Bupivacaine Hydrochloride

- FDA Granted Breakthrough Therapy Designation for Larsucosterol in Alcohol-Associated Hepatitis - Held Type B Meeting with FDA to Discuss Phase 3 Clinical Trial Design - Seeking to Initiate Phase 3 Trial in 2024 with Topline Results Expected in 2H 2026 - Webcast of Earnings Call Today, August 13th at 4:30 p.m. ET CUPERTINO, Calif., Aug. 13, 2024 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX) today announced financial results for the three months ended June 30, 2024 and provided a business update. "Our immediate priority is to finalize the design of our planned pivotal Phase 3 trial of larsucosterol in alcohol-associated hepatitis (AH)," stated James E. Brown, D.V.M., President and CEO of DURECT. "Recently we had a productive Type B meeting with the U.S. Food and Drug Administration (FDA) to discuss our proposed trial design and requirements to obtain approval. We are encouraged by the FDA's feedback on our plans to advance development of larsucosterol, including its granting of Breakthrough Therapy Designation (BTD), and look forward to providing a further update on specifics of the Phase 3 design following expected communications from FDA. Assuming we obtain sufficient funds, we plan to initiate the Phase 3 study by the end of 2024 and would expect to report topline results by the second half of 2026. We are committed to advancing development of larsucosterol and bringing this potentially lifesaving therapy to patients as quickly as possible. If larsucosterol meets our expectations in Phase 3 and we are successful in gaining approval, it would likely be the first FDA-approved treatment for AH." Business Update: The FDA granted Breakthrough Therapy Designation to larsucosterol for the treatment of patients with AH. BTD is designed to expedite the development and review of therapies intended to treat a serious or life-threatening condition and whose preliminary clinical evidence indicates that the drug may demonstrate substantial improvement on one or more clinically significant endpoints over existing available therapies. In July 2024, DURECT held a Type B meeting with the FDA to discuss the design of its planned Phase 3 clinical trial of larsucosterol in AH that, if successful, could support a potential NDA filing. The Company plans to provide additional details of the Phase 3 trial design following receipt of the written minutes from this meeting. DURECT's goal is to initiate its Phase 3 trial in 2024, subject to obtaining sufficient funding, with topline results expected by the second half of 2026. Data from the Company's Phase 2b AHFIRM trial, which evaluated the safety and efficacy of larsucosterol as a treatment for patients with severe AH, were featured in a late-breaking oral presentation at the European Association for the Study of the Liver (EASL) Congress 2024 on June 8, 2024 in Milan, Italy. This was the first presentation of the AHFIRM data at a medical meeting. Top line data from the study were previously announced in 2023. Financial Highlights for Q2 2024: Total revenues were $2.2 million and net loss was $3.7 million for the three months ended June 30, 2024 compared to total revenues of $2.1 million and net loss of $11.2 million for the three months ended June 30, 2023. Cash, cash equivalents and investments were $15.8 million at June 30, 2024, compared to $29.8 million at December 31, 2023. Debt at June 30, 2024 was $12.5 million, compared to $16.7 million at December 31, 2023. Earnings Conference Call We will host a conference call and webcast today at 4:30 p.m. Eastern Time/1:30 p.m. Pacific Time to discuss the second quarter 2024 results and provide a corporate update: Tuesday, August 13 @ 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time Call me™: Participants can use Guest dial-in numbers above and be answered by an operator OR click the Call me™ link for instant telephone access to the event. The Call me™ link will be made active 15 minutes prior to the scheduled start time. The live audio webcast of the presentation will be also available on DURECT's homepage at on the "Events" page, under the "Investors" section. If you are unable to participate during the live webcast, the call will be archived on DURECT's website under the same section, following the completion of the call. About the AHFIRM Trial AHFIRM was a Phase 2b randomized, double-blind, placebo-controlled, international, multi-center study conducted in subjects with severe alcohol-associated hepatitis ( AH) to evaluate the sa Fety and eff Icacy of la Rsucosterol treat Ment (AHFIRM). The study was comprised of three arms and enrolled 307 patients, with approximately 100 patients in each arm: (1) Placebo, which consists of standard of care, with or without methylprednisolone capsules at the investigators' discretion; (2) larsucosterol (30 mg); and (3) larsucosterol (90 mg). Patients in the larsucosterol arms received the same supportive care without steroids. The primary outcome measure was the 90-Day incidence of mortality or liver transplantation for patients treated with larsucosterol compared to those treated with