Kalivir Immunotherapeutics, Inc.

Novel oncolytic immunotherapy being evaluated via IV and intratumoral delivery, both as monotherapy and in combination with checkpoint inhibitors PITTSBURGH, PA, USA I October 08, 2024 I KaliVir Immunotherapeutics, Inc. , a clinical-stage biotechnology company developing cutting-edge, multi-mechanistic oncolytic viral immunotherapy therapeutics, today announced that the first patient has been dosed in its STEALTH-001 study, a Phase 1/1b clinical trial of VET3-TGI for patients with incurable, advanced solid tumors. VET3-TGI is a novel oncolytic immunotherapy which is designed to target and selectively kill tumor cells while also expressing an immuno-stimulatory transgene payload consisting of interleukin-12 and a TGFbeta inhibitor. “The dosing of our first patient in the STEALTH-001 study marks a significant milestone for KaliVir and our innovative VET3-TGI program,” said James Burke, M.D., Chief Medical Officer of KaliVir Immunotherapeutics. “The unique engineering of this platform to selectively target the tumor even in the face of anti-viral immunity holds great promise in delivering potent immune stimulatory cargo intravenously in patients with advanced solid tumors. Both VET3-TGI monotherapy and combination with checkpoint inhibition will be explored in this initial study.” About the STEALTH-001 Clinical Trial STEALTH-001 (ClinicalTrials.gov No. NCT06444815) is a dose escalation and expansion study with VET3-TGI administered by direct injection into tumor(s) or by intravenous infusion. The dose escalation will determine the highest tolerated dose of VET3-TGI when injected directly into the tumor(s), given intravenously and when combined with the checkpoint blockade. Once the maximum tolerated dose is found for each of these groups, expansion cohorts will be initiated to further evaluate the safety and efficacy of VET3-TGI. The study is enrolling patients with pathologically confirmed, advanced, unresectable or metastatic solid tumors. “VET3-TGI has the potential to reshape our approach to treating advanced tumors and provide a new path forward for patients who urgently need better treatment options,” said Jorge Nieva, M.D., Associate Professor of Clinical Medicine at the Keck School of Medicine of the University of Southern California and Section Head of Lung and Head/Neck Tumors at the Norris Comprehensive Cancer Center and a member of KaliVir’s Medical Advisory Board. “This is a pivotal milestone and I look forward to seeing the continued progress of VET3-TGI as a monotherapy and in combination with checkpoint inhibitor therapy.” About KaliVir Immunotherapeutics, Inc. KaliVir Immunotherapeutics is a clinical-stage biotechnology company at the forefront of developing next-generation oncolytic immunotherapies. By harnessing the unique advantages of the vaccinia platform, KaliVir engineers optimized viral backbones to create innovative candidates for cancer treatment. The Company’s proprietary