Clinical Trials and Efficacy - DURECT Corporation's lead candidate, larsucosterol, demonstrated a 41% reduction in mortality at 90 days (p=0.068) for the 30 mg dose and a 35% reduction (p=0.124) for the 90 mg dose compared to placebo in the AHFIRM trial[29]. - The AHFIRM trial enrolled 307 patients with severe alcohol-associated hepatitis (AH), with 76% of patients from the U.S., showing a 57% reduction (p=0.014) in mortality for the 30 mg dose and 58% reduction (p=0.008) for the 90 mg dose in U.S. patients[29]. - The primary endpoint of mortality or liver transplantation at 90 days did not achieve statistical significance for either larsucosterol dose compared to placebo, although numerical improvements were observed[30]. - Larsucosterol 30 mg and 90 mg doses showed 90-day mortality reductions of approximately 41% and 35% compared to placebo, although not statistically significant[33]. - In U.S. patients, 90-day mortality reductions were 57% for the 30 mg group (p=0.014) and 58% for the 90 mg group (p=0.008) compared to placebo[35]. - The Phase 2a clinical trial included 19 patients, with all surviving the 28-day follow-up period and no drug-related serious adverse events reported[43]. - Future clinical trials are required to establish clinically and statistically significant proof of efficacy and safety for larsucosterol[159]. Regulatory Designations and Trials - The FDA granted Breakthrough Therapy Designation to larsucosterol for the treatment of AH in May 2024, with a planned Phase 3 trial to evaluate its safety and efficacy[1]. - The Phase 3 trial is expected to enroll approximately 200 patients in a 1:1 ratio for larsucosterol (30 mg) versus placebo, with a primary outcome measure of 90-day survival[1]. - The planned Phase 3 clinical trial will enroll approximately 200 patients, randomized 1:1 to larsucosterol (30 mg) or placebo, with a primary outcome measure of 90-day survival[46]. - The FDA granted Fast Track Designation for larsucosterol in December 2020 and Breakthrough Therapy Designation in May 2024 for the treatment of alcoholic hepatitis (AH)[45]. - The FDA or other regulatory agencies may require additional information or clinical studies, potentially delaying or preventing regulatory approval for larsucosterol[163]. - The FDA has granted Fast Track and Breakthrough Therapy Designations for larsucosterol, but these designations do not guarantee faster development or approval[175][176]. Financial and Market Considerations - The healthcare costs for hospitalized AH patients are significant, with average charges exceeding $147,000 for patients who died during hospitalization and $53,000 for those discharged[26]. - The average charges for a liver transplant exceed $875,000, with patients requiring lifelong immunosuppressive therapy[27]. - The company is currently facing significant challenges in raising capital to continue operations, with recurring losses and negative cash flows raising doubts about its ability to operate as a going concern[155]. - The company does not have sufficient cash resources to meet its plans for the next twelve months, necessitating additional financing to fund operations[155]. - The company may seek additional funding through equity or debt financings, which could be dilutive to existing stockholders[158]. - The company does not anticipate meaningful revenues from the commercialization of its products and product candidates in the near future, and does not expect revenues to exceed operating expenses[204]. - Indivior accounted for 78% of the company's total revenue in 2024, highlighting the significant reliance on this partnership[76]. - The company sold the ALZET product line for $17.5 million, which may impact future revenue streams[74]. Manufacturing and Supply Chain Risks - The company relies on third-party manufacturers for larsucosterol, increasing the risk of delays in regulatory submissions and commercialization efforts[152]. - The company relies on a limited number of suppliers for key components, which could lead to supply shortages or increased costs[184]. - The company has not established long-term supply agreements for all components, increasing the risk of supply interruptions[186]. - The company anticipates that reliance on third-party contractors for clinical trials and manufacturing may lead to delays and increased expenses if these contractors fail to meet obligations[197]. - Manufacturing delays or issues with third-party contractors could adversely affect the commercialization of larsucosterol[169]. Compliance and Regulatory Challenges - The company faces significant risks related to compliance with FDA regulations, which could delay or preclude the development and marketing of its products[201]. - The FDA's drug development process requires substantial time and financial resources, with no guarantee of timely approval[89]. - Drug manufacturers must adhere to Good Manufacturing Practices (GMP), with risks of non-compliance affecting product availability[104]. - The company may incur significant costs to comply with environmental and health regulations in the future, which could adversely affect its financial condition[209]. - The company may face significant costs and resource diversion due to litigation related to patent rights[84]. Employee and Operational Considerations - As of March 25, 2025, the company had 21 employees, with 43% male and 57% female representation, and 13 employees holding advanced degrees[147]. - The company has reduced its headcount from 58 as of March 26, 2024, to 21 as of March 25, 2025, through targeted reductions and the sale of the ALZET product line[206]. - The company must obtain marketing authorization from foreign regulatory authorities, which varies widely by country[127]. Competitive Landscape - The company faces significant competition from entities with greater resources and capabilities in the pharmaceutical and biotechnology sectors[138]. - The company may experience difficulties in enrolling patients for clinical trials, impacting the timelines for product development[191]. Legislative and Economic Factors - Legislative changes, such as the Affordable Care Act, impose additional fees and rebates on pharmaceutical manufacturers, impacting financial performance[119]. - Future healthcare reforms may impose downward pressure on prices for approved products, potentially harming future revenues[126]. - Macroeconomic uncertainties, including inflation and supply chain disruptions, have adversely impacted the company's operations and may continue to do so[189].

Financial Data and Key Metrics Changes - Total revenues in 2024 were $2 million, a decrease from $2.6 million in 2023, and $0.5 million for the fourth quarter of 2024 compared to $0.9 million for the prior year [5] - R&D expenses were $10.4 million in 2024, down from $29.4 million in the prior year, with fourth quarter expenses at $1.9 million compared to $5.6 million in 2023 [6] - SG&A expenses were $10 million in 2024, compared to $12.7 million in the prior year, and $2 million for the fourth quarter of 2024 compared to $2.2 million for the prior year [7] - Cash and investments at the end of 2024 were $12 million, down from $29.8 million at the end of 2023, with sufficient funds to support operations through the third quarter of 2025 [8] Business Line Data and Key Metrics Changes - The decrease in revenues was attributed to lower earn-out revenue from Indivior, reduced revenue from feasibility agreements, and lower sales of excipients [6] Company Strategy and Development Direction - The company completed the sale of the Allset product line in the fourth quarter of 2024, using proceeds to repay its term loan, resulting in a debt-free status [9] - The focus is on developing larsucosterol for alcohol-associated hepatitis, with plans to explore funding options through strategic partnerships and capital markets [10] Management's Comments on Operating Environment and Future Outlook - Management highlighted the significant mortality associated with alcohol-associated hepatitis, with larsucosterol showing nearly 60% reductions in mortality in Phase 2b trials [11][13] - The FDA granted breakthrough therapy designation for larsucosterol, and the company is committed to advancing its Phase 3 trial, expecting to report top-line data in approximately two years [14][15] Other Important Information - The company is actively exploring strategic partnerships and business development opportunities to support the Phase 3 study [38] Q&A Session Summary Question: Estimated cost of the Phase 3 trial - The estimated cost for the Phase 3 trial is approximately $20 million [18] Question: Clarification on hospitalization to first dose variations - Management explained the importance of timely intervention, noting that in the US, patients are typically treated within four days, while in poorer performing regions, it can take up to two weeks [30] Question: Updates on potential strategic partnerships - The company is actively exploring various possibilities for partnerships to advance the product, though specifics could not be disclosed [38] Question: Possibility of a smaller Phase 2b study - Management indicated that conducting a Phase 3 trial is more efficient than a smaller Phase 2b study, given the need for a larger patient cohort [46] Question: Opportunities for non-funded studies in ex-US countries - There is potential for conducting regional studies with ex-US partners, although the current focus remains solely on alcohol-associated hepatitis [50]

Durect (DRRX) came out with a quarterly loss of $0.06 per share versus the Zacks Consensus Estimate of $0.06. This compares to loss of $0.27 per share a year ago. These figures are adjusted for non-recurring items.This quarterly report represents an earnings surprise of -200%. A quarter ago, it was expected that this specialty pharmaceutical company would post a loss of $0.17 per share when it actually produced a loss of $0.14, delivering a surprise of 17.65%.Over the last four quarters, the company has sur ...

Exhibit 99.1 DURECT Corporation Reports Fourth Quarter and Full Year 2024 Financial Results and Provides Business Update Larsucosterol Phase 2b AHFIRM trial results published in NEJM Evidence in January 2025 Additional AHFIRM data presented in November 2024 at The Liver Meeting 2024 that informed the design of planned Phase 3 trial in alcohol-associated hepatitis (AH) Webcast of earnings call today, March 26 at 4:30 p.m. ET CUPERTINO, Calif., March 26, 2025 /PRNewswire / -- DURECT Corporation (Nasdaq: DRRX) ...

Core Insights - DURECT Corporation has made significant progress in the development of larsucosterol for alcohol-associated hepatitis (AH), with the publication of Phase 2b AHFIRM trial results in a prestigious journal, validating its potential as a treatment [2][9] - The company has strengthened its financial position by selling the ALZET product line, using the proceeds to repay its term loan, which aligns with its strategic goal of advancing larsucosterol development [2][9] - DURECT is planning a Phase 3 trial for larsucosterol, contingent on securing sufficient funding, with topline results expected within two years of trial initiation [9] Financial Highlights - For Q4 2024, DURECT reported total revenues of $0.5 million, a decrease from $0.9 million in Q4 2023, while net income was $7.8 million compared to a net loss of $1.4 million in the same period last year [9] - For the full year 2024, total revenues were $2.0 million, down from $2.6 million in 2023, with a net loss of $7.9 million compared to a net loss of $27.6 million in 2023 [9] - As of December 31, 2024, the company had cash, cash equivalents, and investments totaling $12.0 million, a significant decrease from $29.8 million at the end of 2023 [9] AHFIRM Trial Overview - The AHFIRM trial was a Phase 2b study involving 307 patients with severe AH, evaluating the safety and efficacy of larsucosterol [6] - The primary outcome measure was the 90-day incidence of mortality or liver transplantation, with key secondary endpoints including 90-day survival [6] - The trial received Fast Track and Breakthrough Therapy Designation from the U.S. FDA, highlighting the urgent need for effective treatments for AH [6][11] Larsucosterol Mechanism - Larsucosterol is an epigenetic modulator that inhibits DNA methylation, potentially improving cell survival and reducing inflammation in patients with AH [8][10] - The drug's mechanism of action provides a scientific rationale for its development in treating acute organ injury and chronic diseases [10][11] Future Plans - DURECT aims to initiate the Phase 3 trial for larsucosterol in 2025, with the design incorporating feedback from the FDA and insights from the AHFIRM trial [9] - The company is actively exploring funding options to support the continued development of larsucosterol [2][9]

