In the ever-evolving landscape of the pharmaceutical industry, the once-celebrated AI-driven drug discovery company Exscientia has found itself embroiled in a series of challenges that have shaken its foundations. This article delves into the intricate web of events that have unfolded, painting a sobering picture of the company's fall from grace. Established in 2012, Exscientia was hailed as a pioneer in the field of AI-powered drug development, capturing the attention of both industry insiders and global investors. The company's early successes, including the advancement of the world's first AI-designed drug candidate into clinical trials, propelled it to the forefront of the pharmaceutical landscape. However, the road to success has been paved with setbacks and missteps. Exscientia's clinical pipeline has been plagued by disappointments, with several of its high-profile drug candidates failing to meet expectations. The termination of the I/II clinical trial for the A2A target cancer drug candidate, EXS-21546, highlighted the company's struggles to translate its AI prowess into tangible clinical outcomes. Adding to the company's woes, Exscientia has found itself facing a leadership crisis. The abrupt removal of its founder and CEO, Andrew Hopkins, due to alleged "improper relationships" with employees, has cast a cloud over the company's reputation. This development has had a significant impact on the company's stock price, which has plummeted by over 80% from its peak. Furthermore, Exscientia now faces the looming threat of a shareholder class-action lawsuit, further compounding the challenges it must navigate. The company's reputation has been tarnished, and it must now work to restore confidence among its stakeholders and the broader pharmaceutical community. Despite these setbacks, Exscientia remains committed to its AI-driven approach, focusing its resources on advancing its remaining clinical-stage assets. The company's collaboration with Bristol Myers Squibb on the PKC-θ inhibitor EXS-4318 and the ongoing ELUCIDATE trial for the CDK7-targeting molecule GTAEXS617 represent glimmers of hope in an otherwise turbulent landscape. As the pharmaceutical industry continues to evolve, the fate of Exscientia serves as a cautionary tale, underscoring the need for AI-driven companies to consistently deliver on their promises and maintain the trust of investors and the public. The lessons learned from Exscientia's downfall may pave the way for a more resilient and accountable future in the realm of AI-powered drug discovery.

2024-05-22

·医药魔方Pro

砍管线、解雇CEO后，Exscientia又裁员1/4

5月21日，Exscientia在2024Q1财报中宣布了一项4000万美元的成本节约计划，该计划将在2024年底完成20%-25%的裁员，预计遣散、解雇费用740万至960万美元。截至2023年12月31日，公司共有483名员工。Exscientia历史悠久，是一家成立于2012年的英国老牌AI制药企业。为了实现药物设计自动化的理念，Exscientia搭建了三大技术模块，包括CentaurAI、Centaur Biologist、Centaur Chemist。通过这三大技术模块，Exscientia能够实现更快速、更高效地开发药物。DSP-1181是由Exscientia和住友制药共同开发的一款用于治疗强迫症（OCD）的长效血清素5-HT1A受体激动剂，于2020年1月在日本启动了I期临床研究，是全球首个由人工智能设计进入临床的药物。但2022年因临床I期的研究并未达到预期标准，DSP-1181已被停止开发。虽然开发了全球首个由人工智能设计进入临床的药物，但近几年来Exscientia连续经历了砍管线、解雇CEO、裁员，日子过得并不如意。▌砍管线Exscientia的多款药物曾因临床效果不佳而终止研发。最近的一次是2023年10月，Exscientia宣布因疗效达不到预期，终止癌症候选药物EXS-21546的I/II期研究。EXS-21546是由Exscientia利用其AI驱动的平台和Evotec公司提供的生物学和化学能力共同发明和开发的A2A受体拮抗剂。此前，EXS-21546在健康志愿者Ia期研究的顶线数据表明：EXS-21546可靶向抑制A2A受体信号传导，是一种高效价、选择性、中枢神经系统(CNS)暴露量低的A2AR拮抗剂。此外，2022年初，Exscientia和住友制药共同开发的、用于治疗阿尔兹海默症的、5-HT1A受体激动剂和5-HT2A受体拮抗剂DSP-0038，也因临床疗效达不到而被终止临床。再往前，就是大名鼎鼎的全球首个由人工智能设计进入临床的药物——DSP-1181。该药物于2020年1月在日本启动了I期临床研究。但2022年临床I期的研究未达到预期标准，所以被Exscientia和住友制药停止开发。2023年，Exscientia又缩减了其产品管线，集中资源开发四款核心药物，包括：GTAEX617，一种细胞周期蛋白依赖性激酶7（CDK7）抑制剂正在开发用于多种癌症适应症（与GT Apeiron合作）。EXS4318，一种选择性蛋白激酶C（PKC）θ抑制剂，是Exscientia设计的第一个免疫学炎症候选药物，也是其第四个进入临床的分子（与BMS合作）。EXS74539，一种临床前阶段选择性和可逆赖氨酸特异性去甲基化酶1（LSD1）抑制剂，正在开发用于治疗急性髓系白血病（AML）和小细胞肺癌（SCLC）。EXS73565，一种粘膜相关淋巴组织淋巴瘤易位蛋白 1 （MALT1）抑制剂正在开发用于血液学的潜在适应症。Exscientia整体管线（来源：Exscientia官网）▌解雇CEO2024年2月，时任首席执行官Andrew Hopkins因被指控与两名员工有“不正当”关系而被解雇。公司首席科学官Dave Hallett担任临时首席执行官，直到找到新的继任者。Andrew Hopkins出生于1971年10月，是Exscientia的创始人兼首席执行官，他推动了世界上第一个由AI生成和优化的药物的发现，并进入人体临床试验。1998年，Andrew Hopkins拿到了牛津大学分子生物物理学博士学位后，进入辉瑞工作。2000年，他受命成立一个跨学科药物发现的CADD小组，帮助辉瑞内部发现药物的新适应症。他和团队帮助辉瑞建立了制药行业最早的大型数据库之一，还构建了一系列数据模型来预测蛋白质的靶点效应、药物疗效和安全性。2007年底，Andrew Hopkins离开辉瑞，加入邓迪大学成为一名全职教授，并推动了ChEMBL数据库的建立。如今ChEMBL已经成为药化领域最权威的数据库之一，收录超过210万个化合物、1.4万个靶点，ChEMBL也是众多AI制药公司训练并生成药物分子重要的数据源之一。2012年，Andrew Hopkins与团队在Nature杂志上发表了一篇名为Automated design of ligands to polypharmacological profiles的开创性论文。根据这一成果，Andrew Hopkins孵化出了Exscientia，这是最早将AI用于药物研发的商业公司之一，Andrew Hopkins担任公司创始人兼首席执行官。虽然Exscientia对外表示，“Andrew Hopkins的个人行为不会影响公司的合并财务报表以及公司对财务报告的内部控制，此次罢免与公司的运营或者财务业绩无关”。但作为Exscientia的创始人，Andrew Hopkins自创办以来一直担任公司CEO，是公司的灵魂人物。所以罢免消息一经发出后，公司股价立刻大跌20%。经历了风风雨雨的Exscientia表示，此次成本节约计划预计将使公司的现金跑道延长一年，即从原本的2026年延长到2027年。截至2023年3月底，公司拥有约4.16亿美元的现金、等价物和短期银行存款。Exscientia表示，预计将在今年下半年公布其CDK7抑制剂的I/II期研究剂量递增阶段的顶线数据；2024年底开始其LSD1抑制剂在急性髓系白血病患者中的I/II期试验；2025年初开始其MALT1抑制剂在B细胞恶性肿瘤患者中的I/II期测试。参考资料：[1]https://investors.exscientia.ai/press-releases/press-release-details/2024/Exscientia-Business-Update-for-First-Quarter-2024/default.aspx[2]创始人兼首席执行官被罢免. 来源：佰傲谷BioValley推荐阅读蛋白降解技术盘点：LYTAC、ATAC、AbTAC、PROTAB、REULR、KineTAC、IFLD……里程碑！首个Prime Editing基因编辑疗法获批临床Copyright © 2024 PHARMCUBE. All Rights Reserved.欢迎转发分享及合理引用，引用时请在显要位置标明文章来源；如需转载，请给微信公众号后台留言或发送消息，并注明公众号名称及ID。免责申明：本微信文章中的信息仅供一般参考之用，不可直接作为决策内容，医药魔方不对任何主体因使用本文内容而导致的任何损失承担责任。

