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Merck & Co – known as MSD outside the US and Canada – has acquired Yale University oncology spinout Modifi Biosciences in a deal worth $1.3bn. The agreement gives Merck access to preclinical compounds designed to exploit DNA repair defects in difficult-to-treat cancers, including glioblastomas. Modifi, formed in 2021, has developed a new class of small molecules that target cancer cells lacking expression of a key DNA repair protein called MGMT. Approximately half of all glioblastomas and up to 80% of gliomas lack MGMT, which Modifi says makes these cancers a “natural first target” for its approach. Emerging research has also indicated that this MGMT deficiency is seen in many other tumour types. Merck has acquired all outstanding shares of Modifi for $30m upfront, with Modifi shareholders eligible to receive potential milestone payments totalling up to $1.3bn. David Weinstock, vice president, discovery oncology, Merck Research Laboratories, said: “DNA repair defects are a frequent hallmark of tumour cells and a major cause of resistance to cancer therapy. The… Modifi Biosciences team has developed an innovative approach that we believe has potential for treating some of the most refractory cancer types.” Also commenting on the deal, Modifi’s co-founder, Ranjit Bindra, said: “In founding Modifi Biosciences, we sought to radically change the oncology treatment paradigm for cancer patients with glioblastoma and other tumours. “We are honoured to have Merck recognise the potential of our science, and as an oncology company, [it is] perfectly positioned to advance our innovations through clinical trials and commercialisation.” Merck has made a number of acquisitions this year. In July, it completed its previously announced acquisition of EyeBio in a deal worth $3bn, giving it access to a late-stage candidate for diabetic macular oedema and neovascular age-related macular degeneration, as well as a preclinical pipeline targeting retinal diseases. The company also announced in April that it had acquired University at Buffalo laboratory spinout Abceutics in a deal worth $208m to improve antibody-drug conjugates safety, and acquired immuno-oncology company Harpoon Therapeutics and its pipeline of T-cell engagers for approximately $680m in March.

Biotech investment firm Samsara BioCapital has added three new venture partners in recent months to expand its network, support first-time CEOs in its portfolio and guide more companies by way of board seats. One of the venture partners also has government policy experience, giving the California firm an in-house expert to advise on some of the biggest legislative forces in drug development today, including the Inflation Reduction Act and the ongoing Biosecure bill. The eight-year-old firm has added former Chinook Therapeutics CEO Eric Dobmeier, ex-Atreca CEO John Orwin and previous Alnylam public policy and government relations leader Alan Eisenberg. Samsara now has 14 venture partners, founder and managing partner Srini Akkaraju told Endpoints News in an interview. The team’s expansion comes as Samsara’s portfolio companies have hit some key milestones in recent months, including multiple megarounds, EyeBio’s up to $3 billion exit to Merck , OnKure’s reverse merger with Reneo Pharmaceuticals, IPO planning at Upstream Bio and a Nasdaq listing for Alumis . Akkaraju is quite familiar with Dobmeier and Orwin by way of Seagen. Akkaraju served on the antibody-drug conjugate pioneer’s board for 17 years until 2020, during which Orwin was also a board member. Dobmeier had risen to the role of chief operating officer at the Seattle biotech before departing to become an executive at Silverback Therapeutics and then Chinook, which he oversaw until its $3.2 billion exit to Novartis last year. The Samsara founder said biotech is innovating at a faster clip than ever before, and the deal flow far exceeds the levels he saw in the early days of his investing career two decades ago. That calls for experienced veterans to help guide nascent companies. “The reality is the science and the innovation and the ideas, there’s more of them than experienced CEOs to run these [biotechs],” Akkaraju said. “But everybody has to be a first-time something, and first-time CEOs are always going to be there, and they’re an important part of our ecosystem. I personally think people like Eric and John are phenomenal to help these first-time CEOs do their job as well as they possibly can and grow a little bit faster into it.” Orwin was already chair of Samsara portfolio company Cargo Therapeutics. He’s also on the boards of Travere Therapeutics, AnaptysBio and Nested Therapeutics. Meanwhile, Eisenberg had spent about a decade at the Biotechnology Innovation Organization before working on government relations for Celgene and then Alnylam. “We’ve all been talking about Biosecure, we’ve been talking about the IRA for the last couple of years and the impact that will have and changes to Medicare Part D, etc. We read about it, we see it, and we talk to people about it. We get a little bit of, I’d say, a rudimentary understanding,” Akkaraju said. “Then, Alan’s come in and provided us a much greater level of understanding of this.” Investors could rely on outside experts and call them up when they need counsel on matters related to government policy, IRA implications and the like. But Akkaraju said he’d “rather have that person at the table all the time.” Akkaraju noted the trio of new team members — who are part-time — is not a sign that Samsara will ramp up the number of investments it makes. “It certainly has an impact on deal flow because all of these guys have great networks out there that will bring in opportunities,” Akkaraju said, but “it’s all about doing as good of a job as we possibly can in making a decision to do a deal and managing the investment and working with the portfolio company.”

