Breakthrough Pain

- Enrollment completed in Phase 1b/2a clinical trial of AJ201 for spinal and bulbar muscular atrophy; topline data expected in second quarter of 2024 - - Presented positive BAER-101 preclinical data at American Epilepsy Society (AES) and American Society for Experimental Neurotherapeutics (ASENT) Annual Meetings and in publication Drug Development Research - - Final agreement reached with FDA on study design and analysis approach for Phase 3 safety study of IV tramadol – MIAMI, March 18, 2024 (GLOBE NEWSWIRE) -- Avenue Therapeutics, Inc. (Nasdaq: ATXI) (“Avenue” or the “Company”), a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases, today reported financial results and recent corporate highlights for the year ended December 31, 2023. “We made considerable progress across our pipeline of differentiated neurologic therapies in 2023," said Alexandra MacLean, M.D., Chief Executive Officer of Avenue. “Avenue demonstrated tremendous execution capabilities with our lead clinical program AJ201, a potential first-in-class treatment for spinal and bulbar muscular atrophy (SBMA), also known as Kennedy’s Disease. Within nine months of acquiring the rights to AJ201 in March 2023, we dosed the first patient in the Phase 1b/2a clinical trial, and we completed trial enrollment of 25 SBMA patients across six sites in the U.S. We remain on track to report topline data for AJ201 in the second quarter of 2024, an incredibly exciting milestone for both the Company and patients suffering from SBMA, a debilitating rare neuromuscular disorder with no approved treatments in the U.S. Additionally, we have progressed BAER-101 for the treatment of epilepsy by presenting preclinical data from a translational animal model in multiple peer-reviewed forums. We have also advanced IV tramadol, reaching final agreement with the U.S. Food and Drug Administration (FDA) on the safety study and statistical analysis approach for the final Phase 3 study. Pending additional financing, we look forward to progressing BAER-101 and IV tramadol for patients facing great unmet need. We look forward to another productive year in 2024 as we continue to make significant strides across our clinical pipeline and advance our mission of providing impactful therapies to patients suffering from neurologic diseases.” Recent Corporate Highlights: AJ201 (Nrf1 and Nrf2 activator, androgen receptor degradation enhancer for SBMA) In January 2024, Avenue completed enrollment in the Phase 1b/2a clinical trial of AJ201 for the treatment of SBMA. The 12-week, multicenter, randomized, double-blind Phase 1b/2a clinical trial of AJ201 enrolled 25 patients randomly assigned to AJ201 (600 mg/day) or placebo. The primary endpoint of the study is to assess safety and tolerability of AJ201 in subjects with clinically and genetically defined SBMA. Topline data for the Phase 1b/2a study are anticipated in the second quarter of 2024. More information about this study can be found at ClinicalTrials.gov (Identifier: NCT05517603). BAER-101 (GABAA α2/3 positive allosteric modulator) Avenue presented preclinical results for BAER-101, a potentially best-in-class selective GABAA α2,3 positive allosteric modulator, in three scientific peer-reviewed settings, including the American Epilepsy Society (AES) Annual Meeting in December 2023, the publication Drug Development Research in February 2024 and the American Society for Experimental Neurotherapeutics (ASENT) Annual Meeting in March 2024. The in vivo data showcase BAER-101’s ability to significantly suppress seizures using the SynapCell’s Genetic Absence Epilepsy Rat from Strasbourg (“GAERS”) model of epilepsy. BAER-101 fully suppressed seizure activity in the GAERS model with a minimal effective dose of 0.3 mg/kg, PO, and the effect was fast in onset and stable throughout the duration of testing. The data also demonstrated BAER-101’s ability to selectively target GABAA α2 and α3 subtypes more than α1 and α5, potentially improving anti-convulsant and anxiolytic activity while minimizing the risk of tolerance and abuse associated with existing treatments in this drug class. Subject to obtaining the necessary financing, which could be provided through a strategic partnership, Avenue plans to initiate a Phase 2a clinical trial of BAER-101 to further study its anti-seizure properties in patients with common or rare epilepsies. IV Tramadol In January 2024, Avenue reached final agreement with the FDA on the safety study protocol and statistical analysis approach for the Phase 3 study for intravenous (“IV”) tramadol, which is in development for the treatment of acute post-operative pain in a medically supervised setting. The final non-inferiority study is designed to assess the theoretical risk of opioid-induced respiratory depression related to opioid stacking on IV tramadol compared to IV morphine. The study will randomize approximately 300 post bunionectomy patients to IV tramadol or IV morphine for pain relief administered during a 48-hour post-operative period. Patients will have access to IV hydromorphone, a Schedule II opioid, for rescue of breakthrough pain. Pending additional financing, Avenue aims to initiate the Phase 3 safety study as soon as feasible. The Company believes that the study can be completed and submitted to the FDA within 12 months of the study’s initiation. General Corporate In March 2024, Avenue announced that the Nasdaq Hearings Panel granted the Company’s request for an extension to evidence compliance with all applicable criteria for continued listing on The Nasdaq Capital Market, including the $1.00 bid price and $2.5 million stockholders’ equity requirements, through May 20, 2024. 