Company Overview - DURECT Corporation is a late-stage biopharmaceutical company focused on developing epigenetic therapies targeting dysregulated DNA methylation to treat serious conditions, including acute organ injury [3] - The lead drug candidate, larsucosterol, inhibits DNA methyltransferases associated with hypermethylation in acute hepatitis (AH) patients and is in clinical development [3] Financial Results Announcement - DURECT Corporation will report its fourth quarter and full year 2024 financial results on March 26, 2025, followed by a conference call and webcast at 4:30 pm Eastern Time [1][2] Drug Development and Designations - Larsucosterol has received Fast Track and Breakthrough Therapy designations from the FDA for the treatment of AH, indicating its potential significance in addressing this condition [3] - The company is also exploring larsucosterol for other indications, including MASH [3] Additional Product Information - POSIMIR® (bupivacaine solution) is FDA-approved for infiltration use and utilizes the SABER® platform technology, representing another product in DURECT's portfolio [3]

Core Insights - DURECT Corporation will present at the Oppenheimer 35th Annual Healthcare Life Sciences Conference on February 11-12, 2025, with CEO James E. Brown leading the presentation [1][2] - The company is focused on developing epigenetic therapies, particularly targeting dysregulated DNA methylation to treat serious conditions like acute organ injury [3] Company Overview - DURECT is a late-stage biopharmaceutical company known for its lead drug candidate, larsucosterol, which inhibits DNA methyltransferases associated with alcohol-associated hepatitis (AH) [3] - Larsucosterol is currently in clinical development for AH and has received Fast Track and Breakthrough Therapy designations from the FDA [3] - The company is also exploring larsucosterol for metabolic dysfunction-associated steatohepatitis (MASH) [3] - DURECT's POSIMIR® (bupivacaine solution) is FDA-approved for infiltration use and utilizes the SABER® platform technology [3] Presentation Details - The presentation is scheduled for February 11, 2025, from 2:00 to 2:30 PM ET, and will be available via webcast [2] - DURECT management will engage in one-on-one investor meetings during the conference [2]

The article presents new trial data, including subgroup analyses and liver biomarkers, which have guided the design of the Company's planned Phase 3 trialCUPERTINO, Calif., Jan. 28, 2025 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX) today announced the publication of a peer-reviewed article on the AHFIRM trial data in NEJM Evidence. The full article, entitled, "Larsucosterol for the Treatment of Alcohol-Associated Hepatitis," can be accessed here.The AHFIRM trial was a Phase 2b randomized, double-blind, ...

Durect (DRRX) could be a solid choice for investors given its recent upgrade to a Zacks Rank #1 (Strong Buy). This upgrade is essentially a reflection of an upward trend in earnings estimates -- one of the most powerful forces impacting stock prices.The sole determinant of the Zacks rating is a company's changing earnings picture. The Zacks Consensus Estimate -- the consensus of EPS estimates from the sell-side analysts covering the stock -- for the current and following years is tracked by the system.The p ...

Core Viewpoint - Durect (DRRX) has been upgraded to a Zacks Rank 2 (Buy), indicating a positive outlook on its earnings estimates, which is a significant factor influencing stock prices [1][2]. Earnings Estimates and Stock Price Impact - The Zacks rating system reflects changes in earnings estimates, which are strongly correlated with near-term stock price movements, particularly due to institutional investors adjusting their valuations based on these estimates [3]. - For Durect, the rising earnings estimates and the rating upgrade suggest an improvement in the company's underlying business, likely leading to an increase in stock price [4]. Earnings Estimate Revisions - Durect is expected to earn -$0.50 per share for the fiscal year ending December 2024, representing a 68.2% change from the previous year's reported number [7]. - Over the past three months, the Zacks Consensus Estimate for Durect has increased by 38.2%, indicating a positive trend in earnings expectations [7]. Zacks Rank System - The Zacks Rank system classifies stocks into five groups based on earnings estimates, with a strong historical performance, particularly for Zacks Rank 1 stocks, which have generated an average annual return of +25% since 1988 [6]. - Durect's upgrade to a Zacks Rank 2 places it in the top 20% of Zacks-covered stocks, suggesting a strong potential for market-beating returns in the near term [10].