-4113275
(I.R.S. Employer Identification No.)
1140 Avenue of the Americas, Floor 9, New York NY 10036
(Address of principal executive offices and zip code)
(781) 652-4500
(Registrant’s telephone number, including area code)
Securities registered pursuant to Section 12(b) of the Act:
(Title of Class)
Common Stock, par value $0.0001 per share
Trading Symbol(s)
ATXI
(Name of exchange on which registered)
Nasdaq Global Market
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 ☒
Securities registered pursuant to section 12(g) of the Act: None.
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 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, 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
Non-accelerated filer
Emerging growth company
☐
☒
☒
Accelerated filer
Smaller reporting 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 Rule 12b-2 of the Act). Yes ☐ No ☒
The aggregate market value of the voting stock held by non-affiliates of the registrant the last business day of the registrant’s most recently completed second fiscal quarter:
$72,342,650 based upon the closing sale price of our common stock of $10.77 on that date. Common stock held by each officer and director and by each person known to own
in excess of 5% of outstanding shares of our common stock has been excluded in that such persons may be deemed to be affiliates. The determination of affiliate status in not
necessarily a conclusive determination for other purposes.
Indicate the number of shares outstanding of each of the registrant’s classes of common stock, as of the latest practicable date.
Class of Common Stock
Common Stock, $0.0001 par value
Outstanding Shares as of March 17, 2021
16,748,068
AVENUE THERAPEUTICS, INC.
ANNUAL REPORT ON FORM 10-K
TABLE OF CONTENTS
PART I
Item 1.
Item 1A.
Item 1B.
Item 2.
Item 3.
Item 4.
PART II
Item 5.
Item 7.
Item 8.
Item 9.
Item 9A.
Item 9B.
PART III
Item 10.
Item 11.
Item 12.
Item 13.
Item 14.
PART IV
Item 15.
Item 16.
Business
Risk Factors
Unresolved Staff Comments
Properties
Legal Proceedings
Mine Safety Disclosures
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
Management’s Discussion and Analysis of Financial Condition and Results of Operations
Financial Statements and Supplementary Data
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure
Controls and Procedures
Other Information
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
Exhibits, Financial Statement Schedules
Form 10-K Summary
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SPECIAL CAUTIONARY NOTICE REGARDING FORWARD-LOOKING STATEMENTS
Certain matters discussed in this report may constitute forward-looking statements for purposes of the Securities Act of 1933, as amended (the “Securities Act”) and the
Securities Exchange Act of 1934, as amended (the “Exchange Act”), and involve known and unknown risks, uncertainties and other factors that may cause our actual results,
performance or achievements to be materially different from the future results, performance or achievements expressed or implied by such forward-looking statements. The
words “anticipate,” “believe,” “estimate,” “may,” “expect” and similar expressions are generally intended to identify forward-looking statements. Our actual results may differ
materially from the results anticipated in these forward-looking statements due to a variety of factors, including, without limitation, those discussed under the captions “Risk
Factors,” and elsewhere in this report. All written or oral forward-looking statements attributable to us are expressly qualified in their entirety by these cautionary statements.
Such forward-looking statements include, but are not limited to, statements about our:
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expectations for increases or decreases in expenses;
expectations for the clinical and pre-clinical development, manufacturing, regulatory approval, and commercialization of our pharmaceutical product candidate or
any other products we may acquire or in-license;
our use of clinical research centers and other contractors;
expectations for incurring capital expenditures to expand our research and development and manufacturing capabilities;
expectations for generating revenue or becoming profitable on a sustained basis;
expectations or ability to enter into marketing and other partnership agreements;
expectations or ability to enter into product acquisition and in-licensing transactions;
expectations or ability to build our own commercial infrastructure to manufacture, market and sell our product candidate;
acceptance of our products by doctors, patients or payors;
our ability to compete against other companies and research institutions;
our ability to secure adequate protection for our intellectual property;
our ability to attract and retain key personnel;
availability of reimbursement for our products;
estimates of the sufficiency of our existing cash and cash equivalents and investments to finance our operating requirements, including expectations regarding the
value and liquidity of our investments;
the volatility of our stock price;
expected losses; and
•
expectations for future capital requirements.
The forward-looking statements contained in this report reflect our views and assumptions as of the effective date of this report. Except as required by law, we assume
no responsibility for updating any forward-looking statements.
We qualify all of our forward-looking statements by these cautionary statements.
SUMMARY RISK FACTORS
Our business is subject to risks of which you should be aware before making an investment decision. The risks described below are a summary of the principal risks associated
with an investment in us and are not the only risks we face. You should carefully consider these risk factors, the risk factors described in Item 1A, and the other reports and
documents that we have filed with the Securities and Exchange Commission (“SEC”).
Risks Pertaining to Our Potential Merger with InvaGen Pharmaceuticals, Inc. (“InvaGen”)
• We are set to merge with InvaGen; however, InvaGen has raised several issues with the merger that may prevent it from happening. If successful, InvaGen could
delay or completely prevent the merger from closing, which would have a significant adverse impact on our stockholder value.
• The fact that there is a merger pending could have an adverse effect on our business and results of operations.
•
If the proposed merger is not completed, our business could be materially and adversely affected and our stock price could decline.
Risks Pertaining to the Influence of Fortress Biotech, Inc. (“Fortress”)
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Fortress controls a voting majority of our common stock.
Fortress has the right to receive a significant grant of shares of our common stock annually if the pending merger with InvaGen does not occur, which will result in
the dilution of your holdings of common stock upon each grant, which could reduce their value.
Risks Pertaining to Our Business and Influence
• We currently have no drug products for sale, and only one drug product candidate, Intravenous (“IV”) Tramadol. We are dependent on the success of IV Tramadol
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and cannot guarantee that we will receive regulatory approval, or IV Tramadol will be successfully commercialized.
If serious adverse or unacceptable side effects are identified during the development of IV Tramadol or any future product candidates, we may need to abandon or
limit our development of some of our product candidates.
• We are an “emerging growth company” and a “smaller reporting company,” and the reduced disclosure requirements applicable to emerging growth companies and
smaller reporting companies may make our common stock less attractive to investors.
Risks Pertaining to Our Finances
• We have incurred significant losses since our inception. We expect to incur losses for the foreseeable future, and may never achieve or maintain profitability.
• We do not have any products that are approved for commercial sale and therefore do not expect to generate any revenues from product sales in the foreseeable
future, if ever.
• Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish proprietary rights.
• There is substantial doubt about our ability to continue as a going concern, which may hinder our ability to obtain future financing.
Risks Pertaining to Reliance on Third Parties
• We rely, and expect to continue to rely, on third parties to conduct our preclinical studies and clinical trials, and those third parties may not perform satisfactorily,
including failing to meet deadlines for the completion of such trials or complying with applicable regulatory requirements.
• We rely on clinical data and results obtained by third parties that could ultimately prove to be inaccurate or unreliable.
Risks Pertaining to Regulatory Approval
• Even if IV Tramadol receives regulatory approval, which may not occur, it and any other products we may market will remain subject to substantial regulatory
scrutiny.
• We will need to obtain FDA approval of any proposed product brand names, and any failure or delay associated with such approval may adversely impact our
•
business.
If the DEA decides to reschedule Tramadol from a Schedule IV controlled substance to a more restrictive Schedule, IV Tramadol could lose its competitive
advantage, and our related clinical development and regulatory approval could be delayed or prevented.
Risks Pertaining to the Commercialization of Product Candidates
• Current and future legislation and regulation may increase the difficulty and cost for us to obtain marketing approval of, and to commercialize, our product
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candidate and may affect the prices we are able to obtain.
Public concern regarding the safety of opioid drug products such as IV Tramadol could delay or limit our ability to obtain regulatory approval, result in the inclusion
of serious risk information in our labeling, negatively impact market performance, or require us to undertake other activities that may entail additional costs.
• We expect intense competition for IV Tramadol, and new products may emerge that provide different or better therapeutic alternatives for our targeted indications.
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If IV Tramadol does not achieve broad market acceptance, the revenues that we generate from its sales will be limited.
Risks Pertaining to Intellectual Property and Potential Disputes Thereof
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If we are unable to obtain and maintain patent protection for our technology and products or if the scope of the patent protection obtained is not sufficiently broad,
our competitors could develop and commercialize technology and products similar or identical to ours, and our ability to successfully commercialize our technology
and products may be impaired.
If we are sued for infringing intellectual property rights of third parties, it will be costly and time consuming, and an unfavorable outcome in any litigation would
harm our business.
If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.
Item 1. Business
OVERVIEW
PART I
We are a specialty pharmaceutical company that seeks to develop and commercialize our product principally for use in the acute/intensive care hospital setting. Our current
product candidate is intravenous (IV) Tramadol, for the treatment of post-operative acute pain. Under the terms of certain agreements described herein, we have an exclusive
license to develop and commercialize IV Tramadol in the United States. In 2016, we completed a pharmacokinetic (PK) study for IV Tramadol in healthy volunteers as well as
an end of phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA). In the third quarter of 2017, we initiated a Phase 3 development program of IV
Tramadol for the management of post-operative pain. In December 2019, we submitted a New Drug Application (NDA) for IV Tramadol and received a Complete Response
Letter (CRL) from the FDA in October 2020. In February 2021, we resubmitted the NDA for IV Tramadol. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal
date of April 12, 2021 for the resubmitted IV Tramadol NDA. To date, we have not received approval for the sale of our product candidate in any market and, therefore, have
not generated any sales revenue from our product candidate.
Recent Developments
On November 12, 2018, we entered into a Stock Purchase and Merger Agreement (SPMA) with InvaGen Pharmaceuticals, Inc. (InvaGen), and Madison Pharmaceuticals
Inc. (Merger Sub), pursuant to which we agreed to the sale of the Company in a two-stage transaction, the details of which are summarized below. Recently, InvaGen has
communicated to us that it believes two Material Adverse Effects (as defined in the SPMA) have occurred, which raise substantial doubt as to whether or not the merger will be
consummated.
In October 2020, InvaGen communicated to us that it believes a Material Adverse Effect (as defined in the SPMA) has occurred due to the impact of the COVID-19
pandemic on potential commercialization and projected sales of IV Tramadol. Additionally, in connection with the resubmission of our NDA in February 2021 (details of which
are below), InvaGen communicated to us that it believes the proposed label for IV Tramadol would also constitute a Material Adverse Effect on the purported basis that the
proposed label under certain circumstances would make the product commercially unviable, and in addition that the indication that the FDA approves may fail to satisfy a
condition precedent to InvaGen’s obligation to consummate the second stage closing of the SPMA. While we disagree with InvaGen’s assertions, it is possible InvaGen could
attempt to avoid its obligation to consummate the merger, terminate the SPMA, and/or pursue monetary claims against us.
Over the past several months, we have communicated with InvaGen relating to its assertions that Material Adverse Effects have occurred. Nevertheless, InvaGen has
communicated to us its desire to consider all options on the proposed merger, including the option to not consummate the merger. As a result, the possible timing and likelihood
of the completion of the merger are uncertain, and, accordingly, there can be no assurance that such transaction will be completed on the expected terms, anticipated schedule, or
at all.
Background
On June 26, 2017, we completed an initial public offering (IPO) of our common stock, resulting in net proceeds of approximately $34.2 million after deducting underwriting
discounts, and other offering costs.
We used the proceeds from our IPO to initiate our first Phase 3 trial of IV Tramadol in patients with moderate-to-severe pain following bunionectomy, which had its first
patient dosed in September 2017. In May 2018, we announced the study met its primary endpoint and all key secondary endpoints.
In December 2018, we initiated the second Phase 3 trial in patients with moderate-to-severe pain following abdominoplasty upon successful completion of the bunionectomy
study. In June 2019, we announced the study met its primary endpoint and all key secondary endpoints.
In December 2017, we initiated an open-label safety study, which was completed during the second quarter of 2019. The results showed that IV Tramadol is well-tolerated
with a side effect profile consistent with known pharmacology.
In December 2019, we submitted an NDA pursuant to Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (FDCA). In February 2020, the FDA accepted our
NDA submission and set a PDUFA goal date of October 10, 2020. On October 12, 2020, we announced that we had received a CRL from the FDA regarding our NDA. In
November 2020, we had a Type A Meeting with the FDA to discuss issues raised in the CRL. On February 12, 2021, we resubmitted the NDA to the FDA for IV Tramadol. The
NDA resubmission follows the receipt of official minutes from a Type A meeting with the FDA, which was conducted following receipt of the CRL. The NDA resubmission
included revised language relating to the proposed product label and a report relating to terminal sterilization validation. The FDA assigned a PDUFA goal date of April 12,
2021 for the resubmitted NDA for IV Tramadol.
On November 12, 2018, we entered into the SPMA with InvaGen pursuant to which InvaGen agreed to purchase, for $35 million, common shares representing 33.3% of
the fully diluted capitalization of the Company (the Stock Purchase Transaction) and subsequently acquire the remaining issued and outstanding capital stock of the Company
for $180 million, subject to certain reductions, in a reverse subsidiary merger transaction (the Merger Transaction). Pursuant to the terms and subject to the conditions set forth
in the SPMA, InvaGen will, at second closing, hold 100% of the issued and outstanding equity interests of the Company. Consummation of the Merger Transaction is
conditioned upon, among other things, FDA approval of IV Tramadol by April 30, 2021, its labeling and scheduling and the absence of any Risk Evaluation and Mitigation
Strategy restrictions in effect with respect to IV Tramadol, as well as the filing and expiration of any waiting period applicable to the acquisition under the Hart-Scott-Rodino
Antitrust Improvements Act of 1976, as amended, which filing both parties completed on March 12, 2021.
The aggregate consideration to be paid by InvaGen under the SPMA is $215 million in cash (a portion of which was already paid in connection with the Stock Purchase
Transaction as described below), subject to certain potential reductions, which InvaGen intends to have sufficient immediately available funds to pay. In addition, we are subject
to certain lock-up restrictions and agreed not to (subject to customary exceptions), during the period commencing at the signing of the SPMA until the Merger Transaction,
issue, buy, sell, or otherwise subject to a security interest, pledge, hypothecation, mortgage or lien, any securities of the Company.
The SPMA was approved by a majority of our stockholders, including a majority of our non-affiliated stockholders, at our special shareholder meeting on February 6,
2019. On February 8, 2019, the Company and InvaGen consummated the Stock Purchase Transaction whereby InvaGen acquired 5,833,333 shares of our common stock at
$6.00 per share for total gross consideration of $35.0 million, representing a 33.3% stake in our capital stock on a fully diluted basis.
As described above, in October 2020, InvaGen communicated to us that it believes a Material Adverse Effect (as defined in the SPMA) has occurred due to the impact of
the COVID-19 pandemic on potential commercialization and projected sales of IV Tramadol, which means it is possible InvaGen could attempt to avoid its obligation to
consummate the second stage closing under the SPMA, terminate the SPMA, and/or pursue monetary claims against us. We disagree with InvaGen’s assertion that a Material
Adverse Effect has occurred and we have advised InvaGen of our position. Additionally, in connection with the resubmission of our NDA in February 2021, InvaGen
communicated to us that it believes the proposed label for IV Tramadol under certain circumstances would constitute a Material Adverse Effect (as defined in the SPMA) on the
purported basis that the proposed label under certain circumstances would make the product commercially unviable, and in addition that the indication that the FDA approves
may fail to satisfy a condition precedent to InvaGen’s obligation to consummate the second stage closing of the SPMA. We have notified InvaGen that we disagree with
InvaGen’s assertions. Nevertheless, InvaGen may seek to avoid its obligation to consummate the second stage closing under the SPMA, terminate the SPMA, and/or pursue
monetary claims against us.
Over the past several months, we communicated with InvaGen relating to its assertions that Material Adverse Effects have occurred. Nevertheless, InvaGen has
communicated to us its desire to consider all options on the proposed merger, including the option to not consummate the merger. This indicates that InvaGen may attempt to
avoid its obligations under the SPMA to consummate the merger, terminate the SPMA, and/or pursue monetary claims against Avenue. As a result, the possible timing and
likelihood of the completion of the merger are uncertain, and, accordingly, there can be no assurance that such transaction will be completed on the expected terms, anticipated
schedule, or at all. During the pendency of any dispute regarding these matters, we may be, and so long as the SPMA remains in place we will be, prohibited from engaging in a
change-of-control transaction, selling our rights to IV Tramadol, or effecting an equity or debt financing, in each case without the prior written consent of InvaGen.
In the event that we do not receive FDA approval for IV Tramadol by April 30, 2021, InvaGen will have the right to terminate the SPMA and will have no further
obligations to consummate the second stage closing under the SPMA. In the event that InvaGen does not exercise its right to terminate the SPMA, certain restrictions relating to
financings and strategic alternatives could exist through October 31, 2021, the time at which we can terminate the SPMA. In the event of termination of the SPMA, InvaGen
will retain certain rights pursuant to the Stockholder’s Agreement between us and InvaGen. These rights exist as long as InvaGen maintains at least 75% of the common shares
acquired in the first stage closing. Certain actions relating to equity issuances and changes to capital stock are restricted without the prior written consent of InvaGen during this
time.
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We may need to obtain additional capital through the sale of debt or equity financings or other arrangements to fund our operations and research and development activity;
however, there can be no assurance that we will be able to raise needed capital under acceptable terms, if at all. The sale of additional equity may dilute existing stockholders
and newly issued shares may contain senior rights and preferences compared to currently outstanding shares of common stock. Issued debt securities may contain covenants
and limit our ability to pay dividends or make other distributions to stockholders. If we are unable to obtain such additional financing, future operations would need to be scaled
back or discontinued.
We are a majority controlled subsidiary of Fortress.
CORPORATE INFORMATION
Avenue Therapeutics, Inc. was incorporated in Delaware on February 9, 2015. Our executive offices are located at 1140 Avenue of the Americas, Floor 9, New York, NY
10014. Our telephone number is (781) 652-4500, and our email address is info@avenuetx.com.
We maintain a website with the address www.avenuetx.com. We make available free of charge through our Internet website our annual reports on Form 10-K, quarterly
reports on Form 10-Q and current reports on Form 8-K, and any amendments to these reports, as soon as reasonably practicable after we electronically file such material with,
or furnish such material to, the SEC. We are not including the information on our website as a part of, nor incorporating it by reference into, this report. Additionally, the SEC
maintains a website that contains annual, quarterly, and current reports, proxy statements, and other information that issuers (including us) file electronically with the SEC. The
SEC’s website address is http://www.sec.gov.
OUR STRATEGY
Our primary objective is to establish IV Tramadol as an invaluable part of a treating physician’s repertoire of available pharmaceutical options for the management of
postoperative pain. The key elements of our strategy include:
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Obtain FDA approval of IV Tramadol for the management of postoperative acute pain. We submitted our NDA to the FDA for IV Tramadol in December 2019.
In February 2020, the FDA accepted our NDA submission and set a PDUFA goal date of October 10, 2020. On October 12, 2020, we announced that we had
received a CRL from the FDA regarding our NDA. In November 2020, we had a Type A Meeting with the FDA to discuss issues raised in the CRL. We
resubmitted the NDA on February 12, 2021 that incorporated revised language relating to the proposed product label and a report relating to terminal sterilization
validation. The FDA assigned a PDUFA goal date of April 12, 2021.
Maintain, expand and protect our intellectual property portfolio. We intend to expand and protect our intellectual property in the area of IV administration of
tramadol in order to maintain a defensible and valuable intellectual property portfolio.
The U.S. Postoperative Pain Market
We are currently focused on developing our proprietary product candidate, IV Tramadol, for the management of postoperative acute pain. Even though the postoperative
pain market is entrenched with low cost, generic pain relievers, we believe that there still remains a significant unmet medical need for safer and better-tolerated painkillers,
which are also referred to as analgesics.
According to Decision Resources’ Acute Pain Report of October 2014, or the 2014 Pain Report, sales of analgesics delivered via parenteral routes (IV, subcutaneous, and
intramuscular injections) for the management of acute pain totaled approximately $965 million in the United States in 2013. According to the 2014 Pain Report, there were over
ten million select common inpatient procedures performed, all of which likely required postoperative pain management, in the United States in 2013. According to IMS Health,
injectable analgesics sold approximately $1 billion in the United States in 2017.
The major goal in the management of postoperative pain is minimizing the dose of medications to lessen side effects while still providing adequate pain relief for analgesia.
This is best accomplished with multimodal and preemptive analgesia. An effective pain relief program should be individualized for the particular patient, operation, and
circumstances. In clinical practice, as there is no standard set of guidelines to manage postoperative pain, hospitals and even hospital units have their own practice guidelines
that are often based on physicians’ prescribing practices. These local guidelines are rooted in physician experience as it relates to anticipated severity of pain due to a particular
surgical procedure, and are often modified with consideration to things like staffing limitations, availability of specific drugs and/or formulations, access to patient controlled
analgesia, or PCA, systems, and formulary restrictions. Thus, treatment regimens vary widely from hospital to hospital, physician to physician and patient to patient.
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Understanding the range of available interventions and considering the type of surgery is essential to safe and effective pain management. The general consensus among
pain management practitioners is that use of more than one modality (i.e., molecules with different mechanisms or with different routes of administration) is optimal for
successful postoperative pain management. The most commonly prescribed agents in the immediate postoperative pain market are typically acetaminophen, or APAP, NSAIDS,
and opioid analgesics. APAP and NSAIDs are not sufficiently effective as the sole agent for pain management after major surgery in most patients. However, when used in
conjunction with opioids, APAP and NSAIDs offer substantial benefits as the quality of analgesia is often improved or enhanced due to their differentiated mechanism of action.
Nevertheless, the substantial side effects associated with these agents represent an important concern for patients and physicians to address. NSAIDS in particular have their
own serious side effects, including increased post-surgery bleeding, peptic ulcer disease and renal impairment, and is associated with hepatic side effects.
Traditional opioids offer safe and effective postoperative pain control and can be used in combination with other agents and techniques. However, the side effects of
opioids, such as morphine, include sedation, dizziness, nausea, vomiting, constipation, physical dependence, tolerance, and respiratory depression. Physical dependence and
addiction are clinical concerns that may prevent proper prescribing and, in turn, inadequate pain management. Less common side effects include delayed gastric emptying,
hyperalgesia, immunologic and hormonal dysfunction, muscle rigidity, and myoclonus. Importantly, they are Schedule II opioids and carry a high abuse potential.
Therefore, there is still unmet medical need in the post-surgical setting. We believe that IV Tramadol, if approved, can fill this unmet need. If approved, we believe that IV
Tramadol will be an effective alternative to traditional opioids but carry a lower potential for abuse because tramadol is a Schedule IV opioid in the U.S.
According to the Drug Enforcement Administration (DEA) definition, substances classified as Schedule II have “a high potential for abuse, with use potentially leading to
severe psychological or physical dependence” and substances classified as Schedule IV are “drugs with lower potential for abuse than Schedule II and consist of preparations
containing limited quantities of certain narcotics.”
The table below summarizes the available intravenous analgesic options in postoperative pain management currently available in the United States.
Available Classes
IV narcotics
Pain Levels
Moderate to severe
IV NSAIDS
Mild to severe
IV acetaminophen
Mild to moderate
Our Product Candidate
Common Limitations & Contraindications
Strong sedation
Respiratory depression
Constipation
Risk of dependence
Post-op bleeding risk
GI side effects
Renal impairment
Hepatic impairment
Tramadol, a synthetic dual-acting opioid, is a centrally acting analgesic with weak opioid agonist properties. It also works via the inhibition of serotonin and noradrenaline
re-uptake and blocking nociceptive impulses at the spinal level. These opioid and non-opioid modes of action are synergistic, essentially providing “multimodal therapy” with
the use of a single drug. Tramadol is also commonly combined with APAP or NSAIDS in clinical practice. Tramadol has a well-established efficacy and safety profile and has
been used throughout the world for more than 30 years. In the United States, tramadol is approved and marketed as an oral agent indicated in adults for the management of pain
severe enough to require an opioid analgesic and for which alternative treatments are inadequate. Tramadol was first approved in the United States in 1995, under the trade
name Ultram® immediate release tablet (Ortho-McNeil-Janssen). Ultracet®, a combination product containing tramadol and acetaminophen, is also marketed in the United
States (Ortho-McNeil-Janssen). According to Symphony Health Solutions, approximately 30 million scripts for tramadol and tramadol-containing drugs were filled in retail
pharmacies in the United States in 2020.
Tramadol has low potential for abuse and addiction and is currently classified by the DEA as a Schedule IV controlled substance. For comparison, other opioids which have
a high potential for abuse, including meperidine, morphine, hydromorphone and oxycodone, are all classified as Schedule II controlled substances.
The clinical trials from our development program are summarized below:
•
Lu, L., et al. Comparing the Pharmacokinetics of 2 Novel Intravenous Tramadol Dosing Regimens to Oral Tramadol: A Randomized 3-Arm Crossover Study.
Clinical Pharmacology in Drug Development. October 2019.
• Minkowitz, H., et al. Intravenous Tramadol is Effective in the Management of Postoperative Pain Following Abdominoplasty: A Three-Arm Randomized Placebo-
and Active-Controlled Trial. Drugs in R&D. May 2020.
• Minkowitz, H., et al. IV Tramadol – A New Treatment Option for Management of Post-Operative Pain in the U.S.: An Open-Label, Single-Arm, Safety Trial
•
Including Various Types of Surgery. Journal of Pain Research. May 2020.
Singla, N., et al. Efficacy and Safety of Intravenously Administered Tramadol in Patients with Moderate to Severe Pain Following Bunionectomy: A Randomized,
Double-Blind, Placebo-Controlled, Dose-Finding Study. Pain and Therapy. July 2020.
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Advantages of IV Tramadol
Parenteral tramadol is approved and used for the management of postoperative acute pain throughout much of the world. Parenteral formulations include IV, intramuscular,
or IM, and subcutaneous, or SC, formulations. Based on our review of IMS Health data from 2014 to 2016, we believe that parenteral tramadol accounts for approximately 10%
of the total IV analgesics used in Europe. During the 10-year period from 2010 to 2019, approximately 370 million doses of parenteral tramadol was used in Europe, according
to data from IQVIA (a 3rd party data provider). There is no parenteral formulation currently approved in the United States.
We believe that the introduction of an IV formulation of tramadol in the United States will address many of the shortcomings of opioids, APAP and NSAIDs currently used
in the postoperative setting.
We administered IV Tramadol over approximately 15 minutes in our Phase 3 trials. We believe that our method of administration of IV Tramadol may provide significant
benefits such as reduced side effects, compared to previously approved methods of administration of IV Tramadol in Europe, which is typically accomplished via a slow push
over 2 to 3 minutes. In addition, our IV Tramadol dosing regimen produces a similar Cmax (maximal blood level) and AUC (overall systemic exposure) to those of oral
tramadol at steady state, which we believe ensures an easy transition from IV to oral therapy in the post-surgical setting.
Based on the trials done in Europe and on the data generated with oral tramadol, we believe that IV Tramadol, if approved, will be an attractive option for physicians who
treat postoperative pain in the U.S., due to the following attributes:
•
•
•
As an established analgesic, tramadol has documented efficacy and safety and physicians are already familiar with the drug.
As a Schedule IV controlled substance, tramadol has less potential for addiction and abuse than other narcotics widely prescribed in the post-surgical setting. In the
current environment where the opioid epidemic is a recognized problem in the United States and there are increasing restrictions on Schedule II opioids, a Schedule
IV opioid such as tramadol may become a more attractive option.
Importantly, there is a step-down therapy available for IV Tramadol. Patients are transitioned to oral therapy when they are discharged from the hospital or when
they can tolerate oral medicine. Our IV Tramadol dosing regimen provides a similar PK profile to that of oral tramadol at steady state to ensure a smooth step-
down process.
We believe that IV Tramadol, if approved, will be a useful and effective tool in the management of acute postoperative pain. Its potential advantages compared to current
standard-of-care agents, along with the known efficacy, safety and tolerability profile for oral tramadol support the use of IV Tramadol in this setting. We believe that the risks
associated with the use of IV Tramadol will be benign compared to other opioids, and consistent with that of the currently marketed oral tramadol products. Consequently, with
the industry trend toward multimodal therapy and away from Schedule II narcotics, we believe that, if approved, IV Tramadol’s unique profile could position it to become an
invaluable part of a treating physician’s repertoire of available pharmaceutical options in the management of postoperative pain.
Clinical Development History
Revogenex, the previous Sponsor and Licensor, completed multiple nonclinical PK and toxicology studies in dogs, a Phase 1 dose proportionality study and a thorough
QT/QTc (TQT) study of IV Tramadol in healthy volunteers, or the TQT Study. The dose proportionality study was designed to compare maximum exposure and cumulative
exposures of IV Tramadol to that of oral tramadol, and to assess the dose proportionality of IV Tramadol in healthy adult volunteers. The TQT Study was done to evaluate
whether IV Tramadol has the potential to affect the “corrected QT interval”, or QTc, in healthy volunteers. The QTc represents electrical depolarization and repolarization of
the heart ventricles. A lengthened QTc is a marker for the potential of ventricular arrhythmias. The results of these studies are consistent with tramadol’s known toxicology
profile, pharmacokinetics and pharmacology.
PK Study for IV Tramadol
In general, Phase 2 clinical trials include initial proof-of-concept efficacy studies, dose-finding studies, and initial safety assessments in the target (i.e., to-be-treated)
population. We did not conduct Phase 2 clinical trials for IV Tramadol because tramadol is a known analgesic, and oral tramadol is labeled “for the management of pain severe
enough to require an opioid analgesic and for which alternative treatments are inadequate” in the United States. Instead, we completed pharmacokinetic (PK) simulations and
conducted a pharmacokinetic and safety study in healthy volunteers, in order to select a Phase 3 dose and dosing regimen designed to achieve exposure to tramadol similar to
that provided by oral tramadol. In 2016, we completed a PK study for IV Tramadol in healthy volunteers. A PK study generally involves dosing an experimental medicine in
healthy volunteers and taking a series of blood measurements from the study participants to understand how the body handles the drug. A PK study provides information on
important parameters such as systemic exposure, maximal and minimal levels of drug concentration in the blood and their time courses. The PK study we conducted was used to
select a dose and dosing regimen of IV Tramadol that achieves similar exposure to that provided by oral tramadol at steady state.
7
The PK study was designed as a three-way cross over study in 18 healthy volunteers. Each subject in the study served as his/her own control and received oral tramadol as
well as two different doses of IV Tramadol. Based on the results of the PK study, we decided to use a 50 mg dose in our pivotal Phase 3 program.
Our Clinical Development Strategy for IV Tramadol
At our EOP2 meeting with FDA, we discussed Phase 3 program requirements for IV Tramadol and confirmed the key elements of the Phase 3 program design. We
conducted two pivotal Phase 3 trials to evaluate the safety and efficacy of IV Tramadol, and one additional safety study. All three trials enrolled patients who required IV
analgesia following surgery. Over 1,000 patients were enrolled in the Phase 3 program. We believe that the design of our Phase 3 program is consistent with the design of Phase
3 programs for other analgesics being developed.
Postoperative pain following bunionectomy (orthopedic surgery model). The first Phase 3 trial was conducted in patients undergoing bunionectomy surgery, which is
considered an orthopedic surgical model. 409 patients were randomized and treated in a 1:1:1 ratio to one of two doses of IV Tramadol, or placebo, for 48 hours. The primary
efficacy endpoint was Sum of Pain Intensity Difference over 48 hours (SPID 48), which is a measure of the overall effectiveness of the drug in reducing pain intensity during
the 48-hour period. This trial commenced in the third quarter of 2017. In May 2018, we announced the trial met its primary endpoint and all key secondary endpoints.
Postoperative pain following abdominoplasty (soft tissue model). The second Phase 3 safety and efficacy trial was conducted in patients undergoing abdominoplasty
surgery, which is considered a soft-tissue surgical model. 370 patients were randomized and treated in a 3:3:2 ratio to IV Tramadol, placebo or a standard-of-care comparator
arm. The primary efficacy endpoint was Sum of Pain Intensity Difference over 24 hours (SPID 24). The trial commenced in December 2018. In June 2019, we announced the
trial met its primary endpoint and all key secondary endpoints.
Open-label safety study. We initiated the safety study in December 2017 and ran this study concurrently with the two Phase 3 trials. 251 patients were enrolled in the safety
study, which had an open label, single arm design. We completed this study in May 2019 and the results showed that IV Tramadol was well-tolerated in multiple surgical
models with a side effect profile consistent with known pharmacology.
In December 2019, we submitted a 505(b)(2) NDA, for IV Tramadol pursuant to Section 505(b)(2) of the FDCA. In February 2020, the FDA accepted our NDA
submission and set a PDUFA goal date of October 10, 2020. On October 12, 2020, we announced that we had received a CRL from the FDA regarding our NDA. In November
2020, we had a Type A Meeting with the FDA to discuss issues raised in the CRL. On February 12, 2021, we resubmitted the NDA to the FDA with revised labeling relating to
the proposed product label and a report relating to terminal sterilization validation. The FDA assigned a PDUFA goal date of April 12, 2021.
License Agreement with Revogenex Ireland Ltd.
Effective as of February 17, 2015, Fortress obtained a worldwide (with the exception of Canada, Central America and South America with respect to 50 mg and 100 mg IV
Tramadol HCl injections) exclusive license to make, market and sell IV Tramadol pursuant to an agreement with Revogenex, a privately held company in Dublin, Ireland, or the
License Agreement. Under the terms of the License Agreement, Fortress paid Revogenex an up-front licensing fee of $2.0 million upon execution and an additional $1.0
million on June 17, 2015. A $1.0 million milestone payment was due upon NDA submission in December 2019 which was incurred by us. There is also an additional milestone
totaling $3.0 million due upon the FDA approval of IV Tramadol. Additional high single-digit to low double-digit royalty payments on net sales of licensed products are due.
Royalties will be paid on a product-by-product and country-by-country basis until the expiration in each country of the valid patent claim. In return, Fortress obtained the
exclusive worldwide rights to three U.S. patents related to the “Intravenous Administration of Tramadol”: U.S. Patent No. 8,895,622 (the ’622 patent), which issued on
November 25, 2014; U.S. Patent No. 9,561,195 (the ’195 patent), which issued on February 7, 2017; and U.S. Patent No. 9,566,253 (the ’253 patent), which issued on February
14, 2017 (all with the exception of Canada, Central America and South America with respect to 50 mg and 100 mg IV Tramadol HCl injections). Additionally, Fortress acquired
the rights to an open U.S. Investigational New Drug Application pertaining to IV Tramadol, as well as all supporting documentation and relevant correspondence with the FDA.
Further, under the License Agreement, Fortress assumed the rights and obligations of Revogenex under its current manufacturing agreement with Zaklady Farmaceutyczne
Polpharma (Polpharma), or the Manufacturing Agreement. Fortress transferred all its rights and obligations under the License Agreement and the Manufacturing Agreement to
us pursuant to an Asset Transfer Agreement, dated as of May 13, 2015.
The License Agreement will terminate on a product-by-product and country-by-country basis upon the expiration of the last licensed patent right, unless the agreement is
earlier terminated. In addition to standard early termination provisions, the License Agreement may also be terminated early by: (i) Revogenex if the FDA does not issue an
approval or otherwise issues a “not approvable” notice for the NDA within 27 months after the NDA has been filed with the FDA (December 2019), although this termination
right will be tolled if we are using commercial reasonable efforts in our negotiations with the FDA for approval and if we receive a “not approvable” notice (October 2020), we
will have a 15 month period to correct any issues and re-submit the NDA for approval, (ii) us if we reasonably determine prior to NDA approval that the development of IV
Tramadol is not economically viable, or (iii) either Revogenex or us (provided we are using or have used commercially reasonable efforts to commercialize IV Tramadol) if,
after the third anniversary date of the commercial launch, we fail to achieve annual net sales with respect to IV Tramadol of at least $20 million in any given calendar year, with
certain exceptions.
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Competition
The pharmaceutical industry is characterized by rapidly advancing technologies, intense competition and a strong emphasis of proprietary products. We face competition
and potential competition from a number of sources, including pharmaceutical and biotechnology companies, generic drug companies, drug delivery companies and academic
and research institutions. In addition, companies that are active in different but related fields represent substantial competition for us. Many of our competitors have
significantly greater capital resources, larger research and development staffs and facilities and greater experience in drug development, regulation, manufacturing and
marketing than we do. These organizations also compete with us to recruit qualified personnel, attract partners for joint ventures or other collaborations, and license technologies
that are competitive with ours. To compete successfully in this industry, we must identify novel and unique drugs or methods of treatment and then complete the development of
those drugs as treatments before our competitors do so.
We believe that IV Tramadol, if approved, will compete with a number of opioid and non-opioid drugs that are currently available for the management of acute pain or in
development. The most commonly used opioids in the postoperative and acute pain settings are morphine, hydromorphone and fentanyl. The non-opioid drugs used in this
setting include Ofirmev (IV acetaminophen) and IV formulations of NSAIDs such as Dyloject (diclofenac), Toradol (ketorolac), Anjeso (meloxicam) and Caldolor (ibuprofen).
In addition, we also expect to compete with agents such as Exparel, a liposome injection of bupivacaine indicated for administration into the surgical site to produce postsurgical
analgesia.
In addition to approved products, there are a number of product candidates in development for the management of acute pain. In addition to reformulations and fixed-dose
combination products of already available therapies, there are also several novel agents in clinical development such as HTX-011 (Heron Therapeutics, Inc.), NTM-001
(Neumentum, Inc.) and CA-008 (Concentric Analgesics, Inc.).
Intellectual Property and Patents
General
Our goal is to obtain, maintain and enforce patent protection for our proprietary technologies, including methods of treatment, to preserve our trade secrets, and to operate
without infringing on the proprietary rights of other parties, both in the United States and in other countries. Our policy is to actively seek to obtain, where appropriate, the
broadest intellectual property protection possible for our product candidates, proprietary information and proprietary technology through a combination of contractual
arrangements and patents in the United States.