在GLP-1横扫一切的强势驱动下，无论是业绩和市值，还是各自的产品布局，全球大药企都在经历深刻的变局，甚至可以说进行了颠覆性的重排，仅是下面这张摘要图与半年前相比就有不小的差异。 本文追踪了2024H1全球医药企业的主要管线进度，涵盖礼来、诺和诺德、强生、默沙东等11家全球医药企业。 注：因篇幅原因上篇包含1-5家药企，下篇将继续为念呈现：罗氏ROG、阿斯利康AZN、诺华NVS、辉瑞PFE、赛诺菲SNY、百时美施贵宝BMY。 礼来LLY LLY的业绩确实逆天，尤其2024年第二季度的收入肉眼可见跳了一大格、两年时间内几乎翻倍；而市值的成长却远不止翻倍，仅今年就从$500b飚到最高$850b，虽然近期略有回落，但自季报出炉两个交易日又怒涨了$100b，目前哪怕按公司全年业绩指引的上限也是66x市盈率…… Tirzepatide这个季度的极致爆发已经基本上奠定了与Semaglutide对决的后续基调，攻守之势异也。Mounjaro和Zepbound分别环比增长71%和140%，单季度销售额总共达到$4.3b；与之相比，S药已经连续两个季度走平，目前单季度T药已经追到S药的65%水平。在这个超级引擎的驱动下，公司业绩一路打破预期，几乎每个季度都在调高全年指引。 管线的攻城略地仍在发力：在万众瞩目的代谢板块，Tirzepatide先后公布了OSA三期临床、HFpEF三期临床、MASH二期临床等结果，长效胰岛素也公布了两个三期临床结果，Amylin激动剂启动二期临床，Lp(a) siRNA药物Lepodisiran启动三期临床，但Empagliflozin的心衰三期临床也未能达到终点；阿尔茨海默药物Donanemab终于获得FDA批准；自免板块，以$3.2b 购Morphic获得小分子α4β7抑制剂，IL-13单抗Lebrikizumab在FDA给出CRL后重新提交上市申请，IL23p19单抗Mirikizumab在提交CD适应症上市申请后公布完整三期临床数据；肿瘤板块，去年收购Emergence得到的Nectin-4 ADC管线ETx-22进入临床，CDK4/6抑制剂Abemaciclib连续在mCRPC和HSPC等适应症的三期临床中失败。 诺和诺德NVO NVO自从Semaglutide打开减重之门以来，连续两年多的股价连升势头终于被中断，从最高点$650b左右显著回调到$550b以下，特别是在中报公布当天大跌8%，业绩增长的步伐放缓恰恰与此前星辰大海的预期形成较大落差。 近期正是两大减肥神药Semaglutide和Tirzepatide对决的天王山之战，面对T药的冲击和逼近，S药自身开始走平，连续两个季度环比增长几乎停滞，而对手T药这个季度简直是要疯、环比近乎要翻倍，二者之间的差距在急速缩小。 最重要的研发进展当然还是围绕着Semaglutide，近期公布CKD的三期临床结果并提交该适应症的上市申请，口服25mg剂型的三期临床也公布积极结果，然而 HFpEF的上市申请被撤回、可能被隔壁LLY反超进度；Icodec虽然在欧洲、中国、日本陆续获批，但美国FDA却给了CRL拒绝批准；IcoSema复方公布了两个T2D三期临床结果；血友病双抗Mim8终于公布了三期临床结果；以€1.025b收购Cardior，获得一款靶向miR-132的ASO药物CDR-132L，目前正在开展治疗心衰的二期临床。 强生JNJ JNJ在持续两年多不温不火的业绩之后，医药部分的季度收入首次有了比较可观的增长、到了$14.5b，但市值依然回不到$400b大关，与GLP-1双雄LLY和NOVO的距离仍在越拉越大。 