ENV 201

Endeavor BioMedicines于2月8日宣布完成了1.01亿美元的Ｂ轮融资。融资获得的资金将支持其研发管线项目的推进，包括靶向Hedgehog信号通路中PTCH1受体的小分子抑制剂ENV-101（taladegib），用于治疗癌症和特发性肺纤维化（IPF）；以及用于治疗KRAS驱动癌症的潜在“best-in-class”ULK1/2小分子抑制剂ENV-201。 Endeavor BioMedicines由连续创业家John Hood博士联合创建。Hood博士曾经担任Impact Biomedicines的首席执行官，他和团队的努力让JAK2抑制剂fedratinib的研发项目起死回生，并且最终在2019年获得FDA批准上市。 Endeavor公司的ENV-101（taladegib）是一种口服的Hedgehog信号通路小分子抑制剂，已在包含近200名受试者的6项已完成研究中表现出令人印象深刻的临床疗效和安全性。 PTCH1基因突变是Hedgehog信号通路中的一种致癌基因突变，在大约2%癌症中发现。由于其在多种类型癌症中出现，Endeavor计划在一项不限癌种临床试验中，招募携带任何具有致癌Hedgehog信号通路突变的患者，无论其组织来源如何。 在IPF中，Hedgehog通路激活的肌成纤维细胞功能失调，导致肺部形成纤维化瘢痕。在肺组织中选择性抑制该通路可有效导致肌成纤维细胞发生凋亡，从而消除IPF的关键细胞驱动因素。 ENV-201是一种口服的ULK1/2小分子抑制剂，ULK1/2是细胞自噬（autophagy）过程中的一种关键酶，自噬过程常与KRAS和STK11突变癌症的耐药性有关，具有高自噬水平的肿瘤，如携带KRAS突变的肿瘤，对标准疗法具有耐药性。研究人员还发现，在肺癌、结直肠癌和胰腺癌中经常发现的特定基因突变会导致那些肿瘤高度依赖这种回收途径。 已有研究支持靶向ULK1/2的精准疗法，单独或与现有化疗、靶向和免疫治疗联用，在根据基因突变筛选的癌症中抑制自噬作用。Endeavor计划在明年将项目推进到临床开发阶段。“ Endeavor BioMedicines公司正在开发针对癌症和纤维化遗传原因的精准药物。”Endeavor BioMedicines公司联合创始人兼首席执行官John Hood博士说，“在过去的十年中，研究人员已经对Hedgehog和ULK1信号通路进行了深入研究，现在我们有能力发现从中获益最大的患者。获得的资金使我们能够给正确的患者提供正确的药物，以便获得最佳的临床结果。” 参考资料： [1] Endeavor BioMedicines Closes $101M Series B Financing to Advance Clinical-Stage Precision Medicine Pipeline. Retrieved February 7, 2022, from https://www.businesswire.com/news/home/20220207005151/en [2] 他让新药“起死回生”：独家专访Impact首席执行官John Hood博士. Retrieved February 7, 2022, from https://mp.weixin.qq.com/s?__biz=MzAwMDA5NTIxNQ==&mid=2649971638&idx=1&sn=d76901e108814ed05d5315a98c4f924e&chksm=82e9dd36b59e54200a04c96aae5c53ce4537b8a72d7bc3fe08b1cd79c45d6a080e1b6575f7b6#rd [3] 命运给了他第二次机会，这一次，他让新药顺利上市！Retrieved February 7, 2022, from https://mp.weixin.qq.com/s?__biz=MzAwMDA5NTIxNQ==&mid=2649986171&idx=2&sn=e88604624a9b7d1d3a700febc9c66985 内容来源于网络，如有侵权，请联系删除，谢谢。

San Diego-based Endeavor BioMedicines closed on a Series B financing worth $101 million. The round was led by Ally Bridge Group and Avidity Partners, joined by new investors Perceptive Advisors, Piper Heartland Healthcare Capital, Revelation Partners, funds managed by Tekla Capital Management, and funds and accounts advised by T. Rowe Price Associates. Existing investors also participated — Omega Funds and Longitude Capital. Endeavor focuses on precision medicines for cancer and fibrosis. The company plans to use the monies raised to advance its pipeline, including taladegib (ENV-101), a small molecule inhibitor of the PTCH1 receptor in the Hedgehog signaling pathway for cancer and idiopathic pulmonary fibrosis (IPF). A second top pipeline product is ENV-201, a possible best-in-class small ULK1/2 inhibitor for KRAS-driven cancers. ENV-101 was initially being developed for patients with basal cell carcinoma (BCC) but has been expanded to multiple cancer types driven by PTCH1 in addition to IPF. “Endeavor BioMedicines is developing precision medicines targeting the genetic culprits of cancer and fibrosis,” said John Hood, co-founder, chief executive officer and chairman of Endeavor. “Researchers have investigated Hedgehog and ULK1 signaling pathways over the last decade, but now we have the understanding and capability to identify the patients who will benefit most from them. The capital raised from a committed, top-tier investor syndicate enables us to deliver the right drug to the right patients in order to get the best clinical outcome.” As part of the financing deal, Andrew Lam with Ally and Monal Mehta with Avidity will join the board of directors, joining John Hood, Bernard Davitian of Omega Fund and Patrick Enright of Longitude. On September 22, 2021, Endeavor dosed the first patient in its Phase II study of taladegib for IDF. It is a randomized, placebo-controlled, multi-center trial designed to evaluate the efficacy and safety of the drug by itself in mild to moderate IPF. It is being run in the Asia-Pacific region and will enroll about 60 participants, 30 patients in each arm. The participants will receive either a placebo or taladegib as a daily oral dose for 12 weeks of treatment. After treatment, they will be followed for another six weeks. The primary endpoints include change from baseline in frequency and severity of adverse events and key vital sign measurements. Secondary measures include Forced Vital Capacity, FEV1 and other lung function measures. Depending on the study results, they hope to run a Phase II trial of the drug in combination with standard of care sometime this year. Earlier that month, Endeavor in-licensed a ULK1/2 inhibitor program from the Salk Institute for Biological Studies and Sanford Burnham Prebys. The drug inhibits ULK1/2, an enzyme crucial in a cellular recycling process known as autophagy linked to drug resistance in RAS- and LKB1-mutated cancers. LKB1 mutations are observed in about 15% of all non-small cell lung cancer patients and a significant number of people with other types of cancers, including colorectal carcinoma. The company officially launched in January 2021 with a $62 million Series A financing led by Omega Funds, Longitude Capital and Endeavor’s management. It was co-founded by Hood, who previously founded and acted as chief executive officer of Impact Biomedicines until Celgene acquired it in 2018. Miguel de los Rios is Endeavor’s co-founder and chief scientific officer; he previously was chief executive officer of Rift Biotherapeutics.