Patents and other proprietary rights are crucial to the development of our business. We will be able to protect our proprietary technologies from unauthorized use by third
parties only to the extent that our proprietary rights are covered by valid and enforceable patents, are supported by regulatory exclusivity or are effectively maintained as trade
secrets. We have several patents and patent applications related to our proprietary technology, but we cannot guarantee the scope of protection of the issued patents, or that such
patents will survive a validity or enforceability challenge, or that any of the pending patent applications will issue as patents.
Generally, patent applications in the United States are maintained in secrecy for a period of 18 months or more. The patent positions of biotechnology and pharmaceutical
companies are highly uncertain and involve complex legal and factual questions. Therefore, we cannot predict the breadth of claims allowed in biotechnology and
pharmaceutical patents, or their enforceability. To date, there has been no consistent policy regarding the breadth of claims allowed in biotechnology patents. Third parties or
competitors may challenge or circumvent our patents or patent applications, if issued. If our competitors prepare and file patent applications in the United States that claim
technology also claimed by us, we may have to participate in interference proceedings declared by the USPTO to determine priority of invention, which could result in
substantial cost, even if the eventual outcome is favorable to us. In the case of inventorship contests relating to patent applications filed on or after March 16, 2013, we may
have to participate in derivation proceedings initiated at the Patent Trial and Appeal Board (PTAB), which could also result in substantial cost. Because of the extensive time
required for development, testing and regulatory review of a potential product, it is possible that before we commercialize any of our products, any related patent may expire or
remain in existence for only a short period following commercialization, thus reducing any advantage of the patent. However, the life of a patent covering a product that has
been subject to regulatory approval may have the ability be extended through the patent restoration program, although any such extension could still be minimal.
If a patent is issued to a third party containing one or more preclusive or conflicting claims, and those claims are ultimately determined to be valid and enforceable, we may
be required to obtain a license under such patent or to develop or obtain alternative technology, neither of which may be possible. In the event of litigation involving a third-
party claim, an adverse outcome in the litigation could subject us to significant liabilities to such third party, require us to seek a license for the disputed rights from such third
party, and/or require us to cease use of the technology. Moreover, our breach of an existing license or failure to obtain a license to technology required to commercialize our
products may seriously harm our business. We also may need to commence litigation to enforce any patents issued to us or to determine the scope and validity of third party
proprietary rights. Litigation would involve substantial costs.
IV Tramadol
Pursuant to the License Agreement described above, we have exclusive, worldwide commercialization rights to all Revogenex patents, including patent applications,
divisionals, continuations, and continuations-in-part, that are directed to IV tramadol (with the exception of Canada, Central America, or South America with respect to 50 mg
and 100 mg IV tramadol HCl injections). Currently, this includes U.S. Patent No. 8,895,622 (“the ’622 patent”), U.S. Patent No. 9,561,195 (“the ’195 patent”), U.S. Patent
9,566,253 (“the ’253 patent”), U.S. Patent No. 9,962,343 (“the ’343 patent”), U.S. Patent No. 10,406,122 (“the ’122 patent”), U.S. Patent No. 9,693,949 (“the ’949 patent”), U.S.
Patent 9,968,551 (“the ’551 patent”), U.S. Patent No. 9,980,900 (“the ’900 patent”), U.S. Patent No. 10,022,321 (“the ’321 patent”), U.S. Patent No. 10,537,521 (“the ’521
patent”), U.S. Patent No. 10,624,842 (“the ’842 patent”), U.S. Patent No. 10,751,279 (the ‘279 patent), U.S. Patent No. 10,729,644 (the ‘644 patent), and any related patent
applications or future patents, including divisionals, continuations, and continuations-in-part.
9
The ’622 patent is directed to and claims methods of: treating pain by administering a therapeutically effective dose of tramadol intravenously over a time period from 10
minutes to about 45 minutes (i.e., the rate of IV Tramadol administration); treating pain in humans by intravenously administering tramadol in solution at a range of
concentrations over the same time period; treating acute pain in humans by administering IV Tramadol over 10 to 30 minutes, such that at least one side effect is reduced; and
treating acute postoperative pain by administering tramadol to a human patient intra-operatively at wound closure, or from first demand of analgesia postoperatively,
intravenously over a time period from 10 to 30 minutes, in conjunction with administering further tramadol doses post-operatively and administering a different intravenous
opioid analgesic which is not tramadol. Further claims of the ’622 patent are directed to various effective doses, including 50 mg. These methods of treatment may provide
significant benefits (e.g., reduced side effects) over previously approved methods of administration of IV Tramadol, in which the dose was typically accomplished over a two to
three-minute period. Additional claims of the ’622 patent focus on the intravenous administration of tramadol over 15 (±2) minutes, which represents the preferred method of
administration that we will be pursuing in obtaining approval of our product through the FDA. The ’622 patent further describes and claims pharmacokinetic properties of our
proprietary method of treatment (e.g., Tmax, Cmax and AUC), which are different from the previously achieved pharmacokinetics of prior IV tramadol formulations, such as
Tramal® solution for injection (available outside the U.S.). This patent is scheduled to expire on October 20, 2032, absent possible regulatory patent term extensions.
In view of additional prior art discovered after the issuance of the ’622 patent, we have focused efforts on obtaining further patent coverage for the technology. Pursuant to
the License Agreement, we have exclusive commercialization rights to all continuation patent filings of the ’622 patent. As a first step, we have prosecuted further claims in
multiple continuation patent applications of the ’622 patent, in which extensive searches were conducted and all information known to be material to patentability was brought
to the attention of the USPTO. The goal was to obtain further patent claims which patentably differentiate over the prior art. To date, our efforts have resulted in the issuance of
the ’195 patent, which issued from U.S. Application Serial No. 14/550,279 on February 7, 2017; the ’253 patent, which issued from U.S. Application Serial No. 14/713,775 on
February 14, 2017; the ’343 patent, which issued from U.S. Application Serial No. 14/550,279 on May 8, 2018; and the ’122 patent, which issued from U.S Application Serial
No. 15/972,684 on September 10, 2019; all of which are entitled “Intravenous Administration of Tramadol,” and all of which contain the same disclosure (specification) as that
of the ’622 patent. The ’195, ’253, ’343 and ’122 patents are scheduled to expire on the same day as the expiration of the ’622 patent (October 20, 2032 absent possible
regulatory patent term extensions).
The ’253 patent includes claims directed to a method of treating moderate to severe acute pain in a human patient by a dose of about 50 mg of IV Tramadol over a time
period from 10 minutes to 20 minutes and administering further doses of tramadol at two to six-hour time intervals (each dose being administered intravenously over the same
time period).
The ’343 patent includes claims directed to similar subject matter but varies from the ’253 patent in that it specifically claims treating acute post-operative pain. There is
also a continuation patent application pending with the USPTO.
The ’195 patent includes claims directed to a method of treating moderate to severe acute pain by administering to a human patient a dose of about 50 mg of IV Tramadol
over 10 to 20 minutes, and administering further doses of IV Tramadol at two to six hour time intervals to treat pain in said patient, (each dose administered over 10 to 20
minutes), such that the Cmax does not exceed the Cmax of 100 mg oral tramadol administered every six hours for nine doses. The term Cmax refers to the maximum plasma
concentration of tramadol achieved during a dosing interval. The claims of the ’195 patent therefore further focus on a goal of the technology — that the blood plasma levels of
tramadol resulting from our 50 mg intravenous dose to a patient would not be significantly greater than the blood plasma level of the blood plasma levels of tramadol that are
already routinely experienced by patients in the United States who are administered oral doses of 100 mg tramadol. Tramadol hydrochloride is approved in the United States for
oral administration in an amount from 50 to 100 mg administered every four to six hours, not to exceed 400 mg/day.
The ’122 patent includes claims directed to a method of treating moderate to severe acute pain or acute post-operative pain by administering to a human patient undergoing
an operation a dose of about 50 mg of tramadol at about 2 to about 6 hour time intervals for at least about 48 hours to treat pain in said patient, wherein each dose of tramadol is
administered intravenously over a time period from 10 minutes to 20 minutes, such that the patient is treated for acute postoperative pain. Further claims call for at least one
dose of tramadol to be administered over 15 (±2) minutes.
The ’253, ’195, ’343 and ’122 patents include further claims to the treatment method, including also administering one or more doses of an IV opioid analgesic that is not
tramadol as rescue medicine to the patient to treat breakthrough pain. The claims are further directed to the use of the treatment method for postoperative pain, and claims in the
’195, ’343, and ’122 patents are also directed to the treatment method resulting in a reduction in a side-effect associated with tramadol therapy selected from nausea, vomiting,
or both.
We believe that the administration of a 50 mg IV Tramadol dose over the prolonged time interval is efficacious and also may advantageously lead to a lower incidence of
side effects and increased drug tolerability. Additionally, we believe that the claims of these patents patentably differentiate over all prior art that we are aware of and which was
made of record with the USPTO.
The License Agreement also grants us the exclusive commercialization rights to the ’949 patent and any related patent applications or future patents, including divisionals,
continuations, and continuations-in-part. The ’949 patent is directed to an IV Tramadol dosing regimen and issued on July 4, 2017. This new patent describes and claims a
dosing regimen in which our IV Tramadol product is dosed to a human patient(s) for treating acute pain in a manner such that the plasma levels obtained (including but not
limited to Cmax and AUC) are very similar to treatment with a 100 mg oral dose of tramadol hydrochloride to a human patient(s) every six hours at steady state. This is
accomplished by intravenously administering a first dose of tramadol 50 mg to a human patient; then intravenously administering a second dose of tramadol 50 mg about 2
hours after the first dose; intravenously administering a third dose of tramadol 50 mg about 2 hours after the second dose; and thereafter intravenously administering doses of
tramadol 50 mg at dosage intervals of about 4 hours. It is believed that this dosing regimen may provide advantages over the commercially available oral doing regimen, and
further allows the patient to be stepped down from the IV Tramadol dosing regimen to an oral dosing regimen with less concern about deleterious effects which might occur
from a switch from IV to oral analgesic medicine (e.g., as would be the case where the switch to an oral version of the drug provides a much different Cmax and AUC than the
IV dose provides at steady state). This new dosing regimen is the result of considerable experimentation by us, and a prior art search has not revealed any similar dosing
regimen being used or published with respect to IV Tramadol infusions. The patent term of the ’949 patent is scheduled to expire on May 24, 2036, absent possible regulatory
patent term extensions.
10
A continuation of the ’949 patent issued as the ’551 patent on May 18, 2018, claiming the same dosing regimen except that it includes claims that specify that the mean
Cmax after the third administered dose of tramadol is similar to the mean Cmax at steady-state for a dosing regimen of 100 mg tramadol HCl administered orally every 6 hours,
and/or specifies pharmacokinetic parameters for Cmax and/or AUC at steady-state. The ’551 patent is scheduled to expire on the same day as the ’949 patent (May 24, 2036,
absent possible regulatory patent term extensions).
The ’900 patent (a continuation-in-part of the ’949 patent) issued on May 29, 2018 and is directed to the same dosing regimen, except that it includes claims that specify the
pharmacokinetic parameters after the third administered dose of tramadol. Further continuation patent applications are pending for (i) the 50 mg dosing regimen to human
patients experiencing acute pain or acute post-operative pain; (ii) the 50 mg dosing regimen directed to administering a first dose of tramadol 50 mg to a human patient and
thereafter intravenously administering additional doses of tramadol to the human patient(s) in an amount of about 50 mg tramadol at dosage intervals of about 4 hours, except
that a second dose is intravenously administered as a loading dose at a shortened interval as compared to the dosage interval of about 4 hours, and (iii) administering the 50 mg
dosing regimen as described with an NSAID as well. The ’900 patent is scheduled to expire on the same day as the ’949 patent (May 24, 2036, absent possible regulatory patent
term extensions).
The License Agreement also grants us the exclusive commercialization rights to continuation applications of the ’949, ’551, and ’900 patents (and related applications) that
are currently pending at the USPTO. This includes, but is not limited to, U.S. Application Serial No. 15/976,503 (“the ’503 application”), a continuation of the ’551 patent and
filed on May 10, 2018; U.S. Application Serial No. 16/223,522 (“the ’522 application”), a continuation of the ’199 application and filed on December 18, 2018; U.S.
Application Serial No. 15/986,199 (“the ’199 application”), a continuation of the ’900 patent and filed on May 22, 2018; and U.S. Application Serial No. 16/223,556 (“the ’556
application”), a continuation of the ’503 application and filed on December 18, 2018. The ’503, ’522, and ’199 applications are directed to various dosing regimens for
intravenous administration of a 50 mg dose of tramadol. The ’556 application is directed to various dosing regimens for intravenous administration of a 60 mg dose of tramadol.
The License Agreement further grants us exclusive commercialization rights to new patents/patent applications pending with the USPTO directed to the intravenous
administration of tramadol co-administered with other analgesics. Currently, these patent applications include U.S. Application Serial No. 16/269,213 (“the ’213 application”), a
continuation of the ’556 application and filed February 6, 2019; U.S. Application Serial No. 16/269,124 (“the ’124 application”; now U.S. Patent No. 10,729,644), a
continuation of the ’522 application and filed on February 6, 2019; U.S. Application Serial No. 16/375,363 (“the ’363 application”), a continuation of the ’213 application and
filed on April 4, 2019 (now U.S. Patent No. 10,751,279); and U.S. Application Serial No. 16/376,382 (“the ’382 application”), a continuation of the ’213 application and filed
on April 5, 2019. The ’213 application is directed to intravenously administering a first dose of 60 mg of tramadol, later administering doses every 6 hours (except for the
second dose, which is a loading dose administered in a shorter time period), and also administering another analgesic. The ’124 application is similar, but it claims a dosage of
50 mg. The ’363 application is also similar to the ’213 application, in that it claims 60 mg, but it varies in that it specifies acetaminophen as the other analgesic. The ’382
application is similar to the ’124 application, in that it claims 50 mg, but it varies in that it specifies ketorolac as the other analgesic.
The License Agreement also grants us the exclusive commercialization rights to the ’321 patent, which is directed to an IV Tramadol dosing regimen and issued on July 17,
2018. This new patent describes and claims a dosing regimen in which our IV Tramadol product is dosed to a human patient(s) for treating acute pain by intravenously
administering a first dose of tramadol 25 mg to a human patient; then intravenously administering a second dose of tramadol 25 mg about 2 hours after the first dose;
intravenously administering a third dose of tramadol 25 mg about 2 hours after the second dose; and thereafter intravenously administering doses of tramadol 25 mg at dosage
intervals of about 4 hours. The ’321 patent is scheduled to expire on April 13, 2037, absent possible regulatory patent term extensions.
A continuation of the ’321 patent issued as the ’521 patent on January 21, 2020, claiming the same dosage as the ’321 patent (25 mg), but over dosing intervals of about 4
hours, where the second dose is intravenously administered as a loading dose at a shortened interval as compared to the interval of about 4 hours. It further claims this method of
treatment, where the at least one side effect, selected from nausea, vomiting, and seizure, is reduced. The ’521 patent is scheduled to expire on the same day as the ’321 patent
(April 13, 2037, absent possible regulatory patent term extensions).
With the exception of 50 mg and 100 mg dosages of IV tramadol HCl in Canada, Central America, and South America, the License Agreement also grants us the exclusive
commercialization rights to certain foreign patents and patent applications, including PCT applications. With the exception of the territory constraint listed above, we have the
exclusive commercialization rights to PCT Application No. US/2012/033304 and any related patents or patent applications.
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In sum, we believe that our patent filings will prevent third parties from marketing a generic version of our product without infringing claims of the patent(s) we are
seeking. Further, we have conducted clearance searches of U.S. issued and foreign patents, and have not identified any bars to the commercialization of our tramadol
technology.
Other Intellectual Property Rights
We depend upon trademarks, trade secrets, and continuing technological advances to develop and maintain our competitive position. We also depend upon the skills,
knowledge and experience of our scientific and technical personnel, as well as that of our advisors, consultants and other contractors. This knowledge and experience we call
“know-how.” To help protect our proprietary know-how which is not patentable, and for inventions for which patents may be difficult to enforce, we rely on trade secret
protection and confidentiality agreements to protect our interests. To this end, we require all employees, scientific advisors, consultants, collaborators and other contractors,
upon commencement of a relationship with us, to enter into confidentiality agreements, which prohibit the disclosure of confidential information and, in the case of parties other
than our research and development collaborators, require disclosure and assignment to us of the ideas, developments, discoveries and inventions important to our business.
These agreements are designed to protect our proprietary information and to grant us ownership of technologies that are developed in connection with their relationship with us.
These agreements may not, however, provide protection for our trade secrets in the event of unauthorized disclosure of such information.
Supply and Manufacturing
The chemical name for tramadol hydrochloride is cis-2-[(dimethyl amino) methyl]-1-(3-methyoxyphenyl) cyclohexanol hydrochloride. Unless otherwise specified, the term
tramadol refers to the racemic mixture of the (±) cis isomers. IV Tramadol (Tramadol Hydrochloride Injection) is a sterile solution formulation of tramadol HCl 50 mg/1 mL,
for IV administration. Each unit of IV Tramadol consists of glass ampoules of 50 mg of tramadol HCl and sodium acetate as buffering agent in 1 mL of water for injection. The
final drug product is stable at room temperature.
We do not own or operate manufacturing facilities for the production of IV Tramadol, nor do we have plans to develop or own manufacturing operations in the foreseeable
future. Currently, we have one manufacturer, Polpharma, who subcontracts several activities to another manufacturer, to provide us clinical and commercial supply of IV
Tramadol in accordance with current Good Manufacturing Practice (CGMP) requirements. We also may plan to qualify a backup manufacturer. We will be obligated to
purchase a minimum amount of final packaged drug product from our current manufacturer over the course of five years commencing upon the approval of our NDA for IV
Tramadol. We will pay a fixed per dose unit fee to our current manufacturer in addition to a low single digit royalty on net sales revenue and a milestone payment amount of
$2.0 million upon FDA approval of IV Tramadol.
We and our manufacturer, as well as its key subcontractor, are and will be subject to extensive government regulation in connection with the manufacture of any
pharmaceutical product, including ongoing periodic and unannounced inspections by the FDA, the DEA and corresponding state, European and other foreign agencies to ensure
strict compliance with CGMPs and other applicable state, federal and foreign regulations. We do not have control over third party manufacturers’ compliance with these
regulations and standards, other than through contractual obligations and audit oversight. If they are deemed out of compliance with CGMPs, product recalls could result,
inventory could be destroyed, production could be stopped and supplies could be delayed or otherwise disrupted.
If we need to change manufacturers after commercialization, the FDA and some corresponding foreign regulatory agencies must approve these new manufacturers in
advance, which will involve testing and additional inspections to ensure compliance with CGMPs and other FDA regulations and standards and may require significant lead
times and delay. Furthermore, switching manufacturers may be difficult because the number of potential manufacturers is limited. It may be difficult or impossible for us to find
a replacement manufacturer quickly or on terms acceptable to us, or at all.
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Government and Industry Regulations
General
U.S. Drug Development
In the United States, the FDA regulates drugs under the FDCA, and its implementing regulations. Since our drug product candidate is an opioid, such drugs are also
regulated by the DEA as controlled substances under the Controlled Substances Act, even at the drug development stage. Drugs are also subject to other federal, state and local
statutes and regulations. The process of obtaining regulatory approval and maintaining subsequent compliance with applicable federal, state and local statutes and regulations
require the expenditure of substantial time and financial resources. Failure to comply with the applicable U.S. requirements at any time during product development, the
approval process or after approval may subject an applicant to administrative or judicial sanctions. These sanctions could include, among other actions, the FDA’s refusal to
approve pending applications, withdrawal of an approval, a clinical hold, untitled or warning letters, voluntary product recalls or market withdrawals, product seizures, total or
partial suspension of production or distribution injunctions, fines, consent decrees, refusals of government contracts, restitution, disgorgement or civil and criminal penalties.
Any regulatory, compliance or enforcement action by any agency or judicial enforcement action could have a material adverse effect on our products, or our Company. If we
fail to manufacture our product candidate in sufficient quantities and at acceptable quality and pricing levels, fail to comply with additional DEA requirements related to
controlled substances, or fail to fully comply with CGMP regulations, we may face delays in the commercialization of this product candidate or be unable to meet market
demand, and may be unable to generate potential revenues.
Our product candidate must be approved by the FDA through one of FDA’s available drug approval processes before they may be legally marketed in the United States –
(1) a new drug application (NDA) submitted under section 505(b)(1) of the FDCA; (2) an abbreviated new drug application (ANDA) under section 505(j); or (3) a new drug
application submitted under section 505(b)(2) of the FDCA (505(b)(2) application). We have already submitted our first 505(b)(2) application and intend to utilize the 505(b)(2)
regulatory approval pathway for any additional product candidates. Development and approval of drugs generally involves the following:
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Submission to the FDA of an IND, which must become effective before clinical trials involving humans may begin;
Approval by an independent institutional review board, or IRB, or ethics committee at each clinical trial site before a trial may be initiated at that site;
Performance of adequate and well-controlled human clinical trials in accordance with applicable IND regulations and other good clinical practices, or GCPs;
Submission of an application (NDA, ANDA or 505(b)(2)) to the FDA;
The FDA’s decision within 60 days of its receipt of an NDA to accept it for filing and review;
Satisfactory completion of an FDA pre-approval inspection of the manufacturing facility or facilities where the drug is produced to assess compliance with
CGMPs and assure that the facilities, methods and controls are adequate to preserve the drug’s identity, strength, quality and purity;
Possible FDA audit of the clinical trial sites that generated the data in support of the NDA; and
FDA review and approval of the NDA.
The nonclinical testing, clinical trials and review process requires substantial time, effort and financial resources, and we cannot be certain that any approvals for our
product candidates will be granted on a timely basis, if at all. The data required to support an NDA are generated in two distinct developmental stages: nonclinical and clinical.
The nonclinical development stage generally involves synthesizing the active component, developing the formulation and control procedures and determining the manufacturing
process, as well as carrying out non-human toxicology, pharmacology and drug metabolism studies in the laboratory, which may support subsequent clinical testing in humans.
In the case of documentation to support a 505(b)(2) NDA, this nonclinical data may be referenced in literature or the FDA’s previous findings of safety and efficacy for a listed
drug. The sponsor must submit the results of the nonclinical studies, together with manufacturing information, analytical data, any available clinical data or literature and a
proposed clinical protocol, to the FDA as part of the IND. An IND is a request for authorization from the FDA to administer an investigational drug product to humans, and
must become effective before clinical trials may begin. An IND automatically becomes effective 30 days after receipt by the FDA, unless before that time the FDA raises
concerns or questions related to one or more proposed clinical trials and places the IND on clinical hold. In such a case, the IND sponsor and the FDA must resolve any
outstanding concerns before the clinical trial can begin. As a result, submission of an IND may not result in the FDA allowing clinical trials to commence.
The clinical stage of development involves the administration of the product candidate to healthy volunteers and patients under the supervision of qualified investigators,
generally physicians not employed by or under the sponsor’s control, in accordance with GCPs, which include the requirement that all research subjects provide their informed
consent for their participation in any clinical trial. Clinical trials are conducted under protocols detailing, among other things, the objectives of the trial, dosing procedures,
subject selection and exclusion criteria and the parameters to be used to monitor subject safety and assess efficacy. Each protocol, and any subsequent amendments to the
protocol, must be submitted to the FDA as part of the IND. Further, each clinical trial must be reviewed and approved by an independent IRB for each institution where the trial
will be conducted to ensure that the risks to individuals participating in the clinical trials are minimized and are reasonable in relation to anticipated benefits. The IRB also
approves the informed consent form that must be provided to each subject or his or her legal representative and must monitor the clinical trial until completed.
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Clinical Trials
Clinical trials are generally conducted in three sequential phases, known as Phase 1, Phase 2 and Phase 3, and may overlap.
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Phase 1 clinical trials generally involve a small number of healthy volunteers who are initially exposed to a single dose and then multiple doses of the product
candidate. The primary purpose of these clinical trials is to assess the metabolism, pharmacology, side effect tolerability and safety of the drug.
Phase 2 clinical trials typically involve studies in disease-affected patients to determine the dose required to produce the desired benefits. At the same time, safety
and further pharmacokinetic and pharmacodynamics information is collected, possible adverse effects and safety risks are identified and a preliminary evaluation
of efficacy is conducted.
Phase 3 clinical trials generally involve large numbers of patients at multiple sites and are designed to provide the data necessary to demonstrate the product
candidate’s safety and effectiveness for its intended use, establish its overall benefit/risk relationship, and provide an adequate basis for approval.
Post-approval trials, sometimes referred to as Phase 4, may be conducted after initial marketing approval. These trials are used to gain additional experience from the
management of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of
an NDA.
Before approval, progress reports detailing the results of the clinical trials, among other information, must be submitted at least annually to the FDA, and written IND safety
reports must be submitted to the FDA and investigators for serious and unexpected suspected adverse events, findings from other studies suggesting a significant risk to humans
exposed to the same or similar drugs, findings from animal or in vitro testing suggesting a significant risk to humans, and any clinically important rate increase of a serious
suspected adverse reaction compared to 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, if at all. The FDA or the sponsor may suspend or terminate a clinical trial at any time on various grounds, including a finding that the research
subjects are being exposed to an unacceptable health risk. Similarly, an IRB can suspend or terminate approval of a clinical trial at its institution if the trial is not being
conducted in accordance with the IRB’s requirements or the use of the drug raises any safety concerns. Additionally, some clinical trials are overseen by an independent group
of qualified experts organized by the sponsor, known as a data safety monitoring board or committee. Depending on its charter, this group may determine whether a trial may
move forward at designated check points based on access to certain data from the trial.
There are also requirements governing the reporting of ongoing clinical trials and completed trial results to public registries. Sponsors of certain clinical trials of FDA-
regulated products are required to register and disclose specified clinical trial information, which is publicly available at www.clinicaltrials.gov. Information related to the
product, patient population, phase of investigation, study sites and investigators and other aspects of the clinical trial is then made public as part of the registration. Sponsors are
also obligated to discuss the results of their clinical trials after completion. Disclosure of the results of these trials can be delayed until the new product or new indication being
studied has been approved. However, there are evolving rules and increasing requirements for publication of all trial-related information, and it is possible that data and other
information from trials involving drugs that never garner approval could require disclosure in the future.
Concurrent with clinical trials, companies usually develop additional information about the chemistry and physical characteristics of the drug as well as finalize a process
for manufacturing it in commercial quantities in accordance with CGMP requirements. The manufacturing process must be capable of consistently producing quality batches of
the product candidate, and, among other things, a drug manufacturer must develop methods for testing the identity, strength, quality and purity of the final drug product.
Appropriate packaging must be selected and tested, and stability studies must be conducted to demonstrate that the product candidate does not undergo unacceptable
deterioration over its shelf life.
NDA and FDA Review Process
The results of nonclinical studies and clinical trials, together with other detailed information, including extensive information on manufacturing and drug composition and
proposed labeling, are submitted to the FDA in the form of an NDA requesting approval to market the drug for one or more specified indications. The FDA reviews an NDA to
determine, among other things, whether a drug is safe and effective for its intended use and whether the product is being manufactured in accordance with CGMPs to assure and
preserve the product’s identity, strength, quality and purity. FDA approval of an NDA must be obtained before a drug may be legally marketed in the United States.
Under the PDUFA as amended in 2017, each NDA must be accompanied by a user fee. The FDA adjusts the PDUFA user fees on an annual basis. According to the FDA’s
current fee schedule for fiscal year (FY) 2021, effective through September 30, 2021, the user fee for an application requiring clinical data, such as an NDA, is $2,875,842.
Clinical data, as interpreted by the FDA to assess fees under PDUFA, include (1) study reports or literature reports of what are explicitly or implicitly represented by the
applicant to be adequate and well-controlled trials for safety or effectiveness or (2) reports of comparative activity (other than bioequivalence and bioavailability studies),
immunogenicity, or efficacy, where those reports are necessary to support a claim of comparable clinical effect. The term does not include bioequivalence and bioavailability
studies submitted in support of an NDA. NDAs for which clinical data are not required to demonstrate safety and effectiveness are reduced to half of the amount of the
prescribed user fee, or $1,437,921 for FY 2021. PDUFA also imposes an annual Prescription Drug Program Fee ($336,432 per approved product for FY 2021) for
establishments named as the applicant in a human drug application. An establishment is not to be assessed more than five (5) prescription drug program fees in a given fiscal
year. Fee waivers or reductions are available in certain circumstances, including waiver of the application fee for the first application filed by a small business.
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The FDA performs an administrative review of an NDA before accepting it for filing and may request additional information rather than accepting the applications. The
FDA must make a decision on accepting an NDA for filing within 60 days of receipt. Once the submission is accepted for filing, the FDA begins an in-depth scientific and
technical review of the NDA. Under the goals and policies agreed to by the FDA under PDUFA, the FDA has ten months from the filing date in which to complete its initial
review of a standard NDA and respond to the applicant, and six months from the filing date for an NDA designated for priority review. The FDA does not always meet its
PDUFA goal dates for standard and priority NDAs, and the review process is often significantly extended by FDA requests for additional information or clarification.
Before approving an NDA, the FDA will conduct a pre-approval inspection of the manufacturing facilities for the new product to determine whether they comply with
CGMPs. The FDA will not approve the product unless it determines that the manufacturing processes and facilities are in compliance with CGMP requirements and adequate to
assure consistent production of the product to specifications. The FDA may also audit data from clinical trials to ensure compliance with GCP requirements. Additionally, the
FDA may refer applications for novel drug products or drug products which present difficult questions of safety or efficacy to an advisory committee, typically a panel that
includes clinicians and other experts, for review, evaluation and a recommendation regarding whether the application should be approved and, if so, under what conditions. The
FDA is not bound by the recommendations of an advisory committee, but it considers them carefully when making decisions. NDAs submitted under Section 505(b)(2) are
typically not referred to an Advisory Panel for consideration unless new safety information is revealed in the review cycle. The FDA likely will re-analyze the clinical trial data,
which could result in extensive discussions between the FDA and the applicant during the review process. The review and evaluation of an NDA by the FDA is extensive and
time consuming and may take longer than originally planned to complete, and we may not receive a timely approval, if at all.
After the FDA evaluates an NDA, it will issue an approval letter or a Complete Response Letter. An approval letter authorizes commercial marketing of the drug with
prescribing information for specific indications. A Complete Response Letter indicates that the review cycle of the application is complete and the application will not be
approved in its present form. A Complete Response Letter usually describes the specific deficiencies in the NDA identified by the FDA, and may require additional clinical
data, such as an additional pivotal Phase 3 clinical trial, and other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing. If
a Complete Response Letter is issued, the applicant may resubmit the NDA, addressing all of the deficiencies identified in the letter, or withdraw the application. Even if such
data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval. Data obtained from clinical trials are not always conclusive,
and the FDA may interpret data differently than the sponsor interprets the same data.
There is no assurance that the FDA will approve a product candidate for marketing, and the sponsor may encounter significant difficulties or costs during the review
process. If a product receives marketing approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited,
which could restrict the commercial value of the product. Further, the FDA may require that certain contraindications, warnings or precautions be included in the product
labeling, or it may condition approval on changes to the proposed labeling. The FDA also may condition approval on the development of adequate controls and specifications for
manufacturing and a commitment to conduct post-marketing testing and surveillance to monitor the potential effects of approved products. For example, the FDA may require
Phase 4 trials designed to further assess a drug’s safety and efficacy.
The FDA may also place other conditions on approval including the requirement for a risk evaluation and mitigation strategy, or REMS, to assure the safe use of the drug. If
the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS. The FDA will not approve the NDA without an approved REMS, if required. A
REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk
minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products. Marketing
approval may be withdrawn for non-compliance with regulatory requirements or if problems occur following initial marketing.
Section 505(b)(2) Regulatory Approval Pathway
Section 505(b)(2) was added to the Act by the Drug Price Competition and Patent Term Restoration Act of 1984 (Hatch-Waxman Amendments). Section 505(b)(2) of the
FDCA provides an alternate regulatory pathway for approval of a new drug by allowing the FDA to rely on data not developed by the applicant. Specifically, Section 505(b)(2)
permits the submission of an NDA where one or more of the investigations relied upon by the applicant for approval was not conducted by or for the applicant and for which the
applicant has not obtained a right of reference. The applicant may rely upon published literature and/or the FDA’s findings of safety and effectiveness for an approved drug
already on the market. Approval or submission of a 505(b)(2) application, like those for abbreviated new drugs, or ANDAs, may be delayed because of patent and/or exclusivity
rights that apply to the previously approved drug.
Under the 505(b)(2) regulatory approval pathway, the applicant may reduce some of the burdens of developing a full clinical program by relying on investigations not
conducted by the applicant and for which the applicant has not obtained a right of reference, such as prior investigations involving the listed drug. In such cases, some clinical
trials may not be required or may be otherwise limited.
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A 505(b)(2) application may be submitted for a new chemical entity (NCE), when some part of the data necessary for approval is derived from studies not conducted by or
for the applicant and when the applicant has not obtained a right of reference. Such data are typically derived from published studies, rather than FDA’s previous findings of
safety and effectiveness of a previously approved drug. For changes to a previously approved drug however, an applicant may rely on the FDA’s finding of safety and
effectiveness of the approved drug, coupled with information needed to support the change from the approved drug, such as new studies conducted by the applicant or published
data. When based on an approved drug, the 505(b)(2) drug may be approved for all of the indications permitted for the approved drug, as well as any other indication supported
by additional data.
Section 505(b)(2) applications also may be entitled to marketing exclusivity if supported by appropriate data and information. As discussed in more detail below, three-year
new data exclusivity may be granted to the 505(b)(2) application if one or more clinical investigations conducted in support of the application, other than
bioavailability/bioequivalence studies, were essential to the approval and conducted or sponsored by the applicant. Five years of marketing exclusivity may be granted if the
application is for an NCE, and pediatric exclusivity is likewise available.
Orange Book Listing and Paragraph IV Certification
For NDA submissions, including 505(b)(2) applications, applicants are required to list with the FDA certain patents with claims that cover the applicant’s product. Upon
approval, each of the patents listed in the application is published in Approved Drug Products with Therapeutic Equivalence Evaluations, commonly referred to as the Orange
Book. Any applicant who subsequently files an ANDA or a 505(b)(2) application that references a drug listed in the Orange Book must certify to the FDA that (1) no patent
information on the drug product that is the subject of the application has been submitted to the FDA; (2) such patent has expired; (3) the date on which such patent expires; or
(4) such patent is invalid or will not be infringed upon by the manufacture, use or sale of the drug product for which the application is submitted. This last certification is known
as a Paragraph IV certification.
If an applicant has provided a Paragraph IV certification to the FDA, the applicant must also send notice of the Paragraph IV certification to the holder of the NDA for the
approved drug and the patent owner once the application has been accepted for filing by the FDA. The NDA holder or patent owner may then initiate a patent infringement
lawsuit in response to notice of the Paragraph IV certification. The filing of a patent infringement lawsuit within 45 days of the receipt of a Paragraph IV certification prevents
the FDA from approving the ANDA or 505(b)(2) application until the earlier of 30 months from the date of the lawsuit, the applicant’s successful defense of the suit, or
expiration of the patent.
Pediatric Information
Under the Pediatric Research Equity Act, or PREA, an NDA or supplement to an NDA must contain data to assess the safety and efficacy of the drug for the claimed
indications in all relevant pediatric subpopulations and to support dosing and administration for each pediatric subpopulation in which the product is safe and effective. The
FDA may grant deferrals for submission of pediatric data or full or partial waivers.
The Food and Drug Administration Safety and Innovation Act, or FDASIA, which was signed into law on July 9, 2012, amended the FDCA to require that a sponsor who is
planning to submit an NDA for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration submit an initial Pediatric Study
Plan, or PSP, within 60 days of an end-of-Phase 2 meeting or, if there is no such meeting, as early as practicable before the initiation of the Phase 3 or Phase 2/3 trial. The initial
PSP must include an outline of the pediatric trial(s) that the sponsor plans to conduct, including objectives and design, age groups, relevant endpoints and statistical approach,
or a justification for not including such information and any request for a deferral of pediatric assessments or a full or partial waiver of the requirement to provide data from
pediatric trials. The FDA and the sponsor must reach an agreement on the PSP, but the sponsor can submit amendments to an agreed-upon initial PSP at any time if changes to
the pediatric plan need to be considered based on data collected from nonclinical studies, early phase clinical trials and other clinical development programs.
Post-Marketing Requirements
Following approval, the company and the new product are subject to continuing regulation by the FDA, which include monitoring and recordkeeping activities, reporting of
adverse experiences and complying with promotion and advertising requirements, which include prohibitions on the promotion of the drugs for unapproved, or “off-label” uses.
Although physicians may prescribe legally available drugs for off-label treatments, manufacturers may not promote such non-FDA approved uses. Prescription drug
promotional materials must be submitted to the FDA in conjunction with their first use on an on-going basis. Further, if there are any modifications to the drug, including
changes to indications, labeling, or manufacturing processes or facilities, the applicant may be required to submit and obtain FDA approval of a supplemental NDA or new
NDA, which may require the applicant to develop additional data or conduct additional nonclinical studies or clinical trials.
The FDA regulations require that products be manufactured in specific approved facilities and in accordance with CGMPs. These regulations require, among other things,
quality control and quality assurance, the maintenance of records and documentation and the obligation to investigate and correct any deviations from CGMPs. Drug
manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state
agencies, and are subject to periodic, unannounced inspections by the FDA and certain state agencies for compliance with CGMPs and other laws. Accordingly, manufacturers
must continue to expend time, money and effort in the area of production and quality control to maintain compliance with CGMPs. The discovery of violative conditions,
including failure to conform to CGMPs, could result in enforcement actions, and the discovery of problems with a product after approval may result in restrictions on a product,
manufacturer or holder of an approved NDA, including voluntary recalls and product seizures.
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Discovery of previously unknown problems with a product or the failure to comply with applicable FDA requirements can have negative consequences, including adverse
publicity, judicial or administrative enforcement, untitled or warning letters from the FDA, mandated corrections to advertising or communications to doctors and civil or
criminal penalties, among others. Newly discovered or developed safety or effectiveness data may require changes to a product’s approved labeling, including the addition of
new warnings and contraindications, and also may require the implementation of other risk management measures. New government requirements, including those resulting
from new legislation, may be established, or the FDA’s policies may change, which could delay or prevent regulatory approval of our products under development.
