Adagrasib

11月7日晚，汇宇制药发布公告，其创新药HYP-6589片（项目研发代号为“HY-0006”）用于治疗晚期实体瘤的临床试验获得批准。 HYP-6589片是汇宇制药全资子公司汇宇海玥开发的高选择性SOS1小分子抑制。HYP-6589为新的结构明确的，具有药理作用的化合物，临床试验适应症用于治疗晚期实体瘤。 截至本公告披露日，国内外尚无同类产品获批上市。HYP-6589片可特异性与SOS1的催化区域结合，阻止其与失活状态KRAS-GDP的相互作用并同时阻断SOS1驱动的反馈，减少KRAS-GTP激活状态的形成，从而抑制下游的RAS-RAF-MAPK和RAS-PI3K-AKT-mTOR两条关键信号通路，发挥抗肿瘤作用。 体外试验结果显示，HYP-6589片对不同KRAS突变类型的不同类型肿瘤细胞普遍具有优异的增殖抑制活性。动物体内试验结果显示，HYP-6589片在人胰腺癌、人非小细胞肺癌、结直肠癌等模型中具有显著的单药和联用抑瘤效果。 SOS1作为新型抗肿瘤靶点，SOS1抑制剂可通过抑制SOS1蛋白与KRAS蛋白相互作用，抑制肿瘤细胞恶性进程，可用于非小细胞肺癌、结直肠癌、胰腺癌等多种实体瘤的治疗。而目前已上市的KRASG12C抑制剂如索托拉西布（Sotorasib）、阿达格拉西布（Adagrasib）以及第三代EGFR抑制剂奥希替尼均普遍存在耐药现象，SOS1作为RTK-RAS及其下游信号通路调节枢纽，SOS1抑制剂可以与KARS抑制剂、EGFR抑制剂联用发挥协同增效、克服耐药的作用，具有解决未满足的临床需求的潜力。

Alan Bash is joining Legend Biotech as its president of Carvykti , an unconventional, newly-created role to oversee the commercial future of the biotech’s sole marketed cell therapy, among other aspects. Legend is developing Carvykti in partnership with Johnson & Johnson , which reported $286 million in sales in the third quarter. The BCMA-targeted cell therapy is expected to grow into a blockbuster multiple myeloma treatment — in large part as a result of a label expansion to earlier-line patients in April. Legend said in its press release that Bash’s new role will be to oversee Carvykti’s “commercial, technical operations, and quality functions.” Despite impressive results reported from the drug’s clinical studies, Legend and J&J have struggled to meet the commercial demand for the cell therapy. Carvykti has pulled ahead in a field that includes Bristol Myers Squibb ’s Abecma . But it faces an up-and-coming challenger in Gilead and Arcellx : The two companies announced on Tuesday that they had dosed the first patient in a Phase 3 trial of their experimental cell therapy anito-cel , which they say does not come with certain neurotoxicities reported with Carvykti. Bash had joined targeted therapeutics biotech ZielBio as CEO in early 2023. Before that, he was briefly head of Checkmate Pharmaceuticals as the immuno-oncology biotech sold to Regeneron for $250 million in cash. — Lei Lei Wu → Novo Nordisk said in its Q3 report that North America head Doug Langa will step aside at the end of the year “in order to focus on personal priorities and take up a role as senior advisor to Novo Nordisk’s executive management.” Novo has installed corporate development chief Dave Moore as the head of US commercial operations, while CFO Karsten Munk Knudsen will orchestrate the Danish pharma’s corporate strategy. Two days after the FDA declared that Ozempic and Wegovy were available in all doses, Novo’s semaglutide was on the march again, generating positive results in patients with metabolic dysfunction-associated steatohepatitis (MASH) and setting up a possible showdown with Madrigal Pharmaceuticals in an indication also referred to as NASH. → Moderna CEO Stéphane Bancel had been in charge of commercial operations since last December, when the company parted ways with chief commercial officer Arpa Garay . Bancel is now handing over those duties to president Stephen Hoge at Moderna, which made several other changes to its leadership team. Rose Loughlin , the SVP of research and early development, has been elevated to EVP of research. She came to Moderna from Biogen in 2016 as director of business development. Elsewhere, longtime GSK vet Jacqueline Miller has been promoted to CMO at the Covid vaccine titan after she had been SVP and therapeutic area head for infectious diseases. Finally, HR chief Tracey Franklin has expanded the scope of her responsibilities, becoming chief people and digital technology officer. She was chief HR talent and strategy officer at the end of her 14-year career at Merck . Moderna’s late entry into the RSV race produced only $10 million in third-quarter sales for the vaccine, miles behind the market leaders GSK and Pfizer , who haven’t exactly been scorching the nets themselves. But Moderna did turn in a profit as its shares $MRNA received a momentary boost before falling 3% on Thursday. → Axel Sven Malkomes will be the next CFO of German mRNA vaccine maker CureVac on Nov. 11. He