Zelenectide pevedotin

First human imaging data validate the potential of MT1-MMP as a novel target in the treatment of cancer and demonstrate positive properties of Bicycle Radionuclide Conjugates (BRC ® ) for radiopharmaceutical use Additional preclinical data demonstrate biodistribution of BRCs can be optimized to maintain high tumor uptake while significantly reducing kidney levels Company strategy focuses on pursuing novel targets using a range of isotopes to develop radiopharmaceuticals with first-in-class potential Bicycle Therapeutics to host conference call and webcast today at 8 a.m. ET CAMBRIDGE, England & BOSTON--(BUSINESS WIRE)--Bicycle Therapeutics plc (NASDAQ: BCYC), a pharmaceutical company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle ® ) technology, today announced the presentation of the first human imaging data validating the potential of MT1-MMP as a novel target in the treatment of cancer and demonstrating the positive properties of Bicycle Radionuclide Conjugates (BRC ® ) for radiopharmaceutical use, as well as preclinical data demonstrating optimized BRC radioisotope delivery at the European Association of Nuclear Medicine (EANM) 2024 Congress in Hamburg, Germany. “Since our founding, our goal at Bicycle Therapeutics has been to leverage the power of our platform in areas where we can have the most impact for patients. Over the years, we have built a robust pipeline of oncology therapies that includes targeted drug conjugates, immuno-oncology agents and now, radiopharmaceuticals,” said CEO Kevin Lee, Ph.D. “The exciting data presented at EANM underscore the potential of our Bicycle Radionuclide Conjugates to deliver a range of isotopes to novel cancer targets. Through our strategy of pursuing novel targets with first-in-class potential and selecting the isotope that best aligns with the target biology and indication, we have an opportunity to potentially broaden the use of radiopharmaceuticals to diagnose and treat cancer.” In line with Bicycle Therapeutics’ radiopharmaceuticals strategy, the company selected tumor antigen EphA2 as its second BRC target and signed a letter of intent with leading isotope technology company Eckert & Ziegler to put in place an agreement to supply a range of radioisotopes and develop and manufacture BRC molecules. Bicycle Therapeutics, through its internal pipeline of wholly owned molecules and strategic collaborations with industry and academic leaders in the field, aims to be at the forefront of the development of next-generation radiopharmaceutical therapies. Bicycle ® molecules have ideal properties for radioisotope delivery due to their low molecular weight, high selectivity and affinity for their intended target and rapid systemic clearance. “The data presented at EANM demonstrate how our Bicycle ® platform is a powerful tool for de novo identification of high-quality binders to important cancer targets. We believe the ability to optimize the biodistribution properties of our