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As well as the committee, the adcomm heard from patients, doctors, and parents of children with Barth syndrome. Credit: Salivanchuk Semen via Shutterstock. A US Food and Drug Administration (FDA) advisory committee (AdCom) has voted in support of Stealth BioTherapeutics ’ first-line Barth syndrome drug, despite a trial studying the drug not meeting its primary endpoint. The Cardiovascular and Renal Drugs Advisory Committee voted 10-6 supporting Stealth’s elamipretide for the treatment of Barth syndrome, an ultra-rare genetic disorder caused by mutations in the TAZ gene, which primarily affects males. The life-threatening disease – which causes symptoms like cardiomyopathy and growth delays – has no cure, and no other therapies in late-stage clinical development, according to the Barth syndrome Foundation. The FDA is expected to decide whether to approve the new drug application in January 2025. During the committee meeting, the panel discussed findings from the SPIBA-201 clinical trial (NCT03098797). The trial, which assessed the impact of elamipretide in 12 male patients over 12 weeks of daily treatment, failed to meet the primary endpoint of improving walking distance. Patients treated with elamipretide walked an average of 443.1 metres compared to 443.9 for patients on placebo. While there was a slight increase in walking distance from baseline – 43 metres for the elamipretide group compared to 31 metres for placebo – the difference was not statistically significant. The FDA reviewers told the committee that Stealth’s drug did not meet statistical significance in the primary or secondary endpoints. See Also: Activist investor Starboard cries foul play in exec U-turn at Pfizer Activist investor Starboard forges $1bn stake in Pfizer to swing profits However, the AdCom heard from patients, doctors, and parents of children with Barth syndrome, saying that the drug had helped patients gain weight, strength, and stamina, advocating for elamipretide’s approval. Jacob Wilson, a 24-year-old male with Barth syndrome told the panel the medicine “made him feel like a new person”. Elamipretide has previously faced rejection from the FDA. In August 2021, Stealth filed a new drug application (NDA) for the candidate, however the FDA responded in October of the same year with a refuse-to-file letter, stating that the NDA “did not contain an adequate and well-controlled trial that provides evidence of effectiveness”. Stealth did not conduct another Phase III study, despite advice from the FDA to do so.  Its initial application was linked to the SPIBA-001 study (NCT04689360), a Phase III trial that included both treated patients from SPIBA-201 and new, untreated patients. Despite the trial meeting its primary endpoint, the FDA raised concerns about how the data were analysed. Results were compared to an open-label extension from the Phase II/III SPIBA-201 crossover study and historical control data from 19 subjects monitored between 2012 and 2019 at the Johns Hopkins Kennedy-Krieger Institute. This approach was criticised by the FDA. The panel raised concerns about two potential biases in the SPIBA-001 trial design. Selection bias could result from differences in the natural history control subsample, while a confounding bias may arise due to the lack of randomisation. The panel also argued that the propensity score method used in the Phase III trial failed to adequately correct for these biases. Despite this, the committee ultimately decided to vote in favour of the mitochondrial-targeting peptide drug. The committee also acknowledged “the devastating impact of Barth’s” and “the significant unmet medical need” in a document released in advance of the AdCom meeting. This unmet need was reiterated by Emily Milligan, executive director of the Barth syndrome Foundation: “We strongly urge the FDA to move swiftly toward approving elamipretide for use in Barth syndrome, bringing patients closer to having sustained access to this critical therapy. Our plight is not just about Barth syndrome—it sets an important precedent for how we address the unmet needs of patients and families affected by many rare diseases.” Attention will now turn to the 29 January decision date, as in the briefing document before the AdCom, the FDA said it does not believe that the available evidence establishes the effectiveness of elamipretide for Barth syndrome. While the FDA takes AdCom recommendations into consideration, it are not required to follow them.

