SCIENTIA CLINICAL RESEARCH LIMITED

SAN DIEGO, Jan. 10, 2025 /PRNewswire/ -- Expert Systems, a hybrid AI enabled drug discovery and development accelerator, announced a significant milestone in a development of Traws Pharma, Inc. 's (NASDAQ: TRAW) H5N1 antiviral program. The investigational drug, Tivoxavir Marboxil, has shown encouraging results as a single-dose treatment for H5N1 avian influenza, representing a potentially pivotal advance in addressing this serious health challenge. Continue Reading ​​Expert Systems and Traws Pharma Report Breakthrough in H5N1Bird Flu Antiviral Program Tivoxavir Marboxil, an oral cap-dependent endonuclease inhibitor, targets a highly conserved influenza protein, demonstrating broad-spectrum efficacy against various flu strains, including avian influenza. Preclinical studies have highlighted its potent activity against drug-resistant and highly pathogenic bird flu viruses, both in vitro and in vivo. In a recent randomized, double-blind, placebo-controlled Phase 1 clinical trial, the safety, tolerability, and pharmacokinetics of single ascending doses of Tivoxavir Marboxil were evaluated in healthy, influenza-negative adult volunteers. The trial reported no treatment-related adverse events. Notably, a single dose maintained plasma drug levels above the effective concentration (EC90) for over 23 days, indicating the potential for sustained efficacy with a one-time administration. Dr. Robert R. Redfield, Chief Medical Officer for Traws Pharma and former Director of the U.S. Centers for Disease Control and Prevention (CDC), commented: "The spread of avian influenza in wild and domestic animal populations, including mammals, brings increasing risk for adaptation to humans and subsequent spread in the population. With increasing numbers of human infections and recent reports of severe cases, we should be alert to the rising potential for epidemic or pandemic spread of bird flu." Expert Systems has been instrumental in the ideation, design, incubation, and support of this program, taking advantage of its hybrid human and AI-based drug discovery, development and venture studio startup services platform. This collaboration underscores the effectiveness of integrating artificial intelligence with human expertise and computer-aided drug design and business management, to expedite the development of innovative therapies. "The success of Tivoxavir Marboxil underscores the transformative potential of combining artificial intelligence with human expertise to tackle urgent global health challenges," said Tudor Oprea, Chief Executive Officer of Expert Systems. "We are excited to support Traws Pharma in bringing this innovative flu treatment closer to market." With the completion of Phase 1 trials, plans are underway to initiate Phase 2 efficacy studies in the first half of 2025. This brings Tivoxavir Marboxil closer to becoming a viable treatment option for H5N1 bird flu, addressing a critical need in global health. About Traws Pharma Traws Pharma, Inc. is a clinical-stage biopharmaceutical company dedicated to developing oral small molecule therapies for respiratory viral diseases and