LCB-71

5月6日-7日，基石药业携5款自主研发的重磅产品亮相2025年美国癌症研究协会（AACR）年会，以壁报形式公布了研发管线2.0多款创新产品的临床前研究结果，除两款值得重点关注的三抗和双抗产品CS2009（PD-1/VEGF/CTLA-4）和CS2011（EGFR/HER3）外，还有出自其自有ADC平台的三款创新ADC分子CS5007（EGFR/HER3双特异性ADC）、CS5005（ITGB4 ADC）和CS5006（SSTR2 ADC），其中不乏亮点数据，引发广泛关注。  01   CS2009三抗引领免疫治疗新突破CS2009是一款同时靶向PD-1/VEGFA/CTLA-4的创新型三特异性抗体，覆盖范围广阔，包括非小细胞肺癌、肝癌、胃癌、子宫内膜癌、卵巢癌、肾细胞癌及宫颈癌等，具备first/best in class潜力。具体来说，阻断PD-1可逆转T细胞耗竭，阻断CTLA-4可促进T细胞活化和增殖，而阻断VEGFA则可抑制肿瘤血管生成，从而改善肿瘤微环境（TME）。在抗肿瘤领域，抗PD-1与CTLA-4的双重阻断已在包括非小细胞肺癌在内的多种肿瘤类型中显示出协同效应，可显著提升患者的总生存期（OS）和无进展生存期（PFS）获益。本次披露数据显示，同时结合PD-1、CTLA-4靶点时，CS2009展现出了更高的亲和力，通过优先结合TME中的PD-1/CTLA-4双阳性T细胞，实现了疗效提升。AACR 2025 CS2011公布数据1而通过与VEGFA交联，PD-1和CTLA-4的双重阻断作用能够得到显著增强。尽管前有PD-1/VEGF双抗对比K药展现出了PFS优势，但OS数据却表现平平，而这种三靶点组合的差异化分子设计，则有望发挥更为深化的协同机制，同时在短期缩瘤与长期生存上展现出色疗效。据本次公布数据示，通过与VEGA二聚体交联，CS200使PD-1/CTLA-4双报告基因细胞上的检查点抑制活性提高了约150倍；而在PD-1报告基因细胞中，CS2009/VEGFA相较CS2009免疫检查点活性提高了约300倍。在激活原代T细胞活性的MLR实验中，与VEGFA二聚体交联也显著提高了该产品活性。也就是说，CS2009在VEGFA富集的TME中可以实现活性的显著提升，从而提高其治疗窗口。同时，该产品还可优先结合PD-1和CTLA-4双阳性的肿瘤浸润T细胞，并最大程度上弱化对外周T细胞中CTLA-4调节通路的干扰，在提升疗效的同时降低系统性毒性。AACR 2025 CS2009公布数据2在多数药企执着大热双抗的靶点组合时，基石药业早在2022年就已进入三抗研究阶段。公司表示，相较于潜在竞品（如PD-1/CTLA-4双抗、PD-1/VEGF双抗及抗PD-1/抗CTLA-4联合疗法），CS2009具有更强的抑瘤效力，且安全性突出。通过在同一分子结构中整合以上三种作用机制，有望超越现有PD-(L)1单抗、PD-(L)1/VEGF双抗及PD-(L)1/CTLA-4双抗，成为下一代肿瘤免疫骨架产品，与基石药业目前进展最快的ROR1ADC管线CS5001，共同构成了该司临床阶段核心资产。目前，其全球多中心1期临床研究正在澳大利亚进行，已于今年3月完成首例患者给药，后续将扩展至中国和美国。  02  CS2011双抗靶向精准治疗而本次公布数据另一款重磅产品CS2011则是更为成熟的靶点组合。这是一款EGFR/HER3双特异性抗体，两个靶点同属HER家族受体酪氨酸激酶并在多种肿瘤上高表达，也是晚期实体瘤临床治疗中经过充分验证的靶点。通过协同阻断这两个关键的肿瘤生长信号通路，可有效阻断两个靶点的下游信号传导，从而抑制EGFR/HER3阳性肿瘤细胞的生长。CS2011同样亮点不少。首先，该产品几乎可以阻断除HER2同源二聚体之外的所有HER家族相关信号通路，可有效克服肿瘤异质性。同时，其对EGFR和HER3靶点均有较强的结合力，且能够有效结合EGFR/HER3单独表达和共同表达的肿瘤细胞。AACR 2025 CS2011公布数据此外，针对主要潜在竞品，CS2011在体内和体外研究中均表现出更优的抗肿瘤活性。相较EGFR单抗、HER3单抗和EGFR/HER3竞品，CS2011能够：1.在不同EGFR/HER3表达水平的肿瘤细胞表面触发更高效的内吞2.对EGFR下游信号的抑制作用与EGFR单抗相当，对HER3信号通路的抑制作用优于同类EGFR/HER双抗竞品3.在不同EGFR和HER3表达水平的肿瘤细胞上均能高效抑制肿瘤增殖在体内CDX肿瘤模型中表现出优于EGFR单抗与HER3单抗的肿瘤抑制作用，并与两者联合治疗方案疗效相当当前，CS2011已于2025年3月注册专利，预计将很快递交IND。  03   多款FIC与潜在BIC正式发力的自有ADC平台基石药业多款重磅产品实现关键进展，离不开其搭建的新一代ADC平台的技术支持。以专有连接子为特色，该平台能够针对不同的靶点和有效载体进行优化。着眼此次公布的两款ADC管线CS5005和CS5006，我们也能看出其自有平台的正式开始发力，一举便至少造出两款First in Class 分子。其中，CS5005是一款靶向SSTR2的ADC。分子结构上，该产品搭载了其专有的高亲和力与高选择性的SSTR2全人源抗体，Linker为亲水性的β葡萄糖醛酸连接子，Payload为拓扑异构酶1抑制剂Exatecan，在体外及体内研究中均展现出令人鼓舞的抗肿瘤活性，可精准狙击SSTR2阳性肿瘤，如小细胞肺癌、神经内分泌癌、神经内分泌瘤等。而CS5006则是靶向全新ITGB4靶点的ADC，目前尚未有同靶点ADC进入临床。通过内部开发的机器学习生物信息学算法结合实验验证，该司发现ITGB4在非小细胞肺癌、结直肠癌、食管鳞状细胞癌和头颈部鳞状细胞癌等多瘤种中表达显著上调、而在正常组织中表达极低，接近于HER2的表达模式，且其高表达水平与肿瘤侵袭和转移相关，成为理想的治疗开发靶点。而临床前体外及体内研究也表明，CS5006在多种动物模型中均表现出强效抑瘤作用，不仅能触发快速、高水平的内化，且耐受性良好，展现出优异的治疗潜力。而双抗ADC CS5007则是基石药业在ADC领域创新linker技术的产物。CS5007的EGFR/HER3双抗抗体骨架是前文提及的CS2011，其设计和临床前数据能够解决肿瘤异质性，Linker搭载其专有的亲水性、稳定的β-葡萄糖苷连接子确保该分子拥有较强的内吞效率，而Payload仍是拓扑异构酶1抑制剂Exatecan。该产品可靶向几乎所有HER家族（除HER2同源二聚体外）受体的信号传导，潜在覆盖广泛瘤种并有效克服肿瘤异质性。其分子设计集精准的靶点结合、优化的连接子稳定性及经验证的有效载荷于一身，使其有望成为肿瘤精准靶向治疗中的Best in class候选药物。AACR 2025 CS5007公布数据目前全球范围内EGFR/HER3双抗ADC只有百利天恒的BL-B01D1处于临床阶段（映恩生物的DB-1418在临床前阶段)，得益于亮眼的临床数据，实现了高溢价出海。