Cetuximab

1月13日晚，先声药业官微发布公告称，旗下抗肿瘤创新药公司先声再明宣布与艾伯维达成合作协议，艾伯维将获得SIM0500的许可选择性权益，支付首付款，以及最高10.55亿美元的选择性权益付款和里程碑付款，以及大中华区以外地区的销售分成。 SIM0500是一款人源化GPRC5D-BCMA-CD3三特异性抗体，由先声再明通过其专有的T细胞衔接器多特异性抗体技术平台开发。目前正在中美两国开展针对复发或难治性多发性骨髓瘤（MM）的临床I期研究。 1 业绩拐点，增长势头已现 作为国内老牌BioPharma，手握先必新、恩度、艾拉莫德等现金流品种。 实际上，先声药业的业绩改善势头已现。2024年上半年，先声药业经调整归属于公司权益股东的利润约人民币5.38亿元，较2023年同期约人民币3.94亿元增加约人民币1.44亿元，增幅约36.5%。而全年10亿元的净利润目标，较2023年增长40%。 回顾2024年，先声药业多款产品迎来关键催化，有望为2025年的业绩保驾护航。 第一，先必新舌下片与先必新组成序贯疗法，销售峰值有望达25亿元。2024年12月2日，脑卒中创新药先必新舌下片获国家药品监督管理局批准上市，用于改善急性缺血性脑卒中所致的神经症状、日常生活活动能力和功能障碍。 先必新舌下片III期临床研究(TASTE-SL研究)的主要结果于2024年发表于《美国医学会杂志·神经病学》，与安慰剂相比，先必新舌下片治疗急性缺血性中风安全有效，治疗后第90天功能良好结局的患者比例显著高于安慰剂组（64.4%vs 54.7%；P=0.003）。鉴于公司核心品种先必新注射液销售额已超过20亿元，参考石药集团恩必普，注射剂型主打院内，口服剂型专攻院外，互为协同，斩获超70亿元收入。先必新注射液及舌下片未来放量空间广阔。 图1 TASTE-SL研究主要终点 图片来源：先声药业 第二，恩立妥（西妥昔单抗β）与科赛拉（曲拉西利）顺利进入国家医保目录，2025年放量可期。 作为首款国产EGFR靶向药，恩立妥填补了结直肠癌的EGFR靶向抗体药物国产品种的空白。尽管进口EGFR抗体治疗结直肠癌的疗效已有大量临床数据验证，但仍存在进口可及性无法保证、安全性有待改进等潜在问题。2023年，默克的西妥昔单抗（爱必妥）中国销售额超20亿元人民币。恩立妥纳入医保后，可及性将大幅提升。 科赛拉是同类首创机制（First-in-Class）的短效、可逆性细胞周期蛋白依赖性激酶CDK4/6抑制剂，在化疗前给药，可使骨髓造血干/祖细胞暂时阻滞在G1期，免受化疗药物的杀伤，让化疗减毒增效。曲拉西利于2022年获国家药监局批准上市，但近年来销售表现不佳。核心原因在于与TPO、EPO、G-CSF等传统药物相比，科赛拉价格较高。科赛拉纳入国家医保目录后，有望通过独特的作用机制，快速放量。 2 先声再明厚积薄发 如果传统制药业务为先声药业构筑了牢固的业绩基础，而创新业务——先声再明则有望成为先声药业步入创新转型爆发期的关键。 先声再明成立于2020年，是先声药业集团旗下专注抗肿瘤创新药研发、生产和商业化的生物制药公司。 2024年2月24日，先声药业发布公告，子公司先声再明完成9.7亿元融资。此次融资投前估值75亿元，投后估值84.7亿元。国投招商领投8亿元，中深新创投资1亿元，杏泽资本投资5000万元，中和资本投资2000万元。作为中国医药健康领域最专业的私募股权管理机构之一，国投招商曾深度参与过科伦博泰、亚盛医药、联影医疗和信达生物等企业的投资，可谓硕果累累。而布局先声再明，显然为先声再明的产品管线所吸引。 放眼先声再明的管线，SIM0500（CD3/BCMA/GPRC5D）和SIM0505(CDH6-ADC）值得重点关注。 SIM0500是一款人源化GPRC5D-BCMA-CD3三特异性抗体，通过先声再明自有的T细胞衔接器多特异性抗体技术平台开发。该分子以低亲和力高靶向激活的CD3抗体，与抗肿瘤相关抗体组合，形成特异性靶向肿瘤的T细胞激活药物，具有多个抗体效应的协同作用。BCMA和GPRC5D与多发性骨髓瘤的发病关系密切，多款CAR-T与TCE与该靶点有关。 值得一提的是，制药巨头强生作为多发性骨髓瘤的龙头企业，对这一靶点组合也情有独钟。强生不但布局了多款CD3双抗，如talquetamab（CD3×GPRC5D）和Teclistamab（CD3×GPRC5D），还探索了talquetamab（CD3×GPRC5D）联合Teclistamab（CD3×GPRC5D）的效果，在一项名为RedirecTT-1的Ⅰ期研究中，就RP2D剂量，两款双抗联用的ORR达92%（12/13），超过了talquetamab（ORR=73.6%）和Teclistamab（ORR=63%）单药的效果。除了两款双抗联用外，强生亦布局了JNJ-79635322（GPRC5D-BCMA-CD3），反映出强生对这一靶点组合的高度关注。 作为全球临床进展前三的GPRC5D-BCMA-CD3，SIM0500于2024年5月完成首例患者入组（FPI）。此外，2024年4月，SIM0500获得美国食品药品管理局(FDA)授予的快速通道资格，这将大幅提升SIM0500的临床推进速度。 SIM0505(CDH6-ADC)是一款CDH6 ADC，目前仍处于临床前阶段。CDH6靶点的关注度近年来逐渐提升，2023年，MSD引进第一三共的CDH6 ADC，raludotatug deruxtecan(R-DXd；DS-6000)。在2023年ESMO上，第一三共更新了R-DXd的Ⅰ期结果，50例先前接受过四线治疗的宫颈癌患者ORR达46%，DCR达98%，mDoR达11.2个月，mPFS达7.9个月。考虑到末线宫颈癌治疗手段有限，CDH6 ADC有望填补这一空白市场。2025年1月，先声再明宣布CDH6 ADC在中美两国获批临床。 3 结语 先声药业传统业务增速稳定，2024年经调整净利润增速有望超过40%；创新药业务——先声再明经过多年的积累，收获期渐近，SIM0500（CD3/BCMA/GPRC5D）和SIM0505(CDH6-ADC）创新性强，此次携手艾伯维更是证实了其创新实力。期待老牌制药企业发新芽，再创辉煌，先声夺人。 友情推荐：医药行业深度技术内容，点击“博药”查看详情~ 声明：本内容仅用作医药行业信息传播，为作者独立观点，不代表药智网立场。如需转载，请务必注明文章作者和来源。对本文有异议或投诉，请联系maxuelian@yaozh.com。 责任编辑 | 史蒂文 合作、投稿、转载开白 | 马老师 18323856316（同微信）  阅读原文，是受欢迎的文章哦

Cemsidomide Data Presented at American Society of Hematology (ASH) Annual Meeting Support Best-in-Class Profile; Program Advancing to Next Phase of Clinical Development in Multiple Myeloma and Non-Hodgkin’s Lymphoma CFT1946 Phase 1 Trial Continues to Progress in BRAF V600X Solid Tumors With Monotherapy Dose Escalation Expected to Complete in 1H 2025; Data in Melanoma and Colorectal Cancer Expected in Second Half of 2025 CFT8919 Progressing Through Phase 1 Dose Escalation in Greater China; Phase 1 Data Will Inform Future