cancer. Leveraging expertise in small molecule chemistry, artificial intelligence, and streamlined development processes, Traws Pharma focuses on creating innovative medicines targeting critical health threats, including drug-resistant influenza viruses and avian flu. About Expert Systems Expert Systems is a drug discovery and development accelerator and leader in computer-enabled discovery and development platforms, committed to advancing the development of innovative therapies that address critical unmet medical needs. Combining advanced machine learning algorithms with broad domain expertise, Expert Systems accelerates the development of life-saving treatments in infectious diseases, oncology, CNS, immunology and cardiometabolic diseases. The company's innovative approach is reshaping the future of therapeutics. Media Contact: Bill Farley Chief Business Officer [email protected] SOURCE Expert Systems, Inc. WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

CS5001 is so far the first anti-ROR1 ADC known to show clinical anti-tumor activity in both solid tumors and lymphomas. The data presented at ASH highlighted the latest safety and efficacy of CS5001 as a monotherapy for patients with advanced lymphomas. CS5001 is well tolerated in heavily pre-treated patients with advanced B-cell lymphoma. No dose-limiting toxicity (DLT) has been reported up to dose level 10 (DL10). Encouraging anti-tumor activity with high objective response rate (ORR) was observed regardless of ROR1 expression levels, starting from the effective dose, in advanced Hodgkin lymphomas (HLs) (ORR=60.0%) and non-Hodgkin lymphomas (NHLs) (ORR=56.3%). At the preliminary recommended Phase 2 dose (RP2D) of DL8 (125 μg/kg), a notably higher ORR of 76.9% was observed in advanced B-cell lymphoma, including 3 evaluable HL cases with complete or partial response, and an ORR of 70% in NHL. The global multicenter Phase 1 trials of CS5001 are currently in progress in the USA, Australia, and China. Dose escalation has been completed with ongoing backfilling of patients for selective DLs. A Phase 1b dose-expansion study across multiple tumor types with registration potential is expected to be initiated soon. SUZHOU, China, Dec. 8, 2024 /PRNewswire/ -- CStone Pharmaceuticals ("CStone", HKEX: 2616), an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies, announced today the presentation of the latest clinical data for CS5001, an anti-ROR1 ADC and one of the leading assets in CStone Pipeline 2.0, at the 66th American Society of Hematology (ASH) Annual Meeting. These data highlight the compound's potential as a treatment for lymphoma. Receptor tyrosine kinase-like orphan receptor 1 (ROR1) is an embryonic tyrosine kinase-like molecule implicated in multiple pathways promoting oncogenic signaling. ROR1 is overexpressed at high frequency in hematological malignancies and in a broad spectrum of solid tumors while lower or absent in normal tissues, which makes ROR1 an attractive anti-cancer therapy target. CS5001 is so far the first anti-ROR1 ADC known to show clinical anti-tumor activity in both solid tumors and lymphomas. Dr. Jason Yang, CEO, President of