Tovorafenib

BOSTON, July 28, 2026 (GLOBE NEWSWIRE) -- Bicara Therapeutics Inc. (Nasdaq: BCAX), a clinical-stage biopharmaceutical company committed to bringing transformative bifunctional therapies to patients with solid tumors, today announced the appointments of Jeremy Bender, Ph.D., MBA and Christy Oliger to its Board of Directors. Dr. Bender, who most recently served as Chief Executive Officer at Day One Biopharmaceuticals through its acquisition by Servier in 2026, brings more than 20 years of corporate strategy and operating experience in biotechnology to Bicara. Ms. Oliger brings more than 30 years of commercial and operating experience in global biopharmaceutical organizations, having most recently served as Senior Vice President of the Oncology Business Unit at Genentech. "We are delighted to welcome Jeremy and Christy to our Board of Directors at this pivotal time for Bicara. Together, they bring deep commercial, strategic, and operational expertise that will be invaluable as we continue our evolution from a clinical-stage organization to one focused on successfully delivering ficerafusp alfa to patients,” said Claire Mazumdar, Ph.D., MBA, Chief Executive Officer of Bicara Therapeutics. “Each of these distinguished professionals has an established track record of guiding innovative biopharmaceutical companies through critical stages of growth, including pipeline development, corporate strategy, and commercialization. Their perspectives will strengthen our Board as we advance our portfolio, execute on our long-term vision, and continue building Bicara into a mature biopharmaceutical organization.” In addition, Kiran Mazumdar-Shaw has retired from Bicara’s Board of Directors. "As one of our founding Board members, Kiran has been instrumental in shaping Bicara from its earliest days. Her impact extends beyond the initial seed capital that helped launch the company, but also the strategic guidance and steadfast support that has enabled Bicara to advance ficerafusp alfa into the clinic and reach the important milestone of a registration-enabling clinical study,” said Mike Powell, PhD, Chairman of Board of Bicara Therapeutics. “On behalf of the Board, management team, and Bicara employees, I want to thank Kiran for her vision, leadership, and indelible contributions to Bicara.” About Jeremy Bender, Ph.D., MBADr. Bender most recently served as Chief Executive Officer, President and a member of the Board of Directors of Day One Biopharmaceuticals, Inc. from September 2020 to April 2026, where he led the company through its evolution into a commercial-stage oncology company, including the approval and launch of OJEMDA® for pediatric low-grade