Development Plans Outside of China Cash Runway Expected to Fund Operations Into 2027 WATERTOWN, Mass., Jan. 14, 2025 (GLOBE NEWSWIRE) -- C4 Therapeutics, Inc. (C4T) (Nasdaq: CCCC), a clinical-stage biopharmaceutical company dedicated to advancing targeted protein degradation science, today announced its anticipated 2025 milestones as it continues its evolution into becoming a fully integrated biotechnology company focused on orally bioavailable degraders. “Stellar execution in 2024 has set up 2025 to be a pivotal year for the company as we work to generate important data that will position us to advance programs and bring degrader medicines to patients searching for new therapeutic options,” said Andrew Hirsch, president and chief executive officer of C4 Therapeutics. “The cemsidomide data presented at the ASH Annual Meeting in December support a potentially best-in-class profile and we are preparing for the next phase of development of this molecule. We continue to progress the CFT1946 Phase 1/2 study and will leverage data from the tumor specific cohorts to determine the development path for this program. In addition, we expect data from the CFT8919 Phase 1 dose escalation study run by our partner Betta Pharmaceuticals in China, which will define its potential for non-small cell lung cancer patients with the EGFR L858R mutation. We are excited about the degrader rationale for these programs, which we believe have the potential to deliver value for patients, caregivers, physicians and shareholders.” ANTICIPATED 2025 MILESTONES Cemsidomide: Cemsidomide is an oral degrader of IKZF1/3 for the potential treatment of relapsed/refractory (R/R) multiple myeloma (MM) and R/R non-Hodgkin’s lymphoma (NHL). Multiple Myeloma Enable initiation of the next phase of clinical development to investigate cemsidomide in combination with dexamethasone in the late-line setting, and in combination with other MM agents for earlier lines of treatment. These new studies are expected to initiate in early 2026. Complete Phase 1 dose escalation and present data in the second half of 2025. Non-Hodgkin’s Lymphoma Complete Phase 1 dose escalation and present data in the second half of 2025. Open expansion cohort(s) of the current Phase 1/2 trial in patients with peripheral T-cell lymphoma (PTCL) in the second half of 2025. Enable initiation of the next phase of clinical development to investigate cemsidomide monotherapy in later lines of therapy in PTCL. This new study is expected to initiate in early 2026. CFT1946: CFT1946 is an oral degrader targeting BRAF V600 mutations for the potential treatment of solid tumors including colorectal cancer (CRC), melanoma and other malignancies with V600 mutations. Complete monotherapy Phase 1 dose escalation in BRAF V600 mutant solid tumors in the first half of 2025. Generate data from the Phase 1 cohorts exploring monotherapy CFT1946 in melanoma, CFT1946 in combination with cetuximab in CRC and CFT1946 in combination with trametinib in melanoma. Data from these cohorts will define and enable the next phase of development. Present Phase 1 data in the second half of 2025. These presentations will include: (1) monotherapy in BRAF V600 mutant solid tumors, (2) monotherapy expansion cohorts in melanoma, and (3) in combination with cetuximab in CRC. CFT8919: CFT8919 