R&D, and Executive Director at CStone, commented,"We are very encouraged that CS5001 continues to demonstrate potent anti-tumor activity and manageable safety and tolerability in the ongoing clinical study. The data presented at ASH further validate CS5001's potential, particularly as a monotherapy for patients with advanced lymphomas, most of whom had failed at least 3 prior lines of therapy. We observe encouraging anti-tumor activity in both HLs and NHLs, especially the ORR of 76.9% among the 13 evaluable patients with advanced B-cell lymphoma at DL8 (125 μg/kg). As we move forward with our Phase 1b study, we will further evaluate and optimize the dose. Given CS5001's initial efficacy in both aggressive and indolent lymphomas, we are confident in its broad clinical potential and significant market competitiveness. We remain committed to accelerate the clinical development of CS5001 in bringing this novel therapy to lymphoma patients as soon as possible." Patient baseline characteristics A total of 33 patients with advanced B-cell lymphoma were enrolled, including 17 diffuse large B-cell lymphoma (DLBCL), 11 HLs, 2 follicular lymphoma (FL), 1 mantle cell lymphoma (MCL), 1 marginal zone lymphoma (MZL), and 1 high-grade B-cell lymphoma (HGBCL). Among them, 84.8% were Asian, and the rest were non-Asian. 81.8% of the patients had received at least 3 prior lines of systemic anti-tumor therapy. In the DL8 cohort, patients who had previously received CART and hematopoietic stem cell transplantation therapy each accounted for over 20%. Safety and tolerability Dose escalation has been completed and no DLT has been reported up to DL10 so far. Efficacy Results CS5001 demonstrated encouraging anti-tumor activity in B-cell lymphomas, with an ORR of 48.4% across all dose levels; a notably higher ORR of 76.9% was observed at DL8 (125 μg/kg) among 13 evaluable patients. Hodgkin Lymphoma (HL): objective responses were observed from effective dose of DL5 (50 μg/kg) and above, including 3 complete responses (CRs) and 3 partial responses (PRs) among 10 evaluable patients at DLs 5-9 (ORR: 60.0%). 2 CRs and 1 PR were observed at DL8 (125 μg/kg) among 3 evaluable patients. Non-Hodgkin Lymphoma (NHL): objective responses were observed from effective dose of DL7 (100 μg/kg) and above, including 3 CRs (2 DLBCL and 1 MCL) and 6 PRs (3 DLBCL, 1 MZL, 1 HGBC and 1 FL) among 16 evaluable patients at DLs 7-9 (ORR: 56.3%). A notably higher ORR of 70.0% was observed at DL8 (125 μg/kg) among 10 evaluable patients. The global multicenter Phase 1 trial of CS5001 are currently in progress in the United States, Australia, and China. Dose escalation has been completed. Backfilling at DL8 (125 μg/kg) or DL9 (156μg/kg) is still ongoing. A Phase 1b dose-expansion study with potential for registration across multiple tumor types is expected to be initiated soon. Conference Call and Webcast CStone will host a conference call and webcast to discuss this announcement on December 9, 2024, at 10:00 AM Beijing Time. The conference call can be accessed via this link: About CS5001 (ROR1 ADC) CS5001 is a clinical-stage antibody-drug conjugate ("ADC") targeting