Varegacestat

近日，高瓴旗下专注于二级市场投资的HHLR ADVISORS公布了2024Q3的持仓情况，总体而言，Q3的新建仓股数较少，而清仓和减持力度加大，总持股数量下降了30家，医药领域股票更是如此，多家Biotech也位列名单之中。 Bicycle Therapeutics Bicycle Therapeutics被清仓似乎让人有些意外，毕竟同为百济股东的Baker Brother深度参与了该公司近期的融资事件。2023年时与拜耳和诺华的两项大订单都说明该公司向核药转型的战略的正确性。 不过，高瓴需要规避的风险或许来自于今年年底将要发布一系列临床数据的Zelenectide pevedotin，Zelenectide pevedotin是一款靶向Nectin-4的双环肽偶联药物。对应的竞品自然是辉瑞/Seagen/安斯泰来的Nectin-4-ADC Padcev（enfortumab vedotin），两者疗效相当，安全性似乎是Zelenectide pevedotin更优，有研究表明似乎是ADC结构更容易引起外周神经痛，Bicycle的管线在治疗相关神经疾病方面发生率更低。 不过Padcev的进展更快，此前早早做好了联合K药的临床，这可能使得市场对于年底将要公布和K药临床数据的Zelenectide pevedotin有着较高的预期。 Immunome 高瓴在Q2建仓了Immunome，但又在Q3清仓了Immunome，作为Seagen功勋元老Clay Siegall的再次创业，或许是为了洗脱此前被控家暴的阴霾，Immunome作为ADC Biotech的拓展之路步子迈得非常之大，收购了来自Atreca和Zentalis多款管线。 与此同时带来的问题是，烧钱速度也相当之快，以及并不匹配的现金流储备。 对于初创企业来说，现金赛道把控相当重要，而如今Immunome的现金赛道只够延伸到2026年，而新管线AL102顶线数据预期要到2025年下半年发布，这种情况下，可以说时间紧急。这使得这家初创公司在开始阶段就面临着背水一战的局面。 Cybin 高瓴在Q2建仓了迷幻药公司Cybin，然后在Q3清仓。不管在哪里，迷幻药都是一个充满争议的话题，此前Lykos Therapeutics的MDMA辅助疗法（即毒品摇头丸）就因为不能做到严格双盲的临床遭到FDA拒绝。 即便在Cybin核心管线氘代裸盖菇素类似物CYB003获得突破性疗法认定的情况下，监管机构的态度仍旧不会有利于迷幻药获批。而实际上，Cybin为了临床能够展开，在与FDA的沟通后进行了某种程度上的变更和妥协，这使得CYB003是作为一种辅助性疗法进入III期临床的，这意味着未来市场该药物并不能作为单纯的抗抑郁药物使用，将严重透支该公司的未来市场前景。 而即便CYB003真的能够做到上市，预期的顶线结果要2026年发布，而上市时间可能要拖延到2027年以后，然而Cybin的账面现金只有1.543亿加元，根本不足够支撑到那个时候。因此该公司的未来前景并不容乐观。 另外，Cybin的即将到来的里程碑是核心管线CYB003的II期临床数据将在今年第四季度发布，这一数据对于Cybin来说举足关键。可能是风险也可能是机遇。 总结 总的来说，高瓴本季度除了重点持仓生物医药股没有太大变动外，对于小微型Biotech的清仓和减持力度持续增加。 即便大型药企和商业化阶段的制药公司也难以避免，由此的两个特例分别是，阿斯利康和GERON CORP。阿斯利康可能是受到中国区业务的影响而遭到清仓。GERON CORP虽然已有产品imetelstat上市，迈向了商业化道路，但是与Royalty Pharma和Pharmakon新签订的3.5亿贷款和版税协定，颇有一种拆东墙补西墙的感觉。毕竟此前这家公司依靠大力神资本和硅谷银行的贷款才成功将产品推动上市。imetelstat需要再商业化上展现出足够的优势。 参考来源： https://ir.geron.com/investors/press-releases/press-release-details/2024/Geron-Corporation-Reports-Third-Quarter-2024-Financial-Results-and-Recent-Business-Highlights/default.aspx?_gl=1*1xbtvps*_ga*MTU5Mzk5ODI0MS4xNzMxOTA3ODY5*_ga_3PJFCC35YH*MTczMTkwNzg2OS4xLjAuMTczMTkwNzg4Ny40Mi4wLjA. https://ir.cybin.com/investors/news/news-details/2024/Cybin-Initiates-PARADIGM-A-Multinational-Pivotal-Phase-3-Program-Evaluating-CYB003-for-the-Adjunctive-Treatment-of-Major-Depressive-Disorder-and-Reports-Second-Quarter-Financial-Results/default.aspx https://investors.immunome.com/immunome-appoints-roee-shahar-as-executive-vice-president-commercial/ https://investors.bicycletherapeutics.com/news-releases/news-release-details/bicycle-therapeutics-reports-recent-business-progress-and-0

BOTHELL, Wash. – Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on the development of first-in-class and best-in-class targeted oncology therapies, today announced financial results for the third quarter ended September 30, 2024, and provided a business update. “Immunome continues to advance its pipeline,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer. “Topline data for the RINGSIDE Part B trial of AL102 is expected in the second half of 2025, and IND submissions for IM-1021 and IM-3050 are on track.” “Our discovery team is focused on discovering ADCs that effectively pursue the novel targets we believe will define the next generation of transformative cancer therapies. In particular, the differentiated profile of HC74, our proprietary TOP1 payload, offers exciting opportunities for portfolio expansion when combined with our large repertoire of antibodies.” Pipeline Highlights Full enrollment for the Phase 3 RINGSIDE Part B study of AL102 for the treatment of desmoid tumors was completed in February 2024, and Immunome expects to report topline data for RINGSIDE Part B in the second half of 2025. In parallel, Immunome is performing additional manufacturing and pharmacology work required to support a new drug application filing for AL102. Immunome also anticipates submitting INDs for IM-1021 and IM-3050 in the first quarter of 2025, as previously disclosed. Third Quarter 2024 Financial