is an oral degrader targeting EGFR bearing an oncogenic L858R mutation for the potential treatment of non-small cell lung cancer (NSCLC). Evaluate data from the Phase 1 dose escalation study in Greater China, which is led by partner Betta Pharmaceuticals, in patients with locally or advanced metastatic NSCLC harboring an EGFR L858R mutation. These data will be used to determine the next phase of development. Discovery: C4T will continue to utilize its TORPEDO® platform to develop orally bioavailable degraders for oncology and non-oncology targets for internal research and collaboration programs. To further highlight its deep expertise in drug discovery, C4T plans to: Present and publish preclinical work from its internal pipeline and TORPEDO® platform. Advance internal and collaboration programs to key milestones. 2024 ACCOMPLISHMENTS Cemsidomide: C4T advanced the Phase 1/2 clinical trial and delivered data reinforcing the potential of cemsidomide to become a backbone therapy of choice in MM and NHL where IKZF1/3 degradation is warranted. Multiple Myeloma At ASH, presented data on cemsidomide in combination with dexamethasone. As of the data cutoff date of October 11, 2024, the dose level exploring 75 µg once daily (QD) achieved an overall response rate (ORR) of 36 percent. Cemsidomide was well-tolerated across all dose levels. The maximum tolerated dose has not yet been reached. Patients are enrolling in the 100 µg QD cohort. Non-Hodgkin’s Lymphoma At ASH, presented data on cemsidomide monotherapy. As of the data cutoff date of October 11, 2024, cemsidomide demonstrated a 38 percent ORR across all subtypes and doses studied. In PTCL, cemsidomide achieved a 44 percent ORR and a 25 percent complete metabolic response rate. The maximum tolerated dose has not yet been reached. Patients are enrolling in the 75 µg QD cohort. CFT1946: C4T advanced the Phase 1/2 clinical trial across multiple arms and delivered monotherapy data demonstrating proof of mechanism and early evidence of proof of concept. At the European Society of Medical Oncology (ESMO) Congress, presented monotherapy data demonstrating CFT1946 is well tolerated across all dose levels and demonstrates initial signs of anti-tumor activity across all dose levels. At the TPD Summit, presented new preclinical data demonstrating CFT1946 has the ability to cross the blood-brain barrier, with Kpu,u values in the range of 0.34 to 0.88. Progressed the Phase 1 monotherapy dose escalation study. Began enrolling patients across multiple exploratory cohorts: CFT1946 monotherapy in melanoma, CFT1946 in combination with trametinib in melanoma, and CFT1946 in combination with cetuximab in CRC. CFT8919: Betta Pharmaceuticals, with C4T support, initiated the Phase 1 clinical trial of CFT8919 in Greater China. Discovery: C4T further validated its TORPEDO® platform and advanced key research efforts. Delivered two development candidates for non-oncology targets to collaborator Biogen. Established a new collaboration with Merck KGaA, Darmstadt, Germany focused on two critical oncogenic proteins. Continued to progress its internal discovery portfolio of orally bioavailable degraders. Corporate: C4T further strengthened its leadership across its management team and Board of Directors to supports its evolution into a fully integrated