而在CS5007的临床前数据中，不仅基于CS2011抗体骨架展现出对EGFR+和/或HER3+的肿瘤细胞的高亲和力，而且还触发了这些细胞上的靶向受体的高速内化，高效且有选择性地释放毒素，导致强力且精准的细胞杀伤。这意味着其能够改善同类药物BL-B01D1治疗窗口不显著的问题。如此背景下，CS5007的商业前景不可谓不广阔。  04  管线2.0聚焦研发优势，加速走出寒冬从复杂三抗到精准双抗再到创新分子，基石药业的靶点立项体现出其前瞻性的布局思维和系统性的ADC管线设计，但同时伴随的，还有商业成绩上历经多年的经营亏损。直到2024年上半年，基石药业才首次实现盈利，但仍尚未实现扭亏为盈。2016年成立的基石药业，初时可以说是大放异彩。2018年斩获国内生物医药企业最高单笔B轮融资记录，一度备受资本热捧，2019年便实现上市，用时不到3年。具体来说，这要得益于其成立时采取的VIC模式，即风险投资（VC）、知识产权（IP）、合同制研发服务机构（CRO）三者相结合，通过引进国外先进研究成果建立自己的管线梯队，迅速开展临床，并推进产品上市。如此模式下，该司在2021年一年内便实现了4款产品（普拉提尼、阿伐替尼、艾伏替尼和舒格利单抗）获批上市，进展可谓迅猛。接下来便是不出意外的更大愿景——向biopharma转型。现实是，由于国内市场中PD-(L)1产品的疯狂内卷，加上其他三款进口药定价过高、无法进入医保，其商业化元年，便开局不利，2021年销售收入仅1.63亿元。而早已在全国100多个城市铺开的商业化团队，以及同年试运行、产能却无法得到充分利用的苏州工厂，又无可避免地成为运营开支的两大负担。当年财报显示，亏损高达19.2亿元。2022年，基石药业开始做出一系列重要调整。关停苏州工厂、加速进口药品的地产化、转让部分产品的商业化权益并同步精简销售团队。降本的同时，着力开源。一方面，积极布局海外市场，推进产品出海，充分发挥上市产品的商业价值，另一方面，开展全球管线合作，提升产品预期，进一步吸引投资。具体来说，其biopharma架构向基于成熟商业化模式的biotech架构调整，进一步聚焦自身研发优势，正式推出了管线2.0新战略——开展项目不再局限于国内市场，而是着眼全球权益，致力各靶点研发跻身世界前列。基石药业管线2.0新战略下，公司重点推进两项关键临床项目，即本次披露关键数据的三抗管线 CS2009以及当前进展最快的ROR1 ADC管线CS5001。后者开发进程位列全球第二，在多个血液瘤适应症中均展示出良好的潜在获益，在实体瘤领域也显示了出色的肿瘤抑制活性。当前其I期试验在美国、澳大利亚和中国同步进行中。如此操作下，次年亏损便大幅减少，至2024年上半年，基石药业已实现盈利佳绩，快步走出低谷。考虑到其两款临床阶段核心资产广阔的临床价值与出色的商业化潜力，其前景可谓稳步向好。  结语  基石药业在2025年AACR年会上展现的研发成果，标志着其在肿瘤免疫治疗与ADC领域的加速突破。通过差异化设计与技术创新，公司不仅验证了其技术平台的创新性与高效性，更在临床前数据中凸显出优于现有疗法的潜力。可以想见，市场或将迎来一个找准主线后奋起直追的主力选手。若后续临床试验能延续当前优势，公司或将借助差异化的技术路线，在全球创新药与ADC产品竞争中占据不可忽视的一席之地。引用1.AACR 2025 | 基石药业发布CS2009（PD-1/VEGF/CTLA-4）最新临床前研究结果https://www.cstonepharma.com/html/news/3793.html2.AACR 2025 | 基石药业发布CS2011（EGFR/HER3双特异性抗体）临床前研究结果https://www.cstonepharma.com/html/news/3794.html3.AACR 2025 | 基石药业发布CS5007（EGFR/HER3双特异性ADC）临床前研究结果https://www.cstonepharma.com/html/news/3797.html4.AACR 2025 | 基石药业发布CS5005（SSTR2 ADC）临床前研究结果https://www.cstonepharma.com/html/news/3796.html5.AACR 2025 | 基石药业发布CS5006（ITGB4 ADC）临床前研究结果https://www.cstonepharma.com/html/news/3798.html其他官网资料识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观不本站。

BOTHELL, Wash.--(BUSINESS WIRE)--Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on developing first-in-class and best-in-class targeted cancer therapies, today announced financial results for the quarter ended March 31, 2025 and provided a business update. “Immunome continued to build momentum in the first quarter of 2025,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer. “We remain on track to share topline data for the RINGSIDE trial of varegacestat in the second half of 2025, and we are optimistic that varegacestat will demonstrate differentiated efficacy across multiple endpoints. “Varegacestat is complemented by a robust pipeline of differentiated programs with first-in-class or best-in-class potential. The dose escalation portion of the Phase 1 clinical trial of IM-1021, our ROR1 ADC, is ongoing in solid tumors and lymphoma. Following the recent clearance of the IND for IM-3050, our FAP radiotherapy, we expect to start a clinical trial for that program in the second half of this year. We are making progress on IND-enabling manufacturing