2023 Financial Results: Cash Position: As of December 31, 2023, cash and cash equivalents totaled $1.8 million, compared to $6.7 million at December 31, 2022, a decrease of $4.9 million. In January 2024, the Company completed a warrant inducement transaction resulting in $5.0 million in gross proceeds.R&D Expenses: Research and development expenses for the full year 2023 were $6.1 million, compared to $2.7 million in 2022. Additionally, there was $4.2 million in expense for the acquisition of the AJ201 license in 2023.G&A Expenses: General and administrative expenses for the full year 2023 were $4.2 million, compared to $5.3 million in 2022.Net Loss: Net loss for the full year 2023 was $10.5 million, or $0.98 per share, compared to a net loss of $3.6 million, or $1.63 per share, in 2022. About Avenue TherapeuticsAvenue Therapeutics, Inc. (Nasdaq: ATXI) is a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases. It is currently developing three assets including AJ201, a first-in-class asset for spinal and bulbar muscular atrophy, BAER-101, an oral small molecule selective GABAA α2, α3 receptor positive allosteric modulator for CNS diseases, and IV tramadol, which is in Phase 3 clinical development for the management of acute postoperative pain in adults in a medically supervised healthcare setting. Avenue is headquartered in Miami, FL and was founded by Fortress Biotech, Inc. (Nasdaq: FBIO). For more information, visit www.avenuetx.com. Forward-Looking StatementsThis press release contains predictive or “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of current or historical fact contained in this press release, including statements that express our intentions, plans, objectives, beliefs, expectations, strategies, predictions or any other statements relating to our future activities or other future events or conditions are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “will,” “should,” “would” and similar expressions are intended to identify forward-looking statements. These statements are based on current expectations, estimates and projections made by management about our business, our industry and other conditions affecting our financial condition, results of operations or business prospects. These statements are not guarantees of future performance and involve risks, uncertainties and assumptions that are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed or forecasted in, or implied by, the forward-looking statements due to numerous risks and uncertainties. Factors that could cause such outcomes and results to differ include, but are not limited to, risks and uncertainties arising from: the fact that we currently have no drug products for sale and that our success is dependent on our product candidates receiving regulatory approval and being successfully commercialized; the possibility that serious adverse or unacceptable side effects are identified during the development of our current or future product candidates, such that we would need to abandon or limit development of some of our product candidates; our ability to successfully develop, partner, or commercialize any of our current or future product candidates including AJ201, IV tramadol, and BAER-101; the substantial doubt raised about our ability to continue as a going concern, which may hinder our ability to obtain future financing; the significant losses we have incurred since inception and our expectation that we will continue to incur losses for the foreseeable future; our need for substantial additional funding, which may not be available to us on acceptable terms, or at all, which unavailability of could force us to delay, reduce or eliminate our product development programs or commercialization efforts; our reliance on third parties for several aspects of our operations; our reliance on clinical data and results obtained by third parties that could ultimately prove to be inaccurate, or unreliable, or unacceptable to regulatory authorities; the possibility that we may not receive regulatory approval for any or all of our product candidates, or that such approval may be significantly delayed due to scientific or regulatory reasons; the fact that even if one or more of our product candidates receives regulatory approval, they will remain subject to substantial regulatory scrutiny; the effects of current and future laws and regulations relating to fraud and abuse, false claims, transparency, health information privacy and security, and other healthcare laws and regulations; the effects of competition for our product candidates and