glioma and the company's approximately $2.5 billion acquisition by Servier in 2026. Prior to joining Day One, Dr. Bender was Vice President of Corporate Development at Gilead Sciences, Inc., a pharmaceutical company, from March 2018 to September 2020. Prior to that, he was Chief Operating Officer of Tizona Therapeutics, Inc. from July 2015 to March 2018 and Chief Business Officer of Sutro Biopharma, a biotechnology company specializing in cancer and autoimmune therapeutics, from October 2012 to July 2015. Prior to joining Sutro Biopharma, Inc., he was Vice President of Corporate Development at Allos Therapeutics Inc., a biotechnology company focused on cancer treatments, from January 2006 to September 2012. Dr. Bender began his career in the life sciences practice at Boston Consulting Group, a management consulting company. Dr. Bender also sits on the boards of Mereo BioPharma Group plc and Aura Biosciences, Inc. From October 2023 to June 2024, Dr. Bender also served as a director of Fusion Pharmaceuticals, Inc., a biopharmaceutical company. Dr. Bender holds a B.S. in Biological Sciences from Stanford University, a Ph.D. in Microbiology and Immunology from the University of Colorado, and an MBA from the MIT Sloan School of Management. About Christy OligerMs. Oliger is recognized for building industry leading capabilities and teams and was the Senior Vice President, Business Unit Head for Oncology and Genentech from 2017-2020, managing a portfolio of 15 products, contributing U.S. revenue exceeding $13 billion, delivering launches in lung cancer, breast cancer, chronic lymphocytic leukemia (CLL), non-Hodgkin lymphoma (NHL), melanoma and leading an organization of more than 800 people. Prior to this role, Ms. Oliger served as Senior Vice President and Business Unit Head, Neurology, Rare Disease, Infectious disease where she was responsible for building the teams and driving successful launches in multiple sclerosis (MS) (Ocrevus®), hemophilia (Hemlibra®) and spinal muscular atrophy (SMA) (Evrysdi®), together the most significant growth drivers in the U.S. business. Prior to these roles, she spent three years as Global Head of Portfolio and Project Management where her team was responsible for the Late-Stage Portfolio Committee comprised of a late-stage development portfolio of greater than 300 projects across multiple therapeutic areas. Christy began her career in life sciences at Schering Plough, a pharmaceutical company. In addition to Bicara, Christy also currently sits on the boards of Vera Therapeutics, Karyopharm Therapeutics, and Replimune Inc. She previously served as a director at Nuvalent Inc. prior to acquisition by GSK, Sierra