for IM-1617, IM-1335 and IM-1340, each of which incorporate our differentiated TOP1 inhibitor, HC74.” Pipeline Highlights Varegacestat: Full enrollment for the Phase 3 RINGSIDE Part B study of varegacestat for the treatment of desmoid tumors was completed in February 2024, and Immunome expects to report topline data for RINGSIDE Part B in the second half of 2025. In parallel, Immunome is performing the manufacturing and pharmacology work required to support a new drug application filing for varegacestat. IM-1021: The Phase 1 clinical trial of IM-1021 is ongoing, with the first patient dosed in February 2025. The trial is an open-label, multicenter dose-escalation and expansion study that is expected to include participants with advanced B-cell lymphomas and advanced solid tumors. IM-3050: Immunome received IND clearance for IM-3050 in April 2025 and expects to initiate a Phase 1 clinical trial in the second half of 2025. Preclinical Pipeline: Immunome’s three preclinical ADCs against solid tumor targets, IM-1617, IM-1340 and IM-1335, each of which incorporates HC74, are currently undergoing IND-enabling work. Additional undisclosed ADCs are in discovery and lead optimization. First Quarter 2025 Financial Results As of March 31, 2025, cash, cash equivalents and marketable securities totaled $317.3 million. This total includes net proceeds of $161.7 million from the January 2025 financing and reflects approximately $11 million in payments during the quarter related to non-recurring IM-1021 milestones and 2024 annual performance bonuses. Immunome expects its current cash position to fund operations into 2027. Research and development expenses for the quarter ended March 31, 2025 were $36.9 million, including stock-based compensation costs of $2.4 million. General and administrative expenses for the quarter ended March 31, 2025 were $10.7 million, including stock-based compensation expense of $3.3 million. Immunome reported a net loss of $41.6 million for the quarter ended March 31, 2025. About Immunome, Inc. Immunome is a clinical-stage targeted oncology company committed to developing first-in-class and best-in-class targeted therapies designed to improve outcomes for cancer patients. We are advancing an innovative portfolio of therapeutics, drawing on leadership that previously played key roles in the design, development, and commercialization of cutting-edge targeted cancer therapies, including antibody-drug conjugate therapies (ADCs). Our most advanced pipeline programs are varegacestat (formerly AL102), a gamma secretase inhibitor which is currently in a Phase 3 trial for treatment of desmoid tumors; IM-1021, a ROR1-targeted ADC which is currently in a Phase 1 trial; and IM-3050, a FAP-targeted radioligand, which recently received IND clearance. Our pipeline also includes IM-1617, IM-1335, and IM-1340, all of which are preclinical ADCs pursuing undisclosed targets with expression in multiple solid tumors. For more