succeeds Pierre Kemula , who just started his new CFO gig at Agomab . Malkomes is the ex-finance chief at two other German companies: Cardior Pharmaceuticals , the heart disease biotech that Novo Nordisk bought in March for $1.1 billion; and BioNTech ’s TCR partner Medigene . He’s also a board member at Cellectis . In July, CureVac said it would lay off 30% of its employees as GSK shelled out $429 million upfront for full control of the pair’s flu and Covid vaccine candidates. “It’s never nice to have this kind of news, but I do believe we need to do it now out of a position of financial strength,” CureVac CEO Alexander Zehnder told Endpoints News when the job cuts were announced. → Another notable CFO hire comes from Seaport Therapeutics , the Endpoints 11 winner that followed up its $100 million launch round with a $225 million Series B haul a few weeks ago. Lauren White had held this role for nine months at Elahere developer ImmunoGen , which was purchased by AbbVie for $10.1 billion . She landed her first CFO job at C4 Therapeutics in June 2021 after nine years at the Novartis Institutes for BioMedical Research . Are IPO plans not far behind? Time will tell. “I’m enjoying my brief hiatus as a private CEO right now,” Seaport chief Daphne Zohar said in an interview with Endpoints. → Swedish rare disease specialist Sobi has nominated David Meek as chairman of the board. Not long after Meek’s departure as CEO of Mirati , Bristol Myers swooped in to buy the company and its KRAS drug Krazati to compete with Amgen ’s Lumakras in the space. Meek has also held the top spot at Ipsen and FerGene , and has board seats at uniQure and Cullinan Therapeutics . → Mene Pangalos is the newest board member at Quotient Therapeutics , a Flagship joint that debuted last year and teamed up with Pfizer in August. Since his retirement from AstraZeneca , Pangalos has picked up a board seat at Absci and will join the board of directors at Biogen in January. He’s also on the scientific advisory board at Demis Hassabis ’ Isomorphic Labs. (By the way, check out this week’s Q&A with Hassabis and Andrew Dunn from the Financial Times ’ Global Pharma and Biotech Summit.) → After losing its former CEO Raj Kannan back in July, I-Mab has now locked Sean Fu into the position. Fu has been serving in the interim since Kannan’s exit. Prior to I-Mab, Fu was operating partner of ABio-X and CEO of RVAC Medicines and GeneLeap . Earlier in his career, Fu was with Merck, where he helped lead the integration work of the company following its $42 billion merger with Schering-Plough . It’s been quite a year for I-Mab: Back in April, the company officially spun out its China operations into a new company, I-Mab Biopharma (Hangzhou) , in a bid to win over investors. → Verrica Pharmaceuticals CEO Ted White is out after data for its basal cell carcinoma candidate VP-315 failed to move the needle with investors and job cuts affected 47 staffers. Verrica also drastically reduced its sales presence for its molluscum contagiosum drug Ycanth , from 80 sales territories to 35. In walks Jayson Rieger as president and CEO, and John Kirby as interim finance chief to lead a “leaner and more efficient operating structure,” as chairman Paul Manning put it . Rieger has spent more than a decade with PBM Capital , while Kirby is the former CFO of Aceragen and Idera Pharmaceuticals . → London-based protein degradation biotech Kesmalea Therapeutics has recruited Robert Johnson to steer the Syncona -backed company as CEO. Johnson’s résumé includes stints as CEO of Adrestia Therapeutics (acquired by Insmed ) and co-founder and CBO of Boston-based gene therapy company Affinia Therapeutics . → ElevateBio ’s gene editing sub Life Edit has welcomed Amy Pooler as SVP of R&D. Pooler was VP of neuroscience and head of research in her tenure with Sangamo Therapeutics . While ElevateBio has made eye-popping financing rounds routine, Life Edit formed separate partnerships with Moderna and Novo Nordisk in quick succession last year. → Acumen Pharmaceuticals ’ regulatory affairs leader Janice Hitchcock will retire “at the end of the