the potential for new products to emerge that provide different or better therapeutic alternatives for our targeted indications; the possibility that the government or third-party payors fail to provide adequate coverage and payment rates for our product candidates or any future products; our ability to establish sales and marketing capabilities or to enter into agreements with third parties to market and sell our product candidates; our exposure to potential product liability claims; related to the protection of our intellectual property and our potential inability to maintain sufficient patent protection for our technology and products; our ability to maintain compliance with the obligations under our intellectual property licenses and funding arrangements with third parties, without which licenses and arrangements we could lose rights that are important to our business; the fact that Fortress Biotech, Inc. controls a majority of the voting power of our outstanding capital stock and has rights to receive significant share grants annually;; and those risks discussed in our filings which we make with the SEC. Any forward-looking statements speak only as of the date on which they are made, and we undertake no obligation to publicly update or revise any forward-looking statements to reflect events or circumstances that may arise after the date of this press release, except as required by applicable law. Investors should evaluate any statements made by us in light of these important factors. Contact: Jaclyn JaffeAvenue Therapeutics, Inc. (781) 652-4500ir@avenuetx.com AVENUE THERAPEUTICS, INC.Consolidated Balance Sheets($ in thousands, except for share and per share amounts) December 31, December 31, 2023 2022 ASSETS Current assets: Cash and cash equivalents$1,783 $6,708 Prepaid expenses and other current assets 67 137 Total assets$1,850 $6,845 LIABILITIES AND STOCKHOLDERS’ EQUITY Current liabilities: Accounts payable and accrued expenses$287 $949 Accounts payable and accrued expenses - related party 323 21 Warrant liability 586 2,609 Total current liabilities 1,196 3,579 Total liabilities 1,196 3,579 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, 2023 and 2022, respectively — — Common stock ($0.0001 par value) Common shares, 75,000,000 shares authorized and 25,597,622 shares issued and outstanding as of December 31, 2023; and 20,000,000 shares authorized and 4,773,841 shares issued and outstanding as of December 31, 2022 3 — Additional paid-in capital 92,507 84,456 Accumulated deficit (90,928) (80,551)Total stockholders’ equity attributed to the Company 1,582 3,905 Non-controlling interests (928) (639)Total stockholders’ equity 654 3,266 Total liabilities and stockholders’ equity$1,850 $6,845 AVENUE THERAPEUTICS, INC.Consolidated Statements of Operations($ in thousands, except for share and per share amounts) For the Years Ended December 31, December 31, 2023 2022 Operating expenses Research and development$6,131 $2,698 Research and development - licenses acquired 4,230 — General and administrative 4,179 5,345 Loss from operations (14,540) (8,043) Interest income (126) (20)Financing costs – warrant liabilities 332 1,160 Change in fair value of warrant liabilities (4,258) (5,580)Net loss$(10,488) $(3,603) Net loss attributable to non-controlling interests (111) (51)Net loss attributable to common stockholders$(10,377) $(3,552) Net loss per common share attributable to common stockholders, basic and diluted$(0.98) $(1.63) Weighted average number of common shares outstanding, basic and diluted 10,591,636 2,185,159

Publication Details Positive Results of Clinical Study PF614-102 SAN DIEGO, CA / ACCESSWIRE / February 15, 2024 / Ensysce Biosciences, Inc. (NASDAQ:ENSC)(OTC PINK:ENSCW) ("Ensysce" or "Company"), a clinical-stage company applying transformative chemistry to improve prescription drug safety, today announced online publication of its manuscript entitled, "Clinical evaluation of PF614, a novel TAAP(TM) prodrug of oxycodone, versus OxyContin® in a multi-ascending dose study with a bioequivalence arm in healthy volunteers" published online by the open-access medical journal Clinical and Translational Science (CTS) sponsored by the American Society of Clinical Pharmacology and Therapeutics (ASCPT). The article is authored by members of the Ensysce team plus external experts; D. Lynn Kirkpatrick PhD, Cari Evans RN, Linda A. Pestano PhD, Jeffrey Millard PhD, Matthew Johnston MD, Emily Mick PharmD, and William K. Schmidt PhD. The results from the two-part PF614‑102 study are very significant as we believe they demonstrate a clear dose relationship between PF614 and oxycodone, which is the foundation for the FDA submission. The BE arm showed that plasma oxycodone bioequivalence was successfully achieved between 100 mg PF614 and 40 mg OxyContin. PF614 provided similar oxycodone exposures in both fasted and fed states, showing that it can be taken either on an empty stomach or with food, these data highlight PF614's potential advantage compared to other marketed abuse deterrent formulation (ADF) opioids. PF614 also showed a longer (12 hour) half-life, a major patient benefit in severe pain treatment. This manuscript provides a report of the safety and pharmacokinetics (PK) pro PF614, a Trypsin-Activated Abuse Protection (TAAP™) oxycodone prodrug designed to reduce recreational drug abuse. PF614 was compared to OxyContin® in healthy subjects in the initial multi-ascending dose arm of the study. Additionally, the manuscript details the second arm which evaluated oxycodone release from PF614 and OxyContin administered to 60 subjects in both a fasted and fed state in order to assess whether PF614 is bioequivalent (BE) to OxyContin. The notable distinction identified in this study between PF614 and OxyContin was the longer half-life of PF614, which provides a benefit to the patient as this is a true twice daily pain treatment. We believe this differentiating feature is critically important as steady blood levels can deliver sustained analgesia throughout the day to prevent breakthrough pain and the need for additional therapeutics. Dr. Lynn Kirkpatrick, Chief Executive Officer of Ensysce Biosciences, commented, "We are pleased that the PF614‑102 study not only confirmed findings from our prior Single Ascending Dose study showing 100 mg of PF614 releases oxycodone with a PK pro to 40 mg of OxyContin, but demonstrated the beneficial qualities of PF614 in contrast to alternative commercially available ADFs including its fed/fasted equivalency and longer half-life. As the clinical data and safety package strengthens for PF614 with each study we complete, we continue to move closer to our goal of bringing the ‘next generation' of analgesics for severe pain to market." CTS is a peer-reviewed open-access medical journal that highlights original research and helps to bridge laboratory discoveries with the diagnosis and treatment of human disease. About Ensysce Biosciences Ensysce Biosciences is a clinical-stage company using its proprietary technology platforms to develop safer prescription drugs. Leveraging its Trypsin-Activated Abuse Protection (TAAPTM) and Multi-Pill Abuse Resistance (MPAR®) platforms, the Company is developing unique, tamper-proof treatment options for pain that minimize the risk of both drug abuse and overdose. Ensysce's products are anticipated to provide safer options to treat patients suffering from severe pain and assist in preventing deaths caused by medication abuse. The platforms are covered by an extensive worldwide intellectual property portfolio for a wide array of prescription drug compositions. For more information, please visit . Forward-Looking Statements Statements contained in this press release that are not purely historical may be deemed to be forward-looking statements for the purposes of the safe harbor provisions under The Private Securities Litigation Reform Act of 1995 and other federal securities laws. Without limiting the foregoing, the use of words such as "may," "intends," "can," "might," "will," "expect," "plan," "possible," "believe" and other similar expressions are intended to identify forward-looking statements. The product candidates discussed are in clinic and not approved and there can be no assurance that the clinical programs will be successful in demonstrating safety and/or efficacy, that Ensysce will not encounter problems or delays in clinical development, or that any product candidate will ever receive regulatory approval or be successfully commercialized. All forward-looking statements are based on estimates and assumptions by Ensysce's management that, although Ensysce believes to be reasonable, are inherently uncertain. All forward-looking statements are subject to risks and uncertainties that may cause actual results to differ materially from those that Ensysce expected. In addition, Ensysce's business is subject to additional risks and uncertainties, including among others, the initiation and conduct of preclinical studies and clinical trials; the timing and availability of data from preclinical studies and clinical trials; expectations for regulatory submissions and approvals; potential safety concerns related to, or efficacy of, Ensysce's product candidates; the availability or commercial potential of product candidates; the ability of Ensysce to fund its continued operations, including its planned clinical trials; the dilutive effect of stock issuances from our fundraising; and Ensysce's and its partners' ability to perform under their license, collaboration and manufacturing arrangements. These statements are also subject to a number of material risks and uncertainties that are described in Ensysce's most recent quarterly report on Form 10-Q and current reports on Form 8-K, which are available, free of charge, at the SEC's website at . Any forward-looking statement speaks only as of the date on which it was made. Ensysce undertakes no obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required under applicable law. Ensysce Biosciences Company Contact: Lynn Kirkpatrick, Ph.D. Chief Executive Officer (858) 263-4196 Ensysce Biosciences Investor Relations Contact: Shannon Devine MZ North America Main: 203-741-8811 ENSC@mzgroup.us SOURCE: Ensysce Biosciences Inc. View the original press release on accesswire.com

