Kezar Life Sciences, Inc.

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 · · · · · · · ·

Plus, news about Kezar Life Sciences and Concentra Biosciences: Viatris, Lexicon Pharmaceuticals sign licensing deal for cardio drug: Per the agreement , Viatris will pay $25 million upfront to Lexicon in exchange for the rights to sotagliflozin in all markets outside of the US and Europe. Lexicon may also receive regulatory- and sales-based milestones and tiered royalties. The FDA last year approved the drug to reduce the risk of cardiovascular death, hospitalization for heart failure, and urgent heart failure. — Katherine Lewin Capricor Therapeutics prices $75M public stock offering: The rare disease biotech is selling 4.4 million of its shares at $17.00 apiece. The funds are set to go toward the development and manufacturing of its investigational drugs, as well as “working capital and general corporate purposes.” Capricor’s lead candidate, deramiocel, is a cell therapy currently in Phase 3 development for the treatment of Duchenne muscular dystrophy. Earlier this month, Capricor announced positive longer-term data from the ongoing HOPE-2 trial and that it had filed for approval with the FDA. — Katherine Lewin Kezar Life Sciences rejects Concentra’s unsolicited offer: The Bay Area biotech’s board said “no” to Kevin Tang’s Concentra Biosciences, which had offered $1.10 per share $KZR and 80% of potential asset sale proceeds to buy the company. Concentra made the offer last week after Kezar stopped a Phase 2b in lupus nephritis. On Thursday, Kezar also reiterated that it expects to have Phase 2a data in autoimmune hepatitis in the first half of next year. Kezar’s stock was down about 10% on Thursday morning. — Kyle LaHucik

Earlier this month, Kezar Life Sciences announced that the mid-stage test of zetomipzomib in lupus nephritis had been placed on an FDA clinical hold. Now, that program is being terminated. Kezar Life Sciences is discontinuing a lupus program after four patient deaths occurred during a Phase IIb trial and will focus on developing the same drug in autoimmune hepatitis. Earlier this month, Kezar announced that the mid-stage study of zetomipzomib in lupus nephritis had been placed on an FDA clinical hold. The regulatory action came after the company reported four patient deaths in the Phase IIb PALIZADE trial. Other serious adverse events were reported as well that “showed a similar proximity to dosing.” Kezar voluntarily suspended enrollment and began looking at mitigation strategies for the drug. Now, an independent data monitoring committee that had been examining the PALIZADE trial and the Phase IIa PORTOLA trial of zetomipzomib in hepatitis has recommended that the lupus program be suspended. Kezar will proceed with the hepatitis study and expects a readout in the first half of 2025, according to a Thursday press release. Kezar noted that one of the deaths that occurred in the PALIZADE study was in a patient who had received a placebo. The trial was conducted in Argentina and the Philippines. The trial will be unblinded and a full investigation will be conducted into the safety events, the company said. At the time the study was terminated, 84 patients were enrolled. Kezar promised to release available data at a later time. CEO Chris Kirk said Kezar’s decision was a difficult one, as the company had seen a favorable safety pro clinical activity in an earlier trial called MISSION. The PALIZADE trial also enrolled very quickly. “However, a focused development effort in AIH [autoimmune hepatitis] extends our cash runway and provides flexibility as we work to bring zetomipzomib forward as a treatment for patients living with this life-threatening disease,” Kirk said. The data committee recommended that the PORTOLA trial proceed without modification after examining all safety data from the patients enrolled in the trial. No serious adverse events rated grade 4 or higher, which would indicate a death, have occurred in the PORTOLA trial which is being conducted in the U.S. In other news, Kezar has rejected an unsolicited bid from Concentra Biosciences to acquire the biotech. The offer had been to buy all outstanding shares for $1.10 apiece, plus a contingent value right. Kezar has decided that the value significantly undervalues the company and zetomipzomib. Concentra, meanwhile, has moved to acquire 9.9% of Kezar’s common stock. Kezar has adopted a stockholder rights plan, also known as a “poison pill” defense, to protect against any party buying a controlling stake through the open market without paying stockholders their due. The rights plan does not block a more traditional buyout, even from Concentra, if the board deems it in the best interests of shareholders, Kezar noted. Kezar’s shares were trading at 80 cents on the Nasdaq Capital Market Thursday morning, down more than 9% from the prior close. Concentra is owned by Tang Capital, a life sciences-focused investment firm. The company has made many attempts over the years to buy out struggling biotechs, most recently succeeding in acquiring Theseus Pharmaceuticals. Similar buyouts offered to LianBio, Rain Oncology and Atea Pharmaceuticals were unsuccessful.