ROR1 (receptor tyrosine kinase-like orphan receptor 1). CS5001 has been uniquely designed with proprietary tumor-cleavable linker and pyrrolobenzodiazepine ("PBD") prodrug. Only after reaching the tumor, the linker and prodrug are cleaved to release the PBD toxin, resulting in lethal DNA cross-links in cancer cells. The use of the linker plus PBD prodrug effectively helps address the toxicity associated with traditional PBD payloads, leading to a better safety profile. CS5001 has demonstrated complete tumor suppression in several preclinical cancer models and demonstrated favorable serum half-life and pharmacokinetic characteristics. CS5001 is a promising candidate drug with precision treatment potential in both hematologic tumors and malignant solid tumors. Additionally, CS5001 utilizes site-specific conjugation for a precise drug antibody ratio of which enables homogeneous production and large-scale manufacturing. In October 2020, CStone signed a licensing agreement with LigaChem Biosciences, Inc. (LCB) for the development and commercialization of CS5001 which was originally generated by collaboration of LCB and ABL Bio, both South Korea-based leading biotech companies. Under the agreement, CStone obtains the exclusive global right to develop and commercialize CS5001 outside the Republic of Korea. Preliminary data from the first-in-human study presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting demonstrated that CS5001 is well-tolerated and exhibits encouraging anti-tumor activity across various dose levels in patients with heavily pre-treated advanced solid tumors and lymphomas. About CStone CStone (HKEX: 2616), established in late 2015, is an innovation-driven biopharmaceutical company focused on the research and development of anti-cancer therapies. Dedicated to addressing patients' unmet medical needs in China and globally, the Company has made significant strides since its inception. To date, the Company has successfully launched 4 innovative drugs and secured approvals for 16 new drug applications (NDAs) covering 9 indications. The company's pipeline is balanced by 18 promising candidates, featuring potentially first-in-class or best-in-class antibody-drug conjugates (ADCs), multispecific antibodies, immunotherapies and precision medicines. CStone also prides itself on a management team with comprehensive experiences and capabilities that span the entire drug development spectrum, from preclinical and translational research to clinical development, drug manufacturing, business development, and commercialization. For more information about CStone, please visit . Forward-looking statements The forward-looking statements made in this article only relate to events or information as of the date when the statements are made in this article. Except as required by law, we undertake no obligation to update or publicly revise any forward-looking statements, whether as a result of new information, future events or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. All statements in this article are made on the date of publication of this article and may change due to future developments. Disclaimer: only for communication and scientific use by medical and health professionals. SOURCE CStone Pharmaceuticals WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

