Sutro Biopharma, Inc.

ROR1，一个开发难度较高的靶点。 近期，一个ROR1 ADC管线合作的结束，再一次证明了这一点。 益普生（Ipsen）在审查了ROR1领域的新数据与发展后，决定不再推进与Sutro合作的ROR1 ADC项目STRO-003。 STRO-003 益普生与Sutro关于ROR1 ADC的合作源于2024年4月，益普生以高达9亿美元的总金额，从Sutro公司获得临床前ROR1 ADC候选药物STRO-003的全球权益。当时这笔交易也被视为益普生进军ADC药物开发领域的重要布局。 STRO-003是一款ROR1 ADC，采用β-葡糖醛酸糖苷酶（β-glucuronidase)可裂解连接子，DAR8，依喜替康毒素。STRO-003的临床前数据显示，在三阴性乳腺癌（TNBC）和非小细胞肺癌（NSCLC）中显示出抗肿瘤活性；以及在非人灵长类动物（NHP）中显示出良好的安全性，STRO-003耐受性高达45 mg/kg，无血液学毒性或组织特异性病变迹象。 根据信息查询，合作达成的一年多时间内，STRO-003仍处临床前开发阶段，并未推进临床。 2025年8月7日，Sutro Biopharma在其2025年第二季度财报中披露，益普生在审查ROR1领域的新数据与发展后，决定不再推进与Sutro合作的ROR1 ADC项目STRO-003。Sutro也并未披露对STRO-003的后续计划。Sutro的第二季度收入还标记与益普生决定不推进STRO-003计划而确认的递延收入有关。 ROR1现境 ASH 2020年会上，两款ROR1靶向药物（Zilovertamab vedotin和一款ROR1单抗Cirmtuzumab）显示出初步积极的有效性。 这一创新靶点吸引了来自各大药企们的目光，在2020年末达成了多起ROR1项目授权和相关公司收购。 积极的临床数据和市场交易，也进一步促使ROR1成为热门的肿瘤开发靶点。但是在这几年的开发当中，ROR1 CAR-T的开发显示出不可控的安全性，以及多款ROR1 CAR-T管线停止开发。 — 百时美施贵宝（BMS）在2022年财报当中，宣布削减多达10项资产，其中包括了ROR1 CAR-T项目JCAR-024，该项目当时处于临床1期研究，从Juno公司获得。 — Oncternal Therapeutics，先后在ROR1单抗和ROR1 CAR-T上栽了跟头。Oncternal先是在2023年以联用药物BTK抑制剂快速变化的商业环境为由，结束了zilovertamab（ROR1单抗）的3期并取消优先级；然后在2024年因为安全性问题（报告了患者死亡事件，以及预期可能会出现不良事件），终止了对ONCT-808（ROR1 CAR-T）的研究。目前，该公司已经解散，两个ROR1资产被神秘买家Ho'ola Therapeutics接手。延伸阅读：失败的ROR1，有人来接盘了 — 2024年9月，Lyell Immunopharma宣布终止ROR1 CAR-T LYL797的开发，原因是遇到了安全性问题，且没有足够广泛的治疗窗口。LYL797此前在针对TNBC的I期中报告了一例患者死亡事件。目前，这家最初专注于ROR1 CAR-T开发的公司已经放弃了ROR1工作。延伸阅读：悄然放弃ROR1，主推CD19/CD20 CAR-T 实际上，尽管ROR1 CAR-T的开发遇阻，但ROR1 ADC的开发较为积极。 2025年2月，默沙东宣布启动ROR1 ADC药物Zilovertamab Vedotin联合R-CHP对照R-CHOP一线治疗弥漫性大B细胞淋巴瘤（DLBCL）的关键三期临床试验。另外，默沙东在2024年12月报告，zilovertamab vedotin在II期临床中的两个剂量队里中实现了100%的完全缓解。危险的靶点，100%的CR 2025年2月，石药集团的ROR1 ADC资产SYS6005以高达12.4亿美元的总金额出海。Radiance Biopharma获得ROR1 ADC在美国、欧盟等地区的开发及商业化权益。 参考资料： 1.https://www.sutrobio.com/sutro-biopharma-reports-second-quarter-2025-financial-results-and-business-highlights/ 2.https://www.ipsen.com/press-releases/ipsen-delivers-solid-results-in-2024-driven-by-strong-performance-across-all-therapeutic-areas-and-provides-guidance-for-2025-3025567/ · · · · · · · ·

Ipsen made the decision to terminate its deal with Sutro Biopharma “following the review of new data and developments in the ROR1 landscape,” according to Sutro.\n Ipsen has backed out of a $875 million deal for Sutro Biopharma’s ROR1-directed antibody-drug conjugate.The deal, which was signed in April 2024, saw Ipsen agree to hand over $75 million in a combination of upfront payment and equity investment in return for STRO-003. The ADC targets the receptor tyrosine kinase-like orphan receptor 1 (ROR1) tumor antigen, which is overexpressed in various cancers—including solid tumors and blood cancers.STRO-003 became the first ADC in Ipsen’s armory, although the French company wasted no time in adding a Topo1 inhibitor via a deal with Foreseen Biotechnology two months later.According to Sutro’s own second-quarter earnings release Thursday, Ipsen has since had second thoughts about STRO-003. The Paris-based company “made a strategic decision not to advance the STRO-003 program … following the review of new data and developments in the ROR1 landscape,” Sutro explained.Certainly the most recent data from the ROR1 space have been mixed. On the one hand, Merck & Co. posted phase 2 data on its own ROR1-directed ADC zilovertamab vedotin in lymphoma in May that evidenced the narrow safety and efficacy window for these drugs.Specifically, Merck reported an overall response rate of 56.3% on the middle dose of 1.75 mg/kg, with little effect on response rate shown by increasing the dose. Meanwhile, three of the seven patients on the highest dose stopped taking the ADC because of adverse events, while the middle dose had a lower discontinuation rate.Perhaps more