molecules, significantly reducing kidney retention while retaining rapid, selective uptake in tumors, position Bicycle Radionuclide Conjugates as a potentially best-in-class approach for targeted radionuclide therapy,” said Michael Skynner, Ph.D., chief technology officer of Bicycle Therapeutics. “MT1-MMP is the first target for radiopharmaceutical development that we are pursuing given its expression in many solid tumors such as non-small cell lung cancer, esophageal and triple negative breast cancer.” EANM 2024 Congress Data Highlights During an oral presentation, the German Cancer Consortium (DKTK) presented first human imaging data for a BRC targeting MT1-MMP. They focused on a case study in a 65-year-old male diagnosed with advanced pulmonary adenocarcinoma, the most common type of non-small cell lung cancer, in the lung and lymph nodes confirmed by endobronchial ultrasound (EBUS) biopsy. The patient received fluorine-18-labelled FDG-PET/CT imaging, and two weeks later received MT1-MMP PET/CT imaging up to one hour post injection of the gallium-68-labelled BRC tracer. Both scans revealed multiple lymph node metastases and bone metastases in the sternum. MT1-MMP imaging demonstrated tracer uptake in the primary tumor in the lung and lymph node and bone metastases, consistent with FDG imaging. Additionally, the MT1-MMP BRC tracer showed renal excretion, with all other organs showing only negligible tracer uptake. Clear imaging contrast was also observed at early time points. In an e-poster, Bicycle Therapeutics presented preclinical data demonstrating the suitability of Bicycle molecules to deliver indium to tumors in vivo due to their favorable properties, including specific tumor uptake, rapid tumor penetration and rapid renal elimination. Additionally, imaging showed how the biodistribution pro BRCs can be optimized to maintain high tumor uptake and retention while significantly reducing kidney uptake and retention. These data build on the body of preclinical data the company has published in this area demonstrating the use of Bicycle molecules to effectively deliver various radioisotopes, such as lutetium and lead, to tumors. Altogether, the data presented at EANM validate the potential of MT1-MMP as a novel target in the treatment of cancer, demonstrate the translatability of BRC preclinical data and highlight the potential of Bicycle molecules for targeted radionuclide therapy. The e-poster, “Bicycle Radionuclide Conjugates for radioisotope delivery to solid tumors,” is available in the Publications section of the Bicycle Therapeutics website. Conference Call Details Bicycle Therapeutics will host a conference call and webcast today, Oct. 23, at 8 a.m. ET to review the first human imaging data and outline the company’s radiopharmaceuticals strategy. To access the call, please dial 833-816-1408 (U.S.) or +1-412-317-0501 (international) and ask to join the Bicycle Therapeutics call. A live webcast and replay of the conference call will be