Oncology prior to acquisition by GSK, Reata Pharmaceuticals prior to acquisition by Biogen, Rayze Bio prior to acquisition by BMS, and Lava Oncology prior to acquisition by Xoma Therapeutics. She holds a B.A. in Economics from University of California, Santa Barbara. About Bicara Therapeutics Bicara is a clinical-stage biopharmaceutical company committed to bringing transformative bifunctional therapies to patients with solid tumors. Bicara has built a platform designed to facilitate the development of bifunctional therapies that precisely target the tumor and deliver a tumor-modulating payload to the tumor site. This approach was deployed in the development of Bicara’s lead program ficerafusp alfa, formerly BCA101, a bifunctional epidermal growth factor receptor (EGFR) directed monoclonal antibody bound to a human transforming growth factor beta (TGF-β) ligand trap. By combining these two clinically validated targets, ficerafusp alfa has the potential to exert potent anti-tumor activity by simultaneously blocking both cancer cell-intrinsic EGFR survival and proliferation, as well as the immunosuppressive TGF-β signaling within the tumor microenvironment (TME). Ficerafusp alfa directs the TGF-β inhibitor into the immediate TME through the binding of EGFR on tumor cells, which Bicara believes will lead to deep and durable responses and an increase in overall survival, while reducing the potential adverse effects previously associated with systemic TGF-β inhibition. Ficerafusp alfa is being developed in head and neck squamous cell carcinoma, where there remains a significant unmet need, as well as other solid tumor types. For more information, please visit www.bicara.com or follow us on LinkedIn and X. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. These statements may be identified by words such as “may,” “might,” “will,” “could,” “would,” “should,” “plan,” “anticipate,” “intend,” “believe,” “expect,” “estimate,” “seek,” “predict,” “future,” “project,” “potential,” “continue,” “target” and similar words or expressions, or the negative thereof, are intended to identify forward-looking statements, although not all contain identifying words. Any statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements. These forward-looking statements include, without limitation, express or implied statements regarding Bicara’s strategy, business plans and focus; the clinical development of ficerafusp alfa, including planned and ongoing clinical trials; the expected therapeutic potential and clinical benefits of ficerafusp alfa, including potential efficacy, depth, durability and tolerability; Bicara’s ability to scale and prepare for potential