SAN JOSE, Calif., June 28, 2024 /PRNewswire/ -- BridGene Biosciences, Inc., a leader in developing covalent small molecule drugs for traditional "hard-to-drug" targets, announced today that the first patient has been dosed in its Phase 1 clinical trial of BGC515, a novel TEAD inhibitor discovered through BridGene's cutting-edge chemoproteomic platform, IMTAC™. This milestone highlights the potential of BridGene's innovative chemoproteomics approach. The Phase 1 study will enroll subjects in both the US and China (NCT06452160) to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of BGC515 as a single agent in patients with advanced solid tumors, including malignant mesothelioma, epithelioid hemangioendothelioma, and other solid tumors with hippo pathway dysregulation. Dr. Timothy Yap, Ph.D., FRCP, Professor in the Department of Investigational Cancer Therapeutics (Phase I Program) and Head of Clinical Development, Therapeutics Discovery Division at the University of Texas MD Anderson Cancer Center, is the principal investigator at the initial US site, where the first patient has been enrolled. "We are delighted to begin the clinical evaluation of BGC515 with the dosing of our first patient, and we look forward to the evaluation of the initial safety and efficacy of this exciting compound," said Jeremy Barton, M.D., Chief Medical Officer of BridGene Biosciences. "The initiation and dosing of our first drug in clinical development from our chemoproteomic platform marks a major inflection point for BridGene," stated Ping Cao, Ph.D., Co-Founder and CEO of BridGene Biosciences. "This achievement underscores our commitment to addressing unmet medical needs through innovative therapeutic solutions. BGC515 represents a breakthrough in targeting the TEAD proteins, a critical component in the Hippo signaling pathway. We are proud of the progress we have made in a short time, developing a pipeline that includes previously undruggable targets for prominent oncology and immunology diseases." BridGene Biosciences is advancing multiple novel drug discovery programs toward the clinic and has over a dozen similar opportunities emerging in early discovery. About the Hippo Pathway and BGC515 The Hippo pathway is a key pathway used by cells to control expression of a group of genes by regulating activity of transcription factors YAP and TAZ. YAP and TAZ function in a complex with partner proteins, the TEADs, which are the targets of BGC515. A variety of human cancers depend on activation of YAP and TAZ, which can occur by various mechanisms. BGC515 is an internally-developed, orally-administered, covalent TEAD inhibitor. About BridGene Biosciences BridGene is a biotechnology company focused on discovering and developing innovative small molecules that drug traditionally undruggable targets, providing new paths to treat diseases. By using its proprietary chemoproteomic platform, IMTAC™, BridGene is able to screen small molecules against all proteins in live cells to discover drug candidates for high value and previously undruggable targets. For this purpose, BridGene takes advantage of its proprietary, diverse covalent library of tagged, drug-like small molecules. The ultimate goal is to enable breakthrough small-molecule drug discovery and to expand the mechanisms to treat diseases, with targets previously inaccessible to small molecules. BridGene is advancing a diversified pipeline of first-in-class drugs for targets in multiple disease areas. For more information, visit . Contact Tiberend Strategic Advisors, Inc. Daniel Kontoh-Boateng (investors) 862-213-1398 [email protected] Dave Schemelia (media) [email protected] 609-468-9325 SOURCE BridGene Biosciences

HOUSTON--(BUSINESS WIRE)-- Sporos BioDiscovery, Inc. (a portfolio company of Sporos Bioventures, LLC.), a precision oncology company developing a diversified pipeline of small molecule therapeutic programs targeting cancer vulnerabilities in the tumor and tumor microenvironment, today announced that it will present two posters highlighting preclinical data from the company’s novel TEAD1 / TEAD4 isoform selective inhibitor, SPR1, at the American Association for Cancer Research (AACR) Annual Meeting 2024, taking place April 5-10, 2024, in San Diego, CA. “We look forward to presenting two posters at this year’s AACR meeting that highlight the significant preclinical work we have done to characterize SPR1 as a potential best-in-class TEAD inhibitor. In addition, our team’s expert biological analysis has uncovered a new therapeutic vulnerability that could broaden the potential use of SPR1, a TEAD1/4 inhibitor, to a new subset of cancers with certain homozygous deletions,” said Stephen Rubino, Ph.D., President of Sporos BioDiscovery. Presentation Details: Title: TEAD1/4 inhibitors exhibit deeper biological impact and broader activity compared to TEAD1-only inhibitors in both monotherapy and combination without additional kidney toxicity Session Category: Experimental and Molecular Therapeutics Session Title: New Targets Session Date and Time: Tuesday Apr 9, 2024, 1:30 p.m. - 5:00 p.m. PT Abstract Number: 5913 Poster Number: 27 Title: VGLL4 is the target of the 3p25 homozygous deletion and presents a novel therapeutic vulnerability for TEAD1/4 but not TEAD1 inhibitors Session Category: Experimental and Molecular Therapeutics Session Title: YAP/TAZ/TEAD Modulators Session Date and Time: Wednesday Apr 10, 2024, 9:00 a.m. - 12:30 p.m. PT Abstract Number: 7266 Poster Number: 3 About Sporos BioDiscovery Sporos BioDiscovery, Inc. is a biotechnology research & development company with a diversified pipeline of several small molecule precision oncology therapeutic programs in development, including its lead candidate SPR1, a novel TEAD inhibitor program. Sporos BioDiscovery, Inc. is a portfolio company of Sporos Bioventures, LLC, a private biotechnology company focused on transforming the drug development process across oncology.