GV-101

▎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

The Phase 1 study for OV888/GV101 capsule met its objective, demonstrating a favorable safety and tolerability pro no serious adverse events Secondary endpoint results indicate that the target pharmacokinetic pro achieved at the targeted clinical dose, supporting once daily dosing OV888/GV101 capsule was shown to be biologically active in participants and elicited dose-dependent pharmacodynamic effects within the planned therapeutic dose range A Phase 2 study for the treatment of cerebral cavernous malformations is expected to initiate in the second half of 2024 NEW YORK, July 01, 2024 (GLOBE NEWSWIRE) -- Ovid Therapeutics Inc. (NASDAQ: OVID), a biopharmaceutical company dedicated to improving the lives of people affected by rare epilepsies and brain conditions, and Graviton Bioscience Corporation, a privately held clinical-stage biotechnology company focused on developing Rho-associated coiled-coil containing protein kinase 2 (ROCK2) inhibitors and other innovative therapeutic compounds, today announced the results from their Phase 1 healthy volunteer study evaluating the safety, tolerability, and pharmacokinetic (PK) pro multiple ascending doses of OV888/GV101 capsule. Ovid and Graviton plan to progress to a Phase 2 clinical study in cerebral cavernous malformations (CCM) later this year. “The safety data support progression to a proof-of-concept study in people with CCM, a community that has no FDA-approved pharmacologic treatment available today. The standard of care for people diagnosed with CCM is often ‘watchful waiting’ or high-risk brain surgery for eligible symptomatic patients. We hope to bring an oral, potentially first-in-class, highly selective ROCK2 inhibitor to this community,” said Dr. Jeremy Levin, D.Phil, MB BChir., Chairman and CEO of Ovid Therapeutics. “Our collaboration with Graviton Bioscience is both successful and exciting. We are unpacking the therapeutic potential of inhibiting ROCK2. This mechanism of action has broad potential applications in multiple additional neurovascular and neuro-inflammatory conditions, which we look forward to pursuing together in the future.” “Today’s data reinforce our conviction that OV888/GV101 capsule has the potential to become the first oral treatment for CCM,” said Samuel Waksal, Ph.D., CEO and founder of Graviton. “Based on nonclinical data, we believe the highly selective inhibition of ROCK2 by OV888/GV101 capsule could have a three-pronged effect in CCM: firstly, to restore the barrier function of brain endothelial cells and prevent future bleeds; secondly, to reduce inflammation; and thirdly, to stop consequent fibrosis in the lesions.” Summary of Phase 1 Topline Findings The Phase 1 study was a single-center, double-blinded, randomized, placebo-controlled, multiple ascending dose (MAD) trial to evaluate the safety, tolerability, and PK pro OV888/GV101 capsule in healthy adult volunteers. OV888/GV101 capsule or placebo was administered once daily for seven days. The MAD cohorts evaluated doses of 100 mg, 200 mg, 400 mg, and 600 mg. OV888/GV101 capsule met the study’s primary safety and tolerability objectives and characterized its PK properties. Well tolerated at all tested doses. There were no serious adverse events (SAEs) and no participants met the preset trial stopping criteria. All drug-associated clinical adverse events (AEs) were mild (Grade 1) and resolved. The most commonly reported clinical AE was headache, which occurred in 23% of participants. All participants reporting headaches had transient cases, which resolved. One subject discontinued the study early due to mild headache and nausea, which resolved after study drug discontinuation. Most clinical AEs resolved within 24 hours, all resolved within the study period. There were no AEs reported in the placebo cohort. Target engagement achieved. There was a dose dependent decrease in proinflammatory cytokines IL-17 and IL-21 secretion by stimulated peripheral blood mononuclear cells. These decreases are markers of selective ROCK2 inhibition. These findings indicate that OV888/GV101 is biologically active in humans at the target clinical dose and elicits a pharmacodynamic response. Exