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Medscape
09-07-2025
- Health
- Medscape
Launched: Early-Stage Hodgkin Lymphoma Prediction Tool
The first prediction model to be developed for early-stage classic Hodgkin lymphoma, focusing on just four key risk factors that are assessed via an easy-to-use online risk calculator, provides individualized prediction of patients' 2-year progression-free survival, using continuous variables that enable high precision in the risk assessments. 'Utilizing objective, continuous, and readily available variables in nearly 5400 early-stage classic Hodgkin lymphoma patients, we developed and validated a robust, dynamic, and modern prediction model,' co-author Andrew M. Evens, DO, of the Division of Blood Disorders, Rutgers Cancer Institute, New Brunswick, New Jersey, said in presenting the findings at the 18th International Conference on Malignant Lymphoma (ICML) 2025 in Lugano, Switzerland. 'Male sex, and continuous values of decreasing hemoglobin or albumin, and incrementally increasing maximum tumor diameter were associated with worse progression-free survival,' Evens said of the research, which was simultaneously published in NEJM Evidence . While the vast majority of patients with early-stage classic Hodgkin lymphoma do have favorable outcomes, the cure rate isn't 100%, and the prognostic models currently used, such as those from the European Organisation for Research and Treatment of Cancer (EORTC) or German Hodgkin Study Group (GHSG), have been used for decades, with general assessments as being either favorable or unfavorable, Evens explained. 'These original models were based on data from the early 1970s, when the majority of patients had staging laparotomies and radiation alone as treatment,' he explained. An update from the GHSG in 2013 was performed, but 'overall, it had poor specificity,' he said. 'With more sophistication available in modeling and in contemporary datasets, there has been an unmet need [for a modernized prediction tool] identified,' Evens noted. In response, the new model was developed by Evens and colleagues as part of the HoLISTIC (Hodgkin Lymphoma International Study for Individual Care) international consortium. Called the Early-Stage cHL International Prognostication Index (E-HIPI), the new model was developed with the use of data on 3000 patients with untreated, early-stage classic Hodgkin lymphoma from four seminal, phase 3 clinical trials, including the CCTG-ECOG, EORTC H9, RAPID, and EORTC H10 trials. Those patients, overall, had a median age of 31.2 years, and 77.4% had stage II disease. Their estimated 2-year progression-free survival was 93.7%. Four Key Risk Factors in Early-Stage Classic Hodgkin Lymphoma Based on the analysis, four key parameters that emerged as being significantly associated with progression-free survival were female sex, conveying a lower risk (hazard ratio [HR], 0.59); maximum tumor diameter (HR, 1.06 per 1 cm, ranging from 1.5 to 15.0, hence 'about a 10% increased risk with each centimeter increase,' Evens said); hemoglobin level (HR, 1.09; continuous, ranging from 5.0 to 16.5 g/dL); and albumin level (HR, 0.83; continuous, ranging from 2.5 to 6.0 g/dL), where increases from low levels to high levels were predictive factors for each. The data were validated externally using two separate cohorts of 2360 contemporaneously treated patients from five international cancer registries, including the BC Cancer, Princess Margaret, Iowa/Mayo SPORE, Stanford Registry, and Danish National Lymphoma Registry. In those external validation cohorts, the 2-year progression-free survival was slightly lower, at 90.3% in cohort 1 and 91.6% in cohort 2. After multivariate adjustment in a Cox regression model, the E-HIPI model was significantly associated with progression-free survival, whereas the EORTC measures of favorable or unfavorable status were not. The number of nodal groups was also considered as a potential predictor but was ultimately not found to be significantly associated with progression-free survival in the model. Continuous Variables Provide Greater Context The online risk calculator, in addition to providing a 2-year progression-free survival estimate, also helps to estimate risk according to adjustments based on differing potential disease trajectories. Notably, whereas many other models use basic cutoffs for factors, such as age being categorized as older or younger than 45 years, the model uses continuous variables to provide context for each input in relation to a full range, instead of just being under or over a specific level. 'We know that if you try to dichotomize a continuous factor, you lose a lot of statistical power, and you lose potential nonlinear effects,' Evens explained. With dichotomized values such as age categorized as older or younger than 45 years, 'how can you know, for instance, that outcomes with a 44-year-old are going to be similar to the 18-year-old?' he said. 