placebo, and the key secondary endpoint was 90-Day survival. The Company enrolled patients at clinical trial sites across the U.S., EU, U.K., and Australia. In November 2023, the Company announced topline data for the AHFIRM Trial. Reflecting the life-threatening nature of AH and the lack of therapeutic options, the U.S. Food and Drug Administration (FDA) has granted larsucosterol Fast Track Designation and Breakthrough Therapy Designation for the treatment of AH. For more information, refer to ClinicalTrials.gov Identifier: NCT04563026. About Alcohol-associated Hepatitis (AH) AH is an acute form of alcohol-associated liver disease (ALD) associated with long-term heavy alcohol intake, often following a recent period of increased consumption (i.e., a binge). AH is typically characterized by severe inflammation and liver cell damage, potentially leading to life-threatening complications including liver failure, acute kidney injury and multi-organ failure. There are no FDA approved therapies for AH, and a retrospective analysis of 77 studies published between 1971 and 2016, which included data from 8,184 patients, showed the overall mortality from AH was 26% at 28 days, 29% at 90 days and 44% at 180 days. A subsequent global study published in December 2021, which included 85 tertiary centers in 11 countries across 3 continents, prospectively enrolled 2,581 AH patients with a median Model of End-Stage Liver Disease (MELD) score of 23.5, reported mortality at 28 and 90 days of approximately 20% and 31%, respectively. Stopping alcohol consumption is necessary, but frequently not sufficient for recovery in many moderate (defined as MELD scores of 11-20) and severe (defined as MELD scores >20) patients, and therapies that reduce liver inflammation, such as corticosteroids, are limited by contraindications, have not been shown to improve survival at 90 days or one year, and have demonstrated an increased risk of infection. While liver transplantation is becoming more common for ALD patients, including AH patients, the total number of such transplants is still relatively small, and limited by organ availability. Average charges for a liver transplant exceed $875,000, and patients require lifelong immunosuppressive therapy to prevent organ rejection. About Larsucosterol Larsucosterol is an endogenous sulfated oxysterol and an epigenetic modulator. Epigenetic regulators are compounds that regulate patterns of gene expression without modifying the DNA sequence. DNA hypermethylation, an example of epigenetic dysregulation, results in transcriptomic reprogramming and cellular dysfunction, and has been reported in many acute (e.g., AH) and chronic diseases (e.g., MASH). As an inhibitor of DNA methyltransferases (DNMT1, DNMT3a and 3b), larsucosterol inhibits DNA methylation, which subsequently modulates expression of genes that are involved in cell signaling pathways associated with stress responses, cell death and survival, and lipid biosynthesis. This may ultimately lead to improved cell survival, reduced inflammation, and decreased lipotoxicity. As an epigenetic modulator, the proposed mechanism of action provides further scientific rationale for developing larsucosterol for the treatment of acute organ injury and certain chronic diseases. About DURECT Corporation DURECT is a late-stage biopharmaceutical company pioneering the development of epigenetic therapies that target dysregulated DNA methylation to transform the treatment of serious and life-threatening conditions, including acute organ injury and cancer. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases (DNMTs), epigenetic enzymes that are elevated and associated with hypermethylation found in alcohol-associated hepatitis (AH) patients. Larsucosterol is in clinical development for the potential treatment of AH, for which the FDA has granted Fast Track and Breakthrough Therapy designation; metabolic dysfunction-associated steatohepatitis (MASH) is also being explored. In addition, POSIMIR® (bupivacaine solution) for infiltration use, a non-opioid analgesic utilizing the innovative SABER® platform technology, is FDA-approved and is exclusively licensed to Innocoll Pharmaceuticals for sale and distribution in the United States. For more information about DURECT, please visit and follow us on X (formerly Twitter) at . DURECT Forward-Looking Statements This press release contains forward-looking statements, including statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995, relating to: the Company's ability to commence a Phase 3 trial of larsucosterol in 2024 and report top-line data by the second half of 2026, the potential for a single Phase 3 trial of larsucosterol, if successful, to support an NDA filing, and the potential uses and benefits of laruscosterol in patients with AH and potentially other indications. Actual results may differ materially from those contained in the forward-looking statements contained in this press release, and reported results should not be considered as an indication of future performance. The potential risks and uncertainties that could cause actual results