biotechnology company. Paige Mahaney, Ph.D., was appointed chief scientific officer. Dr. Mahaney is an experienced drug developer who has helped leading pharmaceutical companies build clinical portfolios across a wide range of disease indications and treatment modalities. C4T continued to evolve its governance by appointing three new members to its Board of Directors who bring deep experience across drug discovery, commercialization and lifecycle management. Cash Guidance C4T expects that its cash, cash equivalents and marketable securities as of December 31, 2024, together with anticipated collaboration expense reimbursements, but excluding any collaboration option or milestone payments, will enable the company to fund its operating plan into 2027. JP Morgan Presentation C4T will present at the 43rd Annual J.P. Morgan Healthcare Conference on Wednesday, January 15, 2025 at 2:15 pm PST (5:15 pm EST). A live webcast will be available under “Events & Presentations” in the Investors section of the company’s website at www.c4therapeutics.com. A replay of the webcast will be archived on the C4T website for at least two weeks following the presentation. About C4 Therapeutics C4 Therapeutics (C4T) (Nasdaq: CCCC) is a clinical-stage biopharmaceutical company dedicated to delivering on the promise of targeted protein degradation science to create a new generation of medicines that transforms patients’ lives. C4T is progressing targeted oncology programs through clinical studies and leveraging its TORPEDO® platform to efficiently design and optimize small-molecule medicines to address difficult-to-treat diseases. C4T’s degrader medicines are designed to harness the body’s natural protein recycling system to rapidly degrade disease-causing proteins, offering the potential to overcome drug resistance, drug undruggable targets and improve patient outcomes. For more information, please visit www.c4therapeutics.com. About Cemsidomide Cemsidomide is an investigational, orally bioavailable small-molecule degrader designed to be a more potent and selective degrader of IKZF1/3, transcription factors that drive multiple myeloma (MM) and non-Hodgkin’s lymphomas (NHL), with unique pharmacokinetic properties. Clinical data has shown that cemsidomide is well-tolerated. In MM, cemsidomide displays evidence of anti-myeloma activity and immunomodulatory effects. In NHL, cemsidomide displays evidence of anti-lymphoma activity. More information may be accessed at www.clinicaltrials.gov (identifier: NCT04756726). About CFT1946 CFT1946 is an investigational, orally bioavailable brain penetrant small molecule degrader of BRAF V600 mutations in solid tumors currently being evaluated in a Phase 1/2 global clinical trial in patients refractory to BRAF inhibitors. CFT1946 is designed to be potent and selective against the BRAF V600 mutant form. Initial clinical data from the Phase 1 trial demonstrate that CFT1946 has a well-tolerated safety profile, demonstrates dose-dependent bioavailability and degradation of BRAF V600E protein, and demonstrates evidence of monotherapy anti-tumor activity. CFT1946 is the only degrader of BRAF V600 mutant solid tumors in clinical trials. More information about this trial may be accessed at www.clinicaltrials.gov (identifier: NCT05668585). About CFT8919 CFT8919 is an