'Likewise, with tumor diameters, as opposed to saying simply above or below 10 cm, this approach gives us more richness and more power in individualized prediction to base the risk on the exact tumor dimension.' The 2-year progression-free survival was seen as the most important primary outcome for the model because among the very small proportion of patients who do have a relapse, such events most commonly occur within 2 years, Evens noted. However, with ever-advancing therapies continuously affecting outcomes, and the known small risk for postacute late effects occurring years later, potentially due not to the disease itself but to exposure to treatments such as chemotherapy and radiation, the work on E-HIPI will continue. The current predictor was step 1, Evens told Medscape Medical News . Step 2 will be to look at different treatments and help predict outcomes based on the differing treatments, and step 3 will involve the estimation of postacute late effects, he explained. 'Our model provides more precise and individualized prediction [than existing methods], and in the near future with the second and third iterations of the model, we'll be able to take this to the bedside and help predict not just general outcomes for patients, but more exact treatment options,' he said. The E-HIPI is in fact the second prognostic tool developed by the international consortium. The team has also made available the Advanced-stage cHL International Prognostication Index. Commenting on the study, Alex Herrera, MD, chief of the Division of Lymphoma, Department of Hematology & Hematopoietic Cell Transplantation, City of Hope Medical Center in Duarte, California, said the new model offers some important new insights. 'We rely heavily on early-stage prognostic indices, since patients with early-stage cHL are classified as 'favorable' or 'unfavorable' based on these risk factor indices, and that is what determines the treatment plan,' he told Medscape Medical News . 'Here we see that some of the traditional factors in the GHSG and EORTC risk stratification may not be as useful.' Herrera agreed that a key attribute of the new prediction model is the use of the continuous values. 'An important change [from previous models] is the use of the full range of values (continuous) as opposed to just binary thresholds,' Herrera said. He added that 'albumin and hemoglobin have always been a part of the advanced-stage IPI, but here they were key prognostic factors for early-stage disease.' While the previous indices will continue to determine how to treat patients, 'the online tool will allow this to become a key part of prognostic discussions with patients in the clinic,' Herrera said.
Yahoo
13-05-2025
- Business
- Yahoo
DURECT Corporation Reports First Quarter 2025 Financial Results and Provides Business Update
Planning a registrational Phase 3 trial for larsucosterol in alcohol-associated hepatitis (AH) with topline results expected within two years of trial initiation Larsucosterol Phase 2b AHFIRM trial results published in NEJM Evidence in January 2025 CUPERTINO, Calif., May 13, 2025 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX) today announced financial results for the first quarter ended March 31, 2025 and provided a business update. "Our primary focus continues to be initiating the Phase 3 trial of larsucosterol for severe AH, contingent on securing sufficient funding," stated James E. Brown, D.V.M., President and CEO of DURECT. "We continue to be engaged in active dialogue to explore all options for funding the continued development of larsucosterol, including potential business development and financing transactions. Additionally, the publication of the results of our Phase 2b AHFIRM trial in January 2025 in NEJM Evidence provides important validation of the potential value of larsucosterol as a treatment for AH and supports our planned Phase 3 trial design." Recent business highlights and updates: DURECT is planning a registrational Phase 3 trial to evaluate the safety and efficacy of larsucosterol for the treatment of patients with severe AH. The trial will be a randomized, double-blind, placebo-controlled, multi-center study conducted in the U.S. The primary endpoint will be 90-day survival. The trial design incorporates feedback received from the U.S. Food and Drug Administration (FDA) during a Type B meeting that took place in 2024 under Breakthrough Therapy Designation (BTD) as well as learnings from the prior Phase 2b AHFIRM trial in AH. DURECT's goal is to begin the trial in 2025, subject to obtaining sufficient funding, with topline results expected within two years of trial initiation. Results from the AHFIRM Phase 2b trial were published in NEJM Evidence in January 2025. In addition to highlighting the key findings from this study, the article also included new trial data, including subgroup analyses that explain regional differences in patient populations and in AH treatment regimens. Variations in time from hospitalization to first dose highlighted the importance of timely treatment in patients with severe AH. Top line data from AHFIRM were previously announced in November 2023. On May 6, 2025, Innocoll Pharmaceuticals Limited (Innocoll) transferred all data and know-how related to POSIMIR to us upon termination of the licensing agreement between us and Innocoll. We are evaluating next steps with respect to finding a new partner to