Corbus Pharmaceuticals Holdings, Inc.

Today, a brief rundown of news involving Curium and Sionna Therapeutics, as well as updates from Novo Nordisk, Corbus Pharmaceuticals, Arrowhead Pharmaceuticals and Contineum Therapeutics that you may have missed.The Food and Drug Administration on Tuesday approved a first-of-its-kind generic drug from Curium. The clearance was awarded to Bexlutry, a copycat version of Novartis Lutathera. Like Lutathera, Bexlutry delivers radioactive lutetium to a protein, SSTR, found on the surface of certain neuroendocrine tumors. Its now the first generic radioligand therapy, or targeted radiopharmaceutical for cancer. The approval covers use in treating SSTR-positive neuroendocrine cancers, which include foregut, midgut and hindgut tumors. It was issued after Curium prevailed in a patent dispute with Novartis. Ben Fidler Sionna Therapeutics will lay off nearly half its workforce and alter its clinical development strategy following disappointing results in a key cystic fibrosis drug trial. On Monday, the company said an after-the-fact analysis unearthed multiple confounding factors in its failed trial. The company intends to incorporate the lessons learned into a new Phase 2 study testing a different regimen. Sionnas explanation seems reasonable, but its still very hard to have conviction, wrote Stifel analyst Paul Matteis. The coming job cuts and other cost-saving moves will extend Sionnas financial runway into the second half of 2029 while it pursues its new strategy. Ben FidlerNovo Nordisk will drop the Nordisk in its name as part of a corporate rebranding, the company said Monday. Going forward, Novowill be used as the companys day-to-day name while Novo Nordisk will remain its legal name, according to a Monday statement.The rebrand comes ahead of a capital markets day next week, during which Novo intends to provide investors with an overview of its updated corporate strategy. The company has lost more than two-thirds of its market value since mid-2024 and ceded its leadership position in obesity treatment to rival Eli Lilly. Ben FidlerAn experimental Corbus Pharmaceuticals drug helped people with obesity lose as much as 5 percentage points more than a placebo after 12 weeks in an early-stage trial. Corbus drug, CRB-913, targets a kind of cannabinoid receptor that regulates appetite, an approach that so far has yielded disappointing clinical results. To Jefferies analyst Amin Makarem, the early efficacy results reported Monday were competitive and suggest differentiated tolerability compared to GLP-1 drugs. Still, anywhere from 1.5% to nearly 10% of patients, depending on the dose, stopped treatment because of psychiatric side effects. Those types of side effects are a concern with cannabinoid drugs and the key debate surrounding CRB-913, Makarem wrote in a client note. Corbus plans to start a Phase 2 study next year. Ben FidlerA dual-acting RNA interference therapy from Arrowhead Pharmaceuticals effectively silenced two genes implicated in cardiovascular disease in an early-stage trial,the company said Tuesday. According to Arrowhead, a single dose of that therapy, Aro-Dimer-Pa, reduced levels of the proteins PCSK9 and APOC3 circulating in the blood by 72% and 88%, respectively. Arrowhead is positioning the medicine as a treatment for mixed hyperlipidemia, a common condition characterized by high levels of bad cholesterol and fats in the blood. Mixed hyperlipidemia is a very large market opportunity and Arrowhead now appears