Results As of September 30, 2024, cash, cash equivalents and marketable securities totaled $240.1 million. Immunome’s current cash runway is expected to extend into 2026. Research and development expenses for the quarter ended September 30, 2024 were $37.2 million, including stock-based compensation costs of $1.8 million. In-process research and development expenses for the quarter ended September 30, 2024 were $6.7 million. These expenses were related to Immunome’s business development activity. General and administrative expenses for the quarter ended September 30, 2024 were $9.5 million, including stock-based compensation expense of $3.1 million. Immunome reported a net loss of $47.1 million for the quarter ended September 30, 2024. About Immunome, Inc. Immunome is a clinical-stage targeted oncology company committed to developing first-in-class and best-in-class targeted therapies designed to improve outcomes for cancer patients. We are advancing an innovative portfolio of therapeutics, drawing on leadership that previously played key roles in the design, development and commercialization of cutting-edge targeted cancer therapies, including antibody-drug conjugates (ADCs). In addition to a portfolio of discovery-stage ADCs, our pipeline includes AL102, a gamma secretase inhibitor currently in a Phase 3 trial for treatment of desmoid tumors, as well as IM-1021, a ROR1 ADC, and IM-3050, a FAP-targeted radioligand, both of which are the subject of INDs expected to be submitted in the first quarter of 2025. For more information, visit www.immunome.com. Cautionary Statement Regarding Forward-Looking Statements Statements in this press release that are not purely historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We use words such as “expects,” “believe,” “opportunities,” “anticipates” and similar expressions to identify these forward-looking statements. These forward-looking statements include Immunome’s expected timing for providing topline data for the Phase 3 RINGSIDE Part B trial; Immunome’s expected timing for filing an IND for IM-1021 and IM-3050; Immunome’s expectation that it will commence clinical development of IM-1021 and IM-3050 in early 2025; the potential of Immunome’s ADC targets to provide first-in-class or best-in-class potential; and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future. These forward-looking statements are based on Immunome’s current expectations and involve assumptions that may never materialize or may prove to be incorrect; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including the risk that Immunome will not be able to realize the benefits of its strategic transactions; the risk that regulatory approvals for Immunome’s programs and product candidates are not obtained, are delayed or are subject to unanticipated conditions; the risk that pre-clinical data may not be predictive of clinical data; the risk that Immunome’s product candidates and development candidates fail to achieve their intended endpoints; uncertainties related to Immunome’s capital requirements and Immunome’s expected cash runway; Immunome’s ability to grow and successfully execute on its business plan; and other risks and uncertainties indicated from time to time described in Immunome’s Quarterly Report on Form 10-Q for the quarter ended June 30, 2024, filed with the SEC on August 12, 2024, in Immunome’s Quarterly Report on Form 10-Q for the quarter ended September 30, 2024, being filed with the SEC today, and in Immunome’s other filings with the SEC. Except as required by law, Immunome assumes no obligation and does not intend to update any forward-looking statements included in this press release. View source version on businesswire.com: https://www.businesswire.com/news/home/20241113523555/en/ Investor Contact: Max Rosett Chief Financial Officer investors@immunome.com