commercialize POSIMIR. Financial Highlights for the First Quarter 2025: Total revenues were $0.3 million and net loss was $4.2 million for the three months ended March 31, 2025 compared to total revenues of $0.5 million and net loss of $7.6 million for the three months ended March 31, 2024. As of March 31, 2025, cash, cash equivalents and investments were $8.4 million, compared to cash, cash equivalents and investments of $12.0 million at December 31, 2024. About the AHFIRM TrialAHFIRM 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 saFety and effIcacy of laRsucosterol treatMent (AHFIRM). The study was comprised of three arms and enrolled 307 patients, with approximately 100 patients in each arm: (1) Placebo, which consisted 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. FDA has granted larsucosterol Fast Track Designation and Breakthrough Therapy Designation for the treatment of AH. For more information, refer to 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 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 LarsucosterolLarsucosterol 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 CorporationDURECT 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. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases, epigenetic enzymes that are elevated and associated with hypermethylation found in AH patients. Larsucosterol is in clinical development for the potential treatment of AH, for which the FDA has granted a Fast Track and a Breakthrough Therapy designation; MASH has also been explored. For more information about DURECT, please visit and follow us on X (formerly Twitter) at DURECT Forward-Looking StatementsThis 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: our plans regarding finding a new partner to commercialize POSIMIR, our plans to conduct a Phase 3 clinical trial of larsucosterol, the ability of the Phase 3 trial to be successful and, if successful, to support a New Drug Application filing, the sufficiency of our capital requirements and our ability to secure sufficient funding for a Phase 3 trial of larsucosterol, our expectations for timing of topline results from a Phase trial of larsucosterol and the potential uses of larsucosterol to treat 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 risk that 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 we do not raise sufficient capital to commence or complete the Phase 3 clinical trial of larsucosterol in patients with AH or continue to fund our operations, the risk that the FDA or other government agencies may experience disruptions due to departmental funding shortages or require additional clinical trials for larsucosterol before approving larsucosterol for the treatment of AH, the risk that Breakthrough Therapy designation does not expedite the process for FDA approval and that larsucosterol may never be approved; and risks related to the sufficiency of our cash resources, our anticipated capital requirements, our ability to regain the minimum bid price for continued listing on Nasdaq, 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 filings, including its annual report on Form 10-K for the year ended December 31, 2024 and quarterly report on Form 10-Q for the quarter ended March 31, 2025, 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 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: 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. DURECT CORPORATION CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE LOSS (in thousands, except per share amounts) (unaudited)Three months ended March 31 20252024 Collaborative research and development and other revenue $ 321$ 496Total revenues 321496 Operating expenses: Research and development 1,8834,119Selling, general and administrative 2,5772,681 Total operating expenses 4,4606,800 Loss from operations (4,139)(6,304) Other income (expense): Interest and other income 95321Change in fair value of warrant liabilities (119)(1,718) Other expense, net(24)(1,397) Loss from continuing operations (4,163)(7,701) Income (loss) from discontinued operations (69)58 Net loss$ (4,232)$ (7,643) Net change in unrealized gain on available-for-sale securities, net of reclassification adjustments and taxes $ -$ 4 Total comprehensive loss $ (4,232)$ (7,639) Net loss per share, basic Loss from continuing operations $ (0.13)$ (0.25)Income (loss) from discontinued operations $ -$ -Net loss per common share $ (0.13)$ (0.25) Net loss per share, diluted Loss from continuing operations $ (0.13)$ (0.25)Income (loss) from discontinued operations $ -$ -Net loss per common share $ (0.13)$ (0.25) Weighted-average shares used in computing net income (loss) per share Basic31,04230,637Diluted31,04230,637 DURECT CORPORATION CONDENSED BALANCE SHEETS (in thousands) As ofAs of March 31, 2025December 31, 2024 (1) (unaudited) ASSETS Current assets: Cash and cash equivalents$ 7,963$ 11,011 Short-term Investments297792 Accounts receivable, net330453 Inventories, net85106 Prepaid expenses and other current assets737813 Total current assets9,41213,175Property and equipment, net3841 Operating lease right-of-use assets1,9122,135 Goodwill2,7252,725 Long-term restricted Investments150150 Other long-term assets123123 Total assets$ 14,360$ 18,349LIABILITIES AND STOCKHOLDERS' EQUITY Current liabilities: Accounts payable$ 313$ 309 Accrued liabilities4,6034,771 Operating lease liabilities, current portion1,0901,082 Warrant liabilities1,6671,548 Total current liabilities7,6737,710Operating lease liabilities, noncurrent portion8931,124 Other long-term liabilities443384Stockholders' equity5,3519,131 Total liabilities and stockholders' equity $ 14,360$ 18,349 (1) Derived from audited financial statements. 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Malaysian Reserve