to differ from those projected include, among other things, the risks that the Company is unable to raise sufficient capital to commence the Phase 3 trial of larsucosterol in AH, trial enrollment or completion takes longer than anticipated, future clinical trials of larsucosterol are delayed or do not confirm the results from subset analyses of the AHFIRM trial, including geographic or other segmentation, or of earlier clinical or pre-clinical trials, or do not demonstrate the safety or efficacy of larsucosterol in a statistically significant manner; the risk that the FDA or other government agencies may require additional clinical trials for larsucosterol before approving larsucosterol for the treatment of AH, and that larsucosterol may never be approved; and risks related to the sufficiency of our cash resources, our anticipated capital requirements, our need or desire for additional financing, our ability to continue to meet the minimum bid price for continued listing on Nasdaq, our ability to obtain capital to fund our operations and expenses, and our ability to continue to operate as a going concern. Further information regarding these and other risks is included in DURECT's most recent Securities and Exchange Commission (SEC) filings, including its annual report on Form 10-K for the year ended December 31, 2023 and quarterly report on Form 10-Q for the quarter ended June 30, 2024, when filed, under the heading "Risk Factors." These reports are available on our website under the "Investors" tab and on the SEC's website at . All information provided in this press release and in the attachments is based on information available to DURECT as of the date hereof, and DURECT assumes no obligation to update this information as a result of future events or developments, except as required by law. NOTE: POSIMIR® is a trademark of Innocoll Pharmaceuticals, Ltd. in the U.S. and a trademark of DURECT Corporation outside of the U.S. SABER® is a trademark of DURECT Corporation. Other referenced trademarks belong to their respective owners. Larsucosterol is an investigational drug candidate under development and has not been approved for commercialization by the U.S. Food and Drug Administration or other health authorities for any indication. SOURCE DURECT Corporation

Surpassed 50% Enrollment Milestone in Pivotal Phase 3 STRIVE-ON Safety Trial of GTX-104Company Anticipates Completion of Patient Enrollment in the STRIVE-ON Trial in Late 2024 to Early 2025, with NDA Submission on Track for 1H Calendar 2025Projected Cash Runway into Second Calendar Quarter 2026 PRINCETON, N.J., Aug. 09, 2024 (GLOBE NEWSWIRE) -- Acasti Pharma Inc. (Nasdaq: ACST) (Acasti or the Company), a late-stage, biopharma company advancing GTX-104, its novel injectable formulation of nimodipine that addresses high unmet medical needs for a rare disease, aneurysmal subarachnoid hemorrhage (aSAH), today announced financial results and business highlights for the quarter ended June 30, 2024. “As a result of unrelenting focus on patient enrollment by the Acasti team and participating clinical trial sites, we surpassed the 50% enrollment milestone in our Phase 3 STRIVE-ON safety trial (the STRIVE-ON trial–NCT05995405),” said Prashant Kohli, CEO of Acasti. “Investigators continue to be very enthusiastic about the potential of GTX-104 for the treatment of aSAH. These patients require intensive management and present with a variety of complications that make consistent administration of oral nimodipine difficult, and GTX-104 may provide an effective IV alternative to the current standard of care. Based on enrollment trends and ongoing engagement with investigators, we anticipate randomizing all 100 patients in late 2024 to early 2025. We believe that the STRIVE-ON trial is on track for a potential New Drug Application (NDA) submission to the U.S. Food and Drug Administration (FDA) in the first half of calendar 2025.” First Fiscal Quarter 2025 Highlights Pivotal Phase 3 STRIVE-ON safety trial surpassed the 50% enrollment milestone.100% patient enrollment of STRIVE-ON trial projected for late calendar 2024 or early 2025.NDA submission to FDA for GTX-104 anticipated in the first half of calendar 2025.Conducted a meeting of STRIVE-ON trial investigators in April 2024. First Fiscal Quarter 2025 Financial Results The Company reported a net loss of $2.6 million, or $0.24 loss per share, for the quarter ended June 30, 2024, a decrease of $1.4 million from the net loss of $4.0 million or $0.54 per share for the quarter ended June 30, 2023. The decrease in net loss was primarily due to restructuring costs of $1.5 million during the three months ended June 30, 2023 and a $1.4 million decrease to the fair value of our derivative warrant liabilities, offset in part by a $1.6 million increase in research and development expenses. Total research and development expenses for the quarter ended June 30, 2024 were $2.7 million, compared to $1.1 million for the quarter ended June 30, 2023. This increase of $1.6 million was primarily due to the increase in our research activities for our GTX-104 pivotal Phase 3 