Methylprednisolone

More than 100 patients enrolled from over 100 clinical trial sites active in 12 countries Delivery of the interim data review to Ono Pharmaceutical Co. Ltd. (Ono) expected during Q3 will trigger Ono’s option exercise period LA JOLLA, Calif.--(BUSINESS WIRE)-- Equillium, Inc. (Nasdaq: EQ), a clinical-stage biotechnology company focused on developing novel therapeutics to treat severe autoimmune and inflammatory disorders, today announced that it has surpassed the interim enrollment target for the Phase 3 EQUATOR study of itolizumab in acute graft-versus-host disease (aGVHD). Equillium expects to deliver the results of the EQUATOR interim data review to Ono during the third quarter, which will then trigger Ono’s three-month option exercise period to acquire Equillium’s rights to itolizumab. “Our clinical development team has done an excellent job of recruiting and activating trial sites globally,” said Bruce Steel, chief executive officer at Equillium. “While the interim data will be blinded to Equillium and Ono, our independent data monitoring committee will conduct an unblinded analysis of the data and make a recommendation whether the study should proceed to conclusion based on pre-determined futility and efficacy stopping boundaries. Having now met the enrollment threshold for the interim review, we believe we are well on track to meet our guidance of delivering this final data milestone to Ono during the third quarter, setting the timeline for Ono’s option exercise decision to acquire itolizumab, which will expire three months following delivery of the results of the interim analysis.” If Ono exercises the option, Ono will pay Equillium a one-time payment of JPY 5.0 billion, or approximately $32.2 million based on the currency exchange rate on May 8, 2024. Equillium is also eligible to receive up to $101.4 million upon the achievement of certain development, regulatory, and commercialization milestones. About the EQUATOR Study The Phase 3, randomized, double-blind, placebo-controlled multicenter study (NCT05263999) will compare the efficacy and safety of IV administered itolizumab versus placebo (randomized 1:1) as a first-line therapy in approximately 200 adult and adolescent patients with Grade III-IV aGVHD, or Grade II aGVHD with lower GI involvement, in combination with high doses of corticosteroids, the current standard of care. The primary study endpoint is complete response rate at Day 29; key secondary endpoints include overall response rate at Day 29 and durability of complete response rate from Day 29 through Day 99. Per the study protocol, patients must receive itolizumab within 3-days of the first administration of high-dose corticosteroids with a treatment period from Days 1-99, and a follow-up period from Days 100-365. Approximately 200 eligible subjects will receive 2 mg/kg methylprednisolone or equivalent on Day 1 and will be randomized in a 1:1 ratio to the following two treatment groups: Group A: Itolizumab, 1.6 mg/kg initial dose followed by 6 doses of 0.8 mg/kg once every 2 weeks (q2w), plus systemic corticosteroids (100 subjects) Group B: Placebo, 7 doses q2w, plus systemic corticosteroids (100 subjects) An independent data monitoring committee will regularly review safety data, and an interim analysis for both futility and efficacy will be conducted after approximately 100 subjects have completed Day 29 assessments. About Itolizumab Itolizumab is a clinical-stage, first-in-class anti-CD6 monoclonal antibody that selectively targets the CD6-ALCAM signaling pathway to selectively downregulate pathogenic T effector cells while preserving T regulatory cells critical for maintaining a balanced immune response. This pathway plays a central role in modulating the activity and trafficking of T cells that drive a number of immuno-inflammatory diseases. About Equillium Equillium is a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need. The company’s pipeline consists of the following novel first-in-class immunomodulatory assets and product platform targeting immuno-inflammatory pathways. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15; currently under evaluation in a Phase 2 proof-of-concept clinical study of patients with alopecia areata being conducted in Australia and New Zealand by Equillium’s Australian subsidiary as the trial sponsor. EQ302: an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21; currently in pre-clinical development. The multi-cytokine platform: generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells; currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and recently completed a Phase 1b clinical study of patients with lupus/lupus nephritis. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited and has entered a strategic partnership with Ono Pharmaceutical Co., Ltd., for the development and commercialization of itolizumab under an option and asset purchase agreement. For more information, visit . Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. These statements include, but are not limited to, statements regarding Equillium’s plans to deliver the results of the interim review of the EQUATOR study to Ono Pharmaceutical and related timing thereof, the timing for triggering Ono’s option period and for receiving Ono’s option decision, plans for developing EQ101, EQ302 and itolizumab, the expected timeline for results from clinical studies, anticipated upcoming milestones, the fluctuation of the foreign exchange rate, and the potential benefits of Equillium’s product candidates. Because such statements are subject to risks and uncertainties, many of which are outside of Equillium’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: Equillium’s ability to execute its plans and strategies; risks related to performing clinical and pre-clinical studies; whether the results from clinical and pre-clinical studies will validate and support the safety and efficacy of Equillium’s product candidates; Equillium’s plans and product development, including the initiation and completion of clinical studies and the reporting of data therefrom; changes in the competitive landscape; risks related to Ono’s financial condition and decision to exercise its option, if ever, to purchase itolizumab or terminate the asset purchase agreement; and uncertainties related to Equillium’s capital requirements. These and other risks and uncertainties are described more fully under the caption "Risk Factors" and elsewhere in Equillium's filings and reports, which may be accessed for free by visiting the Securities and Exchange Commission’s website and on Equillium’s website under the heading “Investors.” Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. Equillium 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 law.

- FDA Feedback Supports Single Pivotal Trial for Approval of Larsucosterol in Alcohol-Associated Hepatitis - Webcast of Earnings Call Today, May 13th at 4:30 p.m. ET CUPERTINO, Calif., May 13, 2024 /PRNewswire/ -- DURECT Corporation (Nasdaq: DRRX) today announced financial results for the three months ended March 31, 2024 and provided a business update. "We are pleased that the feedback from the U.S. Food and Drug Administration (FDA) supports the advancement of larsucosterol into a single pivotal Phase 3 clinical trial which, if successful, may serve as the basis for a New Drug Application (NDA) in alcohol-associated hepatitis (AH)," stated James E. Brown, D.V.M., President and CEO of DURECT. "We are in the process of designing the registrational Phase 3 trial incorporating the FDA's comments and insights gained from our Phase 2b AHFIRM trial. In addition, we are excited about the upcoming presentation at the European Association for the Study of the Liver (EASL) Congress 2024, which will be the first presentation of the AHFIRM data at a medical conference. We expect to provide additional details on our planned Phase 3 protocol and present new analyses from AHFIRM later in the year." Business Update: During a Type C meeting with the FDA, DURECT received feedback on the recommendations for a Phase 3 clinical trial for larsucosterol in AH that could support a potential NDA filing. DURECT is in the process of designing its planned Phase 3 clinical trial based on the FDA feedback and the results from its completed Phase 2b AHFIRM clinical trial. DURECT announced the acceptance of a late-breaking oral presentation at the European Association for the Study of the Liver (EASL) Congress 2024 to take place June 5-8, 2024 in Milan, Italy. The presentation will feature 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. Financial Highlights for Q1 2024: Total revenues were $1.8 million and net loss was $7.6 million for the three months ended March 31, 2024 compared to total revenues of $2.1 million and net loss of $12.0 million for the three months ended March 31, 2023. Cash, cash equivalents and investments were $21.6 million at March 31, 2024, compared to $29.8 million at December 31, 2023. Debt at March 31, 2024 was $14.6 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 first quarter 2024 results and provide a corporate update: Monday, May 13 @ 4:30 p.m. Eastern Time / 1:30 p.m. Pacific Time A live audio webcast of the presentation will be also available by accessing 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 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 FDA has granted a Fast Track 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 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 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 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; risks that Innocoll may not commercialize POSIMIR successfully; 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 March 31, 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