22-04-2025
- Health
- Malaysian Reserve
Cellenkos' Off-the-Shelf Treg Cell Therapy Shows Clinical Safety and Preliminary Efficacy in ALS
Cryopreserved allogeneic Treg infusions associated with slowed disease progression and decreased plasma neurofilament level in ALS HOUSTON, April 22, 2025 /PRNewswire/ — New findings published today in NEJM Evidence reveal promising clinical outcome for Cellenkos Inc.'s cryopreserved, allogeneic, T regulatory (Treg) cells derived from umbilical cord blood, for the treatment of Amyotrophic Lateral Sclerosis (ALS)—a neurodegenerative disease with limited therapeutic options. The study reports that patients receiving multiple intravenous infusions of this 'off-the-shelf' Treg therapy showed a measurable slowdown in disease progression. Prior to therapy, participants' ALS Functional Rating Scale-Revised (ALSFRS-R) scores declined at an average rate of −1.66 points per month. During treatment, that rate slowed significantly to −0.41 points per month, with a modest post-treatment decline of −0.60 points per month—suggesting sustained benefit. Clinical improvements were accompanied by reductions in plasma neurofilament levels, a biomarker correlated with neuronal injury. The Treg therapy was administered in an outpatient setting via peripheral IV, with each patient receiving a standardized fixed dose of 100 million cells. The regimen included weekly infusions for the first month, followed by monthly doses for six months, with optional continued dosing based on physician discretion. The therapy required no lymphodepletion, immunosuppression, interleukin-2, or HLA matching, and patients were discharged the same day. Importantly, no dose-limiting toxicities were reported. Six participants, with a median age of 48.5 years (range: 27–66), and a median baseline ALSFRS-R score of 31.5 (range: 23–43), received a median of 11 infusions (range: 6–22), and all were alive at the time of last follow-up. Among participants with sufficient follow-up data (n=4), the median follow-up duration was 18 months. 'These results are both encouraging and transformative for those battling ALS,' said Dr. Simrit Parmar, Founder of Cellenkos and faculty member at Texas A&M University. 'Unlike conventional cell therapies that require complex, individualized cell harvesting and hospitalization, our Treg therapy is cryopreserved, ready-to-use, and outpatient-based. It eliminates the need for HLA matching and preconditioning. These findings offer a compelling proof of concept and lay the foundation for our next-generation neurotropic Tregs, CK0803.' CK0803 Tregs, now in clinical trials, are modified to overexpress CD11a and CXCR3, improving their ability to migrate to inflamed brain regions, specifically, inflamed microglia — potentially enabling direct targeting of ALS-related pathology. These findings offer renewed hope for patients, families, and researchers working toward more accessible, non-invasive, and effective treatments for ALS. About Amyotrophic Lateral Sclerosis (ALS)ALS is a progressive neurodegenerative disease that affects nerve cells responsible for voluntary muscles. As the disease advances, individuals experience worsening muscle weakness, paralysis, and eventual respiratory failure. Most patients succumb to ALS within three to five years of diagnosis. Currently, there is no cure. About Cellenkos®, Inc. Cellenkos is a clinical-stage biotech company, advancing allogeneic, off-the-shelf, cord blood-derived T regulatory cell therapies for rare inflammatory and autoimmune diseases. Its pipeline includes: CK0801 for Aplastic Anemia CK0802 for Acute Respiratory Distress Syndrome CK0803 for ALS CK0804 for Myelofibrosis Using its proprietary CRANE® platform, Cellenkos tailors tissue directed Treg therapies that require no HLA or ABO matching, can be administered in outpatient settings, and are optimized for rapid, point of care delivery. Contactbd@
Yahoo
26-03-2025
- Business
- Yahoo