accessible in the Investor section of the Company’s website at . About Bicycle Therapeutics Bicycle Therapeutics is a clinical-stage pharmaceutical company developing a novel class of medicines, referred to as Bicycle ® molecules, for diseases that are underserved by existing therapeutics. Bicycle molecules are fully synthetic short peptides constrained with small molecule scaffolds to form two loops that stabilize their structural geometry. This constraint facilitates target binding with high affinity and selectivity, making Bicycle molecules attractive candidates for drug development. The company is evaluating zelenectide pevedotin (formerly BT8009), a Bicycle ® Toxin Conjugate (BTC ® ) targeting Nectin-4, a well-validated tumor antigen; BT5528, a BTC molecule targeting EphA2, a historically undruggable target; and BT7480, a Bicycle Tumor-Targeted Immune Cell Agonist ® (Bicycle TICA ® ) targeting Nectin-4 and agonizing CD137, in company-sponsored clinical trials. Additionally, the company is developing Bicycle Radionuclide Conjugates (BRC ® ) for radiopharmaceutical use and, through various partnerships, is exploring the use of Bicycle ® technology to develop therapies for diseases beyond oncology. Bicycle Therapeutics is headquartered in Cambridge, UK, with many key functions and members of its leadership team located in Cambridge, Mass. For more information, visit . Forward Looking Statements This press release may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will” and variations of these words or similar expressions that are intended to identify forward-looking statements, although not all forward-looking statements contain these words. Forward-looking statements in this press release include, but are not limited to, statements regarding validation of MT1-MMP as a target for the treatment of cancer, the suitability of BRCs for radiopharmaceutical use and the potential of this approach; Bicycle’s plans for an agreement with Eckert & Ziegler to develop, manufacture and supply a range of radioisotopes; Bicycle’s anticipated progress across its internal and partnered pipelines in radiopharmaceuticals, the translatability of Bicycle’s BRC preclinical data and the ability of the Bicycle platform to identify binders for cancer targets; Bicycle’s development across its R&D pipeline and the advancement of its product candidates, including zelenectide pevedotin, BT5528 and BT7480; and the therapeutic potential for Bicycles in oncology and other applications. Bicycle may not actually achieve the plans, intentions or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in research and development and in the initiation, progress and completion of preclinical studies and clinical trials and the identification and development of Bicycle’s potential and current product candidates; the risk that Bicycle may not realize the intended benefits of its platform, technology or partnerships; timing of results from preclinical studies and clinical trials; whether