STRIVE-ON safety clinical trial. General and administrative expenses were $2.3 million for the quarter ended June 30, 2024, an increase of $0.4 million from $1.9 million for the year quarter ended June 30, 2023. The increase was primarily a result of increased legal, tax, accounting and other professional fees related to the proposed change in the jurisdiction of incorporation of Acasti from the Province of Québec in Canada to the State of Delaware in the United States. At June 30, 2024 the Company had cash and cash equivalents of $19.4 million, as compared to $23.0 million, as of March 31, 2024. The Company believes it has sufficient cash to support operations into the second calendar quarter of 2026. About aneurysmal Subarachnoid Hemorrhage (aSAH) aSAH is bleeding over the surface of the brain in the subarachnoid space between the brain and the skull, which contains blood vessels that supply the brain. A primary cause of such bleeding is the rupture of an aneurysm. Approximately 70% of aSAH patients experience death or dependence, and more than 30% die within one month of hemorrhage. Approximately 50,000 patients in the United States are affected by aSAH per year, based on market research. Outside of the United States, annual cases of aSAH are estimated at approximately 60,000 in the European Union, and approximately 150,000 in China. About the Acasti Asset Portfolio GTX-104 is a clinical stage, novel, injectable formulation of nimodipine being developed for intravenous (IV) infusion in aSAH patients to address significant unmet medical needs. The unique nanoparticle technology of GTX-104 facilitates aqueous formulation of insoluble nimodipine for a standard peripheral IV infusion. GTX-104 provides a convenient IV delivery of nimodipine in the Intensive Care Unit potentially eliminating the need for nasogastric tube administration in unconscious or dysphagic patients. Intravenous delivery of GTX-104 also has the potential to lower food effects, drug-to-drug interactions, and eliminate potential dosing errors. Further, GTX-104 has the potential to better manage hypotension in aSAH patients. GTX-104 has been administered in over 150 healthy volunteers and was well tolerated with significantly lower inter- and intra-subject pharmacokinetic variability compared to oral nimodipine. The addressable market in the United States for GTX-104 is estimated to be about $300 million, based on market research. GTX-102 is a novel, concentrated oral-mucosal spray of betamethasone intended to improve neurological symptoms of Ataxia-Telangiectasia (A-T), for which there are currently no FDA-approved therapies. GTX-102 is a stable, concentrated oral spray formulation comprised of the gluco-corticosteroid betamethasone that, together with other excipients can be sprayed conveniently over the tongue of the A-T patient and is rapidly absorbed. The further development of GTX-102 has been deprioritized in favor of our focus on development of GTX-104. It is also possible that we may license or sell our GTX-102 drug candidate. GTX-101 is a non-narcotic, topical bio-adhesive film-forming bupivacaine spray designed to ease the symptoms of patients suffering with postherpetic neuralgia (PHN). GTX-101 is administered via a metered-dose of bupivacaine spray and forms a thin bio-adhesive topical film on the surface of the patient’s skin, which enables a touch-free, non-greasy application. It also comes in convenient, portable 30 ml plastic bottles. Unlike oral gabapentin and lidocaine patches, we believe that the biphasic delivery mechanism of GTX-101 has the potential for rapid onset of action and continuous pain relief for up to eight hours. No skin sensitivity was reported in a Phase 1 trial. The further development of GTX-101 has been deprioritized in favor of our focus on development of GTX-104. It is also possible that we may license or sell our GTX-101 drug candidate. About Acasti Acasti is a late-stage biopharma company with drug candidates addressing rare and orphan diseases. Acasti's novel drug delivery technologies have the potential to improve the performance of currently marketed drugs by achieving faster onset of action, enhanced efficacy, reduced side effects, and more convenient drug delivery. Acasti's lead clinical assets have each been granted Orphan Drug Designation by the FDA, which provides seven years of marketing exclusivity post-launch in the United States, and additional intellectual property protection with over 40 granted and pending patents. Acasti's lead clinical asset, GTX-104, is an intravenous infusion targeting aneurysmal Subarachnoid Hemorrhage (aSAH), a rare and life-threatening medical emergency in which bleeding occurs over the surface of the brain in the subarachnoid space between the brain and skull. For more information, please visit: www.acasti.com. Forward-Looking Statements Statements in this press release that are not statements of historical or current fact constitute "forward-looking statements" within the meaning of the U.S. Private Securities Litigation Reform Act of 1995, as amended, Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended, and "forward-looking information" within the meaning of Canadian securities laws (collectively, "forward-looking statements"). Such forward looking statements involve known and unknown risks, uncertainties, and other factors that could cause the actual results of Acasti to be materially different from historical results or from any future results expressed or implied by such forward-looking statements. In addition to statements which explicitly describe such risks and uncertainties, readers are urged to consider statements containing the terms "believes," "belief," "expects," "intends," "anticipates," "estimates", "potential," "should," "may," "will," "plans," "continue", "targeted" or other similar expressions to be uncertain and forward-looking. Readers are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date of this press release. The forward-looking statements in this press release, including statements regarding the Company's anticipated cash runway, the timing of completing full patient enrollment in its Phase 3 STRIVE-ON safety trial of GTX-104, the timing of the Company’s planned NDA submission with the FDA in connection with the Company's Phase 3 STRIVE-ON safety trial, GTX-104’s commercial prospects; the size of the addressable market for GTX-104, the Company’s beliefs regarding the potential benefits of GTX-104, including GTX-104's potential to bring enhanced treatment options to patients suffering from aSAH, and the anticipated benefits and future development, license or sale of the Company's other drug candidates are based upon Acasti's current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, including, without limitation: (i) the success and timing of regulatory submissions of the Phase 3 STRIVE-ON safety trial for GTX-104; (ii) regulatory requirements or developments and the outcome and timing of the proposed NDA application for GTX-104; (iii) changes to clinical trial designs and regulatory pathways; (iv) legislative, regulatory, political and economic developments; and (v) actual costs associated with Acasti's clinical trials as compared to management's current expectations. The foregoing list of important factors that could cause actual events to differ from expectations should not be construed as exhaustive and should be read in conjunction with statements that are included herein and elsewhere, including the risk factors detailed in documents that have been and are filed by Acasti from time to time with the Securities and Exchange Commission and Canadian securities regulators. All forward-looking statements contained in this press release speak only as of the date on which they were made. Acasti undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by applicable securities laws. For more information, please contact: Acasti Contact: Prashant Kohli Chief Executive Officer Tel: 450-686-4555 Email: info@acastipharma.com www.acasti.com Investor Relations: LifeSci Advisors Mike Moyer Managing Director Phone: 617-308-4306 Email: mmoyer@lifesciadvisors.com ---tables to follow--- ACASTI PHARMA INC.Condensed Consolidated Balance Sheets (Unaudited) June 30, 2024 March 31, 2024 (Expressed in thousands except share data)$ $ Assets Current assets: Cash and cash equivalents19,394 23,005 Short-term investments15 — Receivables398 722 Prepaid expenses622 283 Total current assets20,429 24,010 Equipment, net23 24 Intangible assets41,128 41,128 Goodwill8,138 8,138 Total assets69,718 73,300 Liabilities and Shareholders’ equity Current liabilities: Trade and other payables2,600 1,684 Total current liabilities2,600 1,684 Derivative warrant liabilities2,964 4,359 Deferred tax liability4,790 5,514 Total liabilities10,354 11,557 Commitments and contingencies Shareholders’ equity: Class A common shares, no par value per share; unlimited shares authorized; 10,139,861 and 9,399,404 shares issued and outstanding as of June 30, 2024 and March 31, 2024, respectively261,038 261,038 Class B, C, D and E common shares, no par value per share; unlimited shares authorized; none issued and outstanding— — Additional paid-in capital18,100 17,862 Accumulated other comprehensive loss(6,038)(6,038)Accumulated deficit(213,736)(211,119)Total shareholders' equity59,364 61,743 Total liabilities and shareholders’ equity69,718 73,300 ACASTI PHARMA INC.Condensed Consolidated Statements of Loss and Comprehensive Loss (Unaudited) Three months ended June 30, 2024 June 30, 2023 (Expressed in thousands, except share and per share data)$ $ Operating expenses Research and development expenses, net of government assistance(2,708)(1,095)General and administrative expenses(2,255)(1,874)Restructuring cost— (1,485)Loss from operating activities(4,963)(4,454) Foreign exchange (loss) gain(8)8 Change in fair value of derivative warrant liabilities1,395 — Interest income and other expense, net235 134 Total other income, net1,622 142 Loss before income tax recovery(3,341)(4,312) Income tax benefit724 289 Net loss and total comprehensive loss(2,617)(4,023) Basic and diluted loss per share(0.24)(0.54) Weighted-average number of shares outstanding10,928,543 7,435,533