IND-Enabling Toxicology for a Novel Ca2+ Channel Therapeutic to Improve Outcomes Associated with Checkpoint Inhibitor Immunotherapy

Vivreon Biosciences，LLC 卡罗尔峡谷路4940号套件110 San Diego，CA milton@vivreonbiosciences.com Vivreon Biosciences，LLC，NCI SBIR直接进入II期，NIH、CDC和FDA的小型 商业创新研究资助申请，PA-21-259 VV 2003（一种新型CRAC通道治疗剂）的IND使能毒理学，以改善相关结局 检查点抑制剂免疫疗法 项目摘要 Vivreon Biosciences很高兴申请NCI SBIR征集PA-21-259。Vivreon是一种创新的生活 该公司正在开发一种新型小分子钙通道抑制剂VV 2003，以改善 接受免疫检查点抑制剂免疫治疗的人的结果。检查点抑制剂具有 改善了许多癌症的总体生存率，但小肠结肠炎已成为最常见的剂量限制性 与这些疗法相关的毒性。检查点标记物诱导的结肠炎目前用 免疫抑制治疗，削弱了检查点抑制剂免疫治疗的肿瘤杀伤潜力 并在检查点治疗停止后施用。VV 2003是一种口服候选治疗药物， 设计用于选择性和安全地阻断检查点通道诱导的小肠结肠炎， 免疫抑制副作用预期与检查点抑制剂同时使用， 免疫疗法，将其与其他研究性疗法分开。 Vivreon寻求NCI 2期资金用于研究新药（IND）-使良好实验室规范（GLP）成为可能 毒性、安全性和遗传毒性研究。具体而言，NCI的资金将用于剂量范围发现毒性 研究、两种属GLP 28天毒性研究、GLP安全药理学和遗传毒理学、GLP 药理学呼吸安全性评估和GLP心血管遥测。本提案中的活动将 与将由Vivreon种子资助的化学制造和控制（CMC）过程并行运行 投资人。这些研究的完成将支持并写入IND申请，最后一个里程碑 正在向美国食品药品监督管理局（FDA）提交IND申请。

Vivreon Biosciences, LLC 4940 Carroll Canyon Rd. Suite 110 San Diego, CA 92121 milton@vivreonbiosciences.com Vivreon Biosciences, LLC, NCI SBIR Direct to Phase II, Omnibus Solicitation of the NIH, CDC and FDA for Small Business Innovation Research Grant Applications, PA-21-259 IND-Enabling Toxicology for VV2003, a Novel CRAC Channel Therapeutic, to Improve Outcomes Associated with Checkpoint Inhibitor Immunotherapy Project Summary Vivreon Biosciences is pleased to apply for NCI SBIR Solicitation PA-21-259. Vivreon is an innovative life sciences company that is developing a novel small molecule Ca2+ channel inhibitor, VV2003, to improve outcomes in persons undergoing immune checkpoint inhibitor immunotherapy. Checkpoint inhibitors have improved overall survival in numerous cancers, but enterocolitis has emerged as the most frequent dose-limiting toxicity associated with these therapies. Checkpoint inhibitor-induced colitis is currently treated with immunosuppressive therapy, which blunts the tumor-killing potential of the checkpoint inhibitor immunotherapy and is administered following checkpoint therapy discontinuation. VV2003 is an oral candidate therapeutic designed to selectively and safely block checkpoint inhibitor-induced enterocolitis without systemic immunosuppressive side effects. It is intended to be used concomitantly with checkpoint inhibitors, allowing immunotherapy to continue, separating it from other investigational therapies. Vivreon seeks NCI Phase 2 funding for investigational new drug (IND)-enabling good laboratory practice (GLP) toxicity, safety, and genotoxicity studies. Specifically, NCI funding will go towards dose range finding toxicity studies, two-species GLP 28-day toxicity studies, GLP safety pharmacology and genetic toxicology, GLP pharmacological respiratory safety assessment, and GLP cardiovascular telemetry. Activities in this proposal will run in parallel with chemistry manufacturing and controls (CMC) processes that will be funded by Vivreon’s Seed investor. Completion of these studies will support and be written up in an IND application, with the final milestone being IND submission to the US Food and Drug Administration (FDA).