临床1期财报

2024-05-21

·FierceBiotech

Exscientia cuts a quarter of staff while preserving AI-generated pipeline

The efficiency program comes three months after Exscientia fired CEO Andrew Hopkins after the board determined he had engaged in two personal relationships with employees. Exscientia is initiating “efficiency measures” to save cash, which will include a workforce reduction of around a quarter of staff while preserving the AI drug hunter’s existing pipeline. The program is expected to save about $40 million annually beginning in 2025, with expected severance and termination costs between approximately $7.4 million and $9.6 million, according to the company’s Tuesday morning earnings release. The charges will be recorded in the second quarter and stretch through the rest of the year. The cuts are expected to impact between 20% and 25% of staff and will be completed by the end of this year. The company is said to have just under 500 employees. Exscientia also expects to see several multi-year investments come to conclusion, resulting in efficiency improvements. These include projects related to the biotech’s proprietary technology platform. The pipeline, led by the phase 1/2 solid tumor drug GTAEXS617, will remain the same. Initial phase 1 data from the trial is expected in the second half of the year. Next in the clinic is EXS4318, which has been in-licensed by Bristol Myers Squibb and is currently undergoing a phase 1 study in inflammatory diseases. Exscientia slashed down its pipeline in October 2023, keying in on the CDK7 asset GTAEXS617 and the LSD1 inhibitor EXS74539. Several programs were removed from the lineup and prepped for partnerships. Exscientia’s cash runway is expected to stretch “well into 2027,” according to the earnings release. The company had $416.9 million in cash and equivalents as of March 31, compared to $458.8 million at the end of 2023. The efficiency program comes three months after Exscientia fired CEO Andrew Hopkins after the board determined he had engaged in two personal relationships with employees that were deemed “inappropriate and inconsistent” with company values. As a result of the termination, Hopkins forfeited his share options resulting in credits totaling $7.5 million, which also contributed to the decrease in general and administrative expenses for the quarter. These expenses decreased by a total of $9.4 million compared to the same period a year earlier. Chief Scientific Officer Dave Hallett remains as interim CEO as the company conducts a search for a permanent replacement. Elsewhere in the biotech world, Lyra Therapeutics executed a workforce reduction that cost 87 employees their jobs, including Chief Technology Officer John Bishop, Ph.D. The layoffs are effective today for 80 people, and on June 20 for the remaining seven, according to an SEC filing. “The board’s decision was based on cost-reduction initiatives intended to reduce the company’s ongoing operating expenses and maximize shareholder value,” according to the filing.