ATR

▲10月26-27日成都中国临床试验产业发展大会免费报名 注：本文不构成任何投资意见和建议，以官方/公司公告为准；本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及），不代表平台立场。任何文章转载需得到授权。 近年来，随着大型制药公司不再通过并购来补充管线，它们转而通过授权交易来增加新资产。但偶尔，一些交易无法达成，这些资产就会被归还给它们的原生物技术公司，也就是资产遭遇“退货”。 据统计，在过去的12个月中，有4家大型制药公司“退货”。 BMS退货：Agenus癌症双特异性抗体 2024年8月，百时美施贵宝(Bristol Myers Squibb)将TIGIT双特异性抗体项目的所有权归还给Agenus，该项目目前正处于针对实体瘤的早期试验阶段。 这笔交易是在2021年以2亿美元的预付款达成的。吉利德和罗氏都有TIGIT项目，但罗氏最近在获得令人失望的数据后取消了对该候选药物的临床试验。BMS一直在关注竞争格局，公司 这个目标似乎不再可行。 根据该协议，Agenus有资格获得高达13亿美元的里程碑付款，迄今为止已经收到了其中两笔付款：2021年的2000万美元和2024年的2500万美元。 罗氏退货：Repare Therapeutics实体肿瘤资产 今年2月，罗氏以管道审查和不断变化的外部因素为理由，将可能是同类最佳的癌症研究药物camonsertib归还给了Repare Therapeutics。 Camonsertib是一种实验性口服小分子抑制剂，用于治疗失调性毛细血管扩张和rad3相关蛋白激酶(ATR)，根据该公司的网站，ATR对于DNA对损伤的反应至关重要。 外界人士猜测，要么是数据令人失望，要么是考虑到竞争格局因素，商业机会可能不像过去那么大，或者他们不想在这种作用机制上下注。 就在几周前，罗氏向Repare Therapeutics支付了4000万美元，当时罗氏成功地在TAPISTRY的II期研究中给第一位患者服用了camonsertib，该研究旨在评估camonsertib对携带特定致癌突变的不可切除、局部晚期或转移性实体瘤患者的治疗效果。 罗氏在2022年6月预付了1.25亿美元，并承诺为camonsertib提供高达12亿美元的潜在里程碑和特许权使用费。 阿斯利康退货：FibroGen罗沙司他 2024年2月，在FDA拒绝罗沙司他两年多之后，阿斯利康又将罗沙司他在美国和世界其他地区的使用权交还给了FibroGen。这两家公司将保留其在中国和韩国的HIF-PH抑制剂合同，该抑制剂已被批准用于治疗慢性肾脏病患者的贫血。 FDA表示，目前的罗沙司他无法在美国获准使用，并要求在再次使用罗沙司他之前进行另一项临床试验。 2013年，阿斯利康首次投资罗沙司他，预付3.5亿美元，并承诺最高4.65亿美元的里程碑付款，以及潜在的未来与销售相关的里程碑付款和分级特许权使用费。阿斯利康已经在2015年支付了1500万美元的里程碑付款，2015年支付了1.2亿美元，2016年支付了6200万美元。如果中国于2024年年中批准罗沙司他用于治疗化疗引起的贫血，FibroGen仍有可能从阿斯利康获得1,000万美元的里程碑付款。 强生退货：Idorsia高血压药物Tryvio 2023年9月，Idorsia Ltd (SIX: IDIA)宣布，该公司已与强生旗下杨森制药公达成协议，杨森将向Idorsia返还双重内皮素受体拮抗剂Tryvio（aprocitentan 用于治疗顽固性高血压）的专利使用权。 根据协议，Idorsia将从杨森手中重新获得aprocitentan的开发和商业化权利。作为回报，Idorsia将根据Idorsia的收入，向杨森支付至多3.06亿瑞士法郎（25.14亿人民币）的有条件报酬。 然而，在今年的3月，也就是被强生退货半年后，FDA批准Tryvio获批上市，这是首个FDA 批准的针对高血压内皮素通路的药物。 本次批准是基于临床 III 期试验 PRECISION 研究的数据，试验招募了 730 名收缩压 (SBP) ≥140 mmHg 且至少服用三种抗高血压药物的患者。 所以大药企引进或退货，并不是真正判定一款药物价值的有力依据，科学设计的临床试验结果才是硬道理。 参考资料： www.biospace.com 版权声明：本文转自生物药大时代，如不希望被转载的媒体或个人可与我们联系，我们将立即删除 【关于药融圈】 药融圈PRHub旨在帮助生物医药科技型企业进行品牌推广及商务拓展服务，针对客户的真实需求制定系统化解决方案，通过“翻译-降维-场景化”将客户的品牌信息以直白易懂的方式被公众知悉，同时在流量渠道覆盖100万+垂直用户基础上实现合作目的，帮助合作伙伴完成从品牌开始到商务为终的闭环营销服务。我们已经完成了数十场线下1000人规模的生物医药研发类会议，涵盖小分子新药，大分子新药，改良型新药，BD跨境交易等多个领域，服务了百余家上市/独角兽/生物技术/制药企业。