U.S. Marketing Exclusivity
The FDCA provides three years of marketing exclusivity for an NDA, or supplement to an existing NDA, for a drug product that contains a previously approved NCE if
new clinical investigations, other than bioavailability/bioequivalence studies, were essential to the application’s approval (e.g., for new indications, dosages or strengths of an
existing drug). This three-year exclusivity for new data covers only the modification for which the drug received approval on the basis of the new clinical investigations and
does not prohibit the FDA from approving ANDAs for drugs containing the active agent for the original indication. Furthermore, this exclusivity will not delay the submission
or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the nonclinical studies and
adequate and well-controlled clinical trials necessary to demonstrate safety and efficacy.
Pediatric exclusivity is another type of regulatory market exclusivity in the United States, which, if granted, adds six months to existing exclusivity periods and patent terms.
This six-month exclusivity, which runs from the end of other exclusivity protections or patent term, may be granted based on the voluntary completion of a pediatric trial in
accordance with an FDA-issued “Written Request.” The FDA issues a written request for pediatric clinical trials before approval of an NDA only where it determines that
information relating to the use of a drug in a pediatric population, or part of the pediatric population, may produce health benefits in that population.
DEA Regulation
Because our product candidate is subject to the Controlled Substances Act (CSA) we must comply with various statutory requirements set forth by the CSA, as amended,
and its implementing regulations as enforced by the DEA. The CSA imposes various registration, record-keeping and reporting requirements, procurement and manufacturing
quotas, labeling and packaging requirements, security controls, prescription and order form requirements and restrictions on prescription refills for certain kinds of
pharmaceutical products. A principal factor for determining the particular requirements of the CSA applicable to a product, if any, is its actual or potential abuse profile, which
is classified into a DEA schedule. A product may be listed as a Schedule I, II, III, IV or V controlled substance, with Schedule I presenting the highest perceived risk of abuse
and Schedule V presenting the least. For example, Schedule I controlled substances have no currently accepted medical use in treatment in the United States and a lack of
accepted safety for use under medical supervision. The active ingredient in our product candidate is classified as a Schedule IV controlled substance.
Annual registration is required for any facility that manufactures, distributes, dispenses, imports or exports any controlled substance. The registration is specific to the
particular location, activity and controlled substance schedule. For example, separate registrations are needed for import and manufacturing, and each registration will specify
which schedules of controlled substances are authorized. Similarly, separate registrations are also required for separate facilities.
The DEA typically inspects a facility to review its security measures prior to issuing a registration and on a periodic basis. Security requirements vary by controlled
substance schedule, with the most stringent requirements applying to Schedule I and Schedule II controlled substances and less stringent requirements for Schedules III, IV, and
V. Required security measures include background checks on employees and physical control of inventory through measures such as vaults and inventory reconciliations.
Records must be maintained for the handling of all controlled substances, and periodic reports made to the DEA. Reports must also be made for thefts or losses of any
controlled substance, and to obtain authorization to destroy any controlled substance.
In addition, a DEA quota system controls and limits the availability and production of controlled substances in Schedule I or II. Distributions of any Schedule I or II
controlled substance must also be accompanied by special order forms, with copies provided to the DEA. Because the active ingredient in our product candidate is currently
regulated as a Schedule IV controlled substances, it will not be subject to the DEA’s production and procurement quota scheme.
To enforce these requirements, the DEA conducts periodic inspections of registered establishments that handle controlled substances. Failure to maintain compliance with
applicable requirements, particularly as manifested in loss or diversion, can result in administrative, civil or criminal enforcement action. The DEA may seek civil penalties,
refuse to renew necessary registrations or initiate administrative proceedings to revoke those registrations. In some circumstances, violations could result in criminal
proceedings.
In addition to federal scheduling, some drugs may be subject to state-controlled substance regulation and thus more extensive requirements than those determined by the
DEA and FDA.
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Other Healthcare Laws and Compliance Requirements
Manufacturing, sales, promotion and other activities following product approval are also subject to regulation by numerous regulatory authorities in addition to the FDA,
including the Centers for Medicare & Medicaid Services, other divisions of the Department of Health and Human Services, the U.S. Department of Justice, the DEA, the
Consumer Product Safety Commission, the Federal Trade Commission, the Occupational Safety & Health Administration, the Environmental Protection Agency and state and
local governments.
We will also be subject to various federal and state laws targeting fraud and abuse in the healthcare industry. These laws may impact, among other things, our proposed
sales, marketing and educational programs. In addition, we may be subject to patient privacy regulation by both the federal government and the states in which we conduct our
business. The laws that may affect our ability to operate include:
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The federal Anti-Kickback Statute, which prohibits, among other things, persons from knowingly and willfully soliciting, receiving, offering or paying
remuneration, directly or indirectly, in cash or in kind, to induce or reward, or in return for, either (1) the referral of an individual to a person for furnishing any
item or service for which payment is available under a federal health care program, or (2) the purchase, lease, order or recommendation thereof of any good,
facility, service or item for which payment is available under a federal health care program;
The False Claims Act and civil monetary penalty laws, which prohibit, among other things, individuals or entities from knowingly presenting, or causing to be
presented, false or fraudulent claims for payment from the federal government or making or using, or causing to be made or used, a false record or statement
material to a false or fraudulent claim;
The federal Health Insurance Portability and Accountability Act of 1996, or HIPAA, which created new federal criminal statutes that prohibit executing a scheme
to defraud any healthcare benefit program, obtaining money or property of the health care benefit program through false representations or knowingly and
willingly falsifying, concealing or covering up a material fact, making false statements or using or making any false or fraudulent document in connection with
the delivery of, or payment for, health care benefits or services;
HIPAA, as amended by the Health Information Technology for Economic and Clinical Health Act, or HITECH, and its implementing regulations, which imposes
certain requirements relating to the privacy, security and transmission of individually identifiable health information;
The provision under the ACA commonly referred to as the Sunshine Act, which requires applicable manufacturers of covered drugs, devices, biologics and
medical supplies to track and annually report to CMS payments and other transfers of value provided to physicians and teaching hospitals and certain ownership
and investment interests held by physicians or their immediate family members in applicable manufacturers and group purchasing organizations; and
State law equivalents of each of the above federal laws, such as the Anti-Kickback Statute and False Claims Act, and state laws concerning security and privacy of
health care information, which may differ in substance and application from state-to-state thereby complicating compliance efforts.
The ACA broadened the reach of the fraud and abuse laws by, among other things, amending the intent requirement of the federal Anti-Kickback Statute and the applicable
criminal healthcare fraud statutes contained within 42 U.S.C. Section 1320a-7b. Pursuant to the statutory amendment, a person or entity no longer needs to have actual
knowledge of this statute or specific intent to violate it in order to have committed a violation. In addition, the ACA provides that the government may assert that a claim
including items or services resulting from a violation of the federal Anti-Kickback Statute constitutes a false or fraudulent claim for purposes of the civil False Claims Act or the
civil monetary penalties statute. Many states have adopted laws similar to the federal Anti-Kickback Statute, some of which apply to the referral of patients for healthcare items
or services reimbursed by any source, not only the Medicare and Medicaid programs.
As noted above, the federal False Claims Act prohibits anyone from, among other things, knowingly presenting, or causing to be presented, false or fraudulent claims for
payment from federal programs, including Medicare and Medicaid. Although we would not submit claims directly to payors, manufacturers can be held liable under these laws
if they are deemed to “cause” the submission of false or fraudulent claims by, for example, providing inaccurate billing or coding information to customers. In addition, our
future activities relating to the reporting of wholesaler or estimated retail prices for our products, the reporting of prices used to calculate Medicaid rebate information and other
information affecting federal, state, and third-party reimbursement for our products, and the sale and marketing of our products are subject to scrutiny under this law. For
example, pharmaceutical companies have been prosecuted under the federal False Claims Act in connection with their off-label promotion of drugs. Penalties for such violations
could include three times the actual damages sustained by the government, mandatory civil penalties between $10,781 and $21,563 for each separate false claim, exclusion
from participation in federal healthcare programs, and the potential implication of various federal criminal statutes. Private individuals also have the ability to bring actions
under the federal False Claims Act, or qui tam actions, and certain states have enacted laws based on the federal False Claims Act.
Pharmaceutical Coverage, Pricing and Reimbursement
In the United States and markets in other countries, sales of any products for which we receive regulatory approval for commercial sale will depend in part on the
availability of reimbursement from third party payors, including government health administrative authorities, managed care providers, private health insurers and other
organizations. Third party payors are increasingly examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and
efficacy, and, accordingly, significant uncertainty exists as to the reimbursement status of newly approved therapeutics. Adequate third-party reimbursement may not be
available for our products to enable us to realize an appropriate return on our investment in research and product development. We are unable to predict the future course of
federal or state health care legislation and regulations, including any changes, repeal, or judicial invalidation of some or all of the provisions of the Affordable Care Act. The
Affordable Care Act and further changes in the law or regulatory framework could have a material adverse effect on our business.
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International Regulation
In addition to regulations in the United States, there are a variety of foreign regulations governing clinical trials and commercial sales and distribution of any product
candidates. The approval process varies from country to country, and the time may be longer or shorter than that required for FDA approval.
Employees
As of December 31, 2020, we had 4 full-time employees. None of our employees are represented by a labor union and we consider our employee relations to be good.
Item 1A.
Risk Factors
The following information sets forth risk factors that could cause our actual results to differ materially from those contained in the forward-looking statements we have
made in this Form 10-K and those we may make from time to time. You should carefully consider the risks described below, in addition to the other information contained in
this Form 10-K, before making an investment decision. Our business, financial condition or results of operations could be harmed by any of these risks. The risks and
uncertainties described below are not the only ones we face. Additional risks not presently known to us or other factors not perceived by us to present significant risks to our
business at this time also may impair our business operations.
Risks Pertaining to Our Potential Merger with InvaGen Pharmaceuticals
The fact that there is a merger pending could have an adverse effect on our business and results of operations.
While the merger is pending, it creates uncertainty about our future. We are subject to a number of risks that may adversely affect our business and results of operations,
including:
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the diversion of management and employee attention may detract from our ability to obtain regulatory approval for and, if approved, to successfully commercialize
IV Tramadol in a timely manner if the Merger Transaction does not occur;
continuing to incur significant legal expenses related to the merger;
the SPMA restricting us from engaging in certain activities that could be advantageous to our business but that are not permitted without InvaGen’s consent; and
being unable to respond effectively to competitive pressures, industry developments and future opportunities.
In the event that we do not receive FDA approval for IV Tramadol by April 30, 2021, and in the event that InvaGen does not exercise its right to terminate the SPMA,
these risks and restrictions could exist through October 31, 2021, the time at which we can terminate the SPMA. If the SPMA is terminated, we will need to seek alternative
financing arrangements in order to successfully commercialize IV Tramadol.
If we do not receive FDA approval for IV Tramadol by April 30, 2021, InvaGen will have the right to terminate the SPMA and will have no further obligations to
consummate the second stage closing under the SPMA. Regardless of whether it terminates the SPMA, InvaGen will retain certain rights pursuant to the Stockholder’s
Agreement between us and InvaGen. These rights exist as long as InvaGen maintains at least 75% of the common shares acquired in the first stage closing. The following are
some of the actions that shall not be taken without the prior written consent of InvaGen:
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increase in authorized shares of our stock;
any agreement or transaction that would adversely treat the holders of our common shares as compared to the holders of our Class A Preferred Shares;
issuance of any shares of our capital stock or any securities convertible into, or other rights to acquire, shares of our capital stock (including options, warrants or
bonds), except for issuances to our officers for services performed;
any transfer or license of any asset for less than fair market value, as determined by a recognized independent valuation firm agreed upon by us and Invagen; or
entry into any transaction or agreement with any affiliate of ours (including Fortress or its Affiliates).
If the proposed merger is not completed, our business could be materially and adversely affected and our stock price could decline.
On November 12, 2018, the Company entered into the SPMA with InvaGen, and Merger Sub, pursuant to which, among other things and subject to the satisfaction or
waiver of the conditions set forth therein, Merger Sub will merge with and into the Company, with the Company continuing as the surviving entity and becoming a wholly-
owned subsidiary of InvaGen.
Consummation of the Merger Transaction is conditioned upon FDA approval of the application for IV Tramadol by April 30, 2021, including, without limitation,
conditions relating to IV Tramadol’s labelling and intended use, and to the absence of any REMS restrictions required by the FDA with respect to IV Tramadol. Additionally,
the SPMA contains customary representations, warranties, covenants and termination rights, as well as certain customary conditions, including, among others, the expiration of
any waiting period applicable to the acquisition under the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended which filing both parties completed on March 12,
2021. Therefore, the Merger Transaction may not be completed or may not be completed as quickly as expected. If the SPMA is terminated, the market price of our ordinary
shares will likely decline. In addition, our share price may be adversely affected as a result of the fact that we may continue to incur significant legal expenses related to the
Merger Transaction that will not be recovered if the Merger Transaction is not completed. If the Merger Transaction does not occur, or if the SPMA is terminated, our business
could be materially and adversely affected. In October 2020, InvaGen communicated to us that it believes a Material Adverse Effect (as defined in the SPMA) has occurred due
to the impact of the COVID-19 pandemic on potential commercialization and projected sales of IV Tramadol, which means it is possible InvaGen could attempt to avoid its
obligation to consummate the second stage closing under the SPMA, terminate the SPMA, and/or pursue monetary claims against us. We disagree with InvaGen’s assertion that
a Material Adverse Effect has occurred, and we have advised InvaGen of our position. Additionally, in connection with the resubmission of our NDA in February 2021,
InvaGen communicated to us that it believes the proposed label under certain circumstances would constitute a Material Adverse Effect (as defined in the SPMA) on the
purported basis that the proposed label under certain circumstances would make the product commercially unviable, and in addition that the indication that the FDA approves
may fail to satisfy a condition precedent to InvaGen’s obligation to consummate the second stage closing of the SPMA We notified InvaGen that we disagree with InvaGen’s
assertions. Nevertheless, InvaGen may seek to avoid its obligation to consummate the second stage closing under the SPMA, terminate the SPMA, and/or pursue monetary
claims against us. During the pendency of any dispute regarding these matters, we may be, and so long as the SPMA remains in place we will be, prohibited from engaging in a
change-of-control transaction, selling our rights to IV Tramadol, or effecting an equity or debt financing, in each case without the prior written consent of InvaGen. In the event
that the Merger Transaction does not occur, we will need to obtain additional financing.
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If the merger occurs, our shareholders will not be able to participate in any post-merger upside to our business other than through the CVRs; if the required
commercialization milestone under the CVRs is not achieved, shareholders may not realize any value from the CVRs.
If the merger occurs, upon closing of the Merger Transaction our shareholders will receive a cash payment and a CVR to receive additional consideration in cash if certain
milestones related to the commercialization of IV Tramadol are achieved, but will not receive any shares of InvaGen. Even if our business following the merger performs well,
our current shareholders will not receive any additional consideration or be able to share in the increased value of our business by virtue of being equity owners.
Fortress controls a voting majority of our common stock.
Risks Pertaining to the Influence of Fortress
Pursuant to the terms of the Class A Preferred Stock held by Fortress, Fortress will be entitled to cast, for each share of Class A Preferred Stock held by Fortress, the
number of votes that is equal to 1.1 times a fraction, the numerator of which is the sum of (A) the aggregate number of shares of outstanding common stock and (B) the whole
shares of common stock into which the shares of outstanding the Class A Preferred Stock are convertible and the denominator of which is the aggregate number of shares of
outstanding Class A Preferred Stock, or the Class A Preferred Stock Ratio. Thus, Fortress will at all times have voting control of us. Further, for a period of ten years from the
date of the first issuance of shares of Class A Preferred Stock, the holders of record of the shares of Class A Preferred Stock (or other capital stock or securities issued upon
conversion of or in exchange for the Class A Preferred Stock), exclusively and as a separate class, shall be entitled to appoint or elect the majority of our directors. If the
pending Merger Transaction does not occur, this concentration of voting power may delay, prevent or deter a change in control, even when such a change may be in the best
interests of all stockholders, could deprive our stockholders of an opportunity to receive a premium for their common stock as part of a sale of us or our assets, and might affect
the prevailing market price of our common stock.
Fortress has the right to receive a significant grant of shares of our common stock annually, which will result in the dilution of your holdings of common stock upon each
grant, which could reduce their value.
Under the terms of the Amended and Restated Founders Agreement, which became effective September 13, 2016, Fortress will receive a grant of shares of our common
stock equal to 2.5% of the gross amount of any equity or debt financing. Additionally, the holders of Class A Preferred Stock, as a class, will receive an annual dividend,
payable in shares of common stock in an amount equal to 2.5% of our fully-diluted outstanding capital stock as of the business day immediately prior to the date such dividend
is payable. Fortress currently owns all outstanding shares of Class A Preferred Stock. At our Annual Meeting of the Stockholder’s held on June 13, 2018, the Company’s
shareholders approved an amendment to the Company’s Third Amended and Restated Certificate of Incorporation, amending the Class A Preferred dividend payment date from
February 17 to January 1 of each year. This dividend was waived in connection with the Waiver Agreement signed on November 12, 2018 between Avenue, Fortress and
InvaGen These potential future share issuances to Fortress and any other holder of Class A Preferred Stock will dilute your holdings in our common stock and, if our value has
not grown proportionately over the prior year, would result in a reduction in the value of your shares. The Amended and Restated Founders Agreement has a term of 15 years
and renews automatically for subsequent one-year periods unless terminated by Fortress or upon a Change in Control (as defined in the Amended and Restated Founders
Agreement).
We might have received better terms from unaffiliated third parties than the terms we receive in our agreements with Fortress.
The agreements we entered into with Fortress in connection with the separation include the Management Services Agreement, or the MSA, and the Founders Agreement.
While we believe the terms of these agreements are reasonable, they might not reflect terms that would have resulted from arm’s-length negotiations between unaffiliated third
parties. The terms of the agreements relate to, among other things, payment of a royalty on product sales and the provision of employment and transition services. We might
have received better terms from third parties because, among other things, third parties might have competed with each other to win our business. Effective November 12,
2018, the MSA fee and certain royalties pursuant to the Founders Agreement were waived with the Waiver Agreement signed between Avenue, Fortress and InvaGen.
The ownership by our executive officers and some of our directors of equity securities of Fortress and/or rights to acquire equity securities of Fortress might create, or
appear to create, conflicts of interest.
Because of their current or former positions with Fortress, some of our executive officers and directors own shares of Fortress common stock and/or options to purchase
shares of Fortress common stock. Their individual holdings of common stock and/or options to purchase common stock of Fortress may be significant compared to their total
assets. Ownership by our directors and officers, after our separation, of common stock and/or options to purchase common stock of Fortress create or might appear to create
conflicts of interest when these directors and officers are faced with decisions that could have different implications for Fortress than for us. For instance, and by way of
example, if there were to be a dispute between Fortress and us regarding the calculation of the royalty fee due to Fortress under the terms of the Founders Agreement, then
certain of our officers and directors may have and will appear to have a conflict of interest with regard to the outcome of such dispute.
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Risks Pertaining to Our Business and Industry
We currently have no drug products for sale, and only one drug product candidate, IV Tramadol. We are dependent on the success of IV Tramadol and cannot guarantee
that this product candidate will receive regulatory approval or be successfully commercialized.
Our business success depends on our ability to obtain regulatory approval to successfully commercialize, market and sell our only product candidate, IV Tramadol, and any
significant delays in obtaining approval to commercialize, market and sell IV Tramadol will have a substantial adverse impact on our business and financial condition.
If the application for IV Tramadol is approved, our ability to generate revenues from IV Tramadol will depend on our ability to:
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establish and maintain agreements with our contract manufacturers, wholesalers, distributors and group purchasing organizations on commercially reasonable terms;
obtain sufficient quantities of IV Tramadol from qualified third-party manufacturers that manufacture in accordance with CGMP requirements, as required to meet
commercial demand at launch and thereafter;
hire, train, deploy and support our sales force;
create market demand for IV Tramadol through our own marketing and sales activities, and any other arrangements to promote this product candidate we may later
establish;
conduct such marketing and sales activities in a manner that is compliant with federal and state laws, including restrictions on off-label promotion and anti-kickback
requirements;
obtain and maintain government and private payer reimbursement for our product; and
• maintain patent protection and regulatory exclusivity for IV Tramadol.
We may not receive regulatory approval for IV Tramadol or future product candidates, or its or their approvals may be delayed, which would have a material adverse
effect on our business and financial condition.
IV Tramadol and other future product candidates 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 premarket approval and comprehensive regulation by the
FDA, DEA and other regulatory agencies in the United States. Failure to obtain marketing approval for IV Tramadol or any future product candidates will prevent us from
commercializing our product candidates. We have not received approval to market IV Tramadol from regulatory authorities in any jurisdiction. We have only limited
experience in conducting preclinical and clinical studies and filing and supporting the applications necessary to gain marketing approvals and expect to rely on third party
contract research organizations as well as consultants and vendors to assist us in this process. Securing marketing approval requires the submission of extensive preclinical and
clinical data and supporting information to 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.
Our product candidate IV Tramadol or any future product candidates must meet FDA’s standards for safety and efficacy, but may be determined not to be effective, to be
only moderately effective, to not be safe for use in its intended population, or may prove to have undesirable or unintended side effects, toxicities or other characteristics that
may preclude our obtaining marketing approval or prevent or limit commercial use.
On October 12, 2020, we announced that we had received a Complete Response Letter (“CRL”) from the FDA regarding our New Drug Application (“NDA”) for IV
Tramadol. The CRL cited deficiencies related to the terminal sterilization validation and stated that IV Tramadol, intended to treat patients in acute pain who require an opioid,
is not safe for the intended patient population. As described above, our ability to potentially commercialize IV Tramadol, and the timing of potential commercialization, is
dependent on the FDA’s review of our response to the CRL and approval of our resubmitted NDA, potentially the procurement of additional capital.
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We attended a Type A Meeting with the FDA in November 2020 to discuss the issues raised in the CRL. Our response to FDA’s CRL provided an explanation and
scientific justification to address FDA’s conclusions regarding concerns of the safety of IV tramadol for the intended patient population, and these issues were further discussed
during the meeting. We also addressed the FDA’s questions regarding terminal sterilization validation. However, it is possible that FDA will not accept our responses in our
resubmitted NDA or will otherwise conclude that we have not fully satisfied their concerns. Furthermore, if the FDA requires that we conduct further developmental or
regulatory activities that we deem unreasonable or not commercially feasible, the likelihood of our ability to obtain regulatory approval for IV Tramadol may be diminished,
and the Merger Transaction may not occur.
If our product candidate or any future product candidate receives marketing approval, the approved label indication and accompanying label information may be required
to contain information limiting the approved use of our drug, which could limit sales of the product. In addition, our third-party supplier may be subject to an inspection by the
FDA that identifies deficiencies in its manufacturing facilities and concludes they are not operating in compliance with CGMP requirements, which in turn, may force us to
identify, qualify and rely upon additional suppliers.
The process of obtaining marketing approvals, both in the United States and abroad, is expensive, may take many years if approval is granted 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 the regulatory review process for each submitted product application, may
cause delays in the approval or rejection of an application. Regulatory authorities have substantial discretion in the approval process and may refuse to accept any application or
may decide that our data is insufficient for approval and require additional preclinical studies or clinical trials. In addition, varying interpretations of the data obtained from
preclinical 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.
If we experience delays in obtaining approval or if we fail to obtain approval of our product candidate or any future product candidates, the commercial prospects for our
product candidates may be harmed and our ability to generate revenue will be materially impaired.
In addition, even if we were to obtain approval, the approval of the indication for our product candidate by such regulatory authorities may, among other things, be more
limited than we request. Such regulatory authorities may not approve the price we intend to charge for our product, may grant approval contingent on the performance of costly
post-marketing clinical trials, or may approve a product candidate with a label that does not include the labeling claims necessary or desirable for the successful
commercialization of that product candidate. These regulatory authorities may also require the label to contain warnings, contraindications, or precautions that limit the
commercialization of that product. Any of these scenarios could compromise the commercial prospects for our product candidate or any future product candidates.
If serious adverse or unacceptable side effects are identified during the development of IV Tramadol or our future product candidates, we may need to abandon or limit our
development of some of our product candidates.
If our product candidate or future product candidates are associated with undesirable side effects in clinical trials or have characteristics that are unexpected, we may need
to abandon their development or limit development to more narrow 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. In our industry, many compounds that initially showed promise in early stage testing have later been found to cause
undesirable side effects that prevented further development of the compound. In the event that our preclinical or clinical trials reveal a high and unacceptable severity and
prevalence of side effects, our trials could be delayed, suspended or terminated and the FDA or comparable foreign regulatory authorities could order us to cease further
development or deny approval of our product candidate or future product candidates for any or all targeted indications. The FDA could also issue a letter requesting additional
data or information prior to making a final decision regarding whether or not to approve a product candidate. The number of requests for additional data or information issued
by the FDA in recent years has increased, and resulted in substantial delays in the approval of several new drugs. Undesirable side effects caused by our product candidate or
future product candidates could also result in the inclusion of serious risk information in our product labeling, application of burdensome post-market requirements, or the denial
of regulatory approval by the FDA or other regulatory authorities for any or all targeted indications, and in turn prevent us from commercializing and generating revenues from
the sale of our product candidate. Drug-related side effects could affect patient recruitment or the ability of enrolled patients to complete the trial and could result in potential
product liability claims.
For example, some of the adverse events observed in the IV Tramadol clinical trials completed to date include nausea, dizziness, drowsiness, tiredness, sweating, vomiting,
dry mouth, somnolence and hypotension.
Additionally, if one or more of our current or future product candidates receives marketing approval, and we or others later identify undesirable side effects caused by this
product, a number of potentially significant negative consequences could result, including:
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regulatory authorities may require the addition of serious risk-related labeling statements, specific warnings, precautions, or contraindication;
regulatory authorities may suspend or withdraw their approval of the product, or require the suspension of manufacturing, or the recall of the product from the
market;
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regulatory authorities may require implementation of burdensome post-market risk mitigation strategies and practices;
we may be required to change the way the product is administered, conduct additional clinical trials or change the labeling of the product; or
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our reputation may suffer.
Any of these events could prevent us from achieving or maintaining marketing approval and market acceptance of our product candidate or future product candidates or
could substantially increase our commercialization costs and expenses, which in turn could delay or prevent us from generating significant revenues from its sale.
We may not be able to manage our business effectively if we are unable to attract and retain key personnel.
We may not be able to attract or retain qualified management and commercial, scientific and clinical personnel in the future due to the intense competition for qualified
personnel among biotechnology, pharmaceutical and other businesses. If we are not able to attract and retain necessary personnel to accomplish our business objectives, we may
experience constraints that will significantly impede the achievement of our development objectives, our ability to raise additional capital and our ability to implement our
business strategy.
Our employees, consultants, or third-party partners may engage in misconduct or other improper activities, including those that result in noncompliance with certain
regulatory standards and requirements, which could have a material adverse effect on our business.
We are exposed to the risk of employee fraud or other misconduct. Misconduct by employees, consultants, or third-party partners could include intentional failures to
comply with FDA regulations, provide accurate information to the FDA, comply with manufacturing standards we have established, comply with federal and state healthcare
fraud and abuse laws and regulations, 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, consultant, or third-party misconduct could also involve the improper use of information obtained in the course of clinical trials, which could result in
regulatory sanctions and serious harm to our reputation, as well as civil and criminal liability. 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 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 civil and/or criminal sanctions.
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 harm 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 involve the use of hazardous and flammable materials, including chemicals and biological materials.
Our operations also produce hazardous waste products. We generally contract with third parties for the disposal of these materials and wastes. We cannot eliminate the risk of
contamination or injury from these materials. Although we believe that the safety procedures for handling and disposing of these materials comply with the standards prescribed
by these laws and regulations, we cannot eliminate the risk of accidental contamination or injury from these materials. In the event of contamination or injury resulting from our
use of hazardous materials, we could be held liable for any resulting damages, and any liability could exceed our resources. We also could incur significant costs associated with
civil or criminal fines and penalties for failure to comply with such laws and regulations.
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 do not maintain insurance for environmental liability or toxic tort claims
that may be asserted against us in connection with our storage or disposal of biological, hazardous or radioactive materials.
In addition, we may incur substantial costs in order to comply with current or future environmental, health and safety laws and regulations. These current or future laws and
regulations may impair our research, development or production efforts. Our failure to comply with these laws and regulations also may result in substantial fines, penalties or
other sanctions.
We are an “emerging growth company” and a “smaller reporting company,” and the reduced disclosure requirements applicable to emerging growth companies and
smaller reporting companies may make our common stock less attractive to investors.
We are an “emerging growth company” as that term is used in the JOBS Act, and may remain an emerging growth company until the earlier of (1) the last day of the fiscal
year (a) following the fifth anniversary of the completion of the initial public offering of our common stock, (b) in which we have total annual gross revenue of at least $1.07
billion, or (c) in which we are deemed to be a large accelerated filer, which means the market value of our outstanding common stock that are held by non-affiliates exceeds
$700 million as of the prior June 30, and (2) the date on which we have issued more than $1.0 billion in non-convertible debt during the prior three year period. For so long as
we remain an emerging growth company, we are permitted and intend to rely on exemptions from certain disclosure requirements that are applicable to other public companies
that are not emerging growth companies. These exemptions include:
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being permitted to provide only two years of audited financial statements, in addition to any required unaudited interim financial statements, with correspondingly
reduced “Management’s Discussion and Analysis of Financial Condition and Results of Operations” disclosure in this Annual Report on Form 10-K;
not being required to comply with the auditor attestation requirements in the assessment of our internal control over financial reporting;
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not being required to comply with any requirement that may be adopted by the Public Company Accounting Oversight Board regarding mandatory audit firm rotation
or a supplement to the auditor’s report providing additional information about the audit and the financial statements;
reduced disclosure obligations regarding executive compensation; and
exemptions from the requirements of holding a nonbinding advisory vote on executive compensation and shareholder approval of any golden parachute payments not
previously approved.
In addition, the JOBS Act provides that an emerging growth company can take advantage of an extended transition period for complying with new or revised
accounting standards. This allows an emerging growth company to delay the adoption of these accounting standards until they would otherwise apply to private companies. We
have elected to take advantage of this extended transition period.
We are also a smaller reporting company, and we will remain a smaller reporting company until the fiscal year following the determination that our voting and non-
voting common shares held by non-affiliates is more than $250 million measured on the last business day of our second fiscal quarter, or our annual revenues are more than
$100 million during the most recently completed fiscal year and our voting and non-voting common shares held by non-affiliates is more than $700 million measured on the last
business day of our second fiscal quarter. Similar to emerging growth companies, smaller reporting companies are able to provide simplified executive compensation disclosure,
are exempt from the auditor attestation requirements of Section 404, and have certain other reduced disclosure obligations, including, among other things, being required to
provide only two years of audited financial statements and not being required to provide selected financial data, supplemental financial information or risk factors.
We have elected to take advantage of certain of the reduced reporting obligations. We cannot predict whether investors will find our common stock less attractive if we
rely on these exemptions. If some investors find our common stock less attractive as a result, there may be a less active trading market for our common stock and our stock
price may be reduced or more volatile.
We are a “controlled company” within the meaning of NASDAQ listing standards and, as a result, qualify for, and rely on, exemptions from certain corporate governance
requirements. You will not have the same protections afforded to stockholders of companies that are subject to such requirements.
We are a “controlled company” within the meaning of NASDAQ listing standards. Under these rules, a company of which more than 50% of the voting power is held by
an individual, a group or another company is a “controlled company” and may elect not to comply with certain corporate governance requirements of NASDAQ, including (i)
the requirement that a majority of the Board of Directors consist of independent directors, (ii) the requirement that we have a nominating and corporate governance committee
that is composed entirely of independent directors with a written charter addressing the committee’s purpose and responsibilities and (iii) the requirement that we have a
compensation committee that is composed entirely of independent directors with a written charter addressing the committee’s purpose and responsibilities. We intend to rely on
some or all of these exemptions.
Accordingly, you will not have the same protections afforded to stockholders of companies subject to all of the corporate governance requirements of NASDAQ.
Certain of our officers and directors serve in similar roles with our parent company, affiliates, related parties and other parties with whom we transact business; ongoing
and future relationships and transactions between these parties could result in conflicts of interest.
We share directors and/or officers with certain of our parent company, affiliates, related parties or other companies with which we transact business, and such arrangements
could create conflicts of interest in the future, including with respect to the allocation of corporate opportunities. While we believe that we have put in place policies and
procedures to identify such conflicts and that any existing agreements that may give rise to such conflicts and any such policies or procedures were negotiated at arm’s length in
conformity with fiduciary duties, such conflicts of interest may nonetheless arise. The existence and consequences of such potential conflicts could expose us to lost profits,
claims by our investors and creditors, and harm to our results of operations.
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Risks Pertaining to Our Finances
We have incurred significant losses since our inception. We expect to incur losses for the foreseeable future, and may never achieve or maintain profitability.
We are an emerging growth company with a limited operating history. We have focused primarily on in-licensing and developing IV Tramadol, with the goal of supporting
regulatory approval for this product candidate. We have incurred losses since our inception in February 2015.
These losses, among other things, have had and will continue to have an adverse effect on our stockholders’ equity and working capital. We expect to continue to incur
significant operating losses for the foreseeable future. We also do not anticipate that we will achieve profitability for a period of time after generating material revenues, if ever.
If we are unable to generate revenues, we will not become profitable and may be unable to continue operations without continued funding. Because of the numerous risks and
uncertainties associated with developing pharmaceutical products, we are unable to predict the timing or amount of increased expenses or when or if, we will be able to achieve
profitability. In addition, the Company cannot be certain that additional funding will be available on acceptable terms, or at all.
Our net losses may fluctuate significantly from quarter to quarter and year to year. We anticipate that our expenses will increase substantially if:
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IV Tramadol or other future product candidates are approved for commercial sale, due to the necessity in establishing adequate commercial infrastructure to launch such
candidate or candidates without substantial delays, including hiring, sales and marketing personnel, and contracting with third parties for warehousing, distribution, cash
collection and related commercial activities;
we are required by the FDA, or foreign regulatory authorities, to perform studies in addition to those
currently expected;
there are any delays in completing our clinical trials or the development of any of our product candidates;
we execute other collaborative, licensing or similar arrangements and the timing of payments we may make or receive under these arrangements;
there are variations in the level of expenses related to our future development programs;
there are any product liability or intellectual property infringement lawsuits in which we may become
involved; and
there are any regulatory developments affecting IV Tramadol or the product candidates of our competitors.
Our ability to become profitable depends upon our ability to generate revenue. To date, we have not generated any revenue from our development stage product, and we do
not know when, or if, we will generate any revenue. Our ability to generate revenue depends on a number of factors, including, but not limited to, our ability to:
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obtain regulatory approval for IV Tramadol, or any other product candidates that we may license or acquire;
• manufacture commercial quantities of IV Tramadol or other product candidates, if approved, at acceptable
cost levels; and
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develop a commercial organization and the supporting infrastructure required to successfully market and sell IV Tramadol or other product candidates, if approved.
Even if we do achieve profitability, we may not be able to sustain or increase profitability on a quarterly or annual basis. Our failure to become and remain profitable would
depress our value and could impair our ability to raise capital, expand our business, maintain our research and development efforts, diversify our product offerings or even
continue our operations. A decline in our value could also cause you to lose all or part of your investment.
Our short operating history makes it difficult to evaluate our business and prospects.
We were incorporated on February 9, 2015, and have only been conducting operations with respect to IV Tramadol since February 17, 2015. We have not yet demonstrated
an ability to successfully obtain regulatory approvals, manufacture a commercial scale product, or arrange for a third party to do so on our behalf, or conduct sales and
marketing activities necessary for successful product commercialization. Consequently, any predictions about our future performance may not be as accurate as they could be if
we had a history of successfully developing and commercializing pharmaceutical products.
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In addition, as a young business, we may encounter unforeseen expenses, difficulties, complications, delays and other known and unknown factors. We will need to expand
our capabilities to support commercial activities. We may not be successful in adding such capabilities.
We expect our financial condition and operating results to continue to fluctuate significantly from quarter to quarter and year to year due to a variety of factors, many of
which are beyond our control. Accordingly, you should not rely upon the results of any past quarterly period as an indication of future operating performance.
There is substantial doubt about our ability to continue as a going concern, which may hinder our ability to obtain future financing.
Our financial statements as of December 31, 2020 have been prepared under the assumption that we will continue as a going concern for the next twelve months. As of
December 31, 2020, we had cash and cash equivalents of $3.1 million and an accumulated deficit of $73.3 million. We do not believe that our cash and cash equivalents are
sufficient for the next twelve months. As a result of our financial condition and other factors described herein, there is substantial doubt about our ability to continue as a going
concern. Our ability to continue as a going concern will depend on our ability to obtain additional funding, as to which no assurances can be given. We continue to analyze
various alternatives, including amending existing lines of credit, debt or equity financings or other arrangements. Our future success depends on our ability to raise capital and/or
implement the various strategic alternatives discussed above. We cannot be certain that these initiatives or raising additional capital, whether through selling additional debt or
equity securities or obtaining a line of credit or other loan, will be available to us or, if available, will be on terms acceptable to us. If we issue additional securities to raise funds,
these securities may have rights, preferences, or privileges senior to those of our common stock, and our current shareholders may experience dilution. If we are unable to
obtain funds when needed or on acceptable terms, we may be required to curtail our current development programs, cut operating costs, forego future development and other
opportunities or even terminate our operations.
We do not have any products that are approved for commercial sale and therefore do not expect to generate any revenues from product sales in the foreseeable future, if
ever.
We have not generated any product related revenues to date. To obtain revenues from sales of our product candidates, we must succeed, either alone or with third parties, in
developing, obtaining regulatory approval for, manufacturing and marketing products with commercial potential. We may never succeed in these activities, and we may not
generate sufficient revenues to continue our business operations or achieve profitability.
We will require substantial additional funding, which may not be available to us on acceptable terms, or at all. If we fail to raise the necessary additional capital, we may
be unable to raise capital when needed, which would force us to delay, reduce or eliminate our product development programs or commercialization efforts.