worrying was an update in June about Lyell Immunopharma’s ROR1-targeted CAR-T cell therapy. Of 18 evaluable patients in a phase 1 solid tumor trial, four cases of grade 3 pneumonitis were reported, with one of these individuals dying of respiratory failure.Lyell is still proceeding with the study but said at the time that it would vary the doses administered to different patients to account for this safety signal. For its part, Sutro said in yesterday\'s release that STRO-003 “continues to be recognized as a well-engineered ADC candidate.” However, Sutro told Fierce this morning that the company has no plans to develop the drug internally.The collapse of the deal with Ipsen means Sutro misses out on $800 million in combined development and commercial milestone payments. Still, Sutro said its cash runway won’t be impacted by Ipsen’s decision.Sutro ended June with $205.1 million in the bank, which it expects to last until 2027. That estimate excludes any milestone from the company’s remaining partner Astellas, which is collaborating on two R&D programs for dual-payload immunostimulatory ADCs.Sutro is also gearing up to take a crop of in-house therapies into the clinic, including a TF-targeting exatecan ADC and an integrin beta-6 ADC.

Following Interactions with FDA on VAX-31 Adult Program, Including End-of-Phase 2 Meeting, Company Finalizing Phase 3 Clinical Program to Validate VAX-31 as Potential New Standard-of-Care Adult PCV; Pivotal, Non-Inferiority Study Expected to be Initiated in Fourth Quarter of 2025 with Topline Data in 2026 FDA Provided Input on VAX-31 Adult CMC Licensure Requirements Facilitating Progression to Phase 3; Company Plans to Seek Ongoing Input as Program Advances Company Expects Multiple VAX-31 Adult Phase 3 Program Data Readouts in 2026 and 2027 to Support Biologics License Application Submission For VAX-31 Pediatric Program, Company Modifies Ongoing Infant Phase 2 Dose-Finding Study to Add a VAX-31 Optimized Dose Arm (4.4mcg/3.3mcg) and Discontinues Enrollment of Low Dose Arm; Enrollment in Modified Study Expected to Proceed by End of Third Quarter of 2025 with Topline Data from Both Primary Immunization Series and Booster Dose by End of First Half of 2027 Company Remains Focused on Disciplined Capital Allocation; Streamlining Early-Stage Pipeline to Prioritize Resources for PCV Programs and Further Extend Cash Runway Approximately $2.8 Billion in Cash, Cash Equivalents and Investments as of June 30, 2025 SAN CARLOS, CA, USA I August 06, 2025 I Vaxcyte, Inc. (Nasdaq: PCVX), a clinical-stage vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases, today announced financial results for the second quarter ended June 30, 2025, and provided a business update, highlighting key clinical and regulatory progress for VAX-31, a potential best-in-class pneumococcal conjugate vaccine (PCV). “We are laser-focused on advancing the development of VAX-31 in both adults and infants, given its potential to meaningfully elevate the standard-of-care by broadening protection against invasive pneumococcal disease,” said Grant Pickering, Chief Executive Officer and Co-founder of Vaxcyte. “For the adult indication, following a series of interactions with the FDA, including an End-of-Phase 2 meeting, we are finalizing the Phase 3 program, the results of which we believe could validate the best-in-class potential of VAX-31. This work includes final-stage planning for the pivotal, non-inferiority study, which we intend to initiate in the fourth quarter of this year with topline data expected in 2026, consistent with prior readout guidance. We look forward to delivering multiple anticipated Phase 3 data readouts in 2026 and 2027 to support