Vaccinia Enhanced Template (VET™) platform integrates multiple genetic modifications, allowing for the systemic delivery of oncolytic vaccinia candidates and the targeted expression of therapeutic transgenes within tumors. The Company is actively expanding its pipeline using the VET™ platform, with its capabilities validated through strategic global partnerships with Astellas Pharma and Roche. Currently, the Company has two product candidates in Phase 1 clinical trials: ASP1012, exclusively licensed and led by Astellas Pharma, and its internal lead candidate, VET3-TGI. With multiple therapeutic candidates progressing through clinical development, KaliVir is positioned as a leader in innovative cancer therapies. Headquartered in Pittsburgh, Pennsylvania, KaliVir is committed to revolutionizing cancer treatment. For more information, visit kalivir.com . SOURCE: KaliVir Immunotherapeutics

▎药明康德内容团队编辑 本期看点 1. 用于治疗脑海绵状血管畸形（CCM）的ROCK2抑制剂OV888/GV101胶囊在1期临床试验中取得积极结果。 2. T细胞受体（TCR）T细胞疗法SCG142的IND申请获美国FDA批准，该疗法适用于人乳头瘤病毒（HPV）导致的多种恶性肿瘤。 3. 白细胞介素-2（IL-2）突变蛋白HM16390的IND申请获美国FDA批准。在大肠癌动物模型中，该疗法使模型动物获得了完全缓解（CR），且再次将肿瘤细胞注入该模型后，数月内癌症没有复发。 药明康德内容团队整理 OV888/GV101：公布1期临床试验数据 Ovid Therapeutics公司和Graviton Bioscience公司公布其OV888/GV101胶囊在针对健康受试者开展的1期临床试验中的安全性、耐受性和药代动力学结果。OV888/GV101胶囊是一种高选择性的强效ROCK2抑制剂。对ROCK2通路进行适当调节已被证明对血管内皮功能非常重要，因为该通路的异常激活已被证明是中枢神经系统疾病发病机制的关键组成部分，包括出血以及脑和脊髓病变的形成。临床前研究表明，OV888/GV101胶囊能够穿越血脑屏障，对ROCK2具有高度选择性。 该1期研究达到了目标，OV888/GV101胶囊显示出良好的安全性和耐受性，未发生严重不良事件。次要终点结果显示，在目标临床剂量下，OV888/GV101胶囊达到了目标药代动力学特征，支持每日一次给药。此外，OV888/GV101胶囊在受试者体内具有生物活性，并在计划的治疗剂量范围内产生了剂量依赖性的药效学效应。Ovid公司和Graviton公司计划在今年晚些时候针对脑海绵状血管畸形患者开展OV888/GV101胶囊的2期临床研究。 SCG142：IND申请获得FDA许可 星汉德生物（SCG Cell Therapy）宣布，美国FDA已批准其全新一代HPV特异性TCR-T细胞疗法SCG142的1/2期IND申请。SCG142正在被开发用于治疗HPV相关实体瘤患者。 SCG142是利用星汉德生物专有的GianTCR技术平台筛选分离天然高亲和力HPV特异性TCR，并与嵌合开关受体相结合的TCR-T细胞疗法。和传统TCR-T细胞疗法相比，SCG142可显著提升T细胞增殖能力和肿瘤抑制作用，对HPV-16和HPV-52基因型相关宫颈癌等多种肿瘤具有特异性的肿瘤杀伤作用，适用于HPV导致的多种恶性肿瘤，包括宫颈癌、口咽癌、头颈癌、阴道癌、外阴癌和阴茎癌等。在临床前研究中，SCG142在HPV相关肿瘤模型中表现出优异的抗肿瘤活性和良好的安全性。 HM16390：IND申请获得韩国食品药品安全部许可 韩美制药（Hanmi Pharmaceutica）宣布，美国FDA已批准其免疫抗癌剂IL-2突变蛋白HM16390的IND申请。该公司计划在针对晚期或转移性实体瘤患者的1期临床试验中评估HM16390的安全性、耐受性、药代动力学和药效学特征。 HM16390通过免疫细胞分化和增殖调节免疫功能。该疗法加强了IL-2βR（CD122）结合力以提高抗肿瘤效果，优化了IL-2αR（CD25）结合力来改善安全性。在免疫原性较低的恶性黑色素瘤动物模型中，接受HM16390治疗后，肿瘤的生长受到抑制，模型动物的生存期延长。在大肠癌动物模型中观察到肿瘤完全缓解，当再次将肿瘤细胞注入该模型时，肿瘤特异性T细胞被激活，数月内癌症没有复发。此外，在肾癌、胰腺癌动物模型中也确认了其抗肿瘤效果。HM16390有望大幅增加肿瘤渗透淋巴细胞（TIL），使肿瘤微环境从对免疫检查点抑制剂没有应答的“冷肿瘤”转变为能产生免疫反应的“热肿瘤”。 BGC515：1期临床试验完成首例患者给药 BridGene Biosciences公司宣布，其新型口服共价TEAD抑制剂BGC515用于治疗晚期实体瘤患者的1期临床试验已为首例患者用药。Hippo通路是细胞通过调节转录因子YAP和TAZ的活性来控制一组基因表达的关键通路。多种人类癌症依赖于YAP和TAZ的活化，而活化的机制多种多样。TEAD能够与YAP和TAZ组成复合物，BGC515能够通过抑制TEAD发挥抗肿瘤作用。 该1期研究在美国和中国同时招募受试者，旨在评估BGC515作为单药在晚期实体瘤患者中的安全性、耐受性、药代动力学、药效学和初步的抗肿瘤活性，涉及癌种包括恶性间皮瘤、上皮样血管内皮细胞瘤和其他hippo通路失调的实体瘤患者。 NXC680：IND申请获得韩国食品药品安全部许可 Nextgen Bioscience公司宣布，其小分子autotaxin抑制剂NXC680的1期IND申请已获得韩国食品药品安全部的批准，该药物正在开发用于治疗特发性肺纤维化（IPF）。NXC680能够选择性地抑制与多种纤维化疾病有关的autotaxin，从而抑制导致肺纤维化的胶原蛋白的过度生成，并阻断炎症反应。2023年1月，NXC680被美国FDA授予孤儿药资格。 