Our operations have consumed substantial amounts of cash since inception. We expect to significantly increase our spending to advance the clinical development of IV
Tramadol and launch and commercialize any additional product candidates for which we receive regulatory approval, including building our own commercial organizations to
address certain markets. We will require additional capital for the further development and potential commercialization of IV Tramadol or other potential product candidates, as
well as to fund our other operating expenses and capital expenditures, and cannot provide any assurance that we will be able to raise funds to complete the development of our
product.
We cannot be certain that additional funding will be available on acceptable terms, or at all. If we are unable to raise additional capital in sufficient amounts or on terms
acceptable to us, we may have to significantly delay, scale back or discontinue the development or commercialization of one or more of our product candidates. We may also
seek collaborators for product candidates at an earlier stage than otherwise would be desirable or on terms that are less favorable than might otherwise be available. Any of
these events could significantly harm our business, financial condition and prospects.
Our future funding requirements will depend on many factors, including, but not limited to:
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the potential for delays in our efforts to seek regulatory approval for our product candidate, and any costs associated with such delays;
the costs of establishing a commercial organization to sell, market and distribute our product candidates;
the rate of progress and costs of our efforts to prepare for the submission of an NDA for any product candidates that we may in-license or acquire in the future, and the
potential that we may need to conduct additional clinical trials to support applications for regulatory approval;
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the costs of filing, prosecuting, defending and enforcing any patent claims and other intellectual property rights associated with our product candidates, including any
such costs we may be required to expend if our licensors are unwilling or unable to do so;
the cost and timing of securing sufficient supplies of our product candidate from our contract manufacturers in preparation for commercialization;
the effect of competing technological and market developments;
the terms and timing of any collaborative, licensing, co-promotion or other arrangements that we may
establish;
if one or more of our product candidates are approved, the potential that we may be required to file a lawsuit to defend our patent rights or regulatory exclusivities from
challenges by companies seeking to market generic versions of one or more of our product candidates; and
the success of the commercialization of one or more of our product candidates.
In order to carry out our business plan and implement our strategy, we may need to obtain additional financing and may choose to raise additional funds through strategic
collaborations, licensing arrangements, public or private equity or debt financing, bank lines of credit, asset sales, government grants, or other arrangements. We cannot be sure
that any additional funding, if needed, will be available on terms favorable to us or at all. Furthermore, any additional equity or equity-related financing may be dilutive to our
stockholders, and debt or equity financing, if available, may subject us to restrictive covenants and significant interest costs. If we obtain funding through a strategic
collaboration or licensing arrangement, we may be required to relinquish our rights to our product candidate or marketing territories.
Our inability to raise capital when needed would harm our business, financial condition and results of operations, and could cause our stock value to decline or require that
we wind down our operations altogether.
Raising additional capital may cause dilution to our existing stockholders, restrict our operations or require us to relinquish proprietary rights.
Until such time, if ever, as we can generate substantial product revenue, we expect to finance our cash needs through a combination of equity offerings, debt financings,
grants and license and development agreements in connection with any collaborations. To the extent that we raise additional capital through the sale of equity or convertible
debt securities, your ownership interest will be diluted, and the terms of these securities may include liquidation or other preferences that adversely affect your rights as a
stockholder. Debt financing and preferred equity 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 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 any potential product candidates that we would otherwise prefer to develop and market ourselves.
We will continue to incur significant increased costs as a result of operating as a public company, and our management will be required to devote substantial time to new
compliance initiatives.
We are a listed and traded public company. As a public company, we incur significant legal, accounting and other expenses under the Sarbanes-Oxley Act of 2002, as well
as rules subsequently implemented by the Securities and Exchange Commission, or SEC, and the rules of any stock exchange on which we may become listed. These rules
impose various requirements on public companies, including requiring establishment and maintenance of effective disclosure and financial controls and appropriate corporate
governance practices. Our management and other personnel have devoted and will continue to devote a substantial amount of time to these compliance initiatives. Moreover,
these rules and regulations increase our legal and financial compliance costs and make some activities more time-consuming and costly. For example, these rules and
regulations make it more difficult and more expensive for us to obtain director and officer liability insurance, and we may be required to accept reduced policy limits and
coverage or incur substantially higher costs to obtain the same or similar coverage. As a result, it may be more difficult for us to attract and retain qualified persons to serve on
our Board of Directors, our Board committees or as executive officers.
The Sarbanes-Oxley Act of 2002 requires, among other things, that we maintain effective internal controls for financial reporting and disclosure controls and procedures.
As a result, we are required to periodically perform an evaluation of our internal controls over financial reporting to allow management to report on the effectiveness of those
controls, as required by Section 404 of the Sarbanes-Oxley Act. However, while we remain either a non-accelerated filer and/or an emerging growth company, we will not be
required to include an attestation report on internal control over financial reporting issued by our independent registered public accounting firm. To achieve compliance with
Section 404 within the prescribed period, we have engaged in a process to document and evaluate our internal control over financial reporting. These efforts to comply with
Section 404 and related regulations have required, and continue to require, the commitment of significant financial and managerial resources. While we anticipate maintaining
the integrity of our internal controls over financial reporting and all other aspects of Section 404, we cannot be certain that a material weakness will not be identified when we
test the effectiveness of our control systems in the future. If a material weakness is identified, we could be subject to sanctions or investigations by the SEC or other regulatory
authorities, which would require additional financial and management resources, costly litigation or a loss of public confidence in our internal controls, which could have an
adverse effect on the market price of our stock.
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Risks Pertaining to Reliance on Third Parties
If the Merger Transaction does not occur and if IV Tramadol is approved and our contract manufacturer fails to produce the product in the volumes that we require on a
timely basis, to produce the product according to the applicable quality standards and requirements, or to comply with stringent regulations applicable to pharmaceutical
drug manufacturers, we may face delays in the commercialization of this product candidate, lose potential revenues or be unable to meet market demand.
The manufacture of pharmaceutical products requires significant expertise and capital investment, including the development of advanced manufacturing techniques and
process controls, and the use of specialized processing equipment. We have entered into a development and supply agreement for the completion of pre-commercialization
manufacturing development activities and the manufacture of commercial supplies of IV Tramadol. Any termination or disruption of this relationship may materially harm our
business and financial condition, and impact any commercialization efforts for this product candidate.
In order to meet anticipated demand for IV Tramadol, if this product candidate is approved, we currently have one manufacturer to provide us clinical and commercial
supply of IV Tramadol in accordance with the CGMP requirements. We also may plan to qualify a backup manufacturer, in order to ensure an alternative source and to mitigate
any potential supply issues.
All of our contract manufacturers must comply with strictly enforced federal, state and, where applicable, foreign regulations, including CGMP requirements enforced by
the FDA through its inspectional authority over facilities under the FDCA, as well requirements for controlled substance handling and security requirements enforced by DEA,
and while we exercise oversight of our suppliers, we have limited direct control over their compliance with these regulations, as reflected in day-to-day operations. Any failure
to comply with applicable regulations may result in fines and civil penalties, suspension of production, suspension or delay in product approval, product seizure or recall, or
withdrawal of product approval, and would limit the availability of our product. Any quality or compliance issue, manufacturing defect or error discovered after products have
been produced and distributed could result in even more significant consequences, including costly recall procedures, re-stocking costs, damage to our reputation and potential
for product liability claims.
If the commercial manufacturers upon whom we rely to manufacture IV Tramadol, and any other product candidates we may in-license, fail to deliver sufficient
commercial quantities on a timely basis at commercially reasonable prices, we would likely be unable to meet demand for our products and we would lose potential revenues.
We rely, and expect to continue to rely, on third parties to conduct our preclinical studies and clinical trials, and those third parties may not perform satisfactorily, including
failing to meet deadlines for the completion of such trials or complying with applicable regulatory requirements.
We have relied on third party contract research organizations and clinical research organizations to conduct some of our preclinical studies and all of our clinical trials for
IV Tramadol and may do so any future product candidates. We may continue to rely on third parties, such as contract research organizations, clinical research organizations,
clinical data management organizations, medical institutions and clinical investigators, to conduct preclinical studies and clinical trials. The agreements with these third parties
might terminate for a variety of reasons, including a failure to perform by the third parties. If we need to enter into alternative arrangements, that could delay our product
development activities.
Our reliance on these third parties for research and development activities will reduce our control over these activities but will not relieve us of our legal and regulatory
product development responsibilities. For example, we will remain responsible for ensuring that each of our preclinical studies and clinical trials are conducted in accordance
with the general investigational plan and protocols for the trial and for ensuring that our preclinical studies are conducted in accordance with good laboratory practice, or GLP,
as appropriate. Moreover, the FDA requires us to comply with standards, commonly referred to as good clinical practices, or GCPs, 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.
Regulatory authorities enforce these requirements through periodic inspections of trial sponsors, clinical investigators and trial sites. If we or any of our clinical research
organizations fail to comply with applicable GCPs, the clinical data generated in our clinical trials may be deemed unreliable or unacceptable, and the FDA or comparable
foreign regulatory authorities may require us to perform additional clinical trials before approving our marketing applications. We cannot assure you that upon inspection by a
given regulatory authority, such regulatory authority will determine that any of our clinical trials complies with GCP regulations. In addition, our clinical trials must be
conducted using products manufactured and produced in accordance with CGMP regulations. Our failure to comply with these regulations may require us to repeat clinical
trials, which would delay the regulatory approval process. We also are required to register ongoing clinical trials and post the results of completed clinical trials on a
government-sponsored database, ClinicalTrials.gov, within specified timeframes. Failure to do so can result in fines, adverse publicity and civil and criminal sanctions.
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The third parties with whom we have contracted to help perform our preclinical studies or clinical trials 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 preclinical studies or 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 candidate
and will not be able to, or may be delayed in our efforts to, potentially successfully commercialize our product candidate.
If any of our relationships with these third-party contract research organizations or clinical research organizations terminates, we may not be able to enter into arrangements
with alternative contract research organizations or clinical research organizations or to do so on commercially reasonable terms. Switching or adding additional contract
research organizations or clinical research organizations involves additional cost and requires extensive training and management time and focus. In addition, there is a natural
transition period when a new contract research organization or clinical research organization commences work. As a result, delays could occur, which could compromise our
ability to meet our desired development timelines. Though we carefully manage our relationships with our contract research organizations or clinical research organizations,
there can be no assurance that we will not encounter challenges or delays in the future.
We contract with third parties for the manufacture of our product candidates for preclinical and clinical testing and expect to continue to do so for potential
commercialization. This reliance on third parties increases the risk that we will not have sufficient quantities of our potential product candidates or products or such
quantities at an acceptable cost, which could delay, prevent or impair our development or commercialization efforts.
We do not own any manufacturing facilities or personnel. We rely, and expect to continue to rely, on third party manufacturers to manufacture our product candidate for
preclinical and clinical testing, as well as for commercial manufacture, once our product candidate receives marketing approval. This reliance on third parties increases the risk
that we will not have sufficient quantities of our product candidate or products or such quantities at an acceptable cost or quality, which could delay, prevent or impair our
development or potential commercialization efforts.
We may be unable to establish any agreements with such third party manufacturers or to do so on acceptable terms. Even if we are able to establish agreements with third
party manufacturers, reliance on third party manufacturers entails additional risks, including, but not necessarily limited to:
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reliance on the third party for regulatory compliance and quality assurance;
raw material or active ingredient shortages from suppliers the third party has qualified for our product;
the possible breach of the manufacturing agreement by the third party;
manufacturing delays if our third-party manufacturers give greater priority to the supply of other products over our product candidates or otherwise do not satisfactorily
perform according to the terms of the agreement between us;
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 inconvenient for us.
The facilities used by our contract manufacturers to manufacture our product candidate is subject to registration requirements, and inspection by the FDA. A pre-approval
inspection may be conducted after the submission of an application to the FDA. Although we will have oversight over our suppliers and manufacturers, we do not directly
control the manufacturing operations and processes at these facilities, and therefore rely on, our contract manufacturers to ensure full compliance with CGMP regulations with
respect to the day-to-day operations related to the manufacture of our product candidates. Third party manufacturers may, following an inspection, be subject to a Form FDA-
483 or similar inspectional findings, or a Warning Letter, or may not otherwise be able to comply with the CGMP regulations or similar regulatory requirements outside the
United States. The failure of our third-party manufacturers to comply with applicable regulations directly impacts our compliance and could result in sanctions being imposed
on us, including clinical holds, 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 products.
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IV Tramadol and any products that we may develop may compete with other product candidates and products for access to manufacturing facilities. There may be a limited
number of manufacturers that both operate under CGMP regulations and are capable of manufacturing for us. Any performance failure on the part of our existing or future
manufacturers could delay clinical development or marketing approval. We do not currently have arrangements in place for redundant supply or a second source for bulk drug
substance. If our current contract manufacturers cannot perform as agreed, we may be required to replace such manufacturers. We may incur added costs and delays in
identifying and qualifying any replacement manufacturers.
The DEA restricts the importation of a controlled substance finished drug product when the same substance is commercially available in the United States, which could
reduce the number of potential alternative manufacturers for IV Tramadol.
Our current and anticipated future dependence upon others for the manufacture of our product candidate may adversely affect our future profit margins and our ability to
potentially commercialize any products that receive marketing approval on a timely and competitive basis.
We also expect to 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 potential commercialization of our products, producing additional losses and depriving us of potential
product revenue.
We rely on clinical data and results obtained by third parties that could ultimately prove to be inaccurate or unreliable.
As part of our strategy to mitigate development risk, we sought to develop a product candidate with a validated mechanism of action, and we utilize biomarkers to assess
potential clinical efficacy early in the development process. This strategy necessarily relies upon clinical data and other results obtained by third parties that may ultimately
prove to be inaccurate or unreliable. Further, such clinical data and results may be based on products or product candidates that are significantly different from our product
candidate or future product candidates. If the third-party data and results we rely upon prove to be inaccurate, unreliable or not applicable to our product candidate or future
product candidate, we could make inaccurate assumptions and conclusions about our product candidates and our research and development efforts could be compromised and
called into question during the review or any marketing applications we submit.
Risks Pertaining to Regulatory Approval
Even if IV Tramadol receives regulatory approval, which may not occur, it and any other products we may market will remain subject to substantial regulatory scrutiny.
IV Tramadol and any other product candidates we may license or acquire will also be subject to ongoing regulatory and compliance requirements, including regular
inspections by the FDA and other regulatory authorities. These requirements relate to, among others, labeling, packaging, storage, advertising, promotion, record-keeping and
submission of safety and other post-market information and reports, registration and listing requirements, ongoing CGMP requirements relating to manufacturing, quality
control, quality assurance and corresponding maintenance of records and documents, requirements regarding the distribution of samples to physicians and recordkeeping of the
drug.
The FDA may also impose requirements for costly post-marketing studies or clinical trials and surveillance programs to monitor the safety or efficacy of the product. The
FDA closely regulates the post-approval marketing and promotion of drugs to ensure drugs are marketed only for the approved indications and in accordance with the approved
labeling. The FDA imposes stringent restrictions on manufacturers’ communications regarding off-label use and off-label information and if we do not market our products for
only their approved indications and on-label information, we may be subject to enforcement action for off-label marketing as well as false claims liability. Violations of the
FDCA relating to the promotion of prescription drugs may lead to investigations alleging violations of federal and state health care fraud and abuse laws, as well as state
consumer protection laws.
In addition, later discovery of previously unknown adverse events or other problems with our product, manufacturers or manufacturing processes, or failure to comply with
regulatory requirements, may yield various results, including:
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restrictions on such product, operations, manufacturers or manufacturing processes;
restrictions or new requirements related to the promotion, labeling or marketing of a product;
restrictions on product distribution or use, including import and export restrictions;
requirements to conduct post-marketing studies or clinical trials;
Form FDA-483 findings, or warning letters;
recall of the product, or withdrawal of the product from the market;
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refusal to approve pending applications or supplements to approved applications that we submit;
fines, restitution or disgorgement of profits;
suspension or withdrawal of marketing or regulatory approvals;
suspension of any ongoing clinical trials;
refusal to permit the import or export of our product;
product seizure; or
injunctions or the imposition of civil or criminal penalties.
The FDA’s policies, as well as policies of the DEA, who has jurisdiction over controlled substances and opioids, may change and additional government regulations may
be enacted that could prevent, limit or delay regulatory approval of our product candidate. If we are slow or unable to adapt to changes in existing requirements or the adoption
of new requirements or policies, or if we are not able to maintain regulatory compliance, we may lose any marketing approval that we may have obtained.
We will need to obtain FDA approval of any proposed product brand names, and any failure or delay associated with such approval may adversely impact our business.
A pharmaceutical product candidate cannot be marketed in the United States or many other countries until we have completed a rigorous and extensive regulatory review
processes, including obtaining the approval of a brand name. Any brand names we intend to use for our product candidates will require approval from the FDA regardless of
whether we have secured a formal trademark registration from the U.S. Patent and Trademark Office, or USPTO. The FDA typically conducts a review of proposed product
brand names, including an evaluation of potential for confusion with other product names. The FDA may also object to a product brand name if it believes the name
inappropriately implies medical claims. If the FDA objects to any of our proposed product brand name, we may be required to adopt an alternative brand name for our product
candidate. If we adopt an alternative brand name, we would lose the benefit of our existing trademark applications for such product candidate and may be required to expend
significant additional resources in an effort to identify a suitable product brand name that would qualify under applicable trademark laws, not infringe the existing rights of third
parties and be acceptable to the FDA. We may be unable to build a successful brand identity for a new trademark in a timely manner or at all, which would limit our ability to
potentially commercialize our product candidate.
Our current and future relationships with customers and third-party payors in the United States and elsewhere may be subject, directly or indirectly, to applicable anti-
kickback, fraud and abuse, false claims, transparency, health information privacy and security and other healthcare laws and regulations, which could expose us to
criminal sanctions, civil penalties, contractual damages, reputational harm, administrative burdens and diminished profits and future earnings.
Healthcare providers, physicians and third-party payors in the United States and elsewhere will play a primary role in the recommendation and prescription of any product
candidates for which we obtain marketing approval. Our future arrangements with third-party payors, distributors, retailers, marketers and customers may expose us to broadly
applicable fraud and abuse and other healthcare laws and regulations, including, without limitation, the federal Anti-Kickback Statute, the federal False Claims Act, and similar
state or foreign laws which may constrain the business or financial arrangements and relationships through which we sell, market and distribute any product candidates for
which we obtain marketing approval. In addition, we may be subject to transparency laws and patient privacy regulation by U.S. federal and state governments and by
governments in foreign jurisdictions in which we conduct our business. The applicable federal, state and foreign healthcare laws and regulations that may affect our ability to
operate include, but are not necessarily limited to:
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the federal Anti-Kickback Statute, which 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 of, any
good or service, for which payment may be made under federal and state healthcare programs, such as Medicare and Medicaid;
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federal civil and criminal false claims laws and civil monetary penalty laws, including the federal False Claims Act, which impose criminal and civil penalties, including
civil whistleblower or qui tam actions, against individuals or entities for knowingly presenting, or causing to be presented, to the federal government, including the
Medicare and Medicaid programs, claims for payment that are false or fraudulent, making a false statement to avoid, decrease or conceal an obligation to pay money to
the federal government, or the knowing retention of an overpayment from government health care programs; the federal Health Insurance Portability and Accountability
Act of 1996, or HIPAA, which imposes criminal and civil liability for executing 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 of 2009, or HITECH, and their respective implementing regulations,
which impose obligations on covered healthcare providers, health plans, and healthcare clearinghouses, as well as their business associates that create, receive, maintain
or transmit individually identifiable health information for or on behalf of a covered entity, with respect to safeguarding the privacy, security and transmission of
individually identifiable health information;
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the federal Open Payments program, which requires manufacturers of certain drugs, devices, biologics and medical supplies for which payment is available under
Medicare, Medicaid or the Children’s Health Insurance Program, with specific exceptions, to report annually to the Centers for Medicare & Medicaid Services, or CMS,
information related to “payments or other transfers of value” made to physicians, which is defined to include doctors, dentists, optometrists, podiatrists and chiropractors,
and certain teaching hospitals and applicable manufacturers to report annually to CMS ownership and investment interests held by the physicians and their immediate
family members. Data collection began on August 1, 2013 with requirements for manufacturers to submit reports to CMS by March 31, 2014 and 90 days after the end of
each subsequent calendar year. Disclosure of such information was made by CMS on a publicly available website beginning in September 2014; and
analogous state and foreign laws and regulations, such as state anti-kickback and false claims laws, which may apply to sales or marketing arrangements and claims
involving healthcare items or services reimbursed by non-governmental third party payors, including private insurers; state and foreign laws that require pharmaceutical
companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government
or otherwise restrict payments that may be made to healthcare providers; state and foreign laws that require drug manufacturers to report information related to payments
and other transfers of value to physicians and other healthcare providers or marketing expenditures; and state and foreign laws governing the privacy and security of
health information in certain circumstances, many of which differ from each other in significant ways and often are not preempted by HIPAA, thus complicating
compliance efforts.
Efforts to ensure that our business arrangements with third parties will comply with applicable healthcare laws and regulations may 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, including, without limitation, damages, fines, imprisonment, exclusion from participation in
government healthcare programs, such as Medicare and Medicaid, and the curtailment or restructuring of our operations, which could have a material adverse effect on our
business. If any of the physicians or other healthcare providers or entities with whom we expect to do business, including our collaborators, is found not to be in compliance
with applicable laws, it may be subject to criminal, civil or administrative sanctions, including exclusions from participation in government healthcare programs, which could
also materially affect our business.
Regulatory approval for any approved product is limited by the FDA to those specific indications and conditions for which clinical safety and efficacy have been
demonstrated.
Any regulatory approval is limited to the specific labeled indication(s) for which a product is deemed to be safe and effective by the FDA. In addition to the FDA approval
required for new formulations, any new indication for an approved product also requires FDA approval. If we are not able to obtain FDA approval for any desired future
indications for our product, our ability to effectively potentially market and sell our product may be reduced and our business may be adversely affected.
While physicians may choose to prescribe drugs for uses that are not described in the product’s approved labeled indication, or for uses that differ from those tested in
clinical studies, and thus the basis for approval by the regulatory authorities, our ability to promote the products is limited to those indications that are specifically approved by
the FDA. These “off-label” uses are common across medical specialties and may constitute an appropriate treatment for some patients in varied circumstances. Regulatory
authorities in the United States generally do not regulate the practice of medicine by physicians with respect to their choice of treatments. Regulatory authorities do, however,
restrict communications by pharmaceutical companies in terms of their ability to promote off-label uses or disseminate off-label information. If our promotional activities fail to
comply with these requirements, we may be subject to regulatory, compliance, or enforcement action by, these authorities. In addition, our failure to follow FDA requirements
relating to promotion and advertising may result in a Warning Letter, cause the FDA to suspend or withdraw an approved product from the market, require a recall, require the
issuance of corrective advertising, institute fines, or could result in disgorgement of money, operating restrictions, injunctions or civil or criminal prosecution by the
government, any of which could harm our reputation and business.
If the DEA decides to reschedule Tramadol from a Schedule IV controlled substance to a more restrictive Schedule, IV Tramadol could lose its competitive advantage, and
our related clinical development and regulatory approval could be delayed or prevented.
In July 2014, the DEA classified Tramadol as a Schedule IV controlled substance. In comparison, other opioids, which have a high potential for abuse, are classified as
Schedule I and II controlled substances. If approved, IV Tramadol will be the only intravenous Schedule IV opioid on the market. However, in the current environment where
the opioid epidemic is a recognized problem in the United States, there is a possibility that the DEA could reschedule Tramadol to a more restrictive classification (Schedule I,
II or III). Such a rescheduling, or other similar action by DEA, would severely impair IV Tramadol’s current competitive advantage over traditional opioids and may affect our
ability to potentially market IV Tramadol as a safe alternative pain management product.
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Risks Pertaining to the Commercialization of Product Candidate
Current and future legislation and regulation may increase the difficulty and cost for us to obtain marketing approval of, and to commercialize, our product candidate and
may affect the prices we are able to obtain.
In the United States, there have been a number of legislative and regulatory changes and proposed changes regarding the healthcare system that could prevent or delay
marketing approval of our product candidate, restrict or regulate post-approval activities, and affect our ability to profitably sell any product candidates for which we obtain
marketing approval.
In the United States, the Medicare Prescription Drug, Improvement, and Modernization Act of 2003, or the MMA, changed the way Medicare covers and pays for
pharmaceutical products. The legislation expanded Medicare coverage for drug purchases by the elderly and certain disabled people and introduced a reimbursement
methodology based on average sales prices for physician-administered drugs. In addition, this law provided authority for limiting the number of drugs that will be covered in any
therapeutic class. Cost reduction initiatives and other provisions of this law and future laws could decrease the coverage and price that we will receive for any approved
products. While the MMA only applies to drug benefits for Medicare beneficiaries, private payors often follow Medicare coverage policy and payment limitations in setting
their own payment rates. Therefore, any limitations in reimbursement that results from the MMA may result in reductions in payments from private payors.
In March 2010, the Patient Protection and Affordable Care Act, as amended by the Health Care and Education Reconciliation Act of 2010, collectively the ACA, became
law. The ACA is a sweeping law intended to broaden access to health insurance, reduce or constrain the growth of healthcare spending, enhance remedies against fraud and
abuse, add new transparency requirements for the healthcare and health insurance industries, impose new taxes and fees on the health industry and impose additional health
policy reforms.
Among the provisions of the ACA of importance to our potential product candidate are the following:
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an annual, nondeductible fee on any entity that manufactures or imports specified branded prescription drugs and biological products;
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 False Claims Act and the Anti-Kickback Statute, new government investigative powers, and enhanced
penalties for noncompliance;
new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 50% point-of-sale discounts off negotiated prices;
extension of manufacturers’ Medicaid rebate liability to drugs dispensed to Medicaid managed care organization enrollees;
expansion of eligibility criteria for Medicaid programs;
expansion of the entities eligible for discounts under 340B Drug Pricing Program;
new requirements to report financial arrangements with physicians and teaching hospitals;
a new requirement to annually report drug 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.
The Supreme Court upheld the ACA in the main challenge to the constitutionality of the law in 2012. Specifically, the Supreme Court held that the individual mandate and
corresponding penalty was constitutional because it would be considered a tax by the federal government. The Supreme Court also upheld federal subsidies for purchasers of
insurance through federally facilitated exchanges in a decision released in June 2015.
At the end of 2017, Congress passed the Tax Cuts and Jobs Act, which repealed the penalty for individuals who fail to maintain minimum essential health coverage as
required by the ACA. Following this legislation, Texas and 19 other states filed a lawsuit alleging that the ACA is unconstitutional as the individual mandate was repealed,
undermining the legal basis for the Supreme Court’s prior decision. On December 14, 2018, Texas Federal District Court Judge Reed O’Connor issued a ruling declaring that
the ACA in its entirety is unconstitutional. Upon appeal, the Fifth Circuit upheld the district court’s ruling that the individual mandate is unconstitutional. However, the Fifth
Circuit remanded the case back to the district court to conduct a more thorough assessment of the constitutionality of the entire ACA despite the individual mandate being
unconstitutional. The Supreme Court agreed to hear the case on appeal from the Fifth Circuit on March 2, 2020 and held oral arguments on November 10, 2020. While this
lawsuit has no immediate legal effect on the ACA and its provisions, it is ongoing and the outcome may have a significant impact on our business.
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The Bipartisan Budget Act of 2018, the “BBA,” which set government spending levels for Fiscal Years 2018 and 2019, revised certain provisions of the ACA.
Specifically, beginning in 2019, the BBA increased manufacturer point-of-sale discounts off negotiated prices of applicable brand drugs in the Medicare Part D coverage gap
from 50% to 70%, ultimately increasing the liability for brand drug manufacturers. Further, this mandatory manufacturer discount applied to biosimilars beginning in 2019.
The 116th Congress explored legislation intended to address the cost of prescription drugs. Notably, the major committees of jurisdiction in the Senate (Finance Committee,
Health, Education, Labor and Pensions Committee, and Judiciary Committee), have marked up legislation intended to address various elements of the prescription drug supply
chain. Proposals include a significant overhaul of the Medicare Part D benefit design, addressing patent loopholes, and efforts to cap increases in drug prices. On December 12,
2019, the House of Representatives passed broad legislation that would, among other provisions, require HHS to negotiate drug prices and impose price caps. Failure by a
manufacturer to reach an agreement with HHS on the negotiated price could result in significant penalties for prescription drug manufacturers. The 117th Congress convened on
January 3, 2021, and could reintroduce many of the bills targeting drug prices. While we cannot predict what proposals may ultimately become law, the elements under
consideration could significantly change the landscape in which the pharmaceutical market operates.
The Trump Administration took several regulatory steps to redirect ACA implementation. The Department of Health and Human Services (HHS) finalized a hospital
payment reduction for drugs acquired through the 340B Drug Pricing Program.
Under the Trump Administration, HHS finalized several proposals aimed at lowering drug prices for Medicare beneficiaries and increasing price transparency. For
example, the Trump Administration issued an interim final rule on November 27, 2020 implementing a “Most Favored Nation” payment model for Part B drugs that applies
international reference pricing to determine reimbursement for certain drugs paid by Medicare Part B. The interim final rule was enjoined by federal courts prior to its
implementation date of January 1, 2021, and the lawsuit is ongoing. In addition, HHS, in conjunction with the FDA, finalized four pharmaceutical importation pathways in
September 2020: (1) regulations establishing importation of pharmaceuticals from Canada by wholesalers and pharmacists; (2) FDA guidance permitting manufacturers to
import their own pharmaceuticals that were originally intended for marketing in other countries; (3) a request for proposals from private sector entities to import prescription
drugs for personal use under existing statutory authority; and (4) a request for proposals from private sector entities to reimport insulin under existing statutory authority.
Further, on November 11, 2020, the Trump Administration issued a final rule that changes the permissible structure of drug rebates and discounts between drug manufacturers
and third-party payors (including pharmacy benefit managers that negotiate drug prices on behalf of such third-party payors). This final rule, often referred to as the “Rebate
Rule,” could have significant direct and indirect impacts on drug pricing in both government and commercial markets. With respect to price transparency, the Trump
Administration promulgated regulations that require hospitals and third-party payors to disclose prices of items and services, which may impact negotiated rates in the
commercial market.
On January 20, 2021, Joe Biden was inaugurated as the 46th president of the United States. As a presidential candidate, Mr. Biden indicated support for several policies
aimed at lowering drug prices, including government price negotiation, drug importation, international reference pricing, and price increase controls. The incoming Biden
Administration may continue, modify, or repeal many of the drug pricing policies proposed and finalized by the Trump Administration. While we cannot predict which policies
the Biden Administration may support and enforce, the policies finalized in the months prior to the beginning of Mr. Biden’s term, if continued, could significantly change the
landscape in which the pharmaceutical market operates and significantly impact our ability to effectively market and sell our products.
There have been, and likely will continue to be, legislative and regulatory proposals at the federal and state levels directed at broadening the availability of healthcare and
containing or lowering the cost of healthcare products and services. We cannot predict the initiatives that may be adopted in the future. The continuing efforts of the
government, insurance companies, managed care organizations and other payors of healthcare services to contain or reduce costs of healthcare may adversely affect:
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the demand for any products for which we may obtain regulatory approval;
our ability to set a price that we believe is fair for our products;
our ability to generate revenues and achieve or maintain profitability;
the level of taxes that we are required to pay; and
the availability of capital.
In addition, governments may impose price controls, which may adversely affect our future profitability. In January 2020, President Trump signed into law the U.S.-
Mexico-Canada (USMCA) trade deal into law. As enacted, there are no commitments with respect to biological product intellectual property rights or data protection, which
may create an unfavorable environment across these three countries
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We expect that the ACA, as well as other healthcare reform measures that may be adopted in the future, may result in more rigorous coverage criteria and additional
downward pressure on the payment that we receive for any approved drug. Any reduction in reimbursement from Medicare or other government healthcare programs may result
in a similar reduction in payments from private payors. The implementation of cost containment measures or other healthcare reforms may prevent us from being able to
potentially generate revenue, attain profitability, or commercialize our product.
Legislative and regulatory proposals have been made to expand post-approval requirements and restrict sales and promotional activities for pharmaceutical products. We
cannot be sure whether additional legislative changes will be enacted, or whether FDA regulations, guidance or interpretations will be changed, or what the impact of such
changes on the marketing approvals, if any, of our product candidate, may be. In addition, increased scrutiny by the U.S. Congress of the FDA’s approval process may
significantly delay or prevent marketing approval, as well as subject us to more stringent product labeling and post-marketing conditions and other requirements.
Public concern regarding the safety of opioid drug products such as IV Tramadol could delay or limit our ability to obtain regulatory approval, result in the inclusion of
serious risk information in our labeling, negatively impact market performance, or require us to undertake other activities that may entail additional costs.
In light of widely publicized events concerning the safety risk of certain drug products, the FDA, members of Congress, the Government Accountability Office, medical
professionals and the general public have raised concerns about potential controlled substance drug safety issues. These events have resulted in the withdrawal of drug products,
revisions to drug labeling that further limit use of the drug products and the establishment of risk management programs. The Food and Drug Administration Amendments Act
of 2007, or FDAAA, grants significant expanded authority to the FDA much of which is aimed at improving the safety of drug products before and after approval. In particular,
the new law authorizes the FDA to, among other things, require post-approval studies and clinical trials, mandate changes to drug labeling to reflect new safety information and
require risk evaluation and mitigation strategies for certain drugs, including certain currently approved drugs. It also significantly expands the federal government’s clinical trial
registry and results databank, which we expect will result in significantly increased government oversight of clinical trials. Under the FDAAA, companies that violate these and
other provisions of the new law are subject to substantial civil monetary penalties, among other regulatory, civil and criminal penalties. The increased attention to drug safety
issues may result in a more cautious approach by the FDA in its review of data from our clinical trials. Data from clinical trials may receive greater scrutiny, particularly with
respect to safety, which may make the FDA or other regulatory authorities more likely to require additional preclinical studies or clinical trials. If the FDA requires us to conduct
additional preclinical studies or clinical trials prior to approving IV Tramadol, our ability to obtain approval of this product candidate will be delayed. If the FDA requires us to
provide additional clinical or preclinical data following the approval of IV Tramadol, the indications for which this product candidate is approved may be limited or there may
be specific warnings or limitations on production dosing, and our efforts to commercialize IV Tramadol may be otherwise adversely impacted.
Rising public, medical, Congressional, and agency concern around the prescription of controlled substance drug products to patients and a growing movement to reduce the
use of opioid drug products, to develop abuse-deterrent products, and to prevent dependence also could negatively impact our ability to commercialize and generate revenue
from IV Tramadol if it is approved for marketing in the United States. Congress has enacted several laws intended to address opioid use disorder, including the Comprehensive
Addiction and Recovery Act (CARA) in 2016, the 21st Century Cures Act (Cures Act) in 2016, and the Substance Use-Disorder Prevention that Promotes Opioid Recovery and
Treatment for Patients and Communities Act (the SUPPORT Act) in 2018. These laws primarily focus on funding for treatment, research, and education, but also include
provisions intended to encourage reduction in opioid use, such as funding for research on non-opioid pain treatments. Other legislative and administrative measures at the state
and federal level include, or may include in the future, restrictions and limitations on opioid prescribing, limitations on opioid doses dispensed per episode of care, labeling
requirements specific to opioids, limitations on FDA approval of opioids, assessment of fees against opioid manufacturers, or reimbursement disincentives specific to opioids.
We expect intense competition for IV Tramadol, and new products may emerge that provide different or better therapeutic alternatives for our targeted indications.
The biotechnology and pharmaceutical industries are subject to rapid and intense technological change. We face, and will continue to face, competition in the development
and marketing of IV Tramadol from academic institutions, government agencies, research institutions and biotechnology and pharmaceutical companies. There can be no
assurance that developments by others will not render IV Tramadol obsolete or noncompetitive. Furthermore, new developments, including the development of other drug
technologies and methods of preventing the incidence of disease, occur in the pharmaceutical industry at a rapid pace. These developments may render IV Tramadol obsolete or
noncompetitive.
IV Tramadol will compete with well-established products with similar indications. Competing products available for the management of pain include Ofirmev (IV
acetaminophen) and IV formulations of NSAIDs such as Dyloject (diclofenac), Toradol (ketorolac), Anjeso (meloxicam) and Caldolor (ibuprofen). In addition, we also expect
to compete with agents such as Exparel, a liposome injection of bupivacaine indicated for administration into the surgical site to produce postsurgical analgesia. In addition to
approved products, there are a number of product candidates in development for the management of acute pain. The late-stage pain development pipeline is replete with
reformulations and fixed-dose combination products of already available therapies. Among specific drug classes, opioid analgesics and NSAIDs represent the greatest number
of agents in development. Most investigational opioids that have reached the later stages of clinical development are new formulations of already marketed opioids. Likewise,
investigational NSAIDs — mostly lower dose injectable reformulations of already approved compounds — are another significant area of late-stage drug development in the
postoperative pain space.
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Competitors may seek to develop alternative formulations of IV centrally acting synthetic opioid analgesics for our targeted indications that do not directly infringe on our
in-licensed patent rights. The commercial opportunity for IV Tramadol could be significantly harmed if competitors are able to develop alternative formulations outside the
scope of our in-licensed patents. Compared to us, many of our potential competitors have substantially greater:
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development resources, including personnel and technology;
clinical trial experience;
regulatory experience;
expertise in prosecution of intellectual property rights; and
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As a result of these factors, our competitors may obtain regulatory approval of their products more rapidly than we are able to or may obtain patent protection or other
intellectual property rights that limit our ability to develop or potentially commercialize IV Tramadol. Our competitors may also develop drugs that are more effective, safe,
useful and less costly than ours and may be more successful than us in manufacturing and marketing their products.
If the government or third-party payors fail to provide adequate coverage and payment rates for IV Tramadol or any future products we may license or acquire in the
future, if any, or if hospitals choose to use therapies that are less expensive, our potential revenue and prospects for profitability will be limited.