欢迎关注凯莱英药闻 近日，基石药业在第 66 届美国血液学会年会（ASH 2024）上，披露CS5001单药治疗晚期淋巴瘤的最新临床数据。CS5001是一款以受体酪氨酸激酶样孤儿受体1（ROR1）为靶点的抗体偶联药物（ADC），也是首个在实体瘤和淋巴瘤中均观察到临床疗效的ROR1 ADC，具有潜在“同类最佳”的治疗潜力。 关于最新研究数据 本次披露的最新进展的试验是一项首次人体 (FIH) 1a/1b 期研究，以评估 CS5001 在晚期 B 细胞淋巴瘤和实体瘤患者中的安全性、药代动力学特征和抗肿瘤活性。入组的33 名晚期 B 细胞淋巴瘤患者（11 名霍奇金淋巴瘤 [HL] 和 22 名非霍奇金淋巴瘤[NHL]）无论 ROR1 表达状态如何，均接受了 6 个剂量水平 (DL)（33.5 至 156 μg/kg）的治疗。 结果显示： 在疗效上， 所有剂量水平的客观缓解率 (ORR) 为 48.4%；在 13 名可评估患者中，DL8 (125 μg/kg) 的 ORR 明显更高，为 76.9%。 对于HL，从DL5（50 μg/kg）及以上剂量观察到客观缓解，其中10例可评估DL 5-9患者中有3例完全缓解（CR）和3例部分缓解（PR）（ORR：60.0%）。在3例可评估患者中，从DL8（125 μg/kg）剂量观察到2例CR和1例PR。 对于NHL，从DL7（100 μg/kg）及以上剂量观察到客观缓解，其中16例可评估DL 7-9患者中有3例CR和6例PR（ORR：56.3%）。在 10 名可评估患者中，DL8（125 μg/kg）的 ORR 明显较高，为 70.0%。 在安全性上， 32 名 (97.0%) 患者至少经历了一次治疗引起的不良事件 (TEAE)；17 名 (51.5%)患者出现 ≥ 3 级 TEAE。最常见的 (≥20%) TEAE 是贫血 (n=15, 45.5%)、AST 升高 (n=11, 33.3%)、低钾血症 (n=9,27.3%)、食欲下降 (n=8, 24.2%)、白细胞计数减少 (n=8, 24.2%)、GGT 升高、发热、血小板计数减少、低蛋白血症 (n=7, 各 21.2%)。 29 名 (87.9%) 患者发生治疗相关TRAE；15 名 (45.5%)患者发生 ≥ 3 级 TRAE。最常见 (≥20%) TRAE 为贫血 (n=13, 39.4%)、AST 升高 (n=10, 30.3%)、食欲下降 (n=8, 24.2%) 和白细胞计数减少 (n=8, 24.2%)。 关于CS5001 CS5001由人类抗 ROR1 IgG1 单克隆抗体组成，该抗体具有独特的设计，使用肿瘤特异激活的吡咯并苯二氮卓（pyrrolobenzodiazepine, PBD）前毒素载荷（Payload）和连接子(linker)。2020年10月，基石药业以3.5亿美元的总金额与LegoChem Biosciences达成合作，获得了CS5001在韩国以外的权益。 CS5001只在到肿瘤，被肿瘤细胞内吞后，在溶酶体中其连接子被在肿瘤细胞中高表达的特异性酶切割释放PBD前毒素，继而PBD前毒素在肿瘤细胞内被激活，从而杀死肿瘤细胞。这种连接子加前毒素的“双控”机制有效地减少与传统PBD载荷有关的毒性问题，而获得更大的安全窗口。此外，CS5001利用定向偶联技术获得精准的药物抗体比率（DAR），便于实现均质生产及大规模生产。 临床前研究表明，CS5001 在各种淋巴瘤和实体瘤模型中均具有强效抗肿瘤活性。 根据2024 ASCO披露的CS5001的Ⅰ期数据，显示该药物在前九个剂量水平（7至156 μg/kg）的剂量限制性毒性（DLT）的评估中，未观察到DLT，且未达到最大耐受剂量（MTD）。已观察到的药物相关不良事件大多为1级或2级（评价标准NCI-CTCAE v5.0），表明CS5001针对多线经治的晚期实体瘤和淋巴瘤均能表现出良好的耐受性和安全性。药代动力学数据表明CS5001的暴露量与剂量成正比，且ADC和总抗体的暴露量相似，表明CS5001 ADC在血液循环中具有出色的稳定性。 目前，CS5001的全球多中心试验在美国、澳大利亚和中国同步进行。公司将于近期启动涵盖多瘤种、具有注册潜力的1b期剂量扩展研究。 关于靶向ROR1 ADC 人源ROR1包含细胞外部分、跨膜区和细胞内区域；细胞外部分包括免疫球蛋白样结构域（IG）、富含半胱氨酸结构域（CRD）和Kringle结构域（KD）。CRD通过与配体Wnt5a结合来调节非经典WNT信号传导，KD介导ROR1与其他受体如ROR2的相互作用。细胞内部分包括一个酪氨酸激酶结构域、两个富含丝氨酸/苏氨酸的结构域和一个富含脯氨酸的结构域，富含脯氨酸的结构域通过募集SH3结构域来激活细胞迁移和增殖信号。富含丝氨酸/苏氨酸的结构域与衔接蛋白发生物理相互作用减少凋亡。 ROR1可通过介导非经典Wnt信号通路的信号传递，在多种生理过程中发挥重要作用，其中包括调节细胞分裂、增殖、迁移和细胞趋化。Wnt5a是典型的非经典Wnt信号通路的激活因子，参与NF-κB亚基p65的磷酸化，激活肿瘤细胞中NF-κB通路，促进细胞迁移和侵袭、EMT、癌转移等。作为Wnt5a的受体，ROR1参与激活肿瘤细胞NF-κB通路。 在儿童和成人阶段，ROR1在正常组织中表达量很低或几乎不表达，但在多种实体瘤和血液瘤中却存在差异化的高度表达；多项研究发现，ROR1在其他血液学恶性肿瘤、弥漫性大B细胞淋巴瘤、滤泡性淋巴瘤和边缘带淋巴瘤中表达异常。此外，在多种实体瘤中，ROR1已被证明与癌细胞存活和增殖有关。 目前已开发的靶向ROR1抗癌疗法，包括单克隆抗体、抗体偶联药物、双特异性抗体以及CAR-T疗法等多种治疗模式。据不完全统计，目前在研靶向ROR1 ADC约二十余种。 关于基石药业 基石药业成立于2015年底，是一家专注于抗肿瘤药物研发的创新驱动型生物医药企业。截至目前，公司已成功上市4款创新药、获批18项新药上市申请（NDA）以及9项适应症；当前研发管线均衡配置了潜在同类首创或同类最佳的ADC、多特异性抗体、以及免疫疗法和精准治疗药物在内的16款候选药物。 2024年8月，基石药业公布2024年中期业绩，2024年上半年收入达 2.5亿元，归母净利润达1570 万元，现金储备达8.1亿元。 放眼2024 年下半年及2025 年，公司催化较多；其中，舒格利单抗在欧洲和英国一线治疗Ⅳ期NSCLC 的MAA正式批准，预计将在包括西欧在内的多个其他国家和地区建立商业化合作。CS5001 在国际学术会议上披露临床安全性及疗效数据，于2024 年启动具有注册潜力的Ⅰb 期试验；其中多款创新品种，如CS2009（PD-1、CTLA-4和VEGFA三抗）、CS5006（ITGB4 ADC）、CS5005（SSTR2 ADC）、CS5007（EGFR/HER3 ADC）、CS2011/CS5007等均有望于2024年或2025年提交IND申请。 参考资料 1、公司官网 2、西南证券 感谢关注、转发，转载授权、加行业交流群，请加管理员微信号“hxsjjf1618”。 “在看”点一下