“We acknowledge the extraordinary contributions and productivity of our discovery team,” Repare Therapeutics CEO Lloyd Segal said in the company's release. Repare Therapeutics is laying off a quarter of its workforce as the oncology biotech scales back its preclinical work to focus on more advanced candidates such as a synthetic lethal drug handed back by Roche earlier this year.The biotech had a number of synthetic lethal targets in advanced stages of preclinical development, according to the company’s website. But Repare has decided to “materially reduce the scale of its preclinical research and discovery activities,” the company said in a post-market release Aug. 28.This “strategic refocus” will see the company reduce its overall workforce by around 25%, with the biotech’s preclinical group bearing the brunt of the layoffs. Repare had 179 full-time employees as of February, of which 143 were primarily engaged in some form of R&D and 36 were focused on management or general and administrative activities. The redundancies outlined yesterday are expected to incur between $1.5 million and $2 million of costs in the third quarter before generating annual savings of $15 million.Repare ended June with $208.1 million in cash and equivalents, which it had estimated would fund its operations until at least mid-2026. The savings outlined in the Aug. 28 release are expected to pave a cash runway further into that year.“We acknowledge today the extraordinary contributions and productivity of our discovery team, who have enabled the development of our deep, innovative clinical portfolio,” Repare’s CEO Lloyd Segal said in the release.“In our mission to rapidly develop new, practice-changing therapies, we will more fully dedicate our resources to our most promising and advanced precision oncology programs to maximize value for patients and for our shareholders,” Segal added.Those programs include a phase 1 dose expansion trial of a combination of the biotech’s lunresertib and camonsertib in patients with ovarian and endometrial cancers due to read out in the fourth quarter of 2024. Segal has previously touted phase 1 data of the PKMYT1 inhibitor lunresertib as “really phenomenal,” while the ATR inhibitor camonsertib made headlines in February when Roche walked away from a collaboration on the drug just days after the Big Pharma had dosed the first patient in a phase 2 trial. Undeterred by the rejection, Repare has hopes to launch a registrational trial of the lunresertib-camonsertib combo next year. The biotech is also assessing camonsertib as a monotherapy in a phase 2 trial in non-small cell lung cancer, which is due to read out next year.The company’s phase 1 pipeline also consists of a PLK4 inhibitor called RP-1664 that is in a study for patients with TRIM37-high solid tumors along with a Polθ ATPase inhibitor called RP-3467 that is set to enter human trials in the fourth quarter.

Repare Therapeutics is cutting its headcount by about 25%, with most of the layoffs concentrated in the company’s preclinical team, as part of what the company is calling a “strategic prioritization” of its R&D program. The move will allow Repare to focus on clinical-stage oncology candidates. That includes lunresertib and camonsertib, which are currently being evaluated together in a Phase 1 trial for patients with ovarian and endometrial cancers. The trial is now in the dose expansion phase, data are expected in the fourth quarter, and a registrational trial could begin as early as 2025. Camonsertib is also being investigated as a monotherapy in non-small cell lung cancer as part of a Phase 2 trial, with data expected in 2025. Roche had licensed camonsertib, an oral ATR inhibitor, back in 2022 but bowed out in February, shortly after paying $40 million for dosing the first patient with the drug in a different Phase 2 platform study. The deal originally carried up to $1.2 billion in milestones. The company also has RP-1664, an oral inhibitor of PLK4, in a Phase 1 trial in adult and adolescent patients with TRIM37-high solid tumors. Based on safety data, Repare said it will move the therapy into a Phase 1/2 study in pediatric patients with high risk, recurrent neuroblastoma, where prevalence of TRIM37-altered tumors is high. “In our mission to rapidly develop new, practice-changing therapies, we will more fully dedicate our resources to our most promising and advanced precision oncology programs to maximize value for patients and for our shareholders,” Repare president and CEO Lloyd Segal wrote in a statement. The staff reduction will cost the company non-recurring cash payments of about $1.5 million to $2 million in the third quarter of this year — but it expects annual savings of around $15 million that will extend its cash runway into the second half of 2026. Stifel analysts wrote in a Wednesday note that “the reprioritization has a small positive impact,” and that “focusing resources on clinical efforts with near-term inflection points makes sense.”