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) today announced financial results for the fourth quarter and full year ended December 31, 2024 and provided a business update. "We recently achieved significant accomplishments that reinforced our plans for continuing development of larsucosterol for AH and strengthened our balance sheet," stated James E. Brown, D.V.M., President and CEO of DURECT. "We are excited that NEJM Evidence published the results of our Phase 2b AHFIRM trial in January 2025. Publication in such a highly regarded, peer reviewed journal provides additional validation of the potential value of larsucosterol as a treatment for AH. We have incorporated these results, together with the additional AHFIRM data presented at The Liver Meeting 2024, into our planned Phase 3 trial design. Additionally, in the fourth quarter we completed the sale of the ALZET product line and used the proceeds to repay the entirety of our term loan. By strengthening our balance sheet, this transaction furthers our strategic goal of advancing development of larsucosterol for AH. Our primary focus continues to be initiating the Phase 3 trial of larsucosterol for severe AH, contingent on securing sufficient funding. We are engaged in active dialogue to explore all options for funding the continued development of larsucosterol, including potential business development and financing transactions." Recent business highlights and updates: DURECT is planning a registrational Phase 3 trial to evaluate the safety and efficacy of larsucosterol for the treatment of patients with severe AH. The trial will be a randomized, double-blind, placebo-controlled, multi-center study conducted in the U.S. The primary endpoint will be 90-day survival. The trial design incorporates feedback received from the U.S. Food and Drug Administration (FDA) during a Type B meeting that took place in 2024 under Breakthrough Therapy Designation (BTD) as well as learnings from the prior Phase 2b AHFIRM trial in AH. DURECT's goal is to begin the trial in 2025, subject to obtaining sufficient funding, with topline results expected within two years of trial initiation. Results from the AHFIRM Phase 2b trial were published in NEJM Evidence in January 2025. In addition to highlighting the key findings from this study, the article also included new trial data, including subgroup analyses that explain regional differences in patient populations and in AH treatment regimens. Variations in time from hospitalization to first dose highlighted the importance of timely treatment in patients with severe AH. The full article can be accessed here. Top line data from AHFIRM were previously announced in November 2023. DURECT delivered an oral and two poster presentations at The Liver Meeting 2024, organized by the American Association for the Study of Liver Diseases (AASLD), in November 2024, in San Diego, California. These presentations showcased additional data from the Phase 2b AHFIRM trial. The data further support the design of the Company's planned Phase 3 trial of larsucosterol, including the importance of timely treatment in driving clinical outcomes. In November 2024, DURECT sold its ALZET® line of osmotic pumps to Lafayette Instrument Co. (LIC), a portfolio company of Branford Castle Partners II, L.P., a North-American focused private equity firm. DURECT received $17.5 million from LIC. Simultaneous with this transaction, DURECT paid off all remaining obligations under its term loan agreement with Oxford Finance LLC. As a result of the sale, the operating results from our ALZET product line have been excluded from continuing operations and presented as discontinued operations in the accompanying Condensed Statements of Operations and Comprehensive Income (Loss) and Condensed Balance Sheets for all periods presented. Financial Highlights for the Fourth Quarter and Full Year 2024: Total revenues were $0.5 million and net income was $7.8 million for the three months ended December 31, 2024 compared to total revenues of $0.9 million and net loss of $1.4 million for the three months ended December 31, 2023. Total revenues were $2.0 million and net loss was $7.9 million for the full year ended December 31, 2024, compared to total revenues of $2.6 million and net loss of $27.6 million for the full year ended December 31, 2023. As of December 31, 2024, cash, cash equivalents and investments were $12.0 million, compared to cash, cash equivalents and investments of $29.8 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 Fourth Quarter and Full Year 2024 results and provide a corporate update: Toll Free: 1-877-407-0784 International: 1-201-689-8560 Call Me: Participants can use guest dial-in numbers above to reach an operator or they can click the Call meTM link for instant telephone access to the event (dial-out). The Call meTM link will be made active 15 minutes prior to the scheduled start time. Webcast: 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 TrialAHFIRM 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 saFety and effIcacy of laRsucosterol treatMent (AHFIRM). The study was comprised of three arms and enrolled 307 patients, with approximately 100 patients in each arm: (1) Placebo, which consisted 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. FDA has granted larsucosterol Fast Track Designation and Breakthrough Therapy Designation for the treatment of AH. For more information, refer to 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 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 LarsucosterolLarsucosterol 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 CorporationDURECT 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. Larsucosterol, DURECT's lead drug candidate, binds to and inhibits the activity of DNA methyltransferases, epigenetic enzymes that are elevated