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. In both domestic and foreign markets, our sales of any future products will depend in part upon the
availability of coverage and reimbursement from third party payors. Such third-party payors include government health programs such as Medicare and Medicaid, managed care
providers, private health insurers and other organizations. In particular, many U.S. hospitals receive a fixed reimbursement amount per procedure for certain surgeries and other
treatment therapies they perform. Because this amount may not be based on the actual expenses the hospital incurs, hospitals may choose to use therapies which are less
expensive when compared to our product candidate or future product candidates. Accordingly, IV Tramadol or any other product candidates that we may in-license or acquire, if
approved, will face competition from other therapies and drugs for these limited hospital financial resources. We may need to conduct post-marketing studies in order to
demonstrate the cost-effectiveness of any future products to the satisfaction of hospitals, other target customers and their third-party payors. Such studies might require us to
commit a significant amount of management time and financial and other resources. Net prices for drugs may be reduced by mandatory discounts or rebates required by
government healthcare programs or private payors and by implementation of recently promulgated regulations that permit importation of drugs from countries where they may
be sold at lower prices than in the United States. Our future product might not ultimately be considered cost-effective. Adequate third-party coverage and reimbursement might
not be available to enable us to maintain price levels sufficient to realize an appropriate return on investment in product development.
If IV Tramadol does not achieve broad market acceptance, the potential revenues that we generate from its sales will be limited.
The commercial success of IV Tramadol, if approved, will depend upon its acceptance by the medical community, the ability to ensure that the drug is included in hospital
formularies, and coverage and reimbursement for IV Tramadol by third party payors, including government payors. The degree of market acceptance of IV Tramadol or any
other product candidate we may license or acquire would depend on a number of factors, including, but not necessarily limited to:
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the efficacy and safety as demonstrated in clinical trials;
the safety and use of IV Tramadol in its intended patient population;
the timing of market introduction of such product candidate as well as competitive products;
the clinical indications for which the drug is approved;
acceptance by physicians, major operators of cancer clinics and patients of the drug as a safe and effective treatment;
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the safety of such product candidate seen in a broader patient group (i.e., real world use);
the availability, cost and potential advantages of alternative treatments, including less expensive generic drugs;
the availability of adequate reimbursement and pricing by third party payors and government authorities;
the relative convenience and ease of administration of the product candidate for clinical practices;
the product labeling or product insert required by the FDA or regulatory authority in other countries, including any contradictions, warnings, drug interactions, or other
precautions;
the approval, availability, market acceptance and reimbursement for a companion diagnostic, if any;
the prevalence and severity of adverse side effects;
the effectiveness of our sales and marketing efforts;
changes in the standard of care for the targeted indications for our product candidate or future product candidates, which could reduce the marketing impact of any
superiority claims that we could make following FDA approval; and
potential advantages over, and availability of, alternative treatments.
If any product candidate that we develop does not provide a treatment regimen that is as beneficial as, or is not perceived as being as beneficial as, the current standard of
care or otherwise does not provide patient benefit, that product candidate, if approved for commercial sale by the FDA or other regulatory authorities, likely will not achieve
market acceptance. Our ability to effectively promote and potentially sell IV Tramadol and any other product candidates we may license or acquire in the hospital marketplace
will also depend on pricing and cost effectiveness, including our ability to produce a product at a competitive price and achieve acceptance of the product onto hospital
formularies, as well as our ability to obtain sufficient third-party coverage or reimbursement. Since many hospitals are members of group purchasing organizations, which
leverage the purchasing power of a group of entities to obtain discounts based on the collective buying power of the group, our ability to potentially attract customers in the
hospital marketplace will also depend on our ability to effectively potentially promote our product candidate to group purchasing organizations. We will also need to
demonstrate acceptable evidence of safety and efficacy, as well as relative convenience and ease of administration. Market acceptance could be further limited depending on the
prevalence and severity of any expected or unexpected adverse side effects associated with our product candidate. If our product candidate is approved but does not achieve an
adequate level of acceptance by physicians, health care payors and patients, we may not potentially generate sufficient revenue from this product, and we may not become or
remain profitable. In addition, our efforts to educate the medical community and third-party payors on the benefits of our product candidate may require significant resources
and may never be successful.
If we are unable to establish sales, and marketing capabilities or to enter into agreements with third parties to market and sell our product candidate, we may not be
successful in commercializing our product candidate if and when it is approved.
We currently do not have a marketing or sales organization for the marketing and sales of pharmaceutical products since we currently have no drug products for sale, and
only one drug product candidate, IV Tramadol. In order to potentially commercialize any product candidate that receives marketing approval, we would need to build out
marketing, sales, managerial and other non-technical capabilities or enter into agreements with third party contract organizations to perform these services, and we may not be
successful in doing so. In the event of successful development and regulatory approval of IV Tramadol or another product candidate, we might have to build a targeted specialist
sales force to market or co-promote the product. There are risks involved with establishing our own sales and marketing capabilities. For example, recruiting and training a sales
force is expensive and time consuming and could delay any product launch. If the commercial launch of a product candidate for which we recruit a sales force and establish
marketing 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 potential efforts to successfully commercialize our future product, if any, using our own sales and marketing capabilities include, but are not
necessarily limited to:
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our inability to recruit, train and retain adequate numbers of effective sales and marketing personnel;
the inability of sales personnel to obtain access to physicians or persuade adequate numbers of physicians to prescribe any future products;
the lack of complementary or other products to be offered by sales personnel, which may put us at a competitive disadvantage from the perspective of sales efficiency
relative to companies with more extensive product lines; and
unforeseen costs and expenses associated with creating an independent sales and marketing organization.
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As an alternative to establishing our own sales force, we may choose to partner with third parties that have well-established direct sales forces to sell, market and distribute
our products. There are risks involved with partnering with third party sales forces, including ensuring adequate training on the product, regulatory, and compliance
requirements associated with promotion of the product.
If we breach the agreement under which we license rights to IV Tramadol, we could lose the ability to continue to develop and potentially commercialize this product
candidate.
In February 2015, Fortress obtained an exclusive license to IV Tramadol for the U.S. market from Revogenex Ireland Ltd., or Revogenex, pursuant to the License
Agreement; Fortress subsequently transferred the License Agreement to us. Because we have in-licensed the rights to this product candidate from a third party, if there is any
dispute between us and our licensor regarding our rights under the License Agreement, our ability to develop and potentially commercialize this product candidate may be
adversely affected. Any uncured, material breach under the License Agreement could result in our loss of exclusive rights to our product candidate and may lead to a complete
termination of our related product development efforts.
We face potential product liability exposure, and if successful claims are brought against us, we may incur substantial liability for IV Tramadol or other product candidates
we may license or acquire and may have to limit their commercialization.
The use of IV Tramadol and any other product candidates we may license or acquire in clinical trials and the sale of any products for which we obtain marketing approval
expose us to the risk of product liability claims. For example, we may be sued if any product we develop allegedly causes injury or is found to be otherwise unsuitable during
clinical testing, manufacturing, marketing or sale. Any such product liability claims may include allegations of defects in manufacturing, defects in design, a failure to warn of
dangers inherent in the product, negligence, strict liability or a breach of warranties. Product liability claims might be brought against us by consumers, health care providers or
others using, administering or selling our products. If we cannot successfully defend ourselves against these claims, we will incur substantial liabilities. Regardless of merit or
eventual outcome, liability claims may result in:
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withdrawal of clinical trial participants;
termination of clinical trial sites or entire trial programs;
decreased demand for any product candidates or products that we may develop;
initiation of investigations by regulators;
impairment of our business reputation;
costs of related litigation;
substantial monetary awards to patients or other claimants;
loss of revenues;
reduced resources of our management to pursue our business strategy; and
the inability to commercialize our product candidate or future product candidates.
We have limited product liability insurance coverage for our clinical trials. However, our insurance coverage may not reimburse us or may not be sufficient to reimburse us
for any expenses or losses we may suffer. Moreover, insurance coverage is becoming increasingly expensive, and, in the future, we may not be able to maintain insurance
coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability. When needed, we intend to potentially expand our insurance coverage to
include the sale of commercial products if we obtain marketing approval for our product candidate in development, but we may be unable to obtain commercially reasonable
product liability insurance for any products approved for marketing. On occasion, large judgments have been awarded in class action lawsuits based on drugs that had
unanticipated side effects. A successful product liability claim or series of claims brought against us could cause our stock price to fall and, if judgments exceed our insurance
coverage, could decrease our cash and adversely affect our business.
If we are unable to obtain and maintain patent protection for our technology and products or if the scope of the patent protection obtained is not sufficiently broad, our
Risks Pertaining to Intellectual Property and Potential Disputes Thereof
competitors could develop and commercialize technology and products similar or identical to ours, and our ability to successfully commercialize our technology and
products may be impaired.
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Our commercial success will depend in part on obtaining and maintaining patent protection and trade secret protection in the United States with respect to IV Tramadol or
any other product candidates that we may license or acquire and the methods we use to manufacture them, as well as successfully defending these patents and trade secrets
against third party challenges. We seek to protect our proprietary position by filing patent applications in the United States and abroad related to our product candidate. We will
only be able to protect our technologies from unauthorized use by third parties to the extent that valid and enforceable patents or trade secrets cover them.
The patent prosecution process is expensive and time-consuming, and we may not be able to file and prosecute all necessary or desirable patent 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. If our licensors or we fail to obtain or maintain patent protection or trade secret protection for IV Tramadol or any other product candidate we may license or
acquire, third parties could use our proprietary information, which could impair our ability to compete in the market and adversely affect our ability to generate revenues and
achieve profitability. Moreover, should we enter into other collaborations we may be required to consult with or cede control to collaborators regarding the prosecution,
maintenance and enforcement of our patents. Therefore, these patents and applications may not be prosecuted 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. In addition, no consistent policy regarding the breadth of claims allowed in pharmaceutical or biotechnology patents has emerged to date in
the United States. The patent situation outside the United States is even more uncertain. The laws of foreign countries may not protect our rights to the same extent as the laws
of the United States. For example, European patent law restricts the patentability of methods of treatment of the human body more than United States law does. 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 a first filing, or in some cases at all. Therefore, we cannot know with certainty whether we or our licensors were the first to make the inventions claimed in our
owned or licensed patents or pending patent applications, or that we were the first to file for patent protection of such inventions. In the event that a third party has also filed a
U.S. patent application relating to our product candidates or a similar invention, we may have to participate in interference proceedings declared by the USPTO to determine
priority of invention in the United States. The costs of these proceedings could be substantial and it is possible that our efforts would be unsuccessful, resulting in a material
adverse effect on our U.S. patent position. As a result, the issuance, scope, validity, enforceability and commercial value of our or any of our licensors’ patent rights are highly
uncertain. Our pending and future patent applications may not result in patents being issued which protect our technology or products, in whole or in part, or which effectively
prevent others from commercializing competitive technologies and products. 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. For example, the federal courts of the United States have taken an increasingly dim
view of the patent eligibility of certain subject matter, such as naturally occurring nucleic acid sequences, amino acid sequences and certain methods of utilizing same, which
include their detection in a biological sample and diagnostic conclusions arising from their detection. Such subject matter, which had long been a staple of the biotechnology
and biopharmaceutical industry to protect their discoveries, is now considered, with few exceptions, ineligible in the first place for protection under the patent laws of the United
States. Accordingly, we cannot predict the breadth of claims that may be allowed or enforced in our patents (if any) or in those licensed from third parties.
Recent patent reform legislation could increase the uncertainties and costs surrounding the prosecution of our patent applications and affect the validity, enforceability,
scope or defense of our issued patents. On September 16, 2011, the Leahy-Smith America Invents Act, or the Leahy-Smith Act, was signed into law. The Leahy-Smith Act
includes a number of significant changes to United States patent law. These include provisions that affect the way patent applications are prosecuted and may also affect patent
litigation. The USPTO recently developed new regulations and procedures to govern administration of the Leahy-Smith Act, and many of the substantive changes to patent law
associated with the Leahy-Smith Act, and in particular, the first-to-file provisions, only became effective on March 16, 2013. Accordingly, it is not clear what, if any, impact the
Leahy-Smith Act will have on the operation of our business. However, the Leahy-Smith Act and its implementation could increase the uncertainties and costs surrounding the
prosecution of our patent applications and the enforcement or defense of our issued patents, all of which could have a material, adverse effect on our business and financial
condition.
Moreover, we may be subject to a third-party pre-issuance submission of prior art to the USPTO, or become involved in opposition, derivation, reexamination, inter parties
review, post-grant review or interference proceedings challenging our patent rights or the patent rights of others. An adverse determination in any such submission, PTAB trial,
proceeding or litigation could reduce the scope of, render unenforceable, or invalidate, our patent rights, allow third parties to commercialize our technology or products and
compete directly with us, without payment to us, or result in our inability to manufacture or commercialize products without infringing third party patent rights. In addition, if
the breadth or strength of protection provided by our patents and patent applications is threatened, it could dissuade companies from collaborating with us to license, develop or
commercialize current or future 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 licensed patents by developing similar or alternative
technologies or products in a non-infringing manner.
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The issuance of a patent does not foreclose challenges to its inventorship, scope, validity or enforceability. Therefore, 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 and products, or
limit the duration of the patent protection of our technology and products. Given the amount of time required for the development, testing and regulatory review of new product
candidates, patents protecting such product candidates might expire before or shortly after such product candidates are commercialized. As a result, our owned and licensed
patent portfolio may not provide us with sufficient rights to exclude others from commercializing products similar or identical to ours.
The patent rights that we have in-licensed covering the infusion time and pharmacokinetics, or PK, profile for IV Tramadol are limited to a specific IV formulation of
centrally acting synthetic opioid analgesic, and our market opportunity for this product candidate may be limited by the lack of patent protection for the active ingredient
itself and other formulations that may be developed by competitors.
The active ingredients in IV Tramadol have been generic in the United States for a number of years. While we believe that the patent estate covering IV Tramadol
(including but not limited to U.S. Patent Nos. 8,895,622; 9,561,195, 9,566,253 9,962,343, 10,406,122, 9,693,949, 9,968,551, 9,980,900, 10,022,321,10,537,521, 10,624,842,
10,751,277, 10,751,278, 10,751,279, 10,646,433, 10,729,644, 10,729,645, and 10,617,635) provides strong protection, our market opportunity would be limited if a generic
manufacturer could obtain regulatory approval for another IV formulation of tramadol and commercialize it without infringing our patents.
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 issued patents or other intellectual property. To counter infringement or unauthorized use, we may be required to file infringement claims,
which can be expensive and time consuming. Any claims we assert against perceived infringers could provoke these parties to assert counterclaims against us alleging that we
infringe their patents. 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 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. An adverse
result in any litigation proceeding could put one or more of our patents at risk of being invalidated, rendered unenforceable, or interpreted narrowly.
We may become involved in other types of legal proceedings related to our intellectual property that could result in the invalidation or unenforceability of our patents and
could be expensive and time consuming, regardless of the outcome.
Any party can challenge the validity of our patents in post-grant proceedings at the PTAB, which include inter partes review and post-grant review proceedings. Although
these proceedings are more limited, and therefore are often less expensive, than district court litigation, they can still require substantial resources. If the PTAB finds that our
patents are unpatentable, we will be unable to enforce those patents against our competitors. Additionally, our competitors may bring other administrative challenges to our
patents before the USPTO, including opposition, derivation, interference, ex parte reexamination, and inter partes reexamination proceedings. These proceedings may prevent
our patent applications from issuing, or for patents that are already issued, an unsuccessful outcome will render the patent unenforceable.
If we are sued for infringing intellectual property rights of third parties, it will be costly and time consuming, and an unfavorable outcome in any litigation would harm our
business.
Our ability to develop, manufacture, market and potentially sell IV Tramadol or any other product candidates that we may license or acquire depends upon our ability to
avoid infringing the proprietary rights of third parties. Numerous U.S. and foreign patents and pending patent applications, which are owned by third parties, exist in the general
fields of pain treatment and cover the use of numerous compounds and formulations in our targeted markets. Because of the uncertainty inherent in any patent or other litigation
involving proprietary rights, we and our licensors may not be successful in defending intellectual property claims by third parties, which could have a material adverse effect on
our results of operations. Regardless of the outcome of any litigation, defending the litigation may be expensive, time-consuming and distracting to management. In addition,
because patent applications can take many years to issue, there may be currently pending applications, unknown to us, which may later result in issued patents that IV Tramadol
may infringe. There could also be existing patents of which we are not aware that IV Tramadol may inadvertently infringe.
There is a substantial amount of litigation involving patent and other intellectual property rights in the biotechnology and biopharmaceutical industries generally. If a third
party claims that we infringe on their patents or misappropriated their technology, we could face a number of issues, including:
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infringement and other intellectual property claims which, with or without merit, can be expensive and time consuming to litigate and can divert management’s attention
from our core business;
substantial damages for past infringement which we may have to pay if a court decides that our product infringes on a competitor’s patent;
a court prohibiting us from selling or licensing our product unless the patent holder licenses the patent to us, which it would not be required to do;
if a license is available from a patent holder, we may have to pay substantial royalties or grant cross licenses to our patents; and
redesigning our processes so they do not infringe, which may not be possible or could require substantial funds and time.
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We may need to license certain intellectual property from third parties, and such licenses may not be available or may not be available on commercially reasonable terms.
A third party may hold intellectual property, including patent rights that are important or necessary to the development and potential commercialization of our product. It
may be necessary for us to use the patented or proprietary technology of third parties to potentially commercialize our product, in which case we would be required to obtain a
license from these third parties on commercially reasonable terms, or our business could be harmed, possibly materially.
If we fail to comply with our obligations in our intellectual property licenses and funding arrangements with third parties, we could lose rights that are important to our
business.
We are currently party to a license agreement for IV Tramadol. In the future, we may become party to licenses that are important for product development and potential
commercialization. If we fail to comply with our obligations under current or future license and funding agreements, our counterparties may have the right to terminate these
agreements, in which event we might not be able to develop, manufacture or market any product or utilize any technology that is covered by these agreements or may face other
penalties under the agreements. Such an occurrence could materially and adversely affect the value of a product candidate being developed under any such agreement or could
restrict our drug discovery activities. Termination of these agreements or reduction or elimination of our rights under these agreements may result in our having to negotiate new
or reinstated agreements with less favorable terms, or cause us to lose our rights under these agreements, including our rights to important intellectual property or technology.
To the extent we operate in foreign jurisdictions, we may be exposed to increased risk associated with the potential theft of technology and intellectual property.
Our U.S. patents can be enforced against those who make, use, offer to sell, or sell our licensed patented inventions within the U.S., or against those who import our
licensed patented inventions within the U.S. We may depend on foreign intellectual property rights to prevent competitors from manufacturing and selling our products outside
of the U.S. without our authorization. Foreign laws and regulations may not protect our patent rights and trade secret rights to the same extent as U.S. law. It is also possible that
we may be required to compromise protections or waive rights in order to conduct business in a foreign jurisdiction. Such restrictions may limit our ability to profitably compete
in those markets.
We may be subject to claims that our employees have wrongfully used or disclosed alleged trade secrets of their former employers.
As is common in the biotechnology and pharmaceutical industry, we employ individuals who were previously employed at other biotechnology or pharmaceutical
companies, including our competitors or potential competitors. Although no claims against us are currently pending, we may be subject to claims that these employees or we
have inadvertently or otherwise used or disclosed trade secrets or other proprietary information of their former employers. Litigation may be necessary to defend against these
claims. Even if we are successful in defending against these claims, litigation could result in substantial costs and be a distraction to management.
If we are unable to protect the confidentiality of our trade secrets, our business and competitive position would be harmed.
In addition to seeking patent protection for our product candidate or future product candidates, we also rely on trade secrets, including unpatented know-how, technology
and other proprietary information, to maintain our competitive position, particularly where we do not believe patent protection is appropriate or obtainable. However, trade
secrets are difficult to protect. We limit disclosure of such trade secrets where possible but we also seek to protect these trade secrets, in part, by entering into non-disclosure and
confidentiality agreements with parties who do have access to them, such as our employees, our licensors, 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. Despite these efforts, any of these parties may breach the agreements and may unintentionally or willfully 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. Moreover, 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 disclosed to or independently developed by a
competitor, our competitive position would be harmed.
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General Risks
Our business and operations could be adversely affected by the effects of health epidemics, including the ongoing COVID-19 pandemic.
Any potential future clinical trials may experience delays in patient enrolment, potentially due to prioritization of hospital resources toward the COVID-19 pandemic, or
concerns among patients about participating in clinical trials during a public health emergency. The COVID-19 pandemic is affecting the operations of government entities,
such as the FDA, as well as contract research organizations, third-party manufacturers, and other third-parties upon whom we rely. As a result of “shelter-in-place” orders,
quarantines or similar orders or restrictions to control the spread of COVID-19, many companies, including our own, have implemented work-from-home policies for their
employees. The effects of these stay at home orders and work-from-home policies may be negatively impacting productivity, resulting in delays in our timelines. The extent of
the impact on our operations depends in part on the time these restrictions remain in place, and whether restrictions are reinstated as a result of a rising surge in COVID-19
cases. These and similar disruptions in our operations could negatively impact our business, operating results and financial condition.
The spread of COVID-19 has also led to disruption and volatility in the global capital markets, which increases the cost of, and adversely impacts access to, capital and
increases economic uncertainty. To the extent the COVID-19 pandemic adversely affects our business, financial results and value of our common stock, it may also affect our
ability to access capital and obtain financing, which could in the future negatively affect our liquidity.
The global pandemic of COVID-19 continues to evolve rapidly, and the ultimate impact of the COVID-19 pandemic or a similar health epidemic is highly uncertain and
subject to change. We do not yet know the full impact of potential delays or effects on our business, , our ability to access the capital markets, or supply chains or on the global
economy as a whole. However, these effects could have a material impact on our operations, and we will continue to monitor the COVID-19 situation closely.
Our results of operations and liquidity needs could be materially negatively affected by market fluctuations and economic downturn.
Our results of operations could be materially negatively affected by economic conditions generally, both in the United States and elsewhere around the world. Continuing
concerns over inflation, energy costs, geopolitical issues, the availability and cost of credit, the U.S. mortgage market and residential real estate market in the United States have
contributed to increased volatility and diminished expectations for the economy and the markets going forward. These factors, combined with volatile oil prices, declining
business and consumer confidence and increased unemployment, have precipitated an economic recession and fears of a possible depression. Domestic and international equity
markets continue to experience heightened volatility and turmoil. These events and the continuing market upheavals may have an adverse effect on us. In the event of a
continuing market downturn, our results of operations could be adversely affected by those factors in many ways, including making it more difficult for us to raise funds if
necessary, and our stock price may further decline.
Our business and operations would suffer in the event of system failures.
Despite the implementation of security measures, our internal computer systems are vulnerable to damage from computer viruses, unauthorized access, natural disasters,
terrorism, war and telecommunication and electrical failures. Any system failure, accident or security breach that causes interruptions in our operations could result in a material
disruption of our drug development programs. For example, the loss of clinical trial data from completed clinical trials for IV Tramadol 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 results in a loss or damage to our data
or applications, or inappropriate disclosure of confidential or proprietary information, we may incur liability and the further development of our product candidate may be
delayed.
The occurrence of a catastrophic disaster could damage our facilities beyond insurance limits or we could lose key data which could cause us to curtail or cease
operations.
We are vulnerable to damage and/or loss of vital data from natural disasters, such as earthquakes, tornadoes, power loss, fire, health epidemics and pandemics, floods and
similar events, as well as from accidental loss or destruction. If any disaster were to occur, our ability to operate our businesses could be seriously impaired. We have property,
liability and business interruption insurance that may not be adequate to cover losses resulting from disasters or other similar significant business interruptions, and we do not
plan to purchase additional insurance to cover such losses due to the cost of obtaining such coverage. Any significant losses that are not recoverable under our insurance policies
could seriously impair our business, financial condition and prospects. Any of the aforementioned circumstances, including without limitation the emerging COVID-19 virus,
may also impede our employees’ and consultants’ abilities to provide services in-person and/or in a timely manner; hinder our ability to raise funds to finance our operations on
favorable terms or at all; and trigger effectiveness of “force majeure” clauses under agreements with respect to which we receive goods and services, or under which we are
obligated to achieve developmental milestones on certain timeframes. Disputes with third parties over the applicability of such “force majeure” clauses, or the enforceability of
developmental milestones and related extension mechanisms in light of such business interruptions, may arise and may become expensive and time-consuming.
We may become involved in securities class action litigation that could divert management’s attention and harm our business.
The stock markets have from time to time experienced significant price and volume fluctuations that have affected the market prices for the common stock of
biotechnology and pharmaceutical companies. These broad market fluctuations may cause the market price of our stock to decline. In the past, securities class action litigation
has often been brought against a company following a decline in the market price of its securities. This risk is especially relevant for us because biotechnology and
biopharmaceutical companies have experienced significant stock price volatility in recent years and due to the significant stock price decline we experienced following the
announcement of the CRL. We may become involved in this type of litigation in the future. Litigation often is expensive and diverts management’s attention and resources,
which could adversely affect our business.
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Item 1B.
Unresolved Staff Comments
None.
Item 2.
Properties
Our corporate and executive office is located at 1140 Avenue of the Americas, Floor 9, New York, NY 10036. We are not currently under a lease agreement at 1140
Avenue of the Americas. We believe that our existing facilities are adequate to meet our current requirements. We do not own any real property.
Item 3.
Legal Proceedings
We are not involved in any litigation that we believe could have a material adverse effect on our financial position or results of operations.
Item 4.
Mine Safety Disclosures
Not applicable
Item 5.
Market for Registrant’s Common Equity, Related Stockholder Matters and Issuer Purchases of Equity Securities
PART II
Market Information
Our common stock is listed on the Nasdaq Capital Market and trades under the symbol “ATXI”.
Holders
As of March 17, 2021, there were approximately 16.7 million shares of common stock outstanding. The number of record holders of our common stock as of March 17,
2021 was 56.
Dividends
We have never paid or declared any cash dividends on our common stock, and we do not anticipate paying any cash dividends on our common stock in the foreseeable
future. We intend to retain all available funds and any future earnings to fund the development and expansion of our business. Any future determination to pay dividends will be
at the discretion of our board of directors and will depend upon a number of factors, including our results of operations, financial condition, future prospects, contractual
restrictions, restrictions imposed by applicable law and other factors our board of directors deems relevant.
Equity Compensation Plans
On August 15, 2017, we filed a registration statement on Form S-8 under the Securities Act registering the common stock issued, issuable or reserved for issuance under
our 2015 Incentive Plan (“2015 Plan”). The registration statement became effective immediately upon filing, and shares covered by the registration statement are eligible for sale
in the public markets, subject to grant of the underlying awards, vesting provisions and Rule 144 limitations applicable to our affiliates.
Securities Authorized for Issuance under Equity Compensation Plans
Subject to adjustment as provided in the 2015 Plan, the aggregate number of shares of our common stock reserved and available for issuance pursuant to awards granted
under the 2015 Plan is 2,000,000.
Recent Sales of Unregistered Securities.
Not applicable.
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Description of Registrant’s Securities to be Registered.
Not applicable.
Item 6.
Reserved
Item 7.
Management’s Discussion and Analysis of the Results of Operations
Forward-Looking Statements
Statements in the following discussion and throughout this report that are not historical in nature are “forward-looking statements.” You can identify forward-looking
statements by the use of words such as “expect,” “anticipate,” “estimate,” “may,” “will,” “should,” “intend,” “believe,” and similar expressions. Although we believe the
expectations reflected in these forward-looking statements are reasonable, such statements are inherently subject to risk and we can give no assurances that our expectations
will prove to be correct. Actual results could differ from those described in this report because of numerous factors, many of which are beyond our control. These factors
include, without limitation, those described under Item 1A “Risk Factors.” We undertake no obligation to update these forward-looking statements to reflect events or
circumstances after the date of this report or to reflect actual outcomes. Please see “Forward-Looking Statements” at the beginning of this Form 10-K.
The following discussion of our financial condition and results of operations should be read in conjunction with our financial statements and the related notes thereto and other
financial information appearing elsewhere in this Form 10-K. We undertake no obligation to update any forward-looking statements in the discussion of our financial condition
and results of operations to reflect events or circumstances after the date of this report or to reflect actual outcomes.
Overview
We are a specialty pharmaceutical company that seeks to develop and commercialize our product principally for use in the acute/intensive care hospital setting. Our current
product candidate is intravenous (IV) Tramadol, for the treatment of post-operative acute pain. Under the terms of certain agreements described herein, we have an exclusive
license to develop and commercialize IV Tramadol in the United States. In 2016, we completed a pharmacokinetic (PK) study for IV Tramadol in healthy volunteers as well as
an end of phase 2 (EOP2) meeting with the U.S. Food and Drug Administration (FDA). In the third quarter of 2017, we initiated a Phase 3 development program of IV
Tramadol for the management of post-operative pain. In December 2019, we submitted a New Drug Application (NDA) for IV Tramadol and received a Complete Response
Letter (CRL) from the FDA in October 2020. In February 2021, we resubmitted the NDA for IV Tramadol. The FDA assigned a Prescription Drug User Fee Act (PDUFA) goal
date of April 12, 2021 for the resubmitted NDA for IV Tramadol. To date, we have not received approval for the sale of our product candidate in any market and, therefore,
have not generated any sales revenue from our product candidate.
Recent Developments
On November 12, 2018, we entered into a Stock Purchase and Merger Agreement (SPMA) with InvaGen Pharmaceuticals, Inc. (InvaGen), and Madison Pharmaceuticals
Inc. (Merger Sub), pursuant to which we agreed to the sale of the Company in a two-stage transaction, the details of which are summarized below. Recently, InvaGen has
communicated to us that it believes two Material Adverse Effects (as defined in the SPMA) have occurred, which raise substantial doubt as to whether or not the merger will be
consummated.
In October 2020, InvaGen communicated to us that it believes a Material Adverse Effect (as defined in the SPMA) has occurred due to the impact of the COVID-19
pandemic on potential commercialization and projected sales of IV Tramadol. Additionally, in connection with the resubmission of our NDA in February 2021 (details of which
are below), InvaGen communicated to us that it believes the proposed label for IV Tramadol would also constitute a Material Adverse Effect on the purported basis that the
proposed label under certain circumstances would make the product commercially unviable, and in addition that the indication that the FDA approves may fail to satisfy a
condition precedent to InvaGen’s obligation to consummate the second stage closing of the SPMA. While we disagree with InvaGen’s assertions, it is possible InvaGen could
attempt to avoid its obligation to consummate the merger, terminate the SPMA, and/or pursue monetary claims against us.
Over the past several months, we have communicated with InvaGen relating to its assertions that Material Adverse Effects have occurred. Nevertheless, InvaGen has
communicated to us its desire to consider all options on the proposed merger, including the option to not consummate the merger. As a result, the possible timing and likelihood
of the completion of the merger are uncertain, and, accordingly, there can be no assurance that such transaction will be completed on the expected terms, anticipated schedule, or
at all.
Background
On June 26, 2017, we completed an initial public offering (IPO) of our common stock, resulting in net proceeds of approximately $34.2 million after deducting underwriting
discounts, and other offering costs.
We used the proceeds from our IPO to initiate our first Phase 3 trial of IV Tramadol in patients with moderate-to-severe pain following bunionectomy, which had its first
patient dosed in September 2017. In May 2018, we announced the study met its primary endpoint and all key secondary endpoints.
In December 2018, we initiated the second Phase 3 trial in patients with moderate-to-severe pain following abdominoplasty upon successful completion of the bunionectomy
study. In June 2019, we announced the study met its primary endpoint and all key secondary endpoints.
In December 2017, we initiated an open-label safety study, which was completed during the second quarter of 2019. The results showed that IV Tramadol is well-tolerated
with a side effect profile consistent with known pharmacology.
In December 2019, we submitted an NDA pursuant to Section 505(b)(2) of the Federal Food, Drug and Cosmetic Act (FDCA). In February 2020, the FDA accepted our
NDA submission and set a PDUFA goal date of October 10, 2020. On October 12, 2020, we announced that we had received a CRL from the FDA regarding our NDA. In
November 2020, we had a Type A Meeting with the FDA to discuss issues raised in the CRL. On February 12, 2021, we resubmitted the NDA to the FDA for IV Tramadol. The
NDA resubmission follows the receipt of official minutes from a Type A meeting with the FDA, which was conducted following receipt of the CRL. The NDA resubmission
included revised language relating to the proposed product label and a report relating to terminal sterilization validation. The FDA assigned a PDUFA goal date of April 12,
2021 for the resubmitted NDA for IV Tramadol.
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On November 12, 2018, we entered into the SPMA with InvaGen pursuant to which InvaGen agreed to purchase, for $35 million, common shares representing 33.3% of
the fully diluted capitalization of the Company (the Stock Purchase Transaction) and subsequently acquire the remaining issued and outstanding capital stock of the Company
for $180 million, subject to certain reductions, in a reverse subsidiary merger transaction (the Merger Transaction). Pursuant to the terms and subject to the conditions set forth
in the SPMA, InvaGen will, at second closing, hold 100% of the issued and outstanding equity interests of the Company. Consummation of the Merger Transaction is
conditioned upon, among other things, FDA approval of IV Tramadol by April 30, 2021, its labeling and scheduling and the absence of any Risk Evaluation and Mitigation
Strategy restrictions in effect with respect to IV Tramadol, as well as the filing and expiration of any waiting period applicable to the acquisition under the Hart-Scott-Rodino
Antitrust Improvements Act of 1976, as amended, which filing both parties completed on March 12, 2021.
The aggregate consideration to be paid by InvaGen under the SPMA is $215 million in cash (a portion of which was already paid in connection with the Stock Purchase
Transaction as described below), subject to certain potential reductions, which InvaGen intends to have sufficient immediately available funds to pay. In addition, we are subject
to certain lock-up restrictions and agreed not to (subject to customary exceptions), during the period commencing at the signing of the SPMA until the Merger Transaction,
issue, buy, sell, or otherwise subject to a security interest, pledge, hypothecation, mortgage or lien, any securities of the Company.
The SPMA was approved by a majority of our stockholders, including a majority of our non-affiliated stockholders, at our special shareholder meeting on February 6,
2019. On February 8, 2019, the Company and InvaGen consummated the Stock Purchase Transaction whereby InvaGen acquired 5,833,333 shares of our common stock at
$6.00 per share for total gross consideration of $35.0 million, representing a 33.3% stake in our capital stock on a fully diluted basis.
As described above, in October 2020, InvaGen communicated to us that it believes a Material Adverse Effect (as defined in the SPMA) has occurred due to the impact of the
COVID-19 pandemic on potential commercialization and projected sales of IV Tramadol, which means it is possible InvaGen could attempt to avoid its obligation to
consummate the second stage closing under the SPMA, terminate the SPMA, and/or pursue monetary claims against us. We disagree with InvaGen’s assertion that a Material
Adverse Effect has occurred and we have advised InvaGen of our position. Additionally, in connection with the resubmission of our NDA in February 2021, InvaGen
communicated to us that it believes the proposed label for IV Tramadol under certain circumstances would constitute a Material Adverse Effect (as defined in the SPMA) on the
purported basis that the proposed label under certain circumstances would make the product commercially unviable, and in addition that the indication that the FDA approves
may fail to satisfy a condition precedent to InvaGen’s obligation to consummate the second stage closing of the SPMA. We have notified InvaGen that we disagree with
InvaGen’s assertions. Nevertheless, InvaGen may seek to avoid its obligation to consummate the second stage closing under the SPMA, terminate the SPMA, and/or pursue
monetary claims against us.
Over the past several months, we communicated with InvaGen relating to its assertions that Material Adverse Effects have occurred. Nevertheless, InvaGen has
communicated to us its desire to consider all options on the proposed merger, including the option to not consummate the merger. This indicates that InvaGen may attempt to
avoid its obligations under the SPMA to consummate the merger, terminate the SPMA, and/or pursue monetary claims against Avenue. As a result, the possible timing and
likelihood of the completion of the merger are uncertain, and, accordingly, there can be no assurance that such transaction will be completed on the expected terms, anticipated
schedule, or at all. During the pendency of any dispute regarding these matters, we may be, and so long as the SPMA remains in place we will be, prohibited from engaging in a
change-of-control transaction, selling our rights to IV Tramadol, or effecting an equity or debt financing, in each case without the prior written consent of InvaGen.
In the event that we do not receive FDA approval for IV Tramadol by April 30, 2021, InvaGen will have the right to terminate the SPMA and will have no further
obligations to consummate the second stage closing under the SPMA. In the event that InvaGen does not exercise its right to terminate the SPMA, certain restrictions relating to
financings and strategic alternatives could exist through October 31, 2021, the time at which we can terminate the SPMA. In the event of termination of the SPMA, InvaGen
will retain certain rights pursuant to the Stockholder’s Agreement between us and InvaGen. These rights exist as long as InvaGen maintains at least 75% of the common shares
acquired in the first stage closing. Certain actions relating to equity issuances and changes to capital stock are restricted without the prior written consent of InvaGen during this
time.
Our net loss for the years ended December 31, 2020 and 2019 was approximately $5.2 million and $25.9 million, respectively. As of December 31, 2020, we had an
accumulated deficit of approximately $73.3 million. Substantially all our net losses resulted from costs incurred in connection with our research and development program of IV
Tramadol and from general and administrative costs associated with our operations.
We expect to continue to incur research and development costs and increased general and administration related costs and incur operating losses for at least the next several
years as we develop and seek regulatory approval for IV Tramadol in the U.S.
We may need to obtain additional capital through the sale of debt or equity financings or other arrangements to fund our operations, research and development activity or
regulatory approval activity; however, there can be no assurance that we will be able to raise needed capital under acceptable terms, if at all. The sale of additional equity may
dilute existing stockholders and newly issued shares may contain senior rights and preferences compared to currently outstanding shares of common stock. Issued debt
securities may contain covenants and limit our ability to pay dividends or make other distributions to stockholders. If we are unable to obtain such additional financing, future
operations would need to be scaled back or discontinued.
We are a majority controlled subsidiary of Fortress. For related party transactions, see Note 4.