YH35995：IND申请获得韩国食品药品安全部许可 Yuhan公司宣布，其用于治疗戈谢病的葡糖神经酰胺合成酶（GCS）抑制剂YH35995的1期IND申请获得了韩国食品药品安全部的批准。这项1期临床试验旨在评估健康成年男性口服YH35995后的安全性、耐受性、药代动力学、药效学和其他特征。 戈谢病是一种溶酶体贮积病，由基因突变导致的某些酶缺乏引起。YH35995是一种小分子GCS抑制剂，可降低葡萄糖神经酰胺（GL1）的产生，相当于底物减少疗法（SRT）。临床前研究证实了YH35995的有效性、安全性和脑渗透性。与现有治疗剂相比，YH35995可以更有效、更长时间地抑制大脑中GL1的水平。该公司预计YH35995对3型戈谢病患者尤其有益。 VET3-TGI：IND申请获得FDA许可 KaliVir Immunotherapeutics公司宣布，美国FDA已经批准了VET3-TGI的IND申请，可开展VET3-TGI单药或联合免疫检查点抑制剂治疗无法治愈的晚期实体瘤的1/1b期临床试验STEALTH-001。VET3-TGI是一种新型溶瘤免疫疗法，在非临床研究中，它通过表达由白细胞介素-12（IL-12）和TGFβ抑制剂转基因组成的治疗载荷，特异性地直接靶向并优先杀死肿瘤细胞，同时刺激抗癌免疫反应。 RTX001：获批在英国启动1/2期临床试验 Resolution Therapeutics公司宣布，其主要候选药物RTX001已获得英国药品和健康产品管理局（MHRA）的批准，可以开始1/2期EMERALD研究，预计最早于2024年第三季度启动。RTX001是一种工程化自体巨噬细胞疗法，旨在增强对终末期肝病患者的抗纤维化和抗炎效果。该候选产品采用已知可在巨噬细胞中表达的治疗基因的独特组合，旨在增强该疗法的固有再生特性，从而实现优异的疗效和持久性。 ▲欲了解更多前沿技术在生物医药产业中的应用，请长按扫描上方二维码，即可访问“药明直播间”，观看相关话题的直播讨论与精彩回放 参考资料（可上下滑动查看） [1] 星汉德生物全新一代TCR-T细胞疗法SCG142在美获批1/2期临床试验. Retrieved July 2, 2024, from https://www.prnasia.com/story/452623-1.shtml [2] Resolution Therapeutics Receives MHRA Approval to Commence Phase I/II EMERALD Study for Lead Candidate RTX001. Retrieved July 2, 2024, from https://www.prnewswire.com/news-releases/resolution-therapeutics-receives-mhra-approval-to-commence-phase-iii-emerald-study-for-lead-candidate-rtx001-302183655.html [3] 한미약품, ‘차세대 IL-2’ 고형암 1상 “FDA, IND 승인”. Retrieved July 2, 2024, from http://www.biospectator.com/view/news_view.php?varAtcId=22380 [4] KaliVir Immunotherapeutics Announces FDA Clearance of Investigational New Drug (IND) for Oncolytic Immunotherapy VET3-TGI for Solid Tumors. Retrieved July 2, 2024, from https://www.businesswire.com/news/home/20240701304127/en [5] BridGene Biosciences Announces Dosing of First Patient in Phase 1 Study Evaluating Novel TEAD Inhibitor BGC515 in Advanced Solid Tumors. Retrieved July 2, 2024, from https://www.prnewswire.com/news-releases/bridgene-biosciences-announces-dosing-of-first-patient-in-phase-1-study-evaluating-novel-tead-inhibitor-bgc515-in-advanced-solid-tumors-302185160.html [6] Ovid Therapeutics and Graviton Bioscience Announce Topline Data from a Phase 1 Clinical Trial Studying OV888/GV101 Capsule, a Potential First-In-Class Therapy for Cerebral Cavernous Malformations. Retrieved July 2, 2024, from https://www.globenewswire.com/news-release/2024/07/01/2906636/0/en/Ovid-Therapeutics-and-Graviton-Bioscience-Announce-Topline-Data-from-a-Phase-1-Clinical-Trial-Studying-OV888-GV101-Capsule-a-Potential-First-In-Class-Therapy-for-Cerebral-Cavernous.html [7] 넥스트젠, ‘오토택신 저해제’ IPF 1상 “국내 IND 승인”. Retrieved July 2, 2024, from http://www.biospectator.com/view/news_view.php?varAtcId=22369 [8] 유한양행, “첫 희귀” 고셔병 신약 “국내 1상 IND 승인”. Retrieved July 2, 2024, from http://www.biospectator.com/view/news_view.php?varAtcId=22365 免责声明：药明康德内容团队专注介绍全球生物医药健康研究进展。本文仅作信息交流之目的，文中观点不代表药明康德立场，亦不代表药明康德支持或反对文中观点。本文也不是治疗方案推荐。如需获得治疗方案指导，请前往正规医院就诊。 版权说明：本文来自药明康德内容团队，欢迎个人转发至朋友圈，谢绝媒体或机构未经授权以任何形式转载至其他平台。转载授权请在「药明康德」微信公众号回复“转载”，获取转载须知。 分享，点赞，在看，聚焦全球生物医药健康创新