强生医药板块的业绩在大药企中还是相当稳健，其中Ustekinumab和Daratumumab上市十多年还迭创新高，Guselkumab和Macitentan+Selexipag也在高位维持稳步增长，CAR-T药物Cilta-cel在产能瓶颈缓解后开始重拾增长，但Ibrutinib、Infliximab、Abiraterone、Paliperidone等曾经的超重磅品种确实老态渐显。 研发方面也有多项重磅突破：Cilta-cel凭借CARTITUDE-4三期临床的惊艳结果获批2-4LMM适应症，EGFR/cMET双 抗Amivantamab获 批 治 疗EGFRExon20插入突变的1L NSCLC，FcRn单抗Nipocalimab公布重症肌无力三期临床达到主要临床终点，靶向IL-23R的口服多肽JNJ-2113公布了52周治疗斑块状银屑病的二期试验结果，OX2R拮抗剂Seltorexant公布了伴随失眠症状的重度抑郁症三期临床结果，Macitentan与Tadalafil每日一次口服复方制剂获批治疗PAH；此外，公司近期连续完成自免领域的资产收购，包括从Numab以$1.25b收购将进入二期的IL4Rα/IL31双抗NM26，以及以$850m收购Proteologix获得将进入一期的IL13/TSLP双抗PX128和尚在临床前的IL13/IL22双抗PX130。 当然，近期最有想象空间的大事件，就属传奇生物的收购传闻，潜在收购方（也应该是最顺理成章的人选）便是JNJ本尊。 默沙东MRK MRK在新冠药回撤后经历过一小段业绩和股价的波动，但凭借K药坐稳药王且持续增长，市值原本稳稳站在$300b以上，然而就在中报公布当天大跌10%，主要是HPV疫苗在中国因反腐等原因大幅不及预期。 研发进展除了围绕K药的各种扩适应症和联用方案以外，已经展现出更多的未来增长来源：PAH药物Sotatercept和21价肺炎疫苗V116（Capvaxive） 先 后 获 得 FDA批准，RSV抗体Clesrovimab公布了针对婴儿的Ph2b/3期临床达到主要和次 要临床终点，新一代HIV药物Islatravir公布了联用Lenacapavir的二期临床结果，靶向B7H3的DS-7300启动SCLC三期临床，靶向CDH6的DS-6000启动了PROC 的2/3期临床；以$1.3b首付款+$1.7b里程碑收购EyeBio，获得一款靶向LRP5 两个表位和FZD4的三抗；坏消息包括，HER3 ADC管线U3-1402的上市申请被 FDA因生产原因拒绝，Olaparib的NSCLC三期临床和TIGIT单抗Vibostolimab联用K药治疗黑色素瘤的三期临床都遭遇失败。 艾伯维ABBV 艾伯维虽然遭遇Adalimumab和Ibrutinib两大超重磅品种的下滑，所幸Risankizuma、Upadacitinib、Venetoclax、Cariprazine几个新生代贡献一定的增量，整体业绩才算没有太崩坏，外加通过收购获得ADC和精神疾病领域等重要管线，因此市值近期成功突破到$300b以上。 自免板块主要仍以现有重磅的适应症扩展为主，包括Risankizumab获批UC适应症，Upadacitinib公布与Dupilumab头对头的特应性皮炎3/4期临床试验结果、公布治疗巨细胞动脉炎的三期临床结果并提交上市申请，另外还以$210m收购了Landos获得一款治疗IBD的NLRX1激动剂NX-13；此外，偏头痛药物Atogepant公布预防适应症的长期临床结果，CD20/CD3双抗Epcoritamab获批3L+ FL适应症。 注：因篇幅原因上篇包含1-5家药企，下篇将继续为念呈现：罗氏ROG、阿斯利康AZN、诺华NVS、辉瑞PFE、赛诺菲SNY、百时美施贵宝BMY。