Morphic Therapeutic, Inc.

Kronos Bio is letting go nearly all its employees after flashing red lights earlier this month. As part of an 83% workforce downsizing, CEO Norbert Bischofberger is heading out the door and handing the keys to recently hired finance and operating chief Deborah Knobelman. The biotech had eliminated a trio of executives in January and conducted a couple of rounds of layoffs this year and last year . The latest round of layoffs will “substantially” wrap up by Dec. 31, the company said. Bischofberger was the fifth employee at Kronos, and he’s been with it since nearly the beginning, having taken part in the startup’s seed round back in 2018 after a three-decade R&D career at Gilead. “Norbert’s steadfast leadership was instrumental in the founding and building of Kronos Bio,” chair Arie Belldegrun said in a release. Bischofberger’s resignation takes effect Dec. 3, and he’ll continue on the board, according to an SEC filing. His decades of expertise will continue elsewhere: He recently joined the board of Vir Biotechnology and is also a scientific advisor to a new VC firm trying to build up the biotech ecosystem in his native Austria. He was also on the board of Morphic until Eli Lilly bought it for $3.2 billion this summer. Kronos said earlier this month it would seek “strategic alternatives” after looking at data for its CDK9 inhibitor. It determined additional development wasn’t warranted. The biotech had inked a $20 million upfront discovery deal with Genentech last year. At the end of September, the biotech had $124.9 million in cash, equivalents and investments, meaning it could be a target for a reverse merger. There were 10 biotech reverse mergers through the first nine months of 2024, according to a William Blair third-quarter report. At least five more have been disclosed since early October. Kronos went public at $19 per share $KRON in a $250 million IPO in October 2020. It trades below $1 today.

Novartis will pay $150 million upfront to Schrödinger, in a pact announced Tuesday to work together on several preclinical drug programs. Founded in 1990, Schrödinger has been developing and selling its physics-based R&D software to drugmakers like Novartis for decades, outlasting multiple waves of excitement over AI that have come in and out of its space. This latest deal is centered on multiple drug targets that both companies were researching. Schrödinger is not disclosing the targets beyond saying they are highly validated with compelling genetics or human biological evidence and fall outside oncology. “Schrödinger and Novartis are going to combine our efforts on these targets to finish discovery, to identify development candidates, and then Novartis will take on the further development of these programs,” Karen Akinsanya, Schrödinger’s president of R&D, therapeutics, said in an interview. Beyond $150 million upfront, which Schrödinger expects to recognize as revenue over the course of the research, the deal outlines potential payments of up to $892 million for R&D and regulatory achievements and up to $1.38 billion more for possible commercial milestones. Novartis is also ramping up its broader usage of Schrödinger software through a second agreement that includes an undisclosed increase in how much Novartis pays for the software. That fits a trend Schrödinger CEO Ramy Farid sees in pharma giants shifting from using its software as a way to explore or understand experiments to using it at a greater scale, where calculations are relied on more than traditional methods. He pointed to the success of biotech startups like Nimbus Therapeutics , Morphic Therapeutic , Ajax Therapeutics and Structure Therapeutics — all heavy users of Schrödinger software from the start. “I don’t think that can be ignored, and it looks like the industry is not ignoring it anymore,” Farid said. “So now you have companies like Lilly and BMS and Novartis scaling up their usage in a really meaningful way, but we’re in the early days of it. There are many, many more companies that will, I think, transition in the way that Novartis just did.” Schrödinger’s challenge will be turning that vision into a reality that impacts the top line. The company’s software revenue for the third quarter, also announced Tuesday morning, came in below expectations at $31.9 million, up 10% from a year ago. The $1.4 billion biotech has seen its stock price fall 44% this year, as investors await clinical readouts from its own drug pipeline expected in 2025.