to have a highly differentiated drug, wrote Cantor Fitzgerald analyst Prakhar Agrawal. Delilah AlvaradoContineum Therapeutics said Monday an investigational drug its been working on with Johnson & Johnson failed a Phase 2 trialin major depressive disorder. Compared to a placebo over the course of five days, the drug didnt meaningfully improve scores on a widely used depression rating scale, Contineum said. Though the outcome was disappointing, investors had low expectations for the study, wrote RBC Capital Markets analyst Brian Abrahams, noting that the companys main value driver is a fibrosis drug thats also in clinical testing. J&J will evaluate the depression data to inform the next steps for the program. Delilah Alvarado '

今天全球医药研发领域的高价值事件主要集中在HER2突变NSCLC一线ADC、ROS1靶向药一线数据、后线CTLA-4新设计、非GLP-1减重机制人体PoC、TYK2注册推进，以及EGFR早期肺癌长期生存验证。 今日事件速览 今日关键词HER2一线ADCROS1一线靶向CTLA-4新设计CB1减重重启TYK2优先审评EGFR术后长期生存 01｜Enhertu：DESTINY-Lung04完整Ⅲ期数据公布，HER2突变NSCLC一线治疗格局可能改写 AstraZeneca与Daiichi Sankyo公布DESTINY-Lung04Ⅲ期完整数据。在HER2突变、不可切除局部晚期或转移性非鳞NSCLC一线治疗中，Enhertu较pembrolizumab联合铂类/pemetrexed显著延长PFS：14.3个月 vs 8.3个月，HR 0.63，P<0.0001；ORR分别为70.0% vs 44.5%。这是首个在该人群随机Ⅲ期中证明HER2靶向治疗优于全球一线标准方案的研究。 研发看点 这不只是ADC成功，而是HER2突变正在从后线靶点升级为一线驱动基因。如果后续OS同样成熟阳性，HER2检测和治疗决策都可能进一步前移。下一步重点关注OS、ILD以及长期一线治疗的耐受性。 来源：AstraZeneca官方公告 https://www.astrazeneca.com/media-centre/press-releases/2026/enhertu-in-DESTINY-Lung04-Phase-iii-trial.html 02｜Jideytro：ROS1阳性NSCLC一线ORR达94%，GSK准备拓展至一线 GSK在WCLC披露Jideytro（zidesamtinib）ARROS-1Ⅰ/Ⅱ期ROS1 TKI初治人群数据。在94例可评估患者中，确认ORR达到94%，其中CR约15%，中位随访15.2个月。Jideytro已于今年7月获FDA批准用于既往接受过ROS1 TKI的ROS1阳性NSCLC，GSK目前计划基于一线数据进一步推进注册。 研发看点 ROS1赛道已经有repotrectinib、taletrectinib等新一代TKI，Jideytro真正要竞争的是缓解深度、CNS活性、耐药突变覆盖和耐受性。94%的ORR非常亮眼，而GSK以106亿美元收购Nuvalent后，这组数据也直接关系其肺癌战略价值。 来源：GSK官方Jideytro资料 https://www.gsk.com/en-gb/media/press-releases/jideytro-zidesamtinib-approved-in-the-us-for-previously-treated-ros1-positive-non-small-cell-lung-cancer/ 03｜gotistobart：Ⅲ期后线鳞状NSCLC OS显著改善，CTLA-4被重新工程化 BioNTech/OncoC4披露PRESERVE-003Ⅲ期Stage 1更新。Gotistobart是一款肿瘤微环境选择性CTLA-4抗体，用于既往接受PD-(L)1和铂类化疗后进展的转移性鳞状NSCLC。更新数据显示，其OS较docetaxel出现统计学显著且具有临床意义的改善，媒体报道中位生存接近翻倍。 研发看点 CTLA-4并不新，但gotistobart的价值在于通过肿瘤微环境选择性Treg清除重新打开治疗窗。如果更大样本的Stage 2复制这一生存优势，将证明“老靶点+抗体工程优化”依然可以产生真正的产品级创新。 来源：BioNTech PRESERVE-003临床项目 https://clinicaltrials.biontech.com/trials/PRESERVE-003 04｜CRB-913：CB1减重机制重新回归，Ⅰb期12周减重约5% Corbus公布CRB-913 CANYON-1Ⅰb期顶线数据。CRB-913是一款每日一次、高度外周限制性的CB1反向激动剂，旨在保留CB1通路的减重作用，同时尽量避免历史中枢CB1药物的精神神经毒性。60 mg组治疗12周平均体重下降约5%，且尚未观察到减重平台期；公司表示整体耐受性良好，胃肠道表现也具有潜在差异化。 研发看点 这是今天最值得关注的早期代谢事件之一。CB1曾因rimonabant精神副作用而几乎退出减重市场，如今Corbus试图通过限制脑暴露重新药物化这一机制。如果更长期数据能维持减重并控制精神神经AE，CRB-913可能成为GLP-1之外真正有竞争力的口服非incretin路线。 来源：Corbus Pharmaceuticals官方CANYON-1资料 https://ir.corbuspharma.com/news-events/press-releases/detail/477/corbus-pharmaceuticals-to-host-conference-call-to-discuss-topline-data-from-canyon-1-clinical-trial-and-the-potential-of-crb-913-in-obesity 05｜zasocitinib：NDA获FDA优先审评，TYK2第二代竞争进入注册阶段 Takeda宣布FDA受理zasocitinib（TAK-279）用于中重度斑块型银屑病的NDA并授予Priority Review。申请基于近3000例患者数据，关键LATITUDE PsO 3001/3002Ⅲ期均达到主要及全部排序次要终点；16周时约70%的患者达到sPGA 0/1，PASI75约71%–76%。 研发看点 TYK2已有deucravacitinib验证赛道，zasocitinib真正要证明的是更高选择性是否能换来更强疗效，同时保持JAK之外的安全性优势。若获批，Takeda还可进一步向PsA、IBD、白癜风等多个免疫适应症复制。 来源：Takeda官方公告（Business Wire） https://www.businesswire.com/news/home/20260914748441/en/U.S.-FDA-Accepts-New-Drug-Application-Under-Priority-Review-for-Takedas-Zasocitinib-in-Moderate-to-Severe-Plaque-Psoriasis-with-Potential-to-Redefine-Oral-Treatment-Expectations 06｜Tagrisso：ADAURA 8年OS继续拉开差距，早期精准治疗长期价值坐实 AstraZeneca公布ADAURAⅢ期8年随访结果。