orally bioavailable allosteric degrader that is designed to be potent and selective against EGFR bearing an oncogenic L858R mutation. In preclinical studies, CFT8919 is active in in vitro and in vivo models of L858R driven non-small cell lung cancer. Importantly, CFT8919 retains full activity against additional EGFR mutations that confer resistance against approved EGFR inhibitors including L858R-C797S, L858R-T790M, and L858R-T790M-C797S. Forward-Looking Statements This press release contains “forward-looking statements” of C4 Therapeutics, Inc. within the meaning of the Private Securities Litigation Reform Act of 1995. These forward-looking statements may include, but may not be limited to, express or implied statements regarding our ability to develop potential therapies for patients; the design and potential efficacy of our therapeutic approaches; the predictive capability of our TORPEDO® platform in the development of novel, selective, orally bioavailable BiDAC™ and MonoDAC™ degraders; the potential timing, design and advancement of our preclinical studies and clinical trials, including the potential timing for and receipt of regulatory authorization related to clinical trials and other clinical development activities including clinical trial commencement or cohort initiation; our ability and the potential to successfully manufacture and supply our product candidates for clinical trials; our ability to replicate results achieved in our preclinical studies or clinical trials in any future studies or trials; our ability to replicate interim or early-stage results from our clinical trials in the results obtained when those clinical trials are completed or when those therapies complete later-stage clinical trials; regulatory developments in the United States and foreign countries; the anticipated timing and content of presentations of data from our clinical trials; and our ability to fund our future operations. Any forward-looking statements in this press release are based on management’s current expectations and beliefs of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to: uncertainties related to the initiation, timing, advancement and conduct of preclinical and clinical studies and other development requirements for our product candidates; the risk that any one or more of our product candidates will cost more to develop or may not be successfully developed and commercialized; and the risk that sufficient capital to fund our future operations will be available to us on acceptable terms or at the times required. For a discussion of these and other risks and uncertainties, and other important factors, any of which could cause our actual results to differ from those contained in the forward-looking statements, see the section entitled “Risk Factors” in C4 Therapeutics’ most recent Annual Report on Form 10-K and/or Quarterly Report on Form 10-Q, as filed with the Securities and Exchange Commission. All information in this press release is as of the date of the release, and C4 Therapeutics undertakes no duty to update this information unless required by law. Contacts: Investors: Courtney Solberg Senior Manager, Investor Relations CSolberg@c4therapeutics.com Media: Loraine Spreen Senior Director, Corporate Communications & Patient Advocacy LSpreen@c4therapeutics.com