year,” and Amy Schacterle has been named chief regulatory officer & head of quality at the Alzheimer’s biotech. Schacterle and Acumen president/chief development officer Jim Doherty were colleagues at Sage Therapeutics — Schacterle recently left Sage as part of the latest wave of job cuts after the company said it would no longer develop zuranolone for major depressive disorder. Acumen is testing its monoclonal antibody sabirnetug in patients with early Alzheimer’s. → The latest hires at Dublin-headquartered SynOx Therapeutics are based in the US: Medical chief Elyse Seltzer held multiple roles at GSK and is the former chief development officer at UroGen Pharma , while chief commercial officer Robert Francomano was appointed to the same position at Stemline Therapeutics and Sellas Life Sciences . “We are thrilled to welcome Elyse and Robert to the SynOx leadership team as we continue to work to strategically build out our presence within the key US market,” CEO Ray Barlow said in a statement . SynOx’s $92 million Series B includes a $17 million extension from Gilde Healthcare . → MaaT Pharma has recruited Eric Soyer to succeed Siân Crouzet as finance chief. Crouzet spent the last eight years as CFO and will now be MaaT Pharma’s chief of staff. Soyer had been CFO and COO at another French biotech, Erytech Pharma . His new company’s lead program MaaT013 is in a Phase 3 study for acute graft-versus-host disease. → Frits van Alphen has replaced Gerald Parzmair as chief development officer of Memo Therapeutics , a Swiss biotech that pulled together a total of $49 million for its Series C. After eight years at Novartis , van Alphen would go on to be CMO of Vifor Pharma from 2008-13 and Swiss-based Inositec , the undercard in Vifor’s M&A spree that included Sanifit in late 2021. He also worked for Roche as global head of product development excellence in between these two CMO gigs. → Synthetic lethality player Tessellate BIO has selected Lara Boyd as CBO. Boyd had a six-year run with Takeda partner F-star Therapeutics and was elevated to VP, head of business development & corporate strategy in May 2023. Former F-star boss Eliot Forster chairs the board at Tessellate BIO, which raised $8 million in seed funding from BioGeneration Ventures and Forbion . → La Jolla, CA-based I&I biotech CalciMedica has tapped Stephen Bardin as CFO, replacing interim finance chief Daniel Geffken . Earlier this year, Peer Review covered Bardin’s departure as CFO of atai Life Sciences , a position now held by Anne Johnson . He’s also worked for Myovant Sciences as director of corporate development and BridgeBio as SVP of finance and operations. → Joe Truluck has turned in his resignation as CFO of Adial Pharmaceuticals , and Vinay Shah will replace him on Nov. 16. We told you about Shah’s last CFO appointment at Virpax Pharmaceuticals in June 2023 and he’s had the same title at Aravive . Truluck will stay with Adial as a consultant until March 31. → Claudia Lopez has joined Seattle-based breast cancer biotech Atossa Therapeutics as VP, clinical product development. Lopez led the clinical development team at another AbbVie M&A pickup , Landos Biopharma , and the 16-year Takeda vet also spent two years with Arena Pharmaceuticals . → Tony Gibney has been named chairman of the board at Clearside Biomedical , which unspooled positive Phase 2b data last month for its suprachoroidal injection of axitinib called CLS-AX in patients with wet AMD. Gibney tackled the role of chief business & strategy officer at Iveric Bio until it was sold to Astellas last year for $5.9 billion. → Radiotherapy specialist Actinium Pharmaceuticals has elected June Almenoff to the board of directors. Almenoff, a GSK alum and the ex-president/CMO at Furiex Pharmaceuticals , is also on the boards of Avalo Therapeutics and Tenax Therapeutics . → Heron Therapeutics has reserved a seat on its board of directors for Liquidia CFO and COO Michael Kaseta . Before his gig with Liquidia, Kaseta was CFO at Aerami Therapeutics and Aralez Pharmaceuticals , as well as North American CFO, global services over a decade with Sanofi .