Avenue Therapeutics, Inc. was incorporated in Delaware on February 9, 2015. Our executive offices are located at 1140 Avenue of the Americas, Floor 9, New York, NY
10036. Our telephone number is (781) 652-4500, and our email address is info@avenuetx.com.
Critical Accounting Policies and Use of Estimates
Our discussion and analysis of our financial condition and results of operations are based on our financial statements, which have been prepared in accordance with
accounting principles generally accepted in the United States (U.S. GAAP). The preparation of these financial statements requires us to make estimates and judgments that
affect the reported amounts of assets, liabilities, revenues and expenses and the disclosure of contingent assets and liabilities in our financial statements. On an ongoing basis,
we evaluate our estimates and judgments, including those related to accrued expenses and stock-based compensation. We base our estimates on historical experience, known
trends and events and various other factors that are believed to be reasonable 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.
Research and Development
Research and development costs are expensed as incurred. Advance payments for goods and services that will be used in future research and development activities are
expensed when the activity has been performed or when the goods have been received rather than when the payment is made. Upfront and milestone payments due to third
parties that perform research and development services on our behalf will be expensed as services are rendered or when the milestone is achieved. Costs incurred in obtaining
technology licenses are charged to research and development expense if the technology licensed has not reached technological feasibility and has no alternative future use.
45
Research and development costs primarily consist of personnel related expenses, including salaries, benefits, travel, and other related expenses, stock-based compensation,
payments made to third parties for license and milestone costs related to in-licensed products and technology, payments made to third party contract research organizations for
preclinical and clinical studies, investigative sites for clinical trials, consultants, the cost of acquiring and manufacturing clinical trial materials, costs associated with regulatory
filings and patents, laboratory costs and other supplies.
Costs incurred in obtaining technology licenses are charged to research and development expense if the technology licensed has not reached commercial feasibility and has
no alternative future use. The licenses purchased by us require substantial completion of research and development, regulatory and marketing approval efforts in order to reach
commercial feasibility and has no alternative future use. Accordingly, the total purchase price for the licenses acquired are reflected as research and development — licenses
acquired on our Statement of Operations.
Stock-Based Compensation
We expense stock-based compensation to employees, consultants and board members over the requisite service period based on the estimated grant-date fair value of the
awards. Stock-based awards with graded-vesting schedules are recognized on a straight-line basis over the requisite service period for each separately vesting portion of the
award.
The assumptions used in calculating the fair value of stock-based awards represent management’s best estimates and involve inherent uncertainties and the application of
management’s judgment.
Income Taxes
No income tax expense or benefit was recognized in the accompanying financial statements. Our deferred tax assets are comprised primarily of net operating loss
carryforwards. We maintain a full valuation allowance on our deferred tax assets since we have not yet achieved sustained profitable operations. As a result, we have not
recorded any income tax benefit since our inception.
Results of Operations
Comparison of the Years Ended December 31, 2020 and 2019
($ in thousands)
Operating expenses:
Research and development
Research and development - licenses acquired
General and administrative
Loss from operations
Interest income
Net Loss
Research and Development Expenses
For The Years Ended
December 31,
2020
December 31,
2019
Change
$
%
$
$
2,866
-
2,347
(5,213)
(62)
(5,151)
$
$
22,194
1,000
3,071
(26,265)
(357)
(25,908)
$
$
(19,328)
(1,000)
(724)
21,052
(295)
20,757
(87%)
(100%)
(24%)
(80%)
(83%)
(80%)
For the years ended December 31, 2020 and 2019, research and development expenses were $2.9 million and $22.2 million, respectively. The $19.3 million decrease
primarily reflects decreases of $13.4 million in clinical trial costs associated with the completion of the abdominoplasty study in June 2019, $1.3 million in clinical trial costs
associated with the completion of the safety study during the second quarter of 2019 and $3.4 million associated with the submission of our NDA in December 2019. There
were also decreases of $0.6 million in personnel costs, $0.3 million in non-cash stock compensation and $0.2 million in consulting costs.
We expect our research and development activities to continue as we develop our existing product candidate, reflecting costs associated with the following:
•
•
•
•
•
employee-related expenses;
license fees and milestone payments related to in-licensed product and technology;
expenses incurred under agreements with contract research organizations, investigative sites and consultants that conduct our clinical trials;
46
the cost of acquiring and manufacturing clinical trial materials; and
costs associated with non-clinical activities, and regulatory approvals.
Research and Development Expenses – Licenses Acquired
For the years ended December 31, 2020 and 2019, research and development expenses – licenses acquired were $0 and $1.0 million, respectively. The $1.0 million expense
in 2019 represents the milestone payment due to our licensor upon submission of our NDA.
General and Administrative Expenses
General and administrative expenses consist principally of professional fees for legal and consulting services, market research, personnel-related costs, public reporting
company related costs and other general operating expenses not otherwise included in research and development expenses. We expect our general and administrative costs to
continue as we seek potential regulatory approval and potential commercialization of our product candidate.
For the years ended December 31, 2020 and 2019, general and administrative expenses were $2.4 million and $3.1 million, respectively. The $0.7 million decrease primarily
reflects decreases of $0.8 million for non-cash stock compensation, $0.1 million in personnel costs and $0.1 million for commercial marketing preparation costs. These
decreases were partially offset by an increase of $0.3 million for legal costs.
Interest Income
Interest income was $62,000 and $0.4 million for the years ended December 31, 2020 and 2019, respectively. The decrease in interest income was due to the cash used in
operations.
Liquidity and Capital Resources
We have incurred substantial operating losses since our inception and expect to continue to incur significant operating losses for the foreseeable future and may never
become profitable. As of December 31, 2020, we had an accumulated deficit of $73.3 million. We have used the funds from our IPO and from the InvaGen share purchase to
finance our operations and will continue to use the funds primarily for general corporate purposes, which may include financing our growth and developing our product
candidate.
In the event that IV Tramadol is approved by the FDA, this triggers $5.0 million in milestone payments, to which the Company currently does not have sufficient funding. In
the event that IV Tramadol is not approved by the FDA, the Company believes that its cash and cash equivalents should be sufficient to fund its operating expenses through the
end of the third quarter of 2021. We will need to secure additional funds through equity or debt offerings, or other potential sources. We cannot be certain that additional
funding will be available on acceptable terms, or at all. These factors individually and collectively raise substantial doubt about our ability to continue as a going concern.
In addition to the foregoing, based on current assessments, we do not expect any material impact on our development timeline and our liquidity due to the worldwide spread
of the COVID-19 virus (except as may be implicated by the alleged Material Adverse Effect claimed by InvaGen). However, we are continuing to assess the effect on our
operations by monitoring the spread of COVID-19 and the actions implemented to combat the virus throughout the world. We will also continue to assess the alleged Material
Adverse Effect claimed by InvaGen.
Cash Flows for the Years Ended December 31, 2020 and 2019
($ in thousands)
Total cash (used in)/provided by:
Operating activities
Investing activities
Financing activities
Net (decrease) increase in cash
Operating Activities
For The Years Ended
December 31,
2020
2019
$
$
(4,613)
(1,000)
-
(5,613)
$
$
(26,259)
-
32,333
6,074
Net cash used in operating activities was approximately $4.6 million for the year ended December 31, 2020, primarily comprised of our $5.2 million net loss and decrease in
operating assets and liabilities of $0.2 million, partially offset by $0.7 million in share based compensation.
Net cash used in operating activities was approximately $26.3 million for the year ended December 31, 2019, primarily comprised of our $25.9 million net loss and decrease
in operating assets and liabilities of $2.2 million, partially offset by $1.8 million in share based compensation.
47
Investing Activities
Net cash used in investing activities for the year ended December 31, 2020 was $1.0 million and consisted of the milestone payment paid to our licensor pursuant to our
NDA submission.
Net cash provided by investing activities for the year ended December 31, 2019 was $0. We purchased $5.0 million six months certificates of deposits in May 2019 and it
matured in November 2019.
Financing Activities
Net cash provided by financing activities for the year ended December 31, 2019 was $32.3 million which was from the proceeds of our issuance of shares to InvaGen in
connection with the SPMA.
Recently Adopted Accounting Standards
See Note 2 to the financial statements for a full description of recent accounting pronouncements including the respective expected dates of adoption and expected effects on
results of operations and financial condition.
Item 8.
Financial Statements and Supplementary Data.
The information required by this Item is set forth in the financial statements and notes thereto beginning at page F-1 of this Annual Report on Form 10-K.
Item 9.
Changes in and Disagreements with Accountants on Accounting and Financial Disclosure.
Not applicable.
Item 9A.
Controls and Procedures.
Evaluation of Disclosure Controls and Procedures. As of December 31, 2020, management carried out, under the supervision and with the participation of our principal
executive officer and principal financial officer, an evaluation of the effectiveness of the design and operation of our disclosure controls and procedures (as defined in Rules
13a-15(e) and 15d-15(e) under the Exchange Act). Our disclosure controls and procedures are designed to provide reasonable assurance that information we are required to
disclose in the reports that we file or submit under the Exchange Act is recorded, processed, summarized and reported within the time periods specified in applicable rules and
forms. Based upon that evaluation, our principal executive officer and principal financial officer concluded that, as of December 31, 2020, our disclosure controls and
procedures were effective.
Management’s Report on Internal Control over Financial Reporting. Our management is responsible for establishing and maintaining adequate internal control over financial
reporting (as defined in Rule 13a-15(f) or Rule 15d-15(f) under the Exchange Act). Our management assessed the effectiveness of our internal control over financial reporting
as of December 31, 2020. In making this assessment, our management used the criteria set forth by the Committee of Sponsoring Organizations of the Treadway Commission,
known as COSO, in Internal Control-Integrated Framework (2013). Our management has concluded that, as of December 31, 2020, our internal control over financial reporting
was effective based on these criteria.
Changes in Internal Control Over Financial Reporting. There were no changes in our internal control over financial reporting during the most recent fiscal quarter that have
materially affected, or are reasonably likely to materially affect, our internal control over financial reporting.
Limitations on the Effectiveness of Controls. Our management, including our principal executive officer and principal financial officer, does not expect that our disclosure
controls and procedures or our internal control over financial reporting will prevent all errors and all fraud. A control system, no matter how well conceived and operated, can
provide only reasonable, not absolute, assurance that the objectives of the control system are met. Further, the design of a control system must reflect the fact that there are
resource constraints, and the benefits of controls must be considered relative to their costs. Because of the inherent limitations in all control systems, no evaluation of controls
can provide absolute assurance that all control issues and instances of fraud, if any, within our company have been detected.
Item 9B.
Other Information
None.
48
PART III
Item 10.
Directors, Executive Officers and Corporate Governance
OUR DIRECTORS
The following biographies set forth the names of our current directors and director nominees, their ages, the year in which they first became directors, their positions
with us, their principal occupations and employers, any other directorships held by them during the past five years in companies that are subject to the reporting requirements of
the Securities Exchange Act of 1934 (the “Exchange Act”), or any company registered as an investment company under the Investment Company Act of 1940, as well as
additional information, all of which we believe sets forth each director nominee’s qualifications to serve on the Board. There is no family relationship between and among any
of our executive officers or directors. On November 12, 2018, we entered into a Stock Purchase and Merger Agreement (the “SPMA”) with InvaGen and Madison
Pharmaceuticals Inc., pursuant to which InvaGen purchased common stock representing 33.3% of the Company for $35 million. In connection with the execution and delivery
of the SPMA, and as described above, we entered into a Stockholders Agreement pursuant to which, among other things, InvaGen obtained the right to nominate three directors
to the Company’s seven member Board. In February 2019, InvaGen exercised its right to nominate a director to the Board with Dr. Gogtay who’s bio is described below. In
August 2019, InvaGen exercised its right to nominate a second director, Ms. Ingram whose bio is described below. Additionally, InvaGen has the right to appoint an
independent director to the Company’s Board. InvaGen previously appointed Thomas G. Moore as an independent director; however, effective December 31, 2020, Mr. Moore
resigned from his position as a member of the Company’s Board and Audit and Compensation Committees. After giving effect to Mr. Moore’s resignation, the Company’s
Audit Committee no longer consists of three independent members as required by Nasdaq Listing Rule 5605(c)(2)(A). Except as described herein, there are no arrangements or
understandings between any of our executive officers or directors and any other person pursuant to which any of them are elected as an officer or director.
Name
Age
Position
Lindsay A. Rosenwald, M.D.
Lucy Lu, M.D.
Neil Herskowitz
Jay Kranzler, M.D., PhD
Garrett Ingram
Jaideep Gogtay, M.D.
65
46
64
63
55
54
Executive Chairman of the Board of Directors
President, Chief Executive Officer, and Director
Director
Director
Director
Director
Lindsay A. Rosenwald, M.D. — Executive Chairman of the Board of Directors
Director
Since
2015
2015
2015
2017
2019
2019
Dr. Rosenwald, 65, has served as our Executive Chairman of the Board of Directors since inception. Dr. Rosenwald also serves as Chairman, President and Chief Executive
Officer of Fortress Biotech, Inc., a director of Mustang Bio, Inc., and a director of Checkpoint Therapeutics, Inc. Since November 2008, Dr. Rosenwald has served as Co-
Portfolio Manager and Partner of Opus Point Partners Management, LLC, an asset management firm in the life sciences industry, which he joined in 2009. Prior to that, from
1991 to 2008, he served as the Chairman of Paramount BioCapital, Inc. The Board believes that because Dr. Rosenwald, over the last 24 years, has acted as a biotechnology
entrepreneur and has been involved in the founding and recapitalization of numerous public and private biotechnology and life sciences companies, he is exceptionally qualified
to serve on our Board as Executive Chairman. Dr. Rosenwald received his B.S. in finance from Pennsylvania State University and his M.D. from Temple University School of
Medicine.
Lucy Lu, M.D. — President, Chief Executive Officer, and Director
Dr. Lu, 46, has been our President and Chief Executive Officer since inception. From February 2012 to June 2017, Dr. Lu was the Executive Vice President and Chief Financial
Officer of Fortress Biotech, Inc. Prior to working in the biotech industry, Dr. Lu had 10 years of experience in healthcare-related equity research and investment banking.
Additionally, Dr. Lu was a member of the Board of Directors of Veru, Inc. from 2016 – 2018, and has served as a member of the Board of Directors of Iventia Healthcare
Limited since 2018. From February 2007 through January 2012, Dr. Lu was a senior biotechnology equity analyst with Citigroup Investment Research. From 2004 until joining
Citigroup, she was with First Albany Capital, serving as Vice President from April 2004 until becoming a Principal of the firm in February 2006. Dr. Lu holds an M.D. degree
from the New York University School of Medicine and an M.B.A. from the Leonard N. Stern School of Business at New York University. Dr. Lu obtained a B.A. from the
University of Tennessee’s College of Arts and Science. We believe that Dr. Lu is qualified to serve on our Board due to her leadership and management experience, her
understanding of biopharmaceutical companies, and her extensive knowledge of our business and industry.
Neil Herskowitz
Mr. Herskowitz, 64, joined our Board of Directors in August 2015 and has served as the Chairman of our Audit Committee since September 2016. Mr. Herskowitz has served
as the managing member of the ReGen Group of companies, located in New York, since 1998, which include ReGen Capital Investments LLC and Riverside Claims
Investments LLC. He has also served as the President of its affiliate, Riverside Claims LLC, since June 2004. Additionally, Mr. Herskowitz served as a Board member of
National Holdings, Inc. from 2016 – 2019, and has served as a Board member of Mustang Bio, Inc. and Checkpoint Therapeutics, Inc. since 2015. Mr. Herskowitz received a
B.B.A. in Finance from Bernard M. Baruch College in 1978. The Board believes, based on Mr. Herskowitz’s over 16 years of Audit Committee and Board experience in the
biotech industry, that Mr. Herskowitz is uniquely qualified to serve as a member of our Board and as the Chairman of our Audit Committee.
49
Jay Kranzler, M.D., PhD
Dr. Kranzler, 63, joined our Board of Directors in February 2017. Dr. Kranzler has been a Founder, Chief Executive Officer (“CEO”), Board Member, and Advisor to leading
life science companies for over 30 years. He is currently acting as Executive Chairman of Perception Neuroscience, a company that he co-founded, a regenerative medicine
company, and is a Board Member of Pastorus and ImmunoBrain Checkpoint, all companies focused on developing therapeutics for psychiatric or neurological disorders. Dr.
Kranzler started his career at McKinsey & Company where he helped establish the Firm’s pharmaceutical practice. He served as CEO of Cytel Corporation, a company focused
on the development of immunomodulatory drugs. Following Cytel, Dr. Kranzler became the CEO of Cypress Bioscience, where he was credited for the development of
Savella™ (milnacipran) for the treatment of fibromyalgia. Dr. Kranzler was also Vice President, Head of Worldwide External R&D Innovation and Strategic Investments at
Pfizer. During his career, Dr. Kranzler has developed drugs, medical devices, as well as diagnostics, and is the inventor on over 30 patents. Dr. Kranzler graduated from Yale
University School of Medicine with MD and PhD degrees with a focus in psychopharmacology. We believe that Dr. Kranzler is qualified to serve on our Board due to his
management experience, his service as an executive of biopharmaceutical companies and his knowledge of our business and industry.
Jaideep Gogtay, M.D.
Dr. Gogtay, 54, joined our Board of Directors in February 2019. Since 1994, he has been working with Cipla Ltd., a leading global pharmaceutical company, and he currently
serves as their Global Chief Medical Officer. He has closely been involved in the development and introduction of several drugs in various therapeutic fields. He was involved
in setting up the Chest Research Foundation. This Foundation is now an independent research center dedicated to conducting research in the field of respiratory medicine. He
has participated and spoken at several national and international forums and has been actively involved in educational activities. Dr. Gogtay completed his medical graduation
(M.B., B.S) from Grant Medical College and SirJJ Group of Hospitals in Mumbai. He then obtained his M.D, in Pharmacology from Seth GS Medical College and KEM
Hospital. Based on Dr. Gogtay’s pharmaceutical industry experience, the Board believes that Dr. Gogtay has the appropriate set of skills to serve as a member of the Board.
Garrett Ingram
Ms. Ingram, 55, has served as a member of our Board of Directors since August 2019. She currently serves as the President and Chief Executive Officer at Cipla Therapeutics,
Inc. Prior to her new role at Cipla Therapeutics, Inc., Ms. Ingram served as Chief Marketing Officer at MannKind Corporation, based in California. In addition, she has served
in roles as Senior Vice President, Managed Markets at Dexcom and Vice President, Head of Market Access at Sanofi, where she had responsibility across four of the U.S.
Business Units: Diabetes & Cardiovascular, General Medicines, Sanofi Genzyme Specialty Care, and Sanofi Pasteur from 2014 to 2016. Prior to joining Sanofi, she held the
position of Vice President of Market Access Strategy at Bristol Myers Squibb, where she led the access, reimbursement, patient affordability and emerging customer strategy
teams across the portfolio of diabetes, RA, cardiovascular, oncology, immunology, neuroscience and pipeline assets. Ms. Ingram holds a Bachelor of Science degree from East
Carolina University, a Master’s Degree in public health and community education from the University of South Carolina and has completed multiple post graduate studies at
Wharton School of Business.
During 2020, our Board held six meetings and took one action by unanimous written consent.
Audit Committee
CORPORATE GOVERNANCE
The Audit Committee currently consists of Neil Herskowitz and Jay Kranzler, M.D., PhD. Mr. Herskowitz serves as the Chairperson of the Audit Committee.
The Audit Committee was formed on May 15, 2017 and held four meetings during the fiscal year ended December 31, 2020 and took action by one unanimous written
consent. The duties and responsibilities of the Audit Committee are set forth in the Charter of the Audit Committee which was recently reviewed by our Audit Committee. Our
Audit Committee determined that no revisions needed to be made to the charter at this time. A copy of the Charter of the Audit Committee is available on our website, located
at www.avenuetx.com. Among other matters, the duties and responsibilities of the Audit Committee include reviewing and monitoring our financial statements and internal
accounting procedures, the selection of our independent registered public accounting firm and consulting with and reviewing the services provided by our independent
registered public accounting firm. Our Audit Committee has sole discretion over the retention, compensation, evaluation and oversight of our independent registered public
accounting firm.
50
The SEC and Nasdaq have established rules and regulations regarding the composition of audit committees and the qualifications of audit committee members. Our
Board of Directors has examined the composition of our Audit Committee and the qualifications of our Audit Committee members in light of the current rules and regulations
governing audit committees. Based upon this examination, our Board of Directors has determined that each member of our Audit Committee is independent and is otherwise
qualified to be a member of our Audit Committee in accordance with the rules of the SEC and Nasdaq.
Additionally, the SEC requires that at least one member of the Audit Committee have a “heightened” level of financial and accounting sophistication. Such a person is
known as the “audit committee financial expert” under the SEC’s rules. Our Board has determined that Neil Herskowitz is an “audit committee financial expert,” as the SEC
defines that term, and is an independent member of our Board of Directors and our Audit Committee.
Effective December 31, 2020, our audit committee is no longer in compliance with Nasdaq Listing Rule 5605(c)(2)(A). On January 6, 2021, we received a letter from
Nasdaq noting us of this non-compliance. The letter also acknowledged that the Listing Rules provide for a cure period in order for us to regain compliance until the earlier of
the Company’s next annual meeting of stockholders or December 31, 2021 (or, by June 29, 2021, if such meeting is held before June 29, 2021).
Compensation Committee
The Compensation Committee was formed on May 15, 2017. The Compensation Committee did not hold any meetings during the fiscal year ended December 31,
2020 but took action by three unanimous written consents. The Compensation Committee currently consists of Jay Kranzler, M.D. PhD, with Dr. Kranzler serving as Chairman.
The duties and responsibilities of the Compensation Committee are set forth in the Charter of the Compensation Committee. A copy of the Charter of the Compensation
Committee is available on our website, located at www.avenuetx.com. As discussed in its charter, among other things, the duties and responsibilities of the Compensation
Committee include annually reviewing and approving corporate goals and objectives relevant to the compensation of our Chief Executive Officer, reviewing and approving, or
making recommendations to our Board of Directors with respect to, the compensation of our Chief Executive Officer and our other executive officers, overseeing an evaluation
of our senior executives, and overseeing and administering our cash and equity incentive plans. The Compensation Committee applies discretion in the determination of
individual executive compensation packages to ensure compliance with the Company’s compensation philosophy. The Chief Executive Officer makes recommendations to the
Compensation Committee with respect to the compensation packages for officers other than herself. The Compensation Committee may delegate its authority to grant awards to
certain employees, and within specified parameters under the Avenue Therapeutics, Inc. 2015 Incentive Plan (the “2015 Incentive Plan”), to a special committee consisting of
one or more directors who may but need not be officers of the Company. As of February 28, 2021, however, the Compensation Committee had not delegated any such
authority. The Board may engage a compensation consultant to conduct a review of its executive compensation programs in 2021. The Committee did not engage a
compensation consultant in 2020.
Nasdaq has established rules and regulations regarding the composition of compensation committees and the qualifications of compensation committee members. As a
controlled company, we are not required to have a compensation committee composed entirely of independent directors. However, our Board of Directors has examined the
composition of our Compensation Committee and the qualifications of our Compensation Committee members in light of the current rules and regulations governing
compensation committees. Based upon this examination, our Board of Directors has determined that each member of our Compensation Committee is independent and is
otherwise qualified to be a member of our Compensation Committee in accordance with such rules.
Nominating Process
We do not currently have a nominating committee or any other committee serving a similar function. Director nominations are approved by a vote of a majority of our
independent directors as required under the Nasdaq rules and regulations. Although we do not have a written charter in place to select director nominees, our Board of Directors
has adopted resolutions regarding the director nomination process. We believe that the current process in place functions effectively to select director nominees who will be
valuable members of our Board of Directors.
We identify potential nominees to serve as directors through a variety of business contacts, including current executive officers, directors, community leaders and
stockholders. We may, to the extent they deem appropriate, retain a professional search firm and other advisors to identify potential nominees.
We will also consider candidates recommended by stockholders for nomination to our Board. A stockholder who wishes to recommend a candidate for nomination to
our Board must submit such recommendation to our Corporate Secretary, Joseph Vazzano, at our offices located at 1140 Avenue of the Americas, Floor 9, New York, New
York 10036. Any recommendation must be received not less than 50 calendar days nor more than 90 calendar days before the anniversary date of the previous year’s annual
meeting. All stockholder recommendations of candidates for nomination for election to our Board must be in writing and must set forth the following: (i) the candidate’s name,
age, business address, and other contact information, (ii) the number of shares of common stock beneficially owned by the candidate, (iii) a complete description of the
candidate’s qualifications, experience, background and affiliations, as would be required to be disclosed in the proxy statement pursuant to Schedule 14A under the Exchange
Act, (iv) a sworn or certified statement by the candidate in which he or she consents to being named in the proxy statement as a nominee and to serve as director if elected, and
(v) the name and address of the stockholder(s) of record making such a recommendation.
51
We believe that our Board as a whole should encompass a range of talent, skill, and expertise enabling it to provide sound guidance with respect to our operations and
interests. Our independent directors evaluate all candidates to our Board by reviewing their biographical information and qualifications. If the independent directors determine
that a candidate is qualified to serve on our Board, such candidate is interviewed by at least one of the independent directors and our Chief Executive Officer. Other members of
the Board also have an opportunity to interview qualified candidates. The independent directors then determine, based on the background information and the information
obtained in the interviews, whether to recommend to the Board that the candidate be nominated for approval by the stockholders to fill a directorship. With respect to an
incumbent director whom the independent directors are considering as a potential nominee for re-election, the independent directors review and consider the incumbent
director’s service during his or her term, including the number of meetings attended, level of participation, and overall contribution to the Board. The manner in which the
independent directors evaluate a potential nominee will not differ based on whether the candidate is recommended by our directors or stockholders.
We consider the following qualifications, among others, when making a determination as to whether a person should be nominated to our Board: the independence of
the director nominee; the nominee’s character and integrity; financial literacy; level of education and business experience, including experience relating to biopharmaceutical
companies; whether the nominee has sufficient time to devote to our Board; and the nominee’s commitment to represent the long-term interests of our stockholders. We review
candidates in the context of the current composition of the Board and the evolving needs of our business. We believe that each of the current members of our Board (who are
also our director nominees) has the requisite business, biopharmaceutical, financial or managerial experience to serve as a member of the Board, as described above in their
biographies under the heading “Our Board of Directors.” We also believe that each of the current members of our Board has other key attributes that are important to an
effective board, including integrity, high ethical standards, sound judgment, analytical skills, and the commitment to devote significant time and energy to service on the Board
and its committees.
We do not have a formal policy in place with regard to diversity in considering candidates for our Board, but the Board strives to nominate candidates with a variety of
complementary skills so that, as a group, the Board will possess the appropriate talent, skills and expertise to oversee our business.
52
OUR EXECUTIVE OFFICERS
Executive Officers
Our current executive officers are as follows:
Name
Lucy Lu, M.D.
Joseph Vazzano
Age
Position
46
37
President, Chief Executive Officer and Director
Chief Financial Officer and Principal Financial Officer
No executive officer is related by blood, marriage or adoption to any other director or executive officer. To read more about Dr. Lu, please see her description under
“OUR DIRECTORS”.
Joseph Vazzano — Chief Financial Officer and Principal Financial Officer
Mr. Vazzano joined the Company in August 2017 as our Vice President of Finance and Corporate Controller. Effective February 8, 2019, the Board appointed Mr.
Vazzano as the Company’s Chief Financial Officer. Prior to joining Avenue, Mr. Vazzano served as Assistant Corporate Controller at Intercept Pharmaceuticals, Inc., a
publicly-traded biotechnology company, which he joined in 2016. While at Intercept, Mr. Vazzano helped grow the finance and accounting department during Intercept’s
transition from a development-stage company to a fully integrated commercial organization. Prior to joining Intercept, Mr. Vazzano served as the Assistant Controller at Pernix
Therapeutics, a publicly-traded specialty pharmaceutical company, where he successfully built an accounting and finance team after the closure of the South Carolina office
location. From 2010 to 2015, he held various roles of increasing responsibility in finance and accounting at NPS Pharmaceuticals, a publicly-traded biotechnology company
acquired by Shire Pharmaceuticals in 2015. He began his professional career with KPMG, LLP, where he served as a senior auditor. Mr. Vazzano has a Bachelor of Science
degree in Accounting from Lehigh University and is a Certified Public Accountant in the State of New Jersey.
Code of Business Conduct and Ethics
We have adopted a Code of Ethics, or the Code, which applies to all of our directors and employees, including our principal executive officer and principal financial
officer. The Code includes guidelines dealing with the ethical handling of conflicts of interest, compliance with federal and state laws, financial reporting, and our proprietary
information. The Code also contains procedures for dealing with and reporting violations of the Code. We have posted our Code on our website, located at www.avenuetx.com.
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 the shares of our common stock 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% stockholders 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 stock ownership
by our directors, executive officers and 10% stockholders. Based solely on a review of copies of the 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, 2020, all Section 16(a) filing requirements applicable to our
directors, executive officers and 10% stockholders were completed in a timely manner except for one Form 4 filing for Neil Herskowitz.
Item 11.
Executive Compensation
As an emerging growth company, we are eligible to take advantage of certain exemptions from various reporting requirements that are applicable to other public
companies that are not emerging growth companies. These include, but are not limited to, reduced disclosure obligations regarding executive compensation in our proxy
statements, including the requirement to include a Compensation Discussion and Analysis, as well as an exemption from the requirement to hold a non-binding advisory vote on
executive compensation. We have elected to comply with the scaled disclosure requirements applicable to emerging growth companies. Our only executive officers, who we
refer to as our “named executive officers” or our “NEOs” are Lucy Lu, M.D., our Chief Executive Officer, and Joseph Vazzano, our Chief Financial Officer.
53
Summary Compensation Table
The following table sets forth information concerning compensation paid by us to our NEOs for their services rendered to us in all capacities during the years ended
December 31, 2020 and 2019:
Year
2020
2019
2020
2019
Salary ($)
431,627
419,055
206,000
198,113
Bonus ($)
Stock
Awards ($)
-
-
-
-
-
-
-
-
Non-equity
Incentive Plan
Compensation
($)
-
209,528
-
50,000
All Other
Compensation
($) (1)
11,400
11,200
8,890
10,666
Total ($)
442,827
639,783
214,890
258,779
Name and Principal Position
Lucy Lu
Chief Executive Officer
Joseph Vazzano
Chief Financial Officer
(1) Reflects 401(k) company contributions.
Narrative to Summary Compensation Table
Employment Agreement with Dr. Lu
On June 10, 2015, we entered into an Employment Agreement with Lucy Lu, M.D. to serve as our Interim President and Chief Executive Officer upon the completion of
our initial public offering at an annualized salary of $395,000. Dr. Lu’s Employment Agreement became effective on June 26, 2017, and she became our President and Chief
Executive Officer. Dr. Lu’s salary for 2020 and 2019 was $431,627 and $419,055, respectively. Under the terms of Dr. Lu’s Employment Agreement, Dr. Lu’s base salary may
be reduced only in connection with a company-wide decrease in executive compensation. Dr. Lu is also eligible to receive an annual discretionary bonus, not to exceed 50% of
her base salary, if certain financial, clinical development, and/or business milestones are met in the discretion of Board of Directors. Such milestones are established annually by
mutual agreement between Dr. Lu and the Board of Directors.
Dr. Lu’s employment with us is at will and may be terminated by us at any time and for any reason. On November 12, 2018, we amended our Employment Agreement with
Dr. Lu. Under the terms of the Amended Employment Agreement, if we terminate Dr. Lu’s employment without cause (as defined in the Employment Agreement) or if Dr. Lu
resigns her employment for good reason (as defined in the Employment Agreement), Dr. Lu will be entitled to receive the following:
•
•
•
cash severance equal to her annual salary, paid over a period of twelve months;
payment of the premiums to continue health care coverage for Dr. Lu and her eligible dependents under COBRA for up to twelve months;
a pro rata share of her annual bonus, to be paid when and if such bonus would have been paid under the Employment Agreement; and
•
immediate accelerated vesting of all of her unvested equity awards, except for equity awards granted in 2019 pursuant to the SPMA.
If Dr. Lu’s employment is terminated due to her death or complete disability (as defined in the Employment Agreement), she shall be entitled to receive the following:
•
•
•
cash severance equal to ninety days’ annual salary, paid over a period of ninety days;
a pro rata share of her annual bonus, to be paid when and if such bonus would have been paid under the Employment Agreement; and
immediate accelerated vesting of all of her unvested equity awards, except for equity awards granted in 2019 pursuant to the SPMA.
Employment Agreement with Mr. Vazzano
Mr. Vazzano’s salary for 2020 and 2019 was $206,000 and $200,000, respectively. As described in our letter agreement with Mr. Vazzano, Mr. Vazzano is eligible to
receive an annual bonus of up to 25% of his base salary, as determined by the Company in its discretion based upon factors including corporate and individual performance. If
Mr. Vazzano’s employment is terminated by the Company without “cause” or by Mr. Vazzano following the relocation of his primary place of work to a different location that
is greater than 40 miles from his home in Morristown, New Jersey, then he will be entitled to receive severance pay equal to six months’ salary, payable over a six-month
period. Mr. Vazzano is eligible to participate in the Company’s employee benefit plans and programs, subject to the terms and conditions thereof.
54
Annual Incentive Bonus
In 2020, Dr. Lu was eligible to earn an annual bonus equal of up to 50% of her base salary plus additional compensation related to certain stretch goals. In 2020, Mr.
Vazzano was eligible to earn an annual bonus equal of up to 25% of his base salary plus additional compensation related to certain stretch goals. Dr. Lu’s and Mr. Vazzano’s
bonus opportunities for 2020 were based upon the Company’s performance against pre-established corporate goals and objectives, which included a combination of clinical and
regulatory goals related to our product as well as other corporate goals including stretch goals and were also based on the second stage closing with InvaGen.
The corporate performance goals and objectives used to determine Dr. Lu’s and Mr. Vazzano’s bonuses for 2020 were as follows:
•
•
•
Various clinical and regulatory goals — 95% maximum potential weighting (0% achieved);
Various goals related to corporate development — 5% maximum potential weighting (0% achieved).
Various stretch goals related to corporate development — 10% maximum potential weighting (0% achieved).
These goals and objectives were not achieved and accordingly Dr. Lu and Mr. Vazzano were paid 0% of their target bonus amount. The actual amounts paid to the
executives pursuant to their annual cash incentive awards and bonuses are reported in the “Summary Compensation Table” as “Non-equity Incentive Compensation”.
Equity Awards
The Compensation Committee has granted each of Dr. Lu and Mr. Vazzano the following equity awards under our 2015 Incentive Plan. In 2020, Dr. Lu received an
award of 110,959 restricted stock units (“RSUs”), and Mr. Vazzano received an award of 22,727 RSUs, each of which vests as described in Footnote 7 to the Outstanding
Equity Awards Table below. Under United States Generally Accepted Accounting Principles (U.S. GAAP), stock-based compensation for these milestone awards will be
measured and recorded if and when it is probable that the milestone will be achieved, and these awards will be reported in the Summary Compensation Table at such time.
Outstanding Equity Awards at 2020 Fiscal Year End
Name
Lucy Lu
Lucy Lu
Lucy Lu
Lucy Lu
Lucy Lu
Joseph Vazzano
Joseph Vazzano
Joseph Vazzano
Joseph Vazzano
Grant Date
6/10/2015
8/8/2017
8/7/2018
6/3/2019
2/12/2020
8/8/2017
8/7/2018
6/3/2019
2/12/2020
Stock Awards
Number of
Shares or Units of
Stock that Have
Not Vested
Market Value of
Shares or Units of
Stock that Have Not
Vested ($) (1)
-
215,000
250,000
-
-
(3)
(5)
7,500
15,000
(4)
(6)
-
1,279,250
1,487,500
-
-
44,625
89,250
Equity Incentive Plan
Awards: Number of
Unearned Shares, Units
or Other Rights that
Have Not Vested
50,000
(2)
135,617
110,959
(7)
(7)
27,778
22,727
(7)
(7)
Equity Incentive Plan
Awards: Market Value
or Payout Value of
Unearned Shares,
Units or Other Rights
that Have Not Vested
($) (1)
297,500
806,921
660,206
165,279
135,226
(1) The market value of unvested restricted stock awards/units was calculated by multiplying the number of units by $5.95, the closing sales price of our common stock on
December 31, 2020.
(2) Also Represents 166,667 restricted stock awards vesting upon achievement of goals and objectives relating to the development of IV Tramadol of which 50,000 remained
unvested as of December 31, 2020.
(3) Represents restricted stock units vesting as follows: 75% on the earlier of Dr. Lu’s request for the shares or August 8, 2021 and 25% on August 8, 2021.
55
(4) Represents restricted stock units vesting annually in equal installments on August 8, 2018 – 2021.
(5) Represents restricted stock units vesting as follows: 50% on the earlier of Dr. Lu’s request for the shares or August 7, 2021, 25% on August 7, 2021, and 25% on August 7,
2022.
(6) Represents restricted stock units vesting annually in equal installments on August 7, 2019 – 2022.
(7) Represents restricted stock units vesting upon the second stage closing with InvaGen, as defined in the SPMA, of which all remained unvested as of December 31, 2020.
Potential Payments upon Termination or Change in Control
As detailed above, we have an amended employment agreement with Dr. Lu that provides certain compensation and benefits in the event of a termination of her employment or
change in control under certain conditions. In addition, Dr. Lu’s amended employment agreement and our equity plan provide certain equity award benefits in connection with a
termination or change in control.
Dr. Lu’s Restricted Shares
•
•
If we terminate Dr. Lu’s employment without “cause” or Dr. Lu resigns for “good reason,” at any time, then all of her unvested equity awards, except for equity
awards granted in 2019 and 2020 pursuant to the SPMA will become fully vested.
If Dr. Lu’s employment terminates as a result of her death or “disability,” all of her unvested equity awards, except for equity awards granted in 2019 and 2020
pursuant to the SPMA will become fully vested.
Other Awards Granted under the 2015 Incentive Plan
•
•
Unless otherwise provided in an award certificate or any special plan document governing an award, upon the occurrence of a change in control of our
company, (i) all outstanding options, SARs and other awards in the nature of rights that may be exercised will become fully exercisable, (ii) all time-based
vesting restrictions on outstanding awards will lapse; and (iii) the payout opportunities attainable under all outstanding performance-based awards will vest
based on target performance and the awards will pay out on a pro rata basis, based on the time elapsed prior to the change in control.