Phase 1/1b study of VET3-TGI, alone and in combination with checkpoint inhibitor therapy, for advanced solid tumors PITTSBURGH--(BUSINESS WIRE)-- KaliVir Immunotherapeutics, Inc., a biotech company developing cutting-edge, multi-mechanistic oncolytic viral immunotherapy programs, today announced that the FDA has cleared the Investigational New Drug (IND) application for the STEALTH-001 study of VET3-TGI in patients with incurable, advanced solid tumors. VET3-TGI is a novel oncolytic immunotherapy which in nonclinical studies specifically targets and preferentially kills tumor cells directly while stimulating anti-cancer immunity by expressing its therapeutic payload consisting of the transgenes for interleukin-12 and a TGFbeta inhibitor. The Phase 1/1b study (ClinicalTrials.gov ID NCT06444815) will evaluate the safety pro efficacy of VET3-TGI when administered through intravenous infusion or intratumoral injection in patients with advanced, incurable solid tumors. The trial will assess VET3-TGI both as a monotherapy and in combination with checkpoint inhibitor therapy. “The initiation of this Phase 1/1b clinical study marks a pivotal moment in our continued journey to redefine cancer treatment with oncolytic virus therapy and combat advanced, unresectable or metastatic solid tumors,” said Helena Chaye, Ph.D., CEO of KaliVir Immunotherapeutics. “This marks our second initiation of a clinical trial from the VET platform, having announced in 2023 the progress with ASP1012 exclusively licensed to Astellas. We remain fully committed to pushing the boundaries on what is possible with cancer therapies and develop safer, more effective options that have the potential to transform the treatment landscape of oncology.” About KaliVir Immunotherapeutics, Inc. KaliVir Immunotherapeutics is a privately held biotech company developing cutting-edge, multi-mechanistic oncolytic viral immunotherapy programs. The company has developed a unique vaccinia virus-based platform, Vaccinia Enhanced Template “VET” Platform, that can generate potent novel oncolytic vaccinia viruses with modifications to maximize viral replication and to enhance intravenous delivery and spread. VET™ platform utilizes the large transgene capacity of the vaccinia virus to deliver therapeutics matched to tumor immunophenotypes to stimulate patients’ immune systems and modify the tumor microenvironment. KaliVir’s oncolytic virus candidates are designed to be safe, potent and systemically deliverable to treat cancer patients across multiple tumor types. KaliVir has separate collaborations with Roche and Astellas Pharma to design and generate novel oncolytic vaccinia viruses derived from the VET™ platform. In addition, Astellas entered into a world-wide exclusive license to develop and commercialize KaliVir’s initial lead clinical candidate VET2-L2 oncolytic vaccinia virus. KaliVir is currently advancing multiple therapeutic candidates toward the clinic. For more information, please visit kalivir.com.