此次医博会由同写意策划，以“发展新质生产力，共享健康新未来”为主题，用全新的视角瞄准国内外医药及大健康产业发展前沿。诚邀海内外医药及大健康各界嘉宾齐聚中国医药城，共赴时代之约。展位/报告火热征集中！ 从没有人否认自免的巨大市场，就像海妖的歌声，让人心向往之却也心生胆怯。在细胞和基因治疗领域，勇敢的Biotech公司正向这片神秘海域发起挑战。 今年4月，Cullinan Oncology宣布更名为Cullinan Therapeutics，将公司的研发管线扩展至自身免疫性疾病领域。这并非孤例——CRISPR Therapeutics、TG Therapeutics、Atara Biotherapeutics、Mustang Bio和Caribou Biosciences等众多明星Biotech，也都宣布进军自身免疫性疾病领域。 如今，这群冒险航海队列中又加入了一名新成员——Kymera Therapeutics。 1 选择大于努力？ 作为PROTAC明星公司之一的Kymera成立于2016年，2020年8月以每股20美元的发行价在纳斯达克上市。 近期，这家Biotech基于其免疫学项目的“重大进展和潜力”，正在将重点从肿瘤学转移到免疫学领域。 10月底，Kymera的创始人、总裁兼首席执行官Nello Mainolfi博士表示，“将我们的资源和努力集中在免疫学工作上，反映了我们在项目优先排序上的考量，以解决有重大需求的大型患者群体，并明确具有重大的商业机会”。 据Kymera称，他们正在重点推进口服STAT6降解剂KT-621，这款候选产品具有治疗TH2炎症多种适应症的潜力，包括特应性皮炎、哮喘和COPD。Mainolfi补充道，Kymera是第一个将这种机制的候选药物推向临床的公司，I期临床的初步数据预计将在明年上半年公布。 Kymera拥有的自免候选产品还包括一款与赛诺菲合作的KT-474。2020年，两家公司达成数额可高达20亿美元的研发合作，共同开发针对IRAK4的蛋白降解疗法，治疗免疫炎症疾病。 KT-474是一款IRAK4降解剂，正在开发用于治疗化脓性汗腺炎（HS）和特应性皮炎（AD）等有显著患者需求的免疫炎症疾病，以及其他潜在疾病。KT-474通过与IRAK4结合，募集E3泛素连接酶给IRAK4打上泛素的“标签”，这些“标签”会指引IRAK4蛋白被细胞的蛋白酶体降解。E3连接酶筛选是Kymera的关键技术之一。 此前公布的I期临床试验结果显示，在治疗特应性皮炎时，中重度患者在接受治疗28天后，瘙痒程度减轻63%，评估患者疾病程度和严重性的EASI评分下降36%。 7月，在独立数据审查委员会对在研蛋白降解药物KT-474的初步安全性和有效性数据进行审查后，赛诺菲计划扩大正在进行的HS和AD的II期临床试验。Kymera预计正在进行的第二阶段的扩展将加快整体开发时间表，然后是第三阶段试验。 此外，Kymera新闻稿显示，除了上述两款产品外，公司管线中还由一种TYK2降解剂，预计将在2025年上半年进入人体测试。 Kymera管线，图源：公司官网 由于对STAT6降解剂项目的投入，以及其研发部门的持续增长，Kymera第三季度在研发上的支出为6040万美元，去年同期为4810万美元。 2 诸神攻自免 Evaluate的报告，预测了2030年TOP10畅销药。从图中可以明显看出，霸榜多年的肿瘤药正逐渐被替代。除了大热的减肥领域，自免药物也在逐渐加大比重。 TOP10畅销药，图源：Evaluate 沙利文数据预测，到2030年，全球自身免疫性疾病药物市场规模有望达到1760亿美元，2022—2030年复合年增长率为3.6%。 调转船头不是“小而美”Biotech的特权，“巨轮”MNC也在为了生计调整转舵方向。 据不完全统计，仅在2024年上半年，25家被MNC收购的Biotech公司，有11家公司的核心管线专注于自免领域。 7月，礼来以32亿美元收购Morphic Therapeutic，聚焦口服小分子α4β7抑制剂MORF-057。Morphic正在针对溃疡性结肠炎（UC）与克罗恩病（CD）两大适应症开展了2项II期临床试验。 5月，渤健宣布与Human Immunology Biosciences（HI-Bio）达成收购协议，将以11.5亿美元预付款和高达6.5亿美元的潜在里程碑付款收购HI-Bio。后者核心资产felzartamab是一款靶向CD38的单抗，正在开发用于多发性骨髓瘤、原发性膜性肾病、IgA肾病、抗体介导的排斥反应等多个适应症的临床研究。 不过对渤健来说，更可期的未来信号，发生在9月。渤健和优时比也在携手20多年后迎来了在研药物dapirolizumab pegol联合疗法治疗治疗红斑狼疮（SLE）的III期试验达到主要终点的好消息。 4月，Vertex Pharmaceuticals宣布以49亿美元收购Alpine Immune Sciences。Alpine的核心管线是自免药物povetacicept（ALPN-303）——一种突变TACI-Fc融合蛋白。 一项开放标签、多剂量递增的Ib/IIa期研究RUBY-3研究的初步结果表明，povetacicept在IgAN患者中显示出良好的耐受性和疾病活动度的改善，包括UPCR的降低和肾功能的稳定，同时伴随着Gd-IgA1的减少。 还有一个不可不提及的百亿美元巨额交易——默沙东在去年4月以108亿美元收购Prometheus Biosciences，聚焦于其核心产品PRA023。这是一款针对TL1A的抗体，收购后更名为tulisokibart。TL1A是一种重要的细胞因子，在IBD中扮演着关键角色。这款产品目前已进入III期临床阶段，是全球第1款进入III期阶段的TL1A单抗。 自免巨头也在加固城池。 老牌“一哥”艾伯维半年内四次出手，围绕IBD猛圈地。 6月，艾伯维与创新生物制药公司明济生物达成合作，获得其下一代TL1A抗体FG-M701，该药物是一款处于临床前开发阶段的产品，适应症为IBD。 几天后，艾伯维又宣布收购致力于开发炎症性疾病创新疗法的Biotech公司Celsius Therapeutics，其主要研究药物CEL383是一种抗TREM1单抗，适应症依然是IBD。 此前的3月，艾伯维也先后与Parvus Therapeutics和Landos Biopharma达成交易，获得相关IBD候选产品。 对“一哥”之位虎视眈眈的强生，在今年不到半个月的时间里，官宣8.5亿美元和12.5亿美元的两笔自免领域的收购，交易另一方为专注于开发免疫介导疾病双特异性抗体的私营生物技术公司Proteologix，以及Numab的全资子公司Yellow Jersey Therapeutics。 围绕自免进行的重磅交易并不鲜见，整体上看，MNC新布局的自免疾病药物靶点比较新颖，大多还未有药物获批上市。差异化是决胜关键，就看谁先越过终点线。 参考文章： 1、Kymera zeros in on immunology, seeks partners for cancer candidates；fiercepharma 2、潜在“first-in-class”蛋白降解剂临床进展积极，加速挺进关键性临床开发；药明康德 3、渤健求变，挺进自免；同写意 同写意媒体矩阵，欢迎关注↓↓↓