The Compensation Committee may, in its discretion, accelerate the vesting and/or payment of any awards for any reason, subject to certain limitations under
Section 409A of the Internal Revenue Code. The Compensation Committee may discriminate among participants or among awards in exercising such
discretion.
56
DIRECTOR COMPENSATION
Director Compensation Program
Our directors set compensation for non-employee directors on an annual basis in accordance with our 2015 Incentive Plan. Our non-employee directors currently
receive the following compensation for service to the Board:
•
•
•
•
•
•
Cash Compensation:
$50,000 annual retainer;
$10,000 additional annual retainer for the Executive Chairman of the Board; and
$10,000 additional annual retainer for the Audit Committee Chair.
Equity Compensation:
Initial Equity Grant: 50,000 shares of restricted stock, which shares shall vest and become non-forfeitable in equal annual installments over three years,
beginning on the third (3rd) anniversary of the grant date, subject to the director’s continued service on the board of directors on such date. This grant was
waived for the InvaGen appointed directors.
Re-Election Equity Grant: The greater of (i) a number of shares of restricted stock having a fair market value on the grant date of $50,000, or (ii) 10,000 shares
of restricted stock, which shares shall vest and become non-forfeitable on the third (3rd) anniversary of the grant date, subject to the director’s continued
service on the board of directors on such date. This grant was waived for the InvaGen appointed directors and Dr. Rosenwald.
In 2019 and 2020, each of Mr. Herskowitz and Dr. Kranzler was granted 10,000 restricted stock awards each year which vest upon the second stage closing
with InvaGen, as defined in the SPMA. Under U.S. GAAP, stock-based compensation for these milestone awards will be measured and recorded if and when it
is probable that the milestone will be achieved, and these awards will be reported in the Director Compensation Table at such time.
In addition, each non-employee director receives reimbursement for reasonable travel expenses incurred in attending meetings of our board of directors and meetings
of committees of our board of directors.
Director Compensation Table
The following table sets forth the cash and other compensation we paid to the non-employee members of our Board of Directors for all services in all capacities during
2020.
Name
Lindsay A. Rosenwald
Neil Herskowitz
Jay Kranzler
Jaideep Gogtay
Fees Earned
or Paid in
Cash (1)
Stock Awards
($)
-
60,000
50,000
-
-
-
-
-
Total ($)
-
60,000
50,000
-
Thomas Moore (2)
Garrett Ingram
50,000
-
-
-
50,000
-
(1) Represents cash retainer for serving on our Board and committees of the Board.
(2) Resigned from the Board on December 31, 2020.
(3) As of December 31, 2020, the aggregate number of restricted stock and restricted stock units held by each non-employee director was as follows: Dr. Rosenwald, 21,330
restricted stock awards; Mr. Herskowitz, 67,997 restricted stock awards; Dr. Kranzler, 67,997 restricted stock awards; and 0 for each of Dr. Gogtay, Mr. Moore, and Ms.
Ingram.
57
Item 12.
Security Ownership of Certain Beneficial Owners and Management and Related Stockholder Matters
The following table shows information, as of December 31, 2020, concerning the beneficial ownership of our common stock by:
•
•
•
•
each person we know to be the beneficial owner of more than 5% of our common stock;
each of our current directors;
each of our NEOs shown in our Summary Compensation Table; and
all current directors and NEOs as a group.
As of December 31, 2020, there were 16,747,803 shares of our common stock outstanding. Beneficial ownership is determined according to the rules of the SEC and
generally means that a person has beneficial ownership of a security if he, she or it possesses sole or shared voting or investment power of that security, including options and
warrants that are currently exercisable or exercisable within 60 days of December 31, 2020. Shares of our common stock issuable pursuant to stock options are deemed
outstanding for computing the percentage of the person holding such options and the percentage of any group of which the person is a member but are not deemed outstanding
for computing the percentage of any other person. Except as indicated by the footnotes below, we believe, based on the information furnished to us, that the persons named in
the table below have sole voting and investment power with respect to all shares of common stock shown that they beneficially own, subject to community property laws where
applicable. The information does not necessarily indicate beneficial ownership for any other purpose, including for purposes of Section 13(d) and 13(g) of the Securities Act.
Unless otherwise indicated, the address for each director and executive officer listed is: c/o Avenue Therapeutics, Inc., 1140 Avenue of the Americas, Floor 9, New
York, NY 10036.
Name of Beneficial Owner
Lucy Lu
Joseph Vazzano
Lindsay A. Rosenwald
Neil Herskowitz
Jay Kranzler
Jaideep Gogtay
Garrett Ingram
All Executive officers and directors as a group (7 persons)
5% or Greater Stockholders:
Vanguard Index Funds
Vanguard Group, Inc.
Fortress Biotech, Inc.
InvaGen Pharmaceuticals, Inc.
*Less than 1%
Number of Shares
Beneficially Owned
337,333
34,912
251,330
132,224
84,663
-
16,000
689,795
838,827
939,706
3,590,096
5,833,333
(1)
(2)
(3)
(4)
(5)
(6)
Percentage of Shares
Beneficially Owned
2%
*
2%
*
*
*
*
4%
5%
6%
21%
35%
(1) Dr. Rosenwald has warrants convertible into 166,667 shares of our common stock. The warrants were issued by Fortress and are convertible into shares of our common
stock that are owned by Fortress. These do not represent equity compensation by us to Dr. Rosenwald.
(2) The total calculation for all executive officers and directors as a group does not include Dr. Rosenwald’s warrants, which have not yet been exercised.
(3) Based solely upon a Schedule 13G filed on February 8, 2021 by Vanguard Index Funds (“Vanguard Index”). Vanguard Index beneficially owns 838,827 shares of our
common stock and has sole dispositive power of 838,827 shares of our common stock. The address of Vanguard Index is 100 Vanguard Boulevard, Malvern, PA 19355.
(4) Based solely upon a Schedule 13G filed on February 10, 2021 by Vanguard Group Inc. (“Vanguard Group”) and its subsidiaries Vanguard Asset Management, Limited,
Vanguard Fiduciary Trust Company, Vanguard Global Advisors, LLC, Vanguard Group (Ireland) Limited, Vanguard Investments Australia Ltd. Vanguard Investments
Canada Inc., Vanguard Investments Hong Kong Limited, and Vanguard Investments UK, Limited. Consists of 14,919 shares of common stock in which Vanguard Group has
shared voting power, 921,125 shares of common stock in which Vanguard Group has sole dispositive power, and 18,581 shares of common stock in which Vanguard Group
has shares dispositive power. The address of Vanguard Group is 100 Vanguard Boulevard, Malvern, PA 19355
(5) Excludes 250,000 Class A Preferred shares owned by Fortress. See “Relationships and Related Transactions” for a description of Fortress’ ownership.
58
(6) Pursuant to Rule 13d-3 under the Exchange Act, InvaGen Pharmaceuticals, Inc. may be deemed to beneficially own an additional 4,173,429 shares of our common stock
which, combined with the 5,833,333 shares of our common stock indicated in the table above, gives InvaGen Pharmaceuticals, Inc. sole dispositive power of 10,006,762
shares of our common stock. The address of InvaGen is 7 Oser Ave Site b, Hauppauge, NY 11788.
Item 13.
Certain Relationships and Related Transactions, and Director Independence.
Since January 1, 2020, the Company has not been a party to any transaction in which the amount involved exceeded or will exceed $120,000, and in which any of its
directors, named executive officers or beneficial owners of more than 5% of the Company’s capital stock, or an affiliate or immediate family member thereof, had or will have a
direct or indirect material interest, and other than compensation, termination, and change-in-control arrangements.
The written charter of the Audit Committee authorizes, and the Nasdaq Stock Market listing rules require, the Audit Committee to review and approve related-party
transactions. In reviewing related-party transactions, the Audit Committee applies the basic standard that transactions with affiliates should be made on terms no less favorable
to the Company than could have been obtained from unaffiliated parties. Therefore, the Audit Committee reviews the benefits of the transactions, terms of the transactions and
the terms available from unrelated third parties, as applicable. All transactions other than compensatory arrangements between the Company and its officers, directors, principal
stockholders and their affiliates will be approved by the Audit Committee or a majority of the disinterested directors, and will continue to be on terms no less favorable to the
Company than could be obtained from unaffiliated third parties.
The following is a summary of each transaction or series of similar transactions since the inception of Avenue to which it was or is a party and that:
•
•
the amount involved exceeded or exceeds $120,000 or is greater than 1% of our total assets; and
any of our directors or executive officers, any holder of 5% of our capital stock or any member of their immediate family had or will have a direct or indirect
material interest.
Founders Agreement and Management Services Agreement with Fortress
Fortress entered into a Founders Agreement with Avenue in February 2015, pursuant to which Fortress assigned to Avenue all of its rights and interest under Fortress’s
license agreement with Revogenex for IV Tramadol (the “License Agreement”). As consideration for the Founders Agreement, Avenue assumed $3.0 million in debt that
Fortress accumulated for expenses and costs of forming Avenue and obtaining the IV Tramadol license. This debt was repaid to Fortress in 2017. As additional consideration for
the transfer of rights under the Founders Agreement, Avenue shall also: (i) issue annually to Fortress, on the anniversary date of the Founders Agreement, shares of common
stock equal to two and one half percent (2.5%) of the fully-diluted outstanding equity of Avenue at the time of issuance; (ii) pay an equity fee in shares of Avenue common
stock, payable within five (5) business days of the closing of any equity or debt financing for Avenue or any of its respective subsidiaries that occurs after the effective date of
the Founders Agreement and ending on the date when Fortress no longer has majority voting control in Avenue’s voting equity, equal to two and one half percent (2.5%) of the
gross amount of any such equity or debt financing; and (iii) pay a cash fee equal to four and one half percent (4.5%) of Avenue’s annual net sales, payable on an annual basis,
within ninety (90) days of the end of each calendar year. In the event of a change in control (as it is defined in the Founders Agreement), Fortress will be paid a one-time change
in control fee equal to five (5x) times the product of (i) net sales for the twelve (12) months immediately preceding the change in control and (ii) four and one-half percent
(4.5%). This additional consideration was waived on November 12, 2018 with the Waiver Agreement signed between Avenue, Fortress and InvaGen.
On September 13, 2016, we entered into an Amended and Restated the Founders Agreement (“A&R Founders Agreement”) with Fortress. The A&R Founders Agreement
eliminated the Annual Equity Fee in connection with the original agreement and added a term of 15 years, which upon expiration automatically renews for successive one-year
periods unless terminated by Fortress or a Change in Control occurs. Concurrently with the A&R Founders Agreement the Company entered into an Exchange Agreement
whereby the Company exchanged Fortress’ 2.3 million Class A common shares for approximately 2.5 million common shares and 250,000 Class A Preferred shares.
59
Effective as of February 17, 2015, Fortress entered into a Management Services Agreement (the “MSA”) with Avenue and each of Avenue’s current directors and officers
who are directors or officers of Fortress, excluding services provided by Dr. Lucy Lu, the Company’s current Chief Executive Officer as of June 26, 2017 and the former Chief
Financial Officer of Fortress (resigned as of June 26, 2017), to provide services to Avenue pursuant to the terms of the MSA. Pursuant to the terms of the MSA, for a period of
five (5) years, Fortress will render advisory and consulting services to Avenue. Services provided under the MSA may include, without limitation, (i) advice and assistance
concerning any and all aspects of Avenue’s operations, clinical trials, financial planning and strategic transactions and financings and (ii) conducting relations on behalf of
Avenue with accountants, attorneys, financial advisors and other professionals (collectively, the “Services”). Avenue is obligated to utilize clinical research services, medical
education, communication and marketing services and investor relations/public relation services of companies or individuals designated by Fortress, provided those services are
offered at market prices. However, Avenue is not obligated to take or act upon any advice rendered from Fortress and Fortress shall not be liable for any of Avenue’s actions or
inactions based upon their advice. Fortress and its affiliates, including all members of Avenue’s Board of Directors, have been contractually exempt from fiduciary duties to
Avenue relating to corporate opportunities. In consideration for the Services, Avenue will pay Fortress an annual consulting fee of $0.5 million (the “Annual Consulting Fee”),
payable in advance in equal quarterly installments on the first business day of each calendar quarter in each year, provided, however, that such Annual Consulting Fee shall be
increased to $1.0 million for each calendar year in which Avenue has net assets in excess of $100.0 million at the beginning of the calendar year.
For the years ended December 31, 2020 and 2019, we had expenses related to the MSA of $0, respectively. Effective November 12, 2018, the MSA fee was waived with
the Waiver Agreement signed between Avenue, Fortress and InvaGen.
Facility Agreement with Fortress and InvaGen
On June 12, 2020, Avenue, Fortress and InvaGen entered into a Facility Agreement (“Facility Agreement”) whereby beginning on October 1, 2020 we may borrow up to
$2.0 million collectively from Fortress and InvaGen, subject to certain conditions set forth herein. Fortress’ commitment amount is $0.8 million, and InvaGen’s is $1.2 million,
and a 7% per annum interest rate applies (payable on the last day of each fiscal quarter). Repayment of the loan is due upon the earliest of i) the second stage closing ii) April
29, 2021 and iii) the date that is 30 days following the termination of the SPMA. As of December 31, 2020, there have been no amounts drawn on the Facility Agreement.
Item 14.
Principal Accounting Fees and Services
The following presents the aggregate fees billed to the Company for professional services rendered by BDO USA, LLP, (“BDO”) for our years ended December 31,
2020 and 2019:
Audit Fees
For the fiscal years ended December 31, 2020 and 2019, BDO billed us an aggregate of $158,300 and $181,150 respectively, in fees for the professional services
rendered in connection with the audit of our annual financial statements included in our Annual Report on Form 10-K for those two fiscal years, the review of our financial
statements included in our Quarterly Reports on Form 10-Q during those two fiscal years, and other services provided in connection with registration statements.
Audit-Related Fees
During the fiscal years ended December 31, 2020 and 2019, we were not billed by BDO for any fees for audit-related services reasonably related to the performance of
the audits and reviews for those two fiscal years, in addition to the fees described above under the heading “Audit Fees.”
Tax Fees
During the fiscal years ended December 31, 2020 and 2019, we were not billed by BDO for any fees for professional services rendered for tax compliance, tax advice,
and tax planning services.
All Other Fees
During the fiscal years ended December 31, 2020 and 2019, we were not billed by BDO for any fees for services, other than those described above, rendered to us for
those two fiscal years.
60
PART IV
Item 15.
Exhibits, Financial Statement Schedules
(a) Financial Statements.
The following financial statements are filed as part of this report:
Report of Independent Registered Public Accounting Firm
Financial Statements:
Balance Sheets
Statements of Operations
Statements of Stockholders’ Equity (Deficit)
Statements of Cash Flows
Notes to Financial Statements
(b) Exhibits.
F-1
F-2
F-3
F-4
F-5
F-6
Exhibit No.
3.1
Description
Third Amended and Restated Certificate of Incorporation of Avenue Therapeutics, Inc., filed as Exhibit 3.1 to Form 8-K filed on June 27, 2017 (File No. 001-
38114) and incorporated herein by reference.
3.2
3.3
4.1
4.2
4.3
10.1
10.2
10.3
10.4
10.5
10.6
10.7
10.8
10.9
Certificate of Amendment of the Third Amended and Restated Certificate of Incorporation of Avenue Therapeutics, Inc., filed as Exhibit 3.1 to Form 10-Q
filed on August 14, 2018 (File No. 001-38114) and incorporated herein by reference.
Amended and Restated Bylaws of Avenue Therapeutics, Inc., filed as Exhibit 3.1 to Form 8-K filed on February 11, 2019 (File No. 000-38114) and
incorporated herein by reference.
Specimen certificate evidencing shares of Common Stock, filed as Exhibit 4.1 to Form 10-12G filed on January 12, 2017 (File No. 000-55556) and
incorporated herein by reference.
Form of warrant agreement, filed as Exhibit 4.2 to Form 10-12G filed on January 12, 2017 (File No. 000-55556) and incorporated herein by reference.
Description of Securities.
Asset Transfer and License Agreement between Fortress Biotech, Inc. and Revogenex Ireland Limited dated February 17, 2015, filed as Exhibit 10.1 to Form
10-12G/A filed on March 13, 2017 (File No. 000-55556) and incorporated herein by reference.*
First Amendment to Asset Transfer and License Agreement between Fortress Biotech, Inc. and Revogenex Ireland Limited dated June 23, 2016, filed as
Exhibit 10.11 to Form 10-12G/A filed on March 13, 2017 (File No. 000-55556) and incorporated herein by reference.
Second Amendment to Asset Transfer and License Agreement between Fortress Biotech, Inc. and Revogenex Ireland Limited dated May 4, 2017, filed as
Exhibit 10.3 to Form S-1/A filed on May 22, 2017 (File No. 333-217552) and incorporated herein by reference.
Amended and Restated Founders Agreement between Fortress Biotech, Inc. and Avenue Therapeutics, Inc. dated September 13, 2016, filed as Exhibit 10.2 to
Form 10-12G filed on January 12, 2017 (File No. 000-55556) and incorporated herein by reference.
Management Services Agreement between Fortress Biotech, Inc. and Avenue Therapeutics, Inc. effective as of February 17, 2015, filed as Exhibit 10.5 to
Form 10-12G filed on January 12, 2017 (File No. 000-55556) and incorporated herein by reference.
Employment Agreement with Dr. Lucy Lu, MD, dated June 10, 2015, filed as Exhibit 10.6 to Form 10-12G filed on January 12, 2017 (File No. 000-55556)
and incorporated herein by reference.#
Avenue Therapeutics, Inc. 2015 Incentive Plan, filed as Exhibit 10.7 to Form 10-12G filed on January 12, 2017 (File No. 000-55556) and incorporated herein
by reference.
Consulting Agreement with Dr. Scott A. Reines, dated July 22, 2015, filed as Exhibit 10.8 to Form 10-12G filed on January 12, 2017 (File No. 000-55556)
and incorporated herein by reference.#
First Amendment to Consulting Agreement with Dr. Scott A. Reines, dated January 25, 2016, filed as Exhibit 10.9 to Form 10-12G filed on January 12, 2017
(File No. 000-55556) and incorporated herein by reference.#
61
10.10
Second Amendment to Consulting Agreement with Dr. Scott A. Reines, dated August 2, 2016, filed as Exhibit 10.10 to Form 10-12G/A filed on March 13,
2017 (File No. 000-55556) and incorporated herein by reference.#
10.11
Third Amendment to Consulting Agreement with Dr. Scott A. Reines, dated February 28, 2017, filed as Exhibit 10.12 to Form 10-12G/A filed on March 13,
2017 (File No. 000-55556) and incorporated herein by reference.#
10.12
Letter Agreement with Joseph Vazzano, dated July 28, 2017, filed as Exhibit 10.1 to Form 8-K filed on August 15, 2017 (File No. 001-38114) and
incorporated herein by reference.#
10.13
Stock Purchase and Merger Agreement, dated as of November 12, 2018, by and between Avenue Therapeutics, Inc., InvaGen Pharmaceuticals Inc. and
Madison Pharmaceuticals Inc., incorporated herein by reference from the Company’s Form 8-K filed on November 14, 2018.
10.14
Stockholders Agreement, dated as of November 12, 2018, by and between Avenue Therapeutics, Inc., Fortress Biotech, Inc., Dr. Lucy Lu, M.D. and InvaGen
Pharmaceuticals Inc., incorporated herein by reference from the Company’s Form 8-K filed on November 14, 2018.
10.15
Credit Agreement, dated as of November 12, 2018, by and between Avenue Therapeutics, Inc. and InvaGen Pharmaceuticals Inc., incorporated herein by
reference from the Company’s Form 8-K filed on November 14, 2018.
10.16
Guaranty, dated as of November 12, 2018, by and between Fortress Biotech, Inc. and InvaGen Pharmaceuticals Inc., incorporated herein by reference from
the Company’s Form 8-K filed on November 14, 2018.
10.17
Voting and Support Agreement, dated as of November 12, 2018, by and between Avenue Therapeutics, Inc., Fortress Biotech, Inc., Dr. Lucy Lu, M.D. and
InvaGen Pharmaceuticals Inc., incorporated herein by reference from the Company’s Form 8-K filed on November 14, 2018.
10.18
Waiver Agreement, dated as of November 12, 2018, by and between Avenue Therapeutics, Inc., Fortress Biotech, Inc. and InvaGen Pharmaceuticals Inc.,
incorporated herein by reference from the Company’s Form 8-K filed on November 14, 2018.
10.19
Restrictive Covenant Agreement, dated as of November 12, 2018, by and between Fortress Biotech, Inc. and InvaGen Pharmaceuticals Inc., incorporated
herein by reference from the Company’s Form 8-K filed on November 14, 2018.
10.20
Indemnification Agreement, dated as of November 12, 2018, by and between Fortress Biotech, Inc. and InvaGen Pharmaceuticals Inc., incorporated herein by
reference from the Company’s Form 8-K filed on November 14, 2018.
10.21
Restrictive Covenant Agreement, dated as of November 12, 2018, by and between Dr. Lucy Lu, M.D. and InvaGen Pharmaceuticals Inc., incorporated herein
by reference from the Company’s Form 8-K filed on November 14, 2018.
10.22
First Amendment to Executive Employment Agreement, dated as of November 12, 2018, by and between Avenue Therapeutics, Inc. and Dr. Lucy Lu, M.D.,
incorporated herein by reference from the Company’s Form 8-K filed on November 14, 2018.
23.1
24.1
31.1
31.2
32.1
32.2
101
Consent of Independent Registered Public Accounting Firm, BDO USA, LLP.
Power of Attorney (included on signature page)
Certification of Principal Executive Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
Certification of Principal Financial Officer pursuant to Section 302 of the Sarbanes-Oxley Act of 2002.
Certification of Principal Executive Officer pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
Certification of Principal Financial Officer pursuant to Section 906 of the Sarbanes-Oxley Act of 2002.
The following financial information from Avenue Therapeutics, Inc.’s Annual Report on Form 10-K for the year ended December 31, 2020, formatted in
XBRL (eXtensible Business Reporting Language): (i) Balance Sheets, (ii) Statement of Operations, (iii) Statement of Stockholders’ Equity (Deficit), (iv)
Statements of Cash Flows, and (v) the Notes to Financial Statements
* Subject to a request for confidential treatment.
# Management Compensation Arrangement.
Item 16.
None.
Form 10-K Summary
Report of Independent Registered Public Accounting Firm
Balance Sheets
Statements of Operations
Statements of Stockholders’ Equity (Deficit)
62
63
INDEX TO FINANCIAL STATEMENTS
F-1
F-2
F-3
F-4
F-5
F-6 – F-13
REPORT OF INDEPENDENT REGISTERED PUBLIC ACCOUNTING FIRM
Statements of Cash Flows
Notes to Financial Statements
Stockholders and Board of Directors
Avenue Therapeutics, Inc.
New York, New York
Opinion on the Financial Statements
We have audited the accompanying balance sheets of Avenue Therapeutics, Inc. (the “Company”) as of December 31, 2020 and 2019, the related statements of operations,
stockholders’ equity (deficit), and cash flows for the years then ended, and the related notes (collectively referred to as the “financial statements”). In our opinion, the financial
statements present fairly, in all material respects, the financial position of the Company at December 31, 2020 and 2019, and the results of its operations and its cash flows for
each of the two years in the period ended December 31, 2020, in conformity with accounting principles generally accepted in the United States of America.
Going Concern Uncertainty
The accompanying financial statements have been prepared assuming that the Company will continue as a going concern. As discussed in Note 1 to the financial statements, the
Company has suffered recurring losses from operations and has a capital deficiency 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 financial statements do not include any adjustments that might result from the outcome of this uncertainty.
Basis for Opinion
These financial statements are the responsibility of the Company’s management. Our responsibility is to express an opinion on the Company’s financial statements based on our
audits. We are a public accounting firm registered with the Public Company Accounting Oversight Board (United States) (“PCAOB”) and are required to be independent with
respect to the Company in accordance with the U.S. federal securities laws and the applicable rules and regulations of the Securities and Exchange Commission and the
PCAOB.
We conducted our audits in accordance with the standards of the PCAOB. Those standards require that we plan and perform the audit to obtain reasonable assurance about
whether the financial statements are free of material misstatement, whether due to error or fraud. The Company is not required to have, nor were we engaged to perform, an
audit of its internal control over financial reporting. As part of our audits we are required to obtain an understanding of internal control over financial reporting but not for the
purpose of expressing an opinion on the effectiveness of the Company’s internal control over financial reporting. Accordingly, we express no such opinion.
Our audits included performing procedures to assess the risks of material misstatement of the financial statements, whether due to error or fraud, and performing procedures that
respond to those risks. Such procedures included examining, on a test basis, evidence regarding the amounts and disclosures in the financial statements. Our audits also included
evaluating the accounting principles used and significant estimates made by management, as well as evaluating the overall presentation of the financial statements. We believe
that our audits provide a reasonable basis for our opinion.
F-1
AVENUE THERAPEUTICS, INC.
BALANCE SHEETS
(In thousands, except share and per share amounts)
/s/ BDO USA, LLP
We have served as the Company’s auditor since 2016.
New York, NY
March 31, 2021
ASSETS
Current Assets:
Cash and cash equivalents
Prepaid expenses and other current assets
Total Assets
LIABILITIES AND STOCKHOLDERS’ EQUITY
Current Liabilities:
Accounts payable and accrued expenses
Accounts payable and accrued expenses - related party
Licenses payable
Total current liabilities
Total Liabilities
December 31,
2020
December 31,
2019
$
$
$
$
$
$
3,132
113
3,245
857
29
-
886
886
8,745
170
8,915
1,101
14
1,000
2,115
2,115
Commitments and Contingencies
Stockholders’ Equity
Preferred Stock ($0.0001 par value), 2,000,000 shares authorized
Class A Preferred Stock, 250,000 shares issued and outstanding as of December 31, 2020 and 2019, respectively
Common Stock ($0.0001 par value), 50,000,000 shares authorized
Common shares, 16,747,803 and 16,682,190 shares issued and outstanding as of December 31, 2020 and 2019, respectively
Additional paid-in capital
Accumulated deficit
Total Stockholders’ Equity
Total Liabilities and Stockholders’ Equity
The accompanying notes are an integral part of these financial statements.
F-2
AVENUE THERAPEUTICS, INC.
STATEMENTS OF OPERATIONS
(In thousands, except share and per share amounts)
Operating expenses:
Research and development
Research and development - licenses acquired
General and administrative
Loss from operations
Interest income
Net Loss
Net loss per common share outstanding, basic and diluted
-
2
75,625
(73,268)
2,359
3,245
$
-
2
74,915
(68,117)
6,800
8,915
For the Years Ended
December 31,
2020
December 31,
2019
2,866
-
2,347
(5,213)
(62)
(5,151)
(0.31)
$
$
$
22,194
1,000
3,071
(26,265)
(357)
(25,908)
(1.65)
$
$
$
$
Weighted average number of common shares outstanding, basic and diluted
16,506,447
15,721,619
The accompanying notes are an integral part of these financial statements.
F-3
AVENUE THERAPEUTICS, INC.
STATEMENTS OF STOCKHOLDERS’ EQUITY (DEFICIT)
(In thousands, except share amounts)
Year ended December 31, 2020
Additional
Balance at December 31, 2019
Share based compensation
Cashless exercise of warrants
Net loss
Balance at December 31, 2020
Class A Preferred Shares
Shares
Amount
250,000 $
-
-
-
250,000 $
-
-
-
-
-
Common Shares
Shares
16,682,190
65,000
613
-
16,747,803
$
$
Amount
2
-
-
-
2
$
$
$
deficit
paid-in Accumulated
capital
74,915
710
-
-
75,625
(68,117)
-
-
(5,151)
(73,268)
$
Year ended December 31, 2019
Class A Preferred Shares
Common Shares
paid-in Accumulated
Additional
Total
Stockholders’
equity
$
$
6,800
710
-
(5,151)
2,359
Total
Stockholders’
equity
(deficit)
Balance at December 31, 2018
Share based compensation
Issuance of common shares, net of costs
Cashless exercise of warrants
Net loss
Balance at December 31, 2019
Shares
250,000
-
-
-
-
250,000
$
$
Amount
Shares
10,667,714
95,000
5,833,333
86,143
-
16,682,190
$
$
-
-
-
-
-
-
Amount
capital
deficit
1
-
1
-
-
2
$
$
41,577
1,839
31,499
-
-
74,915
$
$
(42,209)
-
-
-
(25,908)
(68,117)
$
$
(631)
1,839
31,500
-
(25,908)
6,800
The accompanying notes are an integral part of these financial statements.
F-4
AVENUE THERAPEUTICS, INC.
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:
Share based compensation
Changes in operating assets and liabilities:
Prepaid expenses and other current assets
Deferred financing costs
Accounts payable and accrued expenses
Accounts payable and accrued expenses - related party
Licenses payable
Net cash used in operating activities
Cash flows from investing activities:
Purchase of Short-term investments (certificates of deposit)
Maturity of Short-term investments (certificates of deposit)
Milestone payment for research and development licenses
Net cash used in investing activities
Cash flows from financing activities:
Issuance of common shares
Offering costs
Net cash provided by financing activities
Net change in cash
Cash and cash equivalents, beginning of period
Cash and cash equivalents, end of period
Non-cash financing activities:
Prior period financing costs
For the Years Ended
December 31,
2020
December 31,
2019
$
(5,151)
$
(25,908)
710
57
-
(244)
15
-
(4,613)
-
-
(1,000)
(1,000)
-
-
-
(5,613)
8,745
3,132
-
$
$
$
$
1,839
(18)
61
(2,760)
(473)
1,000
(26,259)
(5,000)
5,000
-
-
35,000
(2,667)
32,333
6,074
2,671
8,745
833
The accompanying notes are an integral part of these financial statements.
F-5
AVENUE THERAPEUTICS, INC
Notes to Financial Statements
Note 1 - Organization, Plan of Business Operations
Avenue Therapeutics, Inc. (the “Company” or “Avenue”) was incorporated in Delaware on February 9, 2015, as a wholly owned subsidiary of Fortress Biotech, Inc.
(“Fortress”), to develop and market pharmaceutical products for the acute care setting in the United States. The Company is focused on developing its product candidate, an
intravenous (“IV”) formulation of tramadol HCI (“IV Tramadol”), for post-operative acute pain.
Stock Purchase and Merger Agreement
On November 12, 2018, the Company and InvaGen Pharmaceuticals Inc. (“InvaGen”), entered into definitive agreements with two closing stages for a proposed acquisition
of the Company for a total aggregate consideration of $215.0 million (a portion of which was already paid in connection with the Stock Purchase Transaction as described
below) subject to certain potential reductions. The Stock Purchase and Merger Agreement (the “SPMA”) was approved by a majority of the Company’s stockholders, including
a majority of its non-affiliated stockholders, at its special shareholder meeting on February 6, 2019. On February 8, 2019, InvaGen acquired 5,833,333 shares of the Company’s
common stock at $6.00 per share (the “Stock Purchase Transaction”) for net proceeds of $31.5 million after deducting commission fees and other offering costs, representing a
33.3% stake in the Company’s capital stock on a fully diluted basis.
At the second stage closing, InvaGen will acquire the remaining shares of Avenue’s common stock, pursuant to a reverse triangular merger with Avenue remaining as the
surviving entity, for up to $180.0 million in the aggregate (the “Merger Transaction”). The second stage closing is subject to the satisfaction of certain closing conditions,
including conditions pertaining to the U.S. Food and Drug Administration (“FDA”) approval by April 30, 2021, labeling, scheduling and the absence of any Risk Evaluation
and Mitigation Strategy or similar restrictions in effect with respect to IV Tramadol, as well as the filing and expiration of any waiting period applicable to the acquisition under
the Hart-Scott-Rodino Antitrust Improvements Act of 1976, as amended, which filing both parties completed on March 12, 2021.
Subject to the terms and conditions described in the SPMA, InvaGen may also provide interim financing to the Company in an amount of up to $7.0 million during the time
period between the Stock Purchase Transaction (which occurred on February 8, 2019) and the Merger Transaction. Any amounts drawn on the interim financing will be
deducted from the aggregate consideration payable to the Company’s stockholders by virtue of the Merger Transaction. There have been no amounts drawn upon this interim
financing as of December 31, 2020.
In October 2020, InvaGen communicated to the Company that it believes a Material Adverse Effect (as defined in the SPMA) has occurred due to the impact of the
COVID-19 pandemic on potential commercialization and projected sales of IV Tramadol. Additionally, in connection with the resubmission of the Company’s NDA in February
2021, InvaGen communicated to the Company that it believes the proposed label for IV Tramadol would also constitute a Material Adverse Effect on the purported basis that
the proposed label under certain circumstances would make the product commercially unviable, and in addition that the indication that the FDA approves may fail to satisfy a
condition precedent to InvaGen’s obligation to consummate the second stage closing of the SPMA. While the Company disagrees with InvaGen’s assertions, it is possible
InvaGen could attempt to avoid its obligation to consummate the merger, terminate the SPMA, and/or pursue monetary claims against the Company.
Over the past several months, the Company has communicated with InvaGen relating to its assertions that Material Adverse Effects have occurred. Nevertheless, InvaGen
has communicated to the Company its desire to consider all options on the proposed merger, including the option to not consummate the merger. As a result, the possible timing
and likelihood of the completion of the merger are uncertain, and, accordingly, there can be no assurance that such transaction will be completed on the expected terms,
anticipated schedule, or at all.
In the event that the Company does not receive FDA approval for IV Tramadol by April 30, 2021, InvaGen will have the right to terminate the SPMA and will have no
further obligations to consummate the second stage closing under the SPMA. In the event that InvaGen does not exercise its right to terminate the SPMA, certain restrictions
relating to financings and strategic alternatives could exist through October 31, 2021, the time at which the Company can terminate the SPMA. In the event of termination of the
SPMA, InvaGen will retain certain rights pursuant to the Stockholder’s Agreement between the Company and InvaGen. These rights exist as long as InvaGen maintains at least
75% of the common shares acquired in the first stage closing. Certain actions relating to equity issuances and changes to capital stock are restricted without the prior written
consent of InvaGen during this time.
Liquidity and Capital Resources
Going Concern
The Company is not yet generating revenue, has incurred substantial operating losses since its inception and expects to continue to incur significant operating losses for the
foreseeable future as it executes on its product development plan and may never become profitable. As of December 31, 2020, the Company had an accumulated deficit of
$73.3 million.
On October 12, 2020, the Company announced that it had received a Complete Response Letter (“CRL”) from the FDA regarding the Company’s NDA for IV Tramadol.
The CRL cited deficiencies related to the terminal sterilization validation and stated that IV Tramadol, intended to treat patients in acute pain who require an opioid, is not safe
for the intended patient population. On February 12, 2021, the Company resubmitted its NDA to the FDA for IV Tramadol. The NDA resubmission follows the receipt of
official minutes from a Type A meeting with the FDA. The resubmission included revised language relating to the proposed product label and a report relating to terminal
sterilization validation. The FDA assigned a Prescription Drug User Fee Act goal date of April 12, 2021. The Company’s ability to potentially commercialize IV Tramadol, and
the timing of potential commercialization, is dependent on the FDA’s review of the Company’s resubmission of its NDA for IV Tramadol, ultimate FDA approval, and
potentially additional capital.
F-6
AVENUE THERAPEUTICS, INC
Notes to Financial Statements
As of December 31, 2020, the Company had cash and cash equivalents of $3.1 million. In the event that IV Tramadol is approved by the FDA, this triggers $5.0 million in
milestone payments, to which the Company currently does not have sufficient funding. In the event that IV Tramadol is not approved by the FDA, the Company believes that its
cash and cash equivalents should be sufficient to fund its operating expenses through the end of the third quarter of 2021. The Company will need to secure additional funds
through equity or debt offerings, or other potential sources. The Company cannot be certain that additional funding will be available on acceptable terms, or at all. These factors
individually and collectively raise substantial doubt about the Company’s ability to continue as a going concern within one year from the date of these audited financial
statements. The audited financial statements do not contain any adjustments that might result from the resolution of any of the above uncertainty.
In addition to the foregoing, based on current assessments, the Company does not expect any material impact on its development timeline and its liquidity due to the
worldwide spread of the COVID-19 virus (except as may be implicated by the alleged Material Adverse Effect claimed by InvaGen). However, the Company is continuing to
assess the effect on its operations by monitoring the spread of COVID-19 and the actions implemented to combat the virus throughout the world. The Company will also
continue to assess the alleged Material Adverse Effect claimed by InvaGen.
Note 2 — Significant Accounting Policies
Basis of Presentation
The Company’s financial statements have been prepared in conformity with accounting principles generally accepted in the United States of America (“U.S. GAAP”),
include all adjustments necessary for the fair presentation of the Company’s financial position for the periods presented and are stated in U.S. dollars. The Company has no
subsidiaries.
Use of Estimates
The preparation of financial statements in conformity with U.S. GAAP requires management to make estimates and assumptions that affect the reported amounts of assets
and liabilities and disclosure of contingent assets and liabilities at the date of the financial statements and the reported amounts of expenses during the reporting period. Actual
results could differ from those estimates.
Cash and Cash Equivalents
The Company considers all short-term investments with an original maturity of three months or less when purchased to be cash equivalents. Cash and cash equivalents at
December 31, 2020 and 2019 consisted of cash, money market funds and certificates of deposit in institutions in the United States. Balances at certain institutions have
exceeded Federal Deposit Insurance Corporation (“FDIC”) insured limits and U.S. government agency securities.
Accounts Payable and Accrued Expenses – Related Party
Accounts payable and accrued expenses consist of amounts due to Fortress, a related party, and are recorded at the invoiced amount.
Research and Development
Research and development costs are expensed as incurred. Advance payments for goods and services that will be used in future research and development activities are
expensed when the activity has been performed or when the goods have been received rather than when the payment is made. Upfront and milestone payments due to third
parties that perform research and development services on the Company’s behalf will be expensed as services are rendered or when the milestone is achieved.
Research and development costs primarily consist of personnel related expenses, including salaries, benefits, travel, and other related expenses, stock-based compensation,
payments made to third parties for license and milestone costs related to in-licensed products and technology, payments made to third party contract research organizations for
preclinical and clinical studies, investigative sites for clinical trials, consultants, the cost of acquiring and manufacturing clinical trial materials, costs associated with regulatory
filings and patents, laboratory costs and other supplies.
Costs incurred in obtaining technology licenses are charged to research and development expense if the technology licensed has not reached commercial feasibility and
have no alternative future use. The licenses purchased by the Company require substantial completion of research and development, regulatory and marketing approval efforts
in order to reach commercial feasibility and has no alternative future use. Accordingly, the total purchase price including any development milestone payments for the licenses
acquired are reflected as research and development — licenses acquired on the Company’s Statements of Operations.
F-7
AVENUE THERAPEUTICS, INC
Notes to Financial Statements
Annual Stock Dividend
In September 2016, in connection with the Amended and Restated Articles of Incorporation, the Company issued 250,000 Class A preferred shares to Fortress. The Class A
preferred shares entitled the holder to a stock dividend equal to 2.5% of the fully diluted outstanding equity of the Company (“The Annual Stock Dividend”) to be paid on
February 17 of each year. On June 13, 2018, the Company’s Stockholders adopted an amendment to the Company’s Third Amended and Restated Certificate of Incorporation
amending the payment date going forward to January 1 of each year. Concurrently with the execution and delivery of the SPMA, the Company, InvaGen and Fortress entered
into a waiver agreement (“the Waiver Agreement”), pursuant to which, among other things, Fortress irrevocably waived its right to receive dividends of the Company’s
common shares under the terms of the Class A Preferred Stock and any fees, payments, reimbursements or other distributions under a certain management services agreement
between the Company and Fortress and the Founders Agreement (as defined in the SPMA), for the period November 12, 2018 to the termination of InvaGen’s rights under
Section 4 of the Stockholders Agreement that was signed between the Company, certain stockholders of the Company, and InvaGen.
Stock-Based Compensation
The Company expenses stock-based compensation to its employees, consultants and board members over the requisite service period based on the estimated grant-date fair
value of the awards. Stock-based awards with graded-vesting schedules are recognized on a straight-line basis over the requisite service period for each separately vesting
portion of the award.
The assumptions used in calculating the fair value of stock-based awards represent management’s best estimates and involve inherent uncertainties and the application of
management’s judgment.
Income Taxes
The Company accounts for income taxes under ASC 740, Income Taxes (“ASC 740”). ASC 740 requires the recognition of deferred tax assets and liabilities for both the
expected impact of differences between the financial statement and tax basis of assets and liabilities and for the expected future tax benefit to be derived from tax loss and tax
credit carry forwards. ASC 740 additionally requires a valuation allowance to be established when it is more likely than not that all or a portion of deferred tax assets will not
be realized.
ASC 740 also clarifies the accounting for uncertainty in income taxes recognized in an enterprise’s financial statements and prescribes a recognition threshold and
measurement process for financial statement recognition and measurement of a tax position taken or expected to be taken in a tax return. For those benefits to be recognized, a
tax position must be more-likely-than-not to be sustained upon examination by taxing authorities. ASC 740 also provides guidance on de-recognition, classification, interest and
penalties, accounting in interim period, disclosure and transition. Based on the Company’s evaluation, it has been concluded that there are no significant uncertain tax positions
requiring recognition in the Company’s financial statements. The 2017 through 2019 tax years are the only periods subject to examination upon filing of appropriate tax returns.
The Company believes that its income tax positions and deductions would be sustained on audit and does not anticipate any adjustments that would result in a material change
to its financial position.
The Company’s policy for recording interest and penalties associated with audits is to record such expense as a component of income tax expense. There were no amounts
accrued for penalties or interest as of or during the years ended December 31, 2020 and 2019. Management is currently unaware of any issues under review that could result in
significant payments, accruals or material deviations from its position.
Net Loss Per Share
Loss per share is computed by dividing net loss by the weighted-average number of common shares outstanding, excluding unvested restricted stock and stock options and
preferred shares, during the period. Since dividends are declared paid and set aside among the holders of shares of common stock and Class A common stock pro-rata on an as-
if-converted basis, the two-class method of computing net loss per share is not required.
The following table sets forth the potential common shares that could potentially dilute basic income per share in the future that were not included in the computation of
diluted net loss per share because to do so would have been anti-dilutive for the periods presented:
Unvested restricted stock units/awards
Preferred shares
Total potential dilutive effect
For the Years Ended
December 31,
2020
December 31,
2019
1,139,910
250,000
1,389,910
1,045,162
250,000
1,295,162
F-8
AVENUE THERAPEUTICS, INC
Notes to Financial Statements
Recently Adopted Accounting Standards
In December 2019, the Financial Accounting Standards Board (“FASB”) issued ASU No. 2019-12, Income Taxes (Topic 740): Simplifying the Accounting for Income
Taxes, (“ASU 2019-12”) which is intended to simplify various aspects related to accounting for income taxes. ASU 2019-12 removes certain exceptions to the general
principles in Topic 740 and also clarifies and amends existing guidance to improve consistent application. This guidance is effective for fiscal years, and interim periods within
those fiscal years, beginning after December 15, 2020, with early adoption permitted. The Company adopted ASU 2019-12 on January 1, 2021 and its adoption will not have a
material impact on the Company’s financial statements and related disclosures.
Coronavirus Aid, Relief and Economic Security Act (“CARES Act”)
In response to the COVID-19 pandemic, the Coronavirus Aid, Relief and Economic Security Act (“CARES Act”) was signed into law on March 27, 2020. The CARES
Act, among other things, includes tax provisions relating to refundable payroll tax credits, deferment of employer’s social security payments, net operating loss utilization and
carryback periods, modifications to the net interest deduction limitations and technical corrections to tax depreciation methods for qualified improvement property. The CARES
Act has no material impact on the Company’s income tax provision (benefit) for 2020.
On December 27, 2020, the President of the United States signed the Consolidated Appropriations Act, 2021 (“Consolidated Appropriations Act”) into law. The
Consolidated Appropriations Act is intended to enhance and expand certain provisions of the CARES Act, allows for the deductions of expenses related to the Payroll
Protection Program funds received by companies, and provides an update to meals and entertainment expensing for 2021. The Consolidated Appropriations Act has no material
impact to the Company’s income tax provision (benefit) for 2020.
Note 3 — License/Supplier Agreements
Effective as of February 17, 2015, Fortress transferred the Revogenex license and all other rights and obligations under the License Agreement to Avenue, pursuant to the
terms of the Founders Agreement. In connection with the terms of the License Agreement, Fortress purchased an exclusive license to IV Tramadol for the U.S. market from
Revogenex, a privately held company in Dublin, Ireland. Fortress made an upfront payment of $2.0 million to Revogenex upon execution of the exclusive license, and on June
17, 2015, Fortress paid an additional $1.0 million to Revogenex after receiving all the assets specified in the agreement. The $3.0 million cumulative payment was included in
research and development-licenses acquired in the statements of operations. In December 2019, $1.0 million became due to Revogenex in accordance with the Company’s
submission of its NDA. The amount was expensed in research and development-licenses acquired in the statement of operations for the year ended December 31, 2019 and was
included in licenses payable on the Company’s balance sheets as of December 31, 2019 and subsequently paid in the first quarter of 2020. In addition, under the terms of the
agreement, Revogenex is eligible to receive an additional milestone payment totaling $3.0 million upon the approval of IV Tramadol from the FDA as well as royalty payments
for sales of the product.
On October 29, 2018, the Company and Zaklady Farmaceutyczne Polpharma (“Polpharma”) extended the term of their exclusive supply agreement for drug product of IV
Tramadol to eight years from the date of the launch of the product. In addition, under the terms of the amended agreement, Polpharma is eligible to receive a milestone payment
totaling $2.0 million upon the approval of IV Tramadol from the FDA, as well as royalty payments for sales of the product.
Note 4 — Related Party Agreements
Founders Agreement and Management Services Agreement with Fortress
Fortress entered into a Founders Agreement with Avenue in February 2015, pursuant to which Fortress assigned to Avenue all of its rights and interest under Fortress’s
license agreement with Revogenex for IV Tramadol (the “License Agreement”). As consideration for the Founders Agreement, Avenue assumed $3.0 million in debt that
Fortress accumulated for expenses and costs of forming Avenue and obtaining the IV Tramadol license. This debt was repaid to Fortress in 2017. As additional consideration for
the transfer of rights under the Founders Agreement, Avenue shall also: (i) issue annually to Fortress, on the anniversary date of the Founders Agreement, shares of common
stock equal to two and one half percent (2.5%) of the fully-diluted outstanding equity of Avenue at the time of issuance; (ii) pay an equity fee in shares of Avenue common
stock, payable within five (5) business days of the closing of any equity or debt financing for Avenue or any of its respective subsidiaries that occurs after the effective date of
the Founders Agreement and ending on the date when Fortress no longer has majority voting control in Avenue’s voting equity, equal to two and one half percent (2.5%) of the
gross amount of any such equity or debt financing; and (iii) pay a cash fee equal to four and one half percent (4.5%) of Avenue’s annual net sales, payable on an annual basis,
within ninety (90) days of the end of each calendar year. In the event of a change in control (as it is defined in the Founders Agreement), Fortress will be paid a one-time change
in control fee equal to five (5x) times the product of (i) net sales for the twelve (12) months immediately preceding the change in control and (ii) four and one-half percent
(4.5%). This additional consideration was waived on November 12, 2018 with the Waiver Agreement signed between Avenue, Fortress and InvaGen.
On September 13, 2016, the Company entered into an Amended and Restated the Founders Agreement (“A&R Founders Agreement”) with Fortress. The A&R Founders
Agreement eliminated the Annual Equity Fee in connection with the original agreement and added a term of 15 years, which upon expiration automatically renews for
successive one-year periods unless terminated by Fortress or a Change in Control occurs. Concurrently with the A&R Founders Agreement the Company entered into an
Exchange Agreement whereby the Company exchanged Fortress’ 2.3 million Class A common shares for approximately 2.5 million common shares and 250,000 Class A
Preferred shares (see Note 7).
F-9
AVENUE THERAPEUTICS, INC
Notes to Financial Statements
Effective as of February 17, 2015, Fortress entered into a Management Services Agreement (the “MSA”) with Avenue and each of Avenue’s current directors and officers
who are directors or officers of Fortress, excluding services provided by Dr. Lucy Lu, the Company’s current Chief Executive Officer as of June 26, 2017 and the former Chief
Financial Officer of Fortress (resigned as of June 26, 2017), to provide services to Avenue pursuant to the terms of the MSA. Pursuant to the terms of the MSA, for a period of
five (5) years, Fortress will render advisory and consulting services to Avenue. Services provided under the MSA may include, without limitation, (i) advice and assistance
concerning any and all aspects of Avenue’s operations, clinical trials, financial planning and strategic transactions and financings and (ii) conducting relations on behalf of
Avenue with accountants, attorneys, financial advisors and other professionals (collectively, the “Services”). Avenue is obligated to utilize clinical research services, medical
education, communication and marketing services and investor relations/public relation services of companies or individuals designated by Fortress, provided those services are
offered at market prices. However, Avenue is not obligated to take or act upon any advice rendered from Fortress and Fortress shall not be liable for any of Avenue’s actions or
inactions based upon their advice. Fortress and its affiliates, including all members of Avenue’s Board of Directors, have been contractually exempt from fiduciary duties to
Avenue relating to corporate opportunities. In consideration for the Services, Avenue will pay Fortress an annual consulting fee of $0.5 million (the “Annual Consulting Fee”),
payable in advance in equal quarterly installments on the first business day of each calendar quarter in each year, provided, however, that such Annual Consulting Fee shall be
increased to $1.0 million for each calendar year in which Avenue has net assets in excess of $100.0 million at the beginning of the calendar year. Effective November 12, 2018,
the MSA fee was waived with the Waiver Agreement signed between Avenue, Fortress and InvaGen.
Facility Agreement with Fortress and InvaGen
On June 12, 2020, the Company, Fortress and InvaGen entered into a Facility Agreement (“Facility Agreement”) whereby beginning on October 1, 2020 the Company may
borrow up to $2.0 million collectively from Fortress and InvaGen, subject to certain conditions. Fortress’ commitment amount is $0.8 million, and InvaGen’s is $1.2 million,
and a 7% per annum interest rate applies (payable on the last day of each fiscal quarter). Repayment of the loan is due upon the earliest of i) the second stage closing ii) April
29, 2021 and iii) the date that is 30 days following the termination of the SPMA. As of December 31, 2020, there have been no amounts drawn on the Facility Agreement.
Note 5 — Accounts Payable and Accrued Expenses
Accounts payable, accrued expenses and other liabilities consisted of the following (in thousands):
As of December 31, As of December 31,
2020
2019
Accounts payable
Accrued employee compensation
Accrued contracted services and other
Accounts payable and accrued expenses
Note 6 — Commitments and Contingencies
Leases
The Company is not a party to any leases for office space or equipment.
Litigation
$
$
143 $
23
691
857 $
354
477
270
1,101
The Company recognizes a liability for a contingency when it is probable that liability has been incurred and when the amount of loss can be reasonably estimated. When a
range of probable loss can be estimated, the Company accrues the most likely amount of such loss, and if such amount is not determinable, then the Company accrues the
minimum of the range of probable loss. As of December 31, 2020 and 2019, there was no litigation against the Company.
Note 7 — Stockholders’ Equity (Deficit)
Class A Preferred Shares
On September 13, 2016, the Class A Common Stock was eliminated and 2,000,000 shares of Preferred Stock were authorized, of which 250,000 have been designated as
Class A Preferred Stock and the remainder are undesignated preferred stock. The Class A Preferred Stock, with a par value of $0.0001 per share, is identical to undesignated
Common Stock other than as to voting rights, conversion rights, and the PIK Dividend right (as described below). The undesignated Preferred Stock may be issued from time to
time in one or more series. The Company’s Board of Directors is authorized to determine or alter the dividend rights, dividend rate, conversion rights, voting rights, rights and
terms of redemption (including sinking fund provisions, if any), the redemption price or prices, the liquidation preferences and other designations, powers, preferences and
relative, participating, optional or other special rights, if any, and the qualifications, limitations and restrictions granted to or imposed upon any wholly unissued series of
Preferred Stock, and to fix the number of shares of any series of Preferred Stock (but not below the number of shares of any such series then outstanding).
F-10
AVENUE THERAPEUTICS, INC
Notes to Financial Statements
Pursuant to the Company’s Second Amended and Restated Certificate of Incorporation, the holders of the outstanding shares of Class A Preferred Stock shall receive on
each February 17 (each a “PIK Dividend Payment Date”) after the original issuance date of the Class A Preferred Stock until the date all outstanding Class A Preferred Stock is
converted into Common Stock or redeemed (and the purchase price is paid in full), pro rata per share dividends paid in additional fully paid and nonassessable shares of
Common Stock (such dividend being herein called “PIK Dividends”) such that the aggregate number of shares of Common Stock issued pursuant to such PIK Dividend is equal
to two and one-half percent (2.5%) of the Corporation’s fully-diluted outstanding capitalization on the date that is one (1) business day prior to any PIK Dividend Payment Date
(“PIK Record Date”). In the event the Class A Preferred Stock converts into Common Stock, the holders shall receive all PIK Dividends accrued through the date of such
conversion. No dividend or other distribution shall be paid, or declared and set apart for payment (other than dividends payable solely in capital stock on the capital stock of the
Company) on the shares of Common Stock until all PIK Dividends on the Class A Preferred Stock shall have been paid or declared and set apart for payment. All dividends are
non-cumulative. On June 13, 2018, the Company’s Stockholders adopted an amendment to the Company’s Third Amended and Restated Certificate of Incorporation amending
the PIK Dividend Payment Date going forward to January 1 of each year. This PIK Dividend was waived in connection with the Waiver Agreement signed on November 12,
2018 between Avenue, Fortress and InvaGen.
On any matter presented to the stockholders of the Company for their action or consideration at any meeting of stockholders of the Company (or by written consent of
stockholders in lieu of meeting), each holder of outstanding shares of Class A Preferred Stock shall be entitled to cast for each share of Class A Preferred Stock held by such
holder as of the record date for determining stockholders entitled to vote on such matter, the number of votes that is equal to one and one-tenth (1.1) times a fraction, the
numerator of which is the sum of (A) the number of shares of outstanding Common Stock and (B) the whole shares of Common Stock in to which the shares of outstanding
Class A Common Stock and the Class A Preferred Stock are convertible, and the denominator of which is number of shares of outstanding Class A Preferred Stock (the “Class
A Preferred Stock Ratio”). Thus, the Class A Preferred Stock will at all times constitute a voting majority.
Each share of Class A Preferred Stock is convertible, at the option of the holder, into one fully paid and nonassessable share of Common Stock (the “Conversion Ratio”),
subject to certain adjustments. If the Company, at any time effects a subdivision or combination of the outstanding Common Stock (by any stock split, stock dividend,
recapitalization, reverse stock split or otherwise), the applicable Conversion Ratio in effect immediately before that subdivision is proportionately decreased or increased, as
applicable, so that the number of shares of Common Stock issuable on conversion of each share of Class A Preferred Stock shall be increased or decreased, a applicable, in
proportion to such increase or decrease in the aggregate number of shares of Common Stock outstanding. Additionally, if any reorganization, recapitalization, reclassification,
consolidation or merger involving the Company occurs in which the Common Stock (but not the Class A Preferred Stock) is converted into or exchanged for securities, cash or
other property, then each share of Class A Preferred Stock becomes convertible into the kind and amount of securities, cash or other property which a holder of the number of
shares of Common Stock of the Company issuable upon conversion of one share of the Class A Preferred Stock immediately prior to such reorganization, recapitalization,
reclassification, consolidation or merger would have been entitled to receive pursuant to such transaction.
Common Stock
As of December 31, 2020, the Company’s authorized capital stock consists of 50,000,000 shares of common stock, with $0.0001 par value.
Holders of our common stock are entitled to one vote for each share held on all matters submitted to a vote of stockholders and do not have cumulative voting rights. An
election of directors by our stockholders shall be determined by a plurality of the votes cast by the stockholders entitled to vote on the election. Holders of common stock are
entitled to receive proportionately any dividends as may be declared by our Board of Directors, subject to any preferential dividend rights of outstanding preferred stock.
In the event of our liquidation or dissolution, the holders of common stock are entitled to receive proportionately all assets available for distribution to stockholders after the
payment of all debts and other liabilities and subject to the prior rights of any outstanding preferred stock. Holders of common stock have no preemptive, subscription,
redemption or conversion rights. The rights, preferences and privileges of holders of common stock are subject to, and may be adversely affected by, the rights of the holders of
shares of any series of preferred stock that we may designate and issue in the future.
F-11
AVENUE THERAPEUTICS, INC
Notes to Financial Statements
Equity Incentive Plan
The Company has in effect the 2015 Incentive Plan (“2015 Incentive Plan’). The 2015 Incentive Plan was adopted in January 2015 by our stockholders. Under the 2015
Incentive Plan, the compensation committee of the Company’s board of directors is authorized to grant stock-based awards to directors, officers, employees and consultants.
The plan authorizes grants to issue up to 2,000,000 shares of authorized but unissued common stock and expires 10 years from adoption and limits the term of each option to no
more than 10 years from the date of grant.
Total shares available for the issuance of stock-based awards under the Company’s 2015 Incentive Plan was 229,436 shares at December 31, 2020.
Restricted Stock Units and Restricted Stock Awards
The following table summarizes restricted stock unit and award activity for the year ended December 31, 2020:
Unvested balance at December 31, 2019
Granted
Vested
Unvested balance at December 31, 2020
Number of
Units and
Awards
1,045,162 $
176,413 $
(81,665) $
1,139,910 $
Weighted
Average Grant
Date Fair Value
5.10
10.99
5.78
5.96
For the years ended December 31, 2020 and 2019 stock-based compensation expenses associated with the amortization of restricted stock units and restricted stock awards
for employees and non-employees were approximately $0.7 million and $1.8 million, respectively.
For the years ended December 31, 2020, and 2019, the weighted average grant date fair value of restricted stock units and awards granted was $10.99 and $5.95,
respectively. The total fair value of restricted stock units and awards that vested during the years ended December 31, 2020 and 2019 was $0.5 million and $1.2 million,
respectively.
At December 31, 2020, the Company had unrecognized stock-based compensation expense related to restricted stock units and restricted stock awards of $0.4 million,
which is expected to be recognized over the remaining weighted-average vesting period of 1.1 years. This amount does not include, as of December 31, 2020, 487,586 shares of
restricted stock outstanding which are performance-based and vest upon achievement of certain corporate milestones. The expense is recognized over the vesting period of the
award. Stock-based compensation for milestone awards will be measured and recorded if and when it is probable that the milestone will be achieved.
Stock Options
On August 15, 2017, 20,000 stock options were granted to a consultant under the 2015 Incentive Plan. These options were cancelled in January 2019 as the vesting criteria
pertaining to the price of the Company’s stock was not met by the deadline.
Stock Warrants
The following table summarizes the warrant activity for the year ended December 31, 2020:
Outstanding, December 31, 2019
Exercised
Outstanding, December 31, 2020
Note 8 — Income Taxes
Warrants
Weighted
Average
Exercise Price
Aggregate
Intrinsic Value
(in thousands)
16,454 $
(613) $
15,841 $
0.6079 $
0.0001
0.6315 $
148
-
84
The Company has accumulated net losses since inception and has not recorded an income tax provision or benefit during the years ended December 31, 2020 and 2019.
F-12
AVENUE THERAPEUTICS, INC
Notes to Financial Statements
A reconciliation of the statutory U.S. federal rate to the Company’s effective tax rate is as follows:
Statutory federal income tax rate
State taxes, net of federal tax benefit
State tax rate change
Stock-based compensation shortfall
Other
Credits
Change in valuation allowance
Income taxes provision (benefit)
The components of the net deferred tax asset as of December 31, 2020 and 2019 are the following (in thousands):
Deferred tax assets:
Net operating loss carryovers
For the years ended December 31,
2020
2019
21%
13%
0%
6%
0%
0%
(40%)
0%
21%
14%
1%
0%
4%
5%
(45%)
0%
As of December 31,
2020
2019
$
22,240 $
19,953
Stock compensation and other
Amortization of license
Accruals and reserves
Tax credits
Total deferred tax assets
Less valuation allowance
760
1,283
16
2,640
26,939
(26,939)
Deferred tax assets, net of valuation allowance
$
- $
843
1,413
15
2,640
24,864
(24,864)
-
The Company has determined, based upon available evidence, that it is more likely than not that the net deferred tax asset will not be realized and, accordingly, has
provided a full valuation allowance against it. A valuation allowance of approximately $26.9 million and $24.9 million was recorded for the years ended December 31, 2020
and 2019, respectively.
As of December 31, 2020, the Company had federal and state net operating loss carryforwards of approximately $67.0 million and $125.5 million, respectively.
Approximately $52.5 million of the federal net operating loss carryforwards can be carried forward indefinitely. The remaining $14.5 million of federal and all state net
operating loss carryforwards will begin to expire, if not utilized, by 2035 and 2028, respectively. The Company has $2.6 million of research and development credit
carryforwards, which will begin to expire, if not utilized, in 2035. Utilization of the net operating loss and credit carryforwards may be subject to an annual limitation due to the
ownership change limitations provided by Section 382 of the Internal Revenue Code of 1986. Certain tax attributes are subject to an annual limitation as a result of the
Company’s June 2017 initial public offering, which constitutes an ownership change under Section 382. Certain tax attributes may be subject to an annual limitation as a result
of the SPMA with InvaGen, which could constitute an ownership change under Section 382.
There are no significant matters determined to be unrecognized tax benefits taken or expected to be taken in a tax return, in accordance with ASC 740, which clarifies the
accounting for uncertainty in income taxes recognized in the financial statements, that have been recorded on the Company’s financial statements for the periods ended
December 31, 2020 and 2019. The Company does not anticipate a material change to unrecognized tax benefits in the next twelve months.
Additionally, ASC 740 provides guidance on the recognition of interest and penalties related to income taxes. There were no interest or penalties related to income taxes
that have been accrued or recognized as of and for the periods ended December 31, 2020 and 2019.
The federal and state tax returns for the years ended December 31, 2017, 2018, and 2019 are currently open for examination under the applicable federal and state income
tax statues of limitations. The Company is currently under examination by New York City Department of Finance for tax years between 2017 and 2019. At this time, the
Company does not believe that the outcome of any examination will have a material impact on the Company’s results of operations and financial position.
Note 9 – Subsequent Events
On February 12, 2021, the Company resubmitted its NDA to the FDA for IV Tramadol. The NDA for IV Tramadol was resubmitted following the receipt of official
minutes from a Type A meeting with the FDA, which was conducted following a CRL issued by the FDA in October 2020. The resubmission included revised language relating
to the proposed product label and a report relating to terminal sterilization validation. The FDA assigned a Prescription Drug User Fee Act goal date of April 12, 2021 for the
resubmitted NDA for IV Tramadol.
F-13
SIGNATURES
Pursuant to the requirements of Section 12 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.
Avenue Therapeutics, Inc.
By:
/s/ Lucy Lu, M.D.
Name: Lucy Lu, M.D.
Title: President, Chief Executive Officer and Director
March 31, 2021
POWER OF ATTORNEY
We, the undersigned directors and/or executive officers of Avenue Therapeutics, Inc., hereby severally constitute and appoint Lucy Lu, M.D., acting singly, his or her true and
lawful attorney-in-fact and agent, with full power of substitution and resubstitution, for him or her in any and all capacities, to sign this report and to file the same, with all
exhibits thereto and other documents in connection therewith, with the Securities and Exchange Commission, granting unto said attorney-in-fact and agent full power and
authority to do and perform each and every act and thing necessary or appropriate to be done in connection therewith, as fully for all intents and purposes as he or she might or
could do in person, hereby approving, ratifying and confirming all that said attorney-in-fact and agent, or his substitute, may lawfully do or cause to be done by virtue hereof.
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
/s/ Lucy Lu, M.D.
Lucy Lu, M.D.
/s/ Joseph Vazzano
Joseph Vazzano
/s/ Lindsay A. Rosenwald, M.D.
Lindsay A. Rosenwald, M.D.
/s/ Garrett Ingram
Garrett Ingram
/s/ Neil Herskowitz
Neil Herskowitz
President, Chief Executive Officer and Director
(Principal Executive Officer)
Chief Financial Officer
(Principal Financial Officer)
Date
March 31, 2021
March 31, 2021
Executive Chairman of the Board
March 31, 2021
Director
Director
March 31, 2021
March 31, 2021
/s/ Jaideep Gogtay, M.D., Ph.D.
Jaideep Gogtay, M.D., Ph.D.
/s/ Jay Kranzler, M.D., Ph.D.
Jay Kranzler, M.D., Ph.D.
Director
Director
March 31, 2021
March 31, 2021
DESCRIPTION OF THE REGISTRANT’S SECURITIES
REGISTERED PURSUANT TO SECTION 12 OF THE
SECURITIES EXCHANGE ACT OF 1934
DESCRIPTION OF CAPITAL STOCK
Exhibit 4.3
Authorized Capital Stock
Our authorized capital stock consists of 50,000,000 shares of common stock, with $0.0001 par value, and 2,000,000 shares of Preferred Stock, with $0.0001 par value,
of which 250,000 have been designated as Class A Preferred Stock and the remainder of which are undesignated Preferred Stock.
As of March 17, 2021, there were 16,748,068 shares of our common stock outstanding held by 56 record stockholders.
Common Stock
Holders of our common stock are entitled to one vote for each share held on all matters submitted to a vote of stockholders and do not have cumulative voting rights.
An election of directors by our stockholders shall be determined by a plurality of the votes cast by the stockholders entitled to vote on the election. Holders of common stock are
entitled to receive proportionately any dividends as may be declared by our Board of Directors, subject to any preferential dividend rights of outstanding preferred stock.
In the event of our liquidation or dissolution, the holders of common stock are entitled to receive proportionately all assets available for distribution to stockholders
after the payment of all debts and other liabilities and subject to the prior rights of any outstanding preferred stock. Holders of common stock have no preemptive, subscription,
redemption or conversion rights. The rights, preferences and privileges of holders of common stock are subject to, and may be adversely affected by, the rights of the holders of
shares of any series of preferred stock that we may designate and issue in the future.
Our common stock is traded on the Nasdaq Capital Market under the symbol “ATXI.” The transfer agent and registrar for our common stock is VStock Transfer, LLC.
Class A Preferred Stock
DESCRIPTION OF PREFERRED STOCK
Class A Preferred Stock is identical to our common stock other than as to voting rights, the election of directors for a definite period, conversion rights and the PIK
Dividend right (as described below). On any matter presented to our stockholders for their action or consideration at any meeting of our stockholders (or by written consent of
stockholders in lieu of meeting), each holder of outstanding shares of Class A Preferred Stock will be entitled to cast for each share of Class A Preferred Stock held by such
holder as of the record date for determining stockholders entitled to vote on such matter, the number of votes that is equal to one and one-tenth (1.1) times a fraction, the
numerator of which is the sum of (A) the shares of outstanding common stock and (B) the whole shares of common stock in to which the shares of outstanding Class A
Preferred Stock are convertible and the denominator of which is the number of shares of outstanding Class A Preferred Stock, or the Class A Preferred Stock Ratio. Thus, the
Class A Preferred Stock will at all times constitute a voting majority.
For a period of ten years from the date of the first issuance of shares of Class A Preferred Stock, or the Class A Director Period, the holders of record of the shares of
Class A Preferred Stock (or other capital stock or securities issued upon conversion of or in exchange for the Class A Preferred Stock), exclusively and as a separate class, shall
be entitled to appoint or elect the majority of our directors, or the Class A Directors. Thus, the Class A Preferred Stock will be entitled to elect the majority of the Board of
Directors during the Class A Director Period.
The holders of the outstanding shares of Class A Preferred Stock shall receive on January 1 of each year, each a PIK Dividend Payment Date, after the original
issuance date of the Class A Preferred Stock until the date all outstanding Class A Preferred Stock is converted into common stock or redeemed (and the purchase price is paid
in full), pro rata per share dividends paid in additional fully paid and nonassessable shares of common stock, such dividend being herein called PIK Dividends, such that the
aggregate number of shares of common stock issued pursuant to such PIK Dividend is equal to 2.5% of our fully-diluted outstanding capitalization on the date that is one
business day prior to any PIK Dividend Payment Date, or PIK Record Date. In the event the Class A Preferred Stock converts into common stock, the holders shall receive all
PIK Dividends accrued through the date of such conversion.
Each share of Class A Preferred Stock is convertible, at the option of the holder, into one fully paid and nonassessable share of common stock, or the Conversion
Ratio, subject to certain adjustments.
Undesignated Preferred Stock
The undesignated Preferred Stock may be issued from time to time in one or more series. Our Board of Directors is authorized to determine or alter the dividend rights,
dividend rate, conversion rights, voting rights, rights and terms of redemption (including sinking fund provisions, if any), the redemption price or prices, the liquidation
preferences and other designations, powers, preferences and relative, participating, optional or other special rights, if any, and the qualifications, limitations and restrictions
granted to or imposed upon any wholly unissued series of Preferred Stock, and to fix the number of shares of any series of Preferred Stock (but not below the number of shares
of any such series then outstanding).
DESCRIPTION OF WARRANTS
We may issue warrants to purchase shares of our common stock and/or preferred stock in one or more series together with other securities or separately. As of March
17, 2021 there were 15,576 shares of common stock that may be issued upon exercise of outstanding warrants.
DESCRIPTION OF DEBT SECURITIES
We may offer debt securities which may be senior, subordinated or junior subordinated and may be convertible. The terms of the debt securities will include those
stated in the indenture and those made part of the indenture by reference to the Trust Indenture Act of 1939, as in effect on the date of the indenture. We have filed a copy of the
form of indenture as an exhibit to our Form S-3 Registration Statement on May 2, 2018. The indenture will be subject to and governed by the terms of the Trust Indenture Act of
1939.
Debt Securities
The aggregate principal amount of debt securities that may be issued under the indenture is unlimited. The debt securities may be issued in one or more series as may
be authorized from time to time pursuant to a supplemental indenture entered into between us and the trustee or an order delivered by us to the trustee.
General
One or more series of debt securities may be sold as “original issue discount” securities. These debt securities would be sold at a substantial discount below their
stated principal amount, bearing no interest or interest at a rate which at the time of issuance is below market rates. One or more series of debt securities may be variable rate
debt securities that may be exchanged for fixed rate debt securities.
Debt securities may be issued where the amount of principal and/or interest payable is determined by reference to one or more currency exchange rates, commodity
prices, equity indices or other factors. Holders of such debt securities may receive a principal amount or a payment of interest that is greater than or less than the amount of
principal or interest otherwise payable on such dates, depending upon the value of the applicable currencies, commodities, equity indices or other factors.
The term “debt securities” includes debt securities denominated in U.S. dollars or, if specified in the applicable prospectus supplement, in any other freely transferable
currency or units based on or relating to foreign currencies.
Global Securities
The debt securities of a series may be issued in whole or in part in the form of one or more global securities that will be deposited with, or on behalf of, a depositary
identified in the prospectus supplement. Global securities will be issued in registered form and in either temporary or definitive form. Unless and until it is exchanged in whole
or in part for the individual debt securities, a global security may not be transferred except as a whole by the depositary for such global security to a nominee of such depositary
or by a nominee of such depositary to such depositary or another nominee of such depositary or by such depositary or any such nominee to a successor of such depositary or a
nominee of such successor. The specific terms of the depositary arrangement with respect to any debt securities of a series and the rights of and limitations upon owners of
beneficial interests in a global security will be described in the applicable prospectus supplement.
Governing Law
The indenture and the debt securities shall be construed in accordance with and governed by the laws of the State of New York.
DESCRIPTION OF UNITS
We may issue, in one more series, units comprised of shares of our common stock and/or preferred stock, warrants to purchase common stock and/or preferred stock,
debt securities or any combination of those securities. Each unit will be issued so that the holder of the unit is also the holder of each security included in the unit. Thus, the
holder of a unit will have the rights and obligations of a holder of each included security. The unit agreement under which a unit is issued may provide that the securities
included in the unit may not be held or transferred separately, at any time or at any time before a specified date.
We may evidence units by unit certificates that we issue under a separate agreement. We may issue the units under a unit agreement between us and one or more unit
agents. If we elect to enter into a unit agreement with a unit agent, the unit agent will act solely as our agent in connection with the units and will not assume any obligation or
relationship of agency or trust for or with any registered holders of units or beneficial owners of units. We will indicate the name and address and other information regarding
the unit agent in the applicable prospectus supplement relating to a particular series of units if we elect to use a unit agent.
Avenue Therapeutics, Inc.
New York, New York
Consent of Independent Registered Public Accounting Firm
We hereby consent to the incorporation by reference in the Registration Statements on Form S-3 (No. 333-224276) and Form S-8 (No. 333-219972) of Avenue Therapeutics,
Inc. of our report dated March 31, 2021, relating to the financial statements which appears in this Annual Report on Form 10-K. Our report contains an explanatory paragraph
regarding the Company’s ability to continue as a going concern.
Exhibit 23.1
/s/ BDO USA, LLP
New York, New York
March 31, 2021
Certification of
Principal Executive Officer
Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002
Exhibit 31.1
I, Lucy Lu, M.D., certify that:
1.
2.
3.
4.
I have reviewed this Annual Report on Form 10-K of Avenue Therapeutics, Inc.;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light
of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results
of operations and cash flows of the registrant as of, and for, the periods presented in this report;
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, 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 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/ Lucy Lu, M.D.
Lucy Lu, M.D.
President, Chief Executive Officer and Director
(Principal Executive Officer)
March 31, 2021
Certification of
Principal Financial Officer
Pursuant to Section 302 of the Sarbanes-Oxley Act of 2002
Exhibit 31.2
I, Joseph Vazzano, certify that:
1.
2.
3.
4.
I have reviewed this Annual Report on Form 10-K of Avenue Therapeutics, Inc.;
Based on my knowledge, this report does not contain any untrue statement of a material fact or omit to state a material fact necessary to make the statements made, in light
of the circumstances under which such statements were made, not misleading with respect to the period covered by this report;
Based on my knowledge, the financial statements, and other financial information included in this report, fairly present in all material respects the financial condition, results
of operations and cash flows of the registrant as of, and for, the periods presented in this report;
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, 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 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/ Joseph Vazzano
Joseph Vazzano
Chief Financial Officer
(Principal Financial Officer)
March 31, 2021
Certification of
Principal Executive Officer
Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002
Exhibit 32.1
I, Lucy Lu, M.D., Chief Executive Officer of Avenue Therapeutics, Inc. (the “Company”), in compliance with Section 906 of the Sarbanes-Oxley Act of 2002, hereby certify
that, to the best of my knowledge, the Company’s Annual Report on Form 10-K for the period ended December 31, 2020 (the “Report”) filed with the Securities and Exchange
Commission:
•
Fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
• The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
/s/ Lucy Lu, M.D.
Lucy Lu, M.D.
President, Chief Executive Officer and Director
(Principal Executive Officer)
March 31, 2021
Certification of
Principal Financial Officer
Pursuant to Section 906 of the Sarbanes-Oxley Act of 2002
Exhibit 32.2
I, Joseph Vazzano, Principal Financial Officer of Avenue Therapeutics, Inc. (the “Company”), in compliance with Section 906 of the Sarbanes-Oxley Act of 2002, hereby
certify that, to the best of my knowledge, the Company’s Annual Report on Form 10-K for the period ended December 31, 2020 (the “Report”) filed with the Securities and
Exchange Commission:
•
Fully complies with the requirements of Section 13(a) or 15(d) of the Securities Exchange Act of 1934; and
• The information contained in the Report fairly presents, in all material respects, the financial condition and results of operations of the Company.
/s/ Joseph Vazzano
Joseph Vazzano
Chief Financial Officer
(Principal Financial Officer)
March 31, 2021