information, visit www.immunome.com. Cautionary Statement Regarding Forward-Looking Statements Statements in this press release that are not purely historical in nature are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. We use words such as “focused,” “on track,” “optimistic,” “will,” “potential,” “expect,” and similar expressions to identify these forward-looking statements. These forward-looking statements include Immunome’s expected timing for providing topline data for the Phase 3 RINGSIDE Part B trial; Immunome’s expected cash runway and ability to achieve clinical milestones; Immunome’s expectation that it will enroll patients in its Phase 1 clinical trial for IM-1021 and will report resulting clinical trial data, and that it will initiate a Phase 1 clinical trial for IM-3050; Immunome’s expectations regarding regulatory filings; the ability of Immunome to advance its pipeline; the potential of Immunome’s ADC programs to provide first-in-class or best-in-class status; and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future. These forward-looking statements are based on Immunome’s current expectations and involve assumptions that may never materialize or may prove to be incorrect; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including the risk that Immunome will not be able to realize the benefits of its strategic transactions; the risk that regulatory approvals for Immunome’s programs and product candidates are not obtained, are delayed or are subject to unanticipated conditions; the risk that pre-clinical data may not be predictive of clinical data; the risk that Immunome’s programs and product candidates fail to achieve their intended endpoints; uncertainties related to Immunome’s capital requirements and Immunome’s expected cash runway; Immunome’s ability to grow and advance its pipeline and successfully execute on its business plan; and other risks and uncertainties included under the caption “Risk Factors” in Immunome’s Annual Report on Form 10-K for the year ended December 31, 2024, filed with the Securities and Exchange Commission (“SEC”) on March 19, 2025 and in Immunome’s Quarterly Report on Form 10-Q for the quarter ended March 31, 2025, to be filed with the SEC later today. These documents can also be accessed on Immunome’s website at www.immunome.com by clicking on the link “Financials” under the “Investors” tab. The forward-looking statements included in this press release are made only as of the date hereof. Except as required by law, Immunome assumes no obligation and does not intend to update any forward-looking statements included in this press release. 257,613 143,351 59,710 73,952 5,807 4,036 323,130 221,339 10,953 10,113 4,163 4,278 100 100 4,347 4,411 342,693 240,241 9,126 14,189 17,656 33,177 4,015 6,941 30,797 54,307 4,770 4,769 35,567 59,076 — — 9 6 864,530 696,872 (3 ) 57 (557,410 ) (515,770 ) 307,126 181,165 342,693 240,241 Three Months Ended March 31, 2025 2024 ) ) ) ) ) ) ) ) ) ) ) )