our potential BLA submission for the VAX-31 adult indication. For the infant indication, we have leveraged key insights from the robust VAX-24 and VAX-31 data generated to date, as well as our carrier-sparing platform, to support the evaluation of a new, Optimized dose in the ongoing VAX-31 Phase 2 dose-finding study to elicit even stronger immune responses in this population. We expect the modified study to proceed by the end of the third quarter of this year with topline data from both the primary immunogenicity series and the booster dose expected by the end of the first half of 2027. We believe the incorporation of this new, Optimized dose arm, which results in a minor extension to our prior readout timeline, best positions VAX-31 for long-term success.” “With a strong balance sheet totaling approximately $2.8 billion in cash, cash equivalents and investments as of the end of the second quarter, we remain focused on advancing VAX-31, our lead candidate and the broadest-spectrum PCV in the clinic today,” said Andrew Guggenhime, President and Chief Financial Officer of Vaxcyte. “In this dynamic macro environment, we continue to take a disciplined approach to capital allocation, directing resources to further extend our cash runway and fully support the continued progress of our PCV programs, including preparation for our planned VAX-31 adult Phase 3 program and pursuit of potential U.S. commercialization. As part of this focused strategy, among other initiatives, we are streamlining activities across our early-stage pipeline while preserving the option to advance promising programs in the future.” Key Second Quarter and Recent Highlights PCV Program Updates VAX-31 Adult Program Updates VAX-31 Infant Program Updates Early-Stage Pipeline Updates Executive Leadership Team Appointment Anticipated Key PCV Program Milestones Vaxcyte is advancing the clinical development of its PCV programs with several anticipated key upcoming milestones: PCV Franchise Adult Indication VAX-31 PCV Franchise Infant Indication VAX-24 VAX-31 Upcoming Investor Conferences Company management will participate in the following upcoming investor conferences. Second Quarter 2025 Financial Results About Vaxcyte Vaxcyte is a vaccine innovation company engineering high-fidelity vaccines to protect humankind from the consequences of bacterial diseases. VAX-31, a 31-valent PCV candidate advancing to a Phase 3 adult clinical program and being evaluated in a Phase 2 infant clinical program, is being developed for the prevention of IPD and is the broadest-spectrum PCV candidate in the clinic today. VAX-24, a 24-valent PCV candidate, is designed to cover more serotypes than any infant PCV on-market and is being evaluated in a Phase 2 infant study. VAX-31 and VAX-24 are designed to improve upon standard-of-care PCVs by covering the serotypes in circulation that cause a significant portion of IPD and are associated with high case-fatality rates, antibiotic resistance and meningitis, while maintaining coverage of previously circulating strains. Vaxcyte is re-engineering the way highly complex vaccines are made through XpressCF®, its cell-free protein synthesis platform exclusively licensed from Sutro Biopharma, Inc. Unlike conventional cell-based approaches, the Company’s system for producing difficult-to-make proteins and antigens is intended to accelerate its ability to develop high-fidelity vaccines with enhanced immunological benefits. Vaxcyte’s pipeline also includes VAX-A1, a prophylactic vaccine candidate designed to prevent Group A Strep infections, and VAX-GI, a vaccine candidate designed to prevent Shigella. For more information, visit www.vaxcyte.com . SOURCE: Vaxcyte