commercialization of ficerafusp alfa; the potential for U.S. regulatory approval and launch of ficerafusp alfa; and anticipated contributions of members of Bicara’s Board of Directors. Any forward-looking statements in this press release are based on management's current expectations and beliefs and are subject to a number of risks and uncertainties that are difficult to predict. Factors that could cause actual results to differ include, but are not limited to, risks relating to Bicara’s research and development activities; Bicara’s ability to execute on its business plans and strategy, including obtaining the requisite regulatory approvals on the expected timeline, if at all; uncertainties relating to the clinical development of ficerafusp alfa; the Company’s dependence on third parties; risks related to the Company’s financial condition and need for additional funds in order to commercialize ficerafusp alfa, if approved; risks related to regulatory developments and approval processes of the U.S. Food and Drug Administration and comparable foreign regulatory authorities; risks related to establishing and maintaining Bicara’s intellectual property protections; and risks related to the competitive landscape for ficerafusp alfa; as well as other risks described in “Risk Factors,” in Bicara’s most recent Annual Report on Form 10-K and subsequent Quarterly Reports on Form 10-Q, as well as discussions of potential risks, uncertainties, and other important factors in Bicara’s subsequent filings with the U.S. Securities and Exchange Commission (SEC). In addition, any forward-looking statements represent Bicara’s views only as of today and should not be relied upon as representing its views as of any subsequent date. Bicara explicitly disclaims any obligation to update any forward-looking statements. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking statements. Bicara intends to use its Investor Relations website as a means of disclosing material nonpublic information and for complying with its disclosure obligations under Regulation FD. Accordingly, investors should monitor the Company’s Investor Relations website, in addition to following the Company’s press releases, SEC filings, public conference calls, presentations, and webcasts. Contacts InvestorsRachel Frank IR@bicara.com MediaTim PalmerTim.Palmer@bicara.com