the outcomes of preclinical studies will be predictive of clinical trial results; the risk that preclinical studies and clinical trials may have unsatisfactory outcomes; potential adverse effects arising from the testing or use of Bicycle’s product candidates; the risk that Bicycle’s management have not focused the company’s activities on the clinical programs and research areas with the highest potential to maximize value creation; and other important factors, any of which could cause Bicycle’s actual results to differ from those contained in the forward-looking statements, are described in greater detail in the section entitled “Risk Factors” in Bicycle’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (SEC) on May 2, 2024, as well as in other filings Bicycle may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and Bicycle expressly disclaims any obligation to update any forward-looking statements contained herein, whether because of any new information, future events, changed circumstances or otherwise, except as otherwise required by law. Contacts Investors: Stephanie Yao SVP, Investor Relations and Corporate Communications stephanie.yao@bicycletx.com 857-523-8544 Matthew DeYoung Argot Partners ir@bicycletx.com 212-600-1902 Media: Jim O’Connell Weber Shandwick media@bicycletx.com 312-988-2343

据中国国家药监局药品审评中心（NMPA）消息，近期（2024年9月23日~2024年10月6日）共有11款一类创新药/新技术，首次在中国获得临床试验默示许可（IND），其中包括ADC药物、双抗类药物、CAR-T细胞疗法、TCR-T细胞疗法等。下面全球肿瘤医生网帮大家简单汇总一下，以供癌友们参考。 一、首次在中国获批临床的一类新药大汇总 （一）ABBV-706 1、药品信息 ①药物名称： ABBV-706注射用冻干粉。 ②研发公司： AbbVie（艾伯维）。 ③治疗靶点： 靶向SEZ6。 ④适应证： 复发/难治小细胞肺癌。 2、药物介绍 ABBV-706注射用冻干粉是一款靶向SEZ6（是一种跨膜蛋白，在小细胞肺癌、中枢神经系统肿瘤、其他神经内分泌肿瘤中表达）的ADC药物，与拓扑异构酶1抑制剂有效载荷结合，在治疗小细胞肺癌(SCLC)、其他神经内分泌肿瘤(NEN)、中枢神经系统肿瘤(CNS)方面展现出了良好的疗效。 在2024 ASCO大会上，公布了ABBV-706的1期临床研究数据（NCT05599984），本次共入组49例患者（包括22例小细胞肺癌、5例中枢神经系统肿瘤、22例其他神经内分泌肿瘤），既往接受过2.5线治疗（范围1-6）。 结果显示：对于33名RECIST可评估患者，客观缓解率（ORR）达到21%（详见下图），其中7例达到部分缓解（PR）。除了ABBV-706这款在研的ADC药物外，2024全球还获批上市了多款ADC药物，阅读原文了解详情：【速览】2024年全球15款获批ADC药物大汇总，一文掌握！ ▲图源“NMPA”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 值得一提的是，其中一位76岁高级别胃神经内分泌肿瘤（胃部G3 NET转移）患者，既往曾接受过术前肿瘤切除手术+标准一线化疗，入组接受ABBV-706 治疗6周后，达到部分缓解（PR），肿瘤缩小78% ； 治疗第12周，肿瘤进一步缩小至91% （详见下图）！ ▲图源“NMPA”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 （二）INV-9956胶囊 1、药品信息 ①药物名称： INV-9956胶囊。 ②研发公司： 原力生命科学。 ③治疗靶点： CYP11A1。 ④适应证： 晚期转移性去势抵抗性前列腺癌。 2、药物介绍 INV-9956是原力生命科学自主研发的一款强效且高选择性的口服CYP11A1抑制剂，可用于治疗去势抵抗性前列腺癌（CRPC），具有卓越的体内抗肿瘤疗效。2024年9月30日，INV-9956胶囊的新药IND申请获中国国家药监局药品审评中心（NMPA）批准，拟用于治疗晚期转移性去势抵抗性前列腺癌。在此之前（2024年7月16日）INV-9956就已获得美国食品药品监督管理局（FDA）批准，开展临床研究。 （三）JNJ-78278343 1、药品信息 ①药物名称： JNJ-78278343注射液。 ②研发公司： 强生公司。 ③治疗靶点： KLK2-CD3。 ④适应证： 成年男性晚期前列腺癌。 2、药物介绍 JNJ-78278343注射液是由强生公司研发的一款KLK2-CD3双特异性抗体在研新药，通过与T细胞上的CD3结合，从而诱导T细胞活化，并将T细胞重定向至肿瘤细胞，最终导致T细胞介导的KLK2表达肿瘤细胞的裂解。目前JNJ-78278343的新药IND申请已获得中国NMPA的批准，拟用于成年男性的晚期前列腺癌的治疗。 （四）BT8009 1、药品信息 ①药物名称： BT8009。 ②研发公司： Bicycle公司。 ③治疗靶点： Nectin-4。 ④适应证： 尿路上皮癌。 2、药物介绍 BT8009是一种双环毒素结合物（BTC），由一种高度选择性的双环肽组成，该肽靶向nectin-4（是一种粘附分子，在尿路上皮癌等多种肿瘤中表达），通过可裂解的连接体与MMAE连接，可以高亲和性和选择性与靶标结合，具有高肿瘤渗透性。 （五）CG009301 1、药品信息 ①药物名称： 注射用CG009301。 ②研发公司： Cullgen Inc。 ③治疗靶点： GSPT1。 ④适应证： 复发/难治性血液恶性肿瘤。 2、药物介绍 CG009301是一种高选择性GSPT1降解剂，用于治疗复发或难治性血液系统恶性肿瘤[包括但不限于急性髓系白血病（AML）、急性淋巴细胞白血病（ALL）、高风险骨髓增生异常综合征（MDS）]。2024年10月8日，中国国家药品监督管理局(NMPA)已批准CG009301的临床试验(IND)申请，Cullgen将很快在中国启动CG009301的I期临床试验。 （六）SYN818 1、药品信息 ①药物名称： SYN818片。 ②研发公司： 圣域生物。 ③适应证： 晚期实体瘤。 2、药物介绍 SYN818片是由圣域生物自主研发的一款新型强效且高选择性的1类小分子化合物，可精准靶向并高效抑制Polθ（DNA聚合酶θ）的活性，从而抑制肿瘤细胞的DNA损伤修复，最终达到抗肿瘤的目的。2024年9月30日，——SYN818片的新药IND申请，获得中国NMPA批准，用于晚期实体瘤的治疗。 （七）GTA182 1、药品信息 ①药物名称： GTA182片。 ②研发公司： PRMT5。 ③适应证： MTAPnull/lost晚期实体瘤。 2、药物介绍 GTA182是一种是一款可穿透血脑屏障的第二代蛋白质精氨酸甲基转移酶5(PRMT5)抑制剂，具有甲硫腺苷(MTA)协同作用，对MTAP缺失的癌细胞具有高度选择性，而且不针对MTAP正常表达的非癌细胞，这种选择性有望为MTAP缺失型癌症患者提供更有效、更安全的治疗选择。 约有10%的实体瘤存在MTAP缺失，包括胶质母细胞瘤、肺癌、胰腺癌和膀胱癌等，这些肿瘤的治疗选择很有限，患者的大量临床需求尚未得到满足。而GTA182对MTAP缺失型肿瘤的高选择性及其穿透血脑屏障的能力，使其成为可能治疗中枢神经系统肿瘤和非中枢神经系统适应症的临床开发的best-in-class药物，已在先前的研究中展现出具有抑制肿瘤生长和肿瘤消退的显著效果。 （八）PTX-912 1、药品信息 ①药物名称： 注射用PTX-912。 ②研发公司： 博致生物。 ③适应证： 局部晚期/转移性实体瘤。 2、药物介绍 注射用PTX-912是由博致生物自主研发的新一代免疫细胞靶向的IL-2前药融合蛋白，显示出对 PD-1 通路的剂量依赖性抑制，可使IL-2前药在肿瘤微环境中被特异性激活，有助于改善IL-2的外周毒性问题，还可充分发挥IL-2的免疫激活及抗肿瘤功效。2024年10月12日，注射用PTX-912的临床试验默示许可获中国国家药品监督管理局批准，拟用于治疗局部晚期/转移性实体瘤。 （九）YY2201 1、药品信息 ①药物名称： YY2201片。 ②研发公司： 亚尧生物。 ③治疗靶点： ATR。 ④适应证： 晚期实体瘤。 2、药物介绍 YY2201片是由亚尧生物自主研发的一款口服ATR小分子抑制剂，在此前的研究中，展现出良好的体内/体外活性。该药已获得中国NMPA及美国食品药品监督管理局（FDA）的IND临床批件（IND173030），用于晚期实体瘤的治疗。 二、首次在中国获批临床的新技术大汇总 （十）IM96 CAR-T 1、药品信息 ①药物名称： IM96 CAR-T细胞注射液。 ②治疗靶点： GUCY2C。 ③适应证： 结直肠癌。 2、药物介绍 IM96 CAR-T细胞注射液是由我国自主研发的一款靶向GUCY2C的CAR-T细胞产品，目前新药IND申请已获我国NMPA批准，用于治疗晚期结直肠癌。 值得欣慰的是，在2024年美国临床肿瘤学会（ASCO）年会上，我国研究团队携IM96 CAR-T的I期临床数据（NCT05287165）惊艳亮相！结果显示：在19例可评估患者中，疾病控制率（DCR）高达73.7%，客观缓解率（ORR）达到26.3%（详见下图），可见IM96 CAR-T在转移性结直肠癌患者中，具有持久的疗效且安全性可控。此外，在DL3亚组中，无论有无肝转移，客观缓解率（ORR）均能达到40.0%，可见该药在肝转移患者中显示出很高的治疗潜力！ ▲图源“ASCO”，版权归原作者所有，如无意中侵犯了知识产权，请联系我们删除 （十一）IPM001 1、药品信息 ①药物名称： IPM001注射液。 ②研发公司： 臻知医学。 ③治疗靶点： 多抗原靶点。 ④适应证： 进展期原发性肝细胞癌。 2、药物介绍 IPM001注射液是由北京臻知医学自主研发的一款多抗原靶点的自体工程化T细胞（TCR-T）注射液，可靶向数十种肝癌相关抗原与新生抗原。2024年10月9日，IPM001注射液的新药临床研究申请，正式获得国家药品监督管理局（NMPA）默示许可，用于经二线系统性抗肿瘤治疗失败或不耐受的进展期原发性肝细胞癌的治疗，有望成为中国晚期肝癌患者的重要治疗选择之一。 （十二）IX001 TCR-T 1、药品信息 ①药物名称： IX001 TCR-T注射液。 ②研发公司： 镔铁生物。 ③治疗靶点： KRAS G12V突变。 ④适应证： 晚期胰腺癌。 2、药物介绍 IX001 TCR-T注射液是一款针对KRAS G12V突变的创新型TCR-T细胞疗法，可将特异性识别KRAS G12V突变的TCR基因序列，转入T细胞中，使其精准识别并杀伤胰腺癌细胞。2024年10月9日，该药的临床试验默示许可获中国国家药品监督管理局（NMPA）批准，拟用于HLA-A*11:01基因型、KRASG12V抗原表达阳性晚期胰腺癌的治疗。 三、小编寄语 以上新药/新技术仅为众多研发热点中的一小部分，还有多款抗癌新药或新型免疫疗法正在研发中，而且目前有多款在研药物已相继开展临床试验。对现有治疗方案不满意的患者，可将近期影像学及病理检查报告、治疗经历等资料，提交至 全球肿瘤医生网医学部 ，进行初步评估或了解详细的入排标准。 四、参考资料 [1]QI C,et al.Phase I study of GUCY2C CAR-T therapy IM96 in patients with metastatic colorectal cancer[J]. 2024. https://meetings.asco.org/abstracts-presentations/234018 [2]Chandana S R,et al.First-in-human study of ABBV-706, a seizure-related homolog protein 6 (SEZ6)–targeting antibody-drug conjugate (ADC), in patients (pts) with advanced solid tumors[J]. 2024. https://ascopubs-org.libproxy1.nus.edu.sg/doi/10.1200/JCO.2024.42.16_suppl.3001 [3]https://www.cde.org.cn/ 本文为全球肿瘤医生网原创，未经授权严禁转载