and associated with hypermethylation found in AH patients. Larsucosterol is in clinical development for the potential treatment of AH, for which the FDA has granted a Fast Track and a Breakthrough Therapy designation; MASH has also been explored. For more information about DURECT, please visit and follow us on X (formerly Twitter) at DURECT Forward-Looking StatementsThis 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: our plans to conduct a Phase 3 clinical trial of larsucosterol, the ability of the Phase 3 trial to be successful and, if successful, to support a New Drug Application filing, the sufficiency of our capital requirements (including our sale of the our ALZET product line) to further our strategic goal and our ability to secure sufficient funding for a Phase 3 trial of larsucosterol, our expectations for timing of topline results from a Phase trial of larsucosterol and the potential uses of larsucosterol to treat 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 risk that 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 we do not raise sufficient capital to commence or complete the Phase 3 clinical trial of larsucosterol in patients with AH or continue to fund our operations, the risk that the FDA or other government agencies may require additional clinical trials for larsucosterol before approving larsucosterol for the treatment of AH, the risk that Breakthrough Therapy designation does not expedite the process for FDA approval and that larsucosterol may never be approved; and risks related to the sufficiency of our cash resources, our anticipated capital requirements, our ability to regain the minimum bid price for continued listing on Nasdaq, 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 filings, including its annual report on Form 10-K for the year ended December 31, 2024, when filed, and quarterly report on Form 10-Q for the quarter ended September 30, 2024, 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 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: 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. DURECT CORPORATIONCONDENSED BALANCE SHEETS(in thousands)As ofAs ofDecember 31, 2024December 31, 2023 (1)(unaudited)ASSETSCurrent assets: Cash and cash equivalents$ 11,011$ 28,400 Short-term Investments7921,280 Accounts receivable, net453618 Inventories, net106132 Prepaid expenses and other current assets8131,465 Discontinued operations - current assets-2,777Total current assets13,17534,672Property and equipment, net4188Operating lease right-of-use assets2,1353,079Goodwill2,7256,169Long-term restricted Investments150150Other long-term assets123123Discontinued operations - non-current assets-908Total assets$ 18,349$ 45,189LIABILITIES AND STOCKHOLDERS' EQUITYCurrent liabilities: Accounts payable$ 309$ 1,723 Accrued liabilities4,3215,810 Term loan, current portion, net-16,663 Operating lease liabilities, current portion1,0821,171 Warrant liabilities1,5481,224 Discontinued operations - current liabilities-420Total current liabilities7,26027,011Operating lease liabilities, noncurrent portion1,1241,967Other long-term liabilities384594Discontinued operations - non-current liabilities-834Stockholders' equity9,58114,783Total liabilities and stockholders' equity $ 18,349$ 45,189(1) Derived from audited financial statements. DURECT CORPORATION CONDENSED STATEMENTS OF OPERATIONS AND COMPREHENSIVE INCOME (LOSS) (in thousands, except per share amounts) (unaudited)Three months endedTwelve months ended December 31 December 31 2024202320242023 Collaborative research and development and other revenue $ 425$ 620$ 1,896$ 2,277 Product revenue, net28274135313Total revenues4538942,0312,590 Operating expenses:Cost of product revenues 2223878268Research and development 1,8535,61510,38329,351Selling, general and administrative 1,9932,22010,03212,653 Total operating expenses 3,8688,07320,49342,272 Loss from operations(3,415)(7,179)(18,462)(39,682) Other income (expense): Interest and other income 1114498212,129Change in fair value of warrant liabilities 1,5894,982(323)13,583Issuance cost for warrants ---(1,627)Loss on issuance of warrants ---(2,033) Other income (expense), net 1,7005,43149812,052 Loss from continuing operations (1,715)(1,748)(17,964)(27,630) Income from discontinued operations 9,46930710,0906 Net income (loss)$ 7,754$ (1,441)$ (7,874)$ (27,624) Net change in unrealized gain (loss) on available-for-sale securities, net of reclassification adjustments and taxes $ (1)$ (2)$ 13$ (1) Total comprehensive income (loss) $ 7,753$ (1,443)$ (7,861)$ (27,625) Net loss per share, basic Loss from continuing operations $ (0.06)$ (0.06)$ (0.58)$ (1.05)Income from discontinued operations $ 0.31$ 0.01$ 0.33$ -Net income (loss) per common share $ 0.25$ (0.05)$ (0.25)$ (1.05) Net loss per share, diluted Loss from continuing operations $ (0.06)$ (0.11)$ (0.58)$ (1.20)Income from discontinued operations $ 0.30$ 0.01$ 0.33$ -Net income (loss) per common share $ 0.24$ (0.10)$ (0.25)$ (1.20) Weighted-average shares used in computing net income (loss) per share Basic31,04129,46430,94026,256Diluted31,36630,04630,94026,520 View original content to download multimedia: SOURCE DURECT Corporation