对于完全切除的IB–IIIA期EGFR突变NSCLC患者，奥希替尼辅助治疗长期OS优势持续：II–IIIA期死亡风险降低47%（HR 0.53），IB–IIIA期整体死亡风险降低48%（HR 0.52）；8年OS率分别达到74% vs 58%和79% vs 64%。 研发看点 ADAURA早已改变标准治疗，但8年数据进一步说明，奥希替尼不是简单“把复发往后推”，而是真正把DFS优势转化成了长期生存获益。这也强化了驱动基因阳性肿瘤治疗向更早疾病阶段前移的开发逻辑。 来源：AstraZeneca官方公告 https://www.astrazeneca.com/media-centre/press-releases/2026/tagrisso-demonstrated-eight-year-landmark-survival-in-adaura-phase-iii-trial.html PharmaRadar 今日观察 1｜今天最有意思的两条是“重新药物化” CRB-913重新挑战过去因安全性失败的CB1减重机制，Jideytro则继续尝试用更高选择性和脑穿透性改进成熟ROS1赛道。这两条说明创新并不只是找新靶点，也包括把旧靶点做得更安全、更持久、更精准。 2｜肺癌正在同时发生“靶向前移”和“治疗标准重构” Enhertu把HER2 ADC推向一线，Jideytro准备从经治ROS1阳性NSCLC进入一线，Tagrisso则进一步证明早期辅助靶向的长期生存价值。共同趋势非常明确：分子分型后的精准治疗持续向更早线、更早疾病阶段前移。 3｜代谢赛道正在从GLP-1单中心竞争走向多机制竞争 CRB-913选择非incretin的CB1机制，说明肥胖药竞争正在从单一GLP-1赛道扩展到更广泛机制。未来核心可能逐渐从“谁减得更多”变成疗效、肌肉保留、胃肠耐受、精神安全、给药便利性和长期依从性的综合竞争。 今日最值得继续跟踪的3个项目 CRB-913 下一节点：CANYON-1完整剂量数据及下一阶段开发方案。 核心问题：5%的12周减重能否继续扩大，同时真正避免历史CB1药物的中枢安全性问题？ Jideytro 下一节点：ROS1 TKI初治适应症注册申报。 核心问题：94% ORR能否转化为足够长的DoR/PFS，并在CNS控制和耐受性上体现best-in-class优势？ Enhertu 下一节点：DESTINY-Lung04 OS成熟和全球一线适应症申报。 核心问题：PFS优势能否进一步转化为OS，并在长期一线治疗中保持可接受的ILD风险？ PharmaRadar｜研发速递

Corbus Pharmaceuticals’ phase 1b obesity trial has generated evidence that its CB1 inverse agonist may be less prone to the neuropsychiatric side effects that haunted Novo Nordisk and Sanofi. Sanofi won European approval for a CB1 receptor blocker weight loss drug, Acomplia, in 2006, only for evidence that the medicine doubles the risk of psychiatric disorders to force the product off the market three years later. Novo resurrected interest in the mechanism in 2023 by inking a deal to buy Inversago Pharma for up to $1.1 billion. But the following year the Danish drugmaker reported neuropsychiatric side effects from Inversago's drug monlunabant in a phase 2 trial. With Novo axing monlunabant, Corbus has a chance to establish CRB-913 as the frontrunner in the CB1 race. The phase 1b data contain positive signs mixed with scope to question whether Corbus has seized the opportunity, leaving the biotech’s stock up 4% at $8.48 in early trading. At a Jefferies event in June, Corbus CEO Yuval Cohen, Ph.D., said “pretty much the only question is are we going to look safer than monlunabant in terms of the neuropsych [adverse events].” The study succeeded by Cohen’s yardstick, with Corbus reporting lower rates of depression, anxiety, irritability and insomnia than Novo saw in its phase 2a trial. Rates of the adverse events on the highest dose of CRB-913 ranged from 0% to 9.7%. Corbus compared its data to placebo and GLP-1 receptor agonists, showing that small numbers of people report psychiatric events while taking drugs such as Novo’s Wegovy and Eli Lilly’s Zepbound. Corbus reported placebo-adjusted weight loss of up to 5% at Week 12, in line with the 5.8% that Novo saw at Week 16 of its phase 2a trial and well ahead of the efficacy of Acomplia. The CRB-913 result is in the same ballpark as the phase 3 data that Novo published on oral Wegovy. There was no evidence that weight loss was plateauing at Week 12, pointing to the potential for deeper declines in longer trials. Little evidence suggests that CRB-913 can improve significantly on the efficacy of oral Wegovy, but Corbus’ candidate could be a more tolerable option. CRB-913’s rates of vomiting, nausea and constipation compare favorably to data for Wegovy pill and Lilly’s Foundayo, although numerically more people had diarrhea on CRB-913 than on the existing oral obesity drugs.