磷脂酰肌醇 3-激酶（PI3K）通路异常激活是人类肿瘤最常见的分子特征之一，PIK3CA 突变在约 13% 的实体瘤中存在，其中子宫内膜癌（42.3%）、乳腺癌（35.1%）、宫颈癌（27.7%）发生率最高。尽管 PI3K 抑制剂（阿培利司、库潘尼西等）已获 FDA 批准，但临床应用面临两大核心挑战：一是剂量依赖性毒性限制了治疗窗口，二是通路代偿性激活易导致耐药。联合用药是克服上述瓶颈的关键策略，但传统 2D 细胞培养模型难以模拟肿瘤微环境复杂性，3D 多细胞肿瘤球筛选亟需高通量精准给药平台。本研究在 29 种多细胞肿瘤球模型中系统评估 4 种 PI3K 抑制剂（伊纳沃利布、阿培利司、杜韦利西布、库潘尼西）与 16 种靶向药物的联合效应；I.DOT 非接触纳升级移液系统以 62.5 nL 体积完成 384 孔板化合物的精准分配，为高通量联合筛选提供可靠的给药基础 [1]。 实验方法 1、 核心平台与材料设计 以多细胞肿瘤球（mct-tumor spheroids）为核心筛选模型，由 60% 恶性肿瘤细胞、25% 人脐静脉内皮细胞（HUVEC）、15% 人间充质干细胞（hMSC）共培养构建，模拟实体瘤微环境。共评估 29 种肿瘤模型：包含 26 种 NCI 患者来源细胞系（结肠癌 13 种、直肠癌 3 种、膀胱癌 3 种、头颈鳞癌 2 种、宫颈鳞癌 2 种、小肠腺癌 1 种、浸润性乳腺癌 1 种、肺鳞癌 1 种）及 3 种 NCI-60 乳腺癌细胞系（MDA-MB-231、MDA-MB-468、T-47D）；其中 20 种（~69%）携带 PIK3CA 突变。筛选化合物包括 4 种 PI3K 抑制剂（伊纳沃利布、阿培利司：PI3Kα 选择性；杜韦利西布：PI3Kδ/γ选择性；库潘尼西：泛 PI3K 抑制剂）及 16 种靶向药物（MEK/ERK/RAF 抑制剂、KRAS 突变特异性抑制剂、mTOR/AKT 抑制剂等）。核心检测指标为细胞活力（CellTiter-Glo 3D），采用 Bliss 独立性模型评估联合效应（Figure 1）。 图1. PI3K 抑制剂单药活性及所有联合用药平均 Bliss 独立性评分汇总。(A) 29 种多细胞肿瘤球对 4 种 PI3K 抑制剂（阿培利司、伊纳沃利布、杜韦利西布、库潘尼西）的浓度-响应曲线；灰色符号代表 PIK3CA 野生型，红色符号代表 PIK3CA 突变型。(B) 浓度-响应曲线下面积（AUC）热图，红色表示低 AUC（高活性），蓝色表示高 AUC（低活性）；下方标注 PIK3CA、KRAS、EGFR、BRAF 突变状态。(C) 所有 64 种联合用药在 29 种肿瘤球中的平均 Bliss 评分热图，蓝色表示协同，灰色表示相加，红色表示拮抗。 2、关键操作与 I.DOT 核心应用 高通量联合给药：所有化合物的梯度浓度分配均通过 I.DOT 非接触纳升级移液系统完成。将 800× 储备液以 62.5 nL 纳升级体积精准分配至 384 孔肿瘤球培养板，自动生成 5×5 浓度梯度组合矩阵；全程非接触设计避免交叉污染，体积误差 <5%，确保每孔药物终浓度精确一致，为 1856 组联合用药的 Bliss 模型分析提供标准化数据基础。 实验流程整合：肿瘤细胞、HUVEC、hMSC 按比例混合后接种于 384 孔超低粘附板，培养 3 天形成肿瘤球；I.DOT 完成给药后继续培养 7 天，采用 CellTiter-Glo 3D 检测细胞活力；923 块筛选板平均 Z' 因子 0.73，确保检测稳定性。采用 Bliss 独立性模型评估联合效应：Bliss 评分 >0 表示协同（细胞活力低于预期），评分 =0 表示相加，评分 <0 表示拮抗；对所有联合用药进行层次聚类分析（Figure 2、Figure 3）。 图2. MEK 抑制剂司美替尼与 PI3K 抑制剂（阿培利司、伊纳沃利布、库潘尼西）的联合效应。司美替尼与（A）阿培利司、（B）伊纳沃利布、（C）库潘尼西联合的浓度-响应数据（上图，均值 ± 标准差，n = 3 技术重复）及对应 Bliss 独立性评分矩阵（下图，n = 3 技术重复的均值）以数值和热图形式展示（蓝色表示协同，灰色表示相加，红色表示拮抗）；标注肿瘤细胞系特征，包括模型名称、癌种及 PIK3CA 突变状态。 图3. ERK1/2 抑制剂 ravoxertinib 与 PI3K 抑制剂（阿培利司、伊纳沃利布、库潘尼西）的联合效应。ravoxertinib 与（A）阿培利司、（B）伊纳沃利布、（C）库潘尼西联合的浓度-响应数据（上图，均值 ± 标准差，n = 3 技术重复）及对应 Bliss 独立性评分矩阵（下图，n = 3 技术重复的均值）以数值和热图形式展示（蓝色表示协同，灰色表示相加，红色表示拮抗）；标注肿瘤细胞系特征，包括模型名称、癌种及 PIK3CA 突变状态。 实验结果 1、库潘尼西单药活性最强，PIK3CA 突变与敏感性无显著关联 单药筛选结果显示：泛 PI3K 抑制剂库潘尼西在多数肿瘤球中达到 IC₅₀，活性最强；PI3Kα 选择性抑制剂阿培利司与伊纳沃利布活性谱高度相似（Pearson r = 0.83, p < 0.0001）；PI3Kδ/γ 选择性抑制剂杜韦利西布活性最弱。值得注意的是，PIK3CA 突变状态与任一 PI3K 抑制剂的敏感性均无显著关联（Figure 1）。 2、PI3K 与 RAS/MEK/ERK 通路双重抑制展现广泛协同效应 PI3K 抑制剂与 MEK 抑制剂司美替尼、ERK 抑制剂 ravoxertinib、RAF 抑制剂 tovorafenib（DAY101）的联合用药展现一致的相加/协同效应：在结肠癌、直肠癌模型中观察到显著协同，宫颈癌、乳腺癌模型中以相加效应为主。阿培利司与伊纳沃利布与司美替尼联合的 Bliss 评分高度相关（Pearson r = 0.8, p < 0.0001），库潘尼西联合效应通常更强（Figure 2、Figure 3、Figure 4）。 图4. II 型 RAF 抑制剂 tovorafenib（DAY101）与 PI3K 抑制剂（阿培利司、库潘尼西）的联合效应。tovorafenib 与（A）阿培利司、（B）库潘尼西联合的浓度-响应数据（上图，均值 ± 标准差，n = 3 技术重复）及对应 Bliss 独立性评分矩阵（下图，n = 3 技术重复的均值）以数值和热图形式展示（蓝色表示协同，灰色表示相加，红色表示拮抗）；标注肿瘤细胞系特征，包括模型名称、癌种及 PIK3CA、BRAF 突变状态。 3、KRAS 突变特异性抑制剂与 PI3K 抑制剂联合具有基因型选择性 KRAS G12D 抑制剂 MRTX1133 与阿培利司、伊纳沃利布、库潘尼西联合在 KRAS G12D 突变肿瘤球中展现相加/协同效应；库潘尼西联合的细胞杀伤深度优于两种 PI3Kα 选择性抑制剂。KRAS G12C 抑制剂索托拉西布与 PI3K 抑制剂联合在唯一测试的 G12C 模型中效应较弱。杜韦利西布与任一 KRAS 抑制剂联合均无显著活性（Figure 5）。 图5. PI3K 抑制剂与 KRAS 突变特异性抑制剂 MRTX1133（G12D）、索托拉西布（G12C）在携带相应蛋白变异的肿瘤细胞中的联合效应。