Zetomipzomib

Plus, news about Nippon Shinyaku, Atsena, Orna Therapeutics, Ovid Therapeutics, Graviton Bioscience, Eupraxia, Entero Therapeutics, Journey Therapeutics, Theravance Biopharma, Alpha Cognition and Travere Therapeutics: 89bio’s $125M offering: The liver and cardiometabolic biotech is selling shares $ETNB at $8.50 apiece, or about 55 cents below Tuesday’s closing price. Its stock slid nearly 10% on Tuesday. — Kyle LaHucik FDA places partial hold on Kezar study: The company is testing an immunoproteasome inhibitor called zetomipzomib in autoimmune hepatitis. The currently enrolled patients will be allowed to complete the trial, but four patients who are still in the blinded portion cannot proceed to the open-label extension. It’s the second hold for the drug since the start of October when another trial was placed on full clinical hold after four patients died. Topline data are expected in the first half of 2025. — Max Gelman Nippon Shinyaku licenses Atsena’s gene therapy in the US and Japan: Financial details of the deal were not disclosed, though Nippon Shinyaku will reimburse Atsena for continued development work for the rare eye disease treatment, including an expected pivotal study. Atsena also gets to keep the rights to a priority review voucher if it receives one. Nippon Shinyaku plans to market the therapy in the US via its subsidiary, NS Pharma. — Lei Lei Wu Orna cuts more staffers: The circular RNA-focused biotech told Endpoints News in a statement that it “restructured its team” as part of a broader pipeline prioritization, but did not disclose the number of cuts. The drugmaker previously laid off less than 25% of its staff in November 2023 in what it described as a “defensive reduction.” — Ayisha Sharma Ovid, Graviton pause starting Phase 2 trial: The companies are holding back from initiating their study of OV888 in people with cerebral cavernous malformations (CCM) to “evaluate clinical design learnings emerging from competitor” readouts. In September, Recursion Therapeutics’ CCM drug showed strong safety but mixed efficacy in a Phase 2 trial. — Ayisha Sharma Eupraxia touts additional Phase 1b/2a data: The company said that data from two cohorts of the trial, which is investigating EP-104GI as a treatment for eosinophilic esophagitis, showed reductions in the severity, symptoms and extent of the disease. In one cohort, a patient achieved complete histological remission. Eupraxia CEO James Helliwell said that “higher dosing levels are yielding improved patient responses.” — Katherine Lewin Entero’s reverse merger: The company is handing its Nasdaq spot to ADC biotech Journey Therapeutics three months after letting go of nearly all its employees and seeking strategic alternatives. Journey will get 99% of Entero’s equity, and its CEO Henry Ji will lead the combined company. — Kyle LaHucik Theravance forms strategic review committee: In its third-quarter financial