MIAMI, Jan. 04, 2024 (GLOBE NEWSWIRE) -- Avenue Therapeutics, Inc. (Nasdaq: ATXI) (“Avenue” or the “Company”), a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases, today announced that it has reached final agreement with the U.S. Food and Drug Administration (“FDA”) on the Phase 3 safety study protocol and statistical analysis approach, including the primary endpoint, for intravenous (IV) tramadol, which is in development for the treatment of acute post-operative pain in a medically supervised setting. The final non-inferiority study is designed to assess the theoretical risk of opioid-induced respiratory depression related to opioid stacking on IV tramadol compared to IV morphine. “We have worked collaboratively with the FDA over the last year to design a study that will address a theoretical safety risk. We are pleased with the agreed-upon plan for the clinical trial and believe that this trial will support a safe profile for IV tramadol administration for acute pain in the post-operative period,” said Alexandra MacLean, M.D., Chief Executive Officer of Avenue. The study will randomize approximately 300 post bunionectomy patients to IV tramadol or IV morphine for pain relief administered during a 48-hour post-operative period. Of note, IV tramadol demonstrated safety and efficacy in this same surgical model in two Phase 3 efficacy trials. Patients will have access to IV hydromorphone, a Schedule II opioid, for rescue of breakthrough pain. The primary endpoint is a composite of elements indicative of respiratory depression. Avenue believes the study can be completed within 12 months and submitted to the FDA to address the CRL and potentially lead to approval of IV tramadol. Dr. MacLean continued, “Subject to obtaining the necessary financing, which could be provided through a strategic partnership, Avenue plans to initiate the Phase 3 safety study as soon as possible, and could potentially have study results in-hand as early as the end of this year. We expect that a positive study outcome could result in the FDA approval of IV tramadol, potentially improving the current treatment paradigm available for U.S. patients in managing post-operative pain and providing significant near-term value for Avenue shareholders.” About Avenue TherapeuticsAvenue Therapeutics, Inc. (Nasdaq: ATXI) is a specialty pharmaceutical company focused on the development and commercialization of therapies for the treatment of neurologic diseases. It is currently developing three assets including AJ201, a first-in-class asset for spinal and bulbar muscular atrophy, BAER101, an oral small molecule selective GABAA α2/3 receptor positive allosteric modulator for CNS diseases, and IV tramadol, which is in Phase 3 clinical development for the management of acute postoperative pain in adults in a medically supervised healthcare setting. Avenue is headquartered in Miami, FL and was founded by Fortress Biotech, Inc. (Nasdaq: FBIO). For more information, visit www.avenuetx.com. Forward-Looking StatementsThis press release contains predictive or “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. All statements other than statements of current or historical fact contained in this press release, including statements that express our intentions, plans, objectives, beliefs, expectations, strategies, predictions or any other statements relating to our future activities or other future events or conditions are forward-looking statements. The words “anticipate,” “believe,” “continue,” “could,” “estimate,” “expect,” “intend,” “may,” “plan,” “predict,” “project,” “will,” “should,” “would” and similar expressions are intended to identify forward-looking statements. These statements are based on current expectations, estimates and projections made by management about our business, our industry and other conditions affecting our financial condition, results of operations or business prospects. These statements are not guarantees of future performance and involve risks, uncertainties and assumptions that are difficult to predict. Therefore, actual outcomes and results may differ materially from what is expressed or forecasted in, or implied by, the forward-looking statements due to numerous risks and uncertainties. Factors that could cause such outcomes and results to differ include, but are not limited to, risks and uncertainties arising from: 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 candidates; 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; expectations for future capital requirements; and those risks discussed in our filings which we make with the SEC. Any forward-looking statements speak only as of the date on which they are made, and we undertake no obligation to publicly update or revise any forward-looking statements to reflect events or circumstances that may arise after the date of this press release, except as required by applicable law. Investors should evaluate any statements made by us in light of these important factors. Contact: Jaclyn JaffeAvenue Therapeutics, Inc. (781) 652-4500ir@avenuetx.com