MRTX1133 或索托拉西布与（A）阿培利司、（B）伊纳沃利布、（C）库潘尼西联合的浓度-响应数据（上图，均值 ± 标准差，n = 3 技术重复）及对应 Bliss 独立性评分矩阵（下图，n = 3 技术重复的均值）以数值和热图形式展示（蓝色表示协同，灰色表示相加，红色表示拮抗）；标注肿瘤细胞系特征，包括模型名称、癌种及 PIK3CA、KRAS 突变状态。 4、PI3K/AKT/mTOR 通路垂直抑制以相加效应为主，特定模型存在协同 PI3K 抑制剂与 mTORC1/2 抑制剂 sapanisertib 联合主要为相加效应，但在结肠癌（PIK3CA C420R、KRAS G12D）、膀胱癌（PIK3CA E545K）、三阴性乳腺癌（PIK3CA H1047R）模型中观察到协同。PI3K 抑制剂与 AKT 抑制剂 ipatasertib、afuresertib 联合在结肠癌模型中同样展现协同效应（Figure 6、Figure 7）。 图6. mTORC1/2 抑制剂 sapanisertib 与 PI3K 抑制剂（阿培利司、伊纳沃利布、库潘尼西）的联合效应。sapanisertib 与（A）阿培利司、（B）伊纳沃利布、（C）库潘尼西联合的浓度-响应数据（上图，均值 ± 标准差，n = 3 技术重复）及对应 Bliss 独立性评分矩阵（下图，n = 3 技术重复的均值）以数值和热图形式展示（蓝色表示协同，灰色表示相加，红色表示拮抗）；标注肿瘤细胞系特征，包括模型名称、癌种及 PIK3CA 突变状态。 图7. PI3K 抑制剂（阿培利司、库潘尼西）与 AKT 抑制剂 ipatasertib、afuresertib 的联合效应。ipatasertib（左）或 afuresertib（右）与（A）阿培利司、（B）库潘尼西联合的浓度-响应数据（上图，均值 ± 标准差，n = 3 技术重复）及对应 Bliss 独立性评分矩阵（下图，n = 3 技术重复的均值）以数值和热图形式展示（蓝色表示协同，灰色表示相加，红色表示拮抗）；标注肿瘤细胞系特征，包括模型名称、癌种及 PIK3CA 突变状态。 总结与讨论 本研究在 29 种模拟肿瘤微环境的多细胞肿瘤球中系统评估了 4 种 PI3K 抑制剂与 16 种靶向药物的 64 种联合方案。核心发现包括：PI3K 与 RAS/MEK/ERK 通路双重抑制具有最广泛的协同效应；KRAS 突变特异性抑制剂与 PI3K 抑制剂联合具有基因型选择性；PI3K/AKT/mTOR 通路垂直抑制在特定分子亚型中存在协同。I.DOT 非接触纳升级移液系统的 62.5 nL 精准给药为 1856 组联合用药的高通量筛选提供了标准化保障。 本研究的临床转化价值在于：库潘尼西与司美替尼在较低浓度下即展现协同，为降低 PI3K 抑制剂剂量、减轻毒性提供了联合用药策略；阿培利司与 MRTX1133 的协同效应已进入 I 期临床（NCT04449874）。I.DOT 赋能的多细胞肿瘤球高通量筛选平台，可高效识别具有临床潜力的 PI3K 抑制剂联合方案，为实体瘤精准治疗提供重要的临床前证据。 同腾睿杰（上海）生物科技有限公司作为CYTENA DISPENDIX I.DOT中国总代理商，为您提供优质的售前售后服务。 联系电话：021-50826962 联系邮箱：sales@ttbiotech.com 参考文献： [1] Dexheimer TS, Davoudi Z, Coussens NP, et al. Combinatorial screen of targeted agents with the PI3K inhibitors inavolisib, alpelisib, duvelisib, and copanlisib in multi-cell type tumor spheroids. SLAS Discovery. 2025;32(2):100222. 上海同腾生物科技有限公司 上海同腾生物科技有限公司是一家专注于为生物医药研发，制药工艺开发、生产制造等环节提供先进设备及耗材的高新技术企业。 公司成立于2018年，目前在上海浦东张江拥有800平米办公场地，同时在江苏太仓，子公司同腾新创(苏州)科技有限公司拥有占地2200平米的生产工厂。 上海同腾生物是新加坡ESCO生物安全柜/培养箱、德国Cryotherm液氮罐、美国Revvity微流控核酸分析仪/小动物活体成像、Cytek®流式细胞分析仪等实验室通用设备品牌国内主要服务商，为生命科学、生物制药等行业提供实验室设备售前售后全流程技术解决方案。 旗下子公司同腾睿杰（上海）生物科技有限公司，是德国Bruker Dynamic Biosensors Helix系列分子互作分析系统、德国Cytena DISPENDIX I.DOT非接触式纳升级液体处理系统、英国Roylan StoragePod 多模式化合物存储仓等诸多国际知名品牌产品在中国的核心服务商，为生命科学、细胞治疗、生物制药等重点行业提供从研发到生产的高端仪器设备和完整技术解决方案。 2022年初，子公司同腾新创（苏州）科技有限公司投资5000万元在江苏太仓建立生产工厂，目前已投产上市自主研发的CEL-G® Culture Ad60/Ad600固定床生物反应器、CEL-G® TFF lab/Scientific外泌体浓缩系统、CEL-G®Culture MSC无血清培养基和CelGrid™ Culture Single & Quadra微型固定床生物反应器等产品，全面为细胞和基因治疗、抗体和疫苗生产企业、细胞外囊泡（外泌体）研究和生产等行业提供高质量的本土化研发和生产解决方案。 2024年同腾新创自主研发投产的“外泌体一体化制备平台”，通过其特有的3D固定化培养和高效纯化系统，为外泌体行业带来产业革新！ 上海同腾生物科技有限公司2019年通过高新技术企业认证，拥有3项发明专利，31项实用新型专利和14项软件著作权；同腾新创（苏州）科技有限公司拥有6项发明专利，22项实用新型专利和11项软件著作权。通过了ISO9001质量管理体系认证、环境管理认证、职业健康安全管理认证等资质认证。 公司秉持“诚信，专注，专业，高效”的经营理念，立志成为“生物制药研发及生产领域的先进设备制造商和技术解决方案提供商”。 END