results , the company said it would “assess all strategic alternatives,” including those related to its COPD drugs Yupelri and Trelegy. Theravance pulled in $16.9 million in revenue this quarter, but it all came from the Viatris collaboration for Yupelri. Along with announcing the review, Theravance separated the roles of board chair and CEO, naming Susannah Gray as chair while Rick Winningham will continue as CEO. The company made staff and program cuts last year. Its stock $TBPH was up about 11% on Wednesday morning. — Katherine Lewin Alpha Cognition prices $50M upsized public offering: The neuro biotech received a notice of allowance for its patent application covering its Alzheimer’s drug, called Zunveyl, through 2044. The funds from the public offering are expected to go toward the commercialization and launch of Zunveyl, R&D and other commercial and general corporate purposes. Zunveyl scored FDA approval in July. — Katherine Lewin Travere upsized its public offering . It raised a total of $143.8 million. — Jaimy Lee

Kezar Life Sciences流年不利。 今年先是管线KZR-261因疗效不佳暂停开发，后是核心管线zetomipzomib的狼疮肾炎临床中发生4例患者死亡事件。 近一年，该公司股价更是常处于1美元以下低位，存在退市风险。 如果没有转机，Kezar可以说已经来到了绝境。就在这时候，Concentra Biosciences主动提出收购要约。Kezar公司股价受到该消息影响上涨。 延伸阅读：被抄底资本觊觎的“事故”管线 然而在思考了一周后，Kezar公司可以说是强硬的拒绝了该份收购要约，表示Concentra的提案严重低估了Kezar公司价值。 同时，Kezar公司采用了一项股东权益计划（也称为毒丸计划），以防御已经拥有Kezar公司9.9%普通股的Concentra进行恶意收购，保住公司控股权。 那么，Kezar公司的底气何在？ 临床出事的管线 Kezar公司的底气应该还是在zetomipzomib，这款在临床试验中发生了4例患者死亡事件的核心管线上。 Zetomipzomib是一种first-in-class的免疫蛋白酶体（immunoproteasome）抑制剂。值得注意的是，国内云顶新耀拥有Zetomipzomib在大中华区和东南亚，韩国等国家和地区的权益。 Zetomipzomib有两个开发方向，一个是狼疮性肾炎（LN），一个是自身免疫性肝炎（AIH）。 然而，在狼疮性肾炎（LN）上，Zetomipzomib因安全性问题已经被停止了。 本月早些时候，Zetomipzomib针对LN的IIb期临床试验PALIZADE中，在菲律宾和阿根廷入组的患者中发生了4例5级（致命）严重不良事件（SAE），其中3例死亡病例表现出常见的症状模式和接近给药时间，以及其他非致命性ASE。随后，该试验被FDA喊停。 在最近的更新中，Kezar公司报告PALIZADE试验所发生的4例5级（致命）SAE，有1例是发生在安慰剂组。Kezar公司将揭盲试验，并对研究中的所有安全事件进行全面调查，将于晚些时候报告PALIZADE的可用数据。 也是在同一份更新中，Kezar公司宣布停止针对LN的PALIZADE试验，将资源集中在自身免疫性肝炎（AIH）的临床开发上。 寄希望于另一适应症 Zetomipzomib治疗自身免疫性肝炎（AIH），是Kezar公司抓住的救命稻草。 隔壁LN试验出了事，这边AIH试验也很忐忑。 独立数据监测委员会 （IDMC）对Zetomipzomib治疗AIH的2a期试验PORTOLA进行审查后，认为该试验可以继续进行，不需要进行修改。 迄今为止，在美国临床中心进行的PORTOLA试验中尚未观察到4级或5级SAE。目前，PORTOLA已经完成患者入组，计划将在2025年上半年报告顶线数据。 这使得Kezar公司松一口气，并将全部注码压在该适应症上——将公司所有的资源集中在该适应症的开发上。 健康的现金流 LN适应症开发的停止，只进行AIH的临床工作，这大大缓解了Kezar公司的资金压力。 根据Kezar公司报告，截止2024年9月30日，未经审计的现金状况约为1.48亿美元，包括现金、现金等价物和有价证券。而截止至2024年6月30日，则为1.642亿美元。 Kezar公司作为一家小分子疗法开发公司，其研发支出并不非常高，1.48亿美元的现金流，对于现在仅剩一个适应症临床项目开发的Kezar公司来说，足可以说是健康的。 这也是Kezar公司能够从容拒绝收购的一大原因。 另外，Concentra的每股1.10美元的现金价格收购提案，也确实有点低。 现在，最大的问题是，Zetomipzomib治疗自身免疫性肝炎（AIH）是否真的能成功，给Kezar公司带来转机？ 参考资料： 1.https://ir.kezarlifesciences.com/news-releases/news-release-details/kezar-board-unanimously-rejects-unsolicited-concentra-proposal 2.https://ir.kezarlifesciences.com/news-releases/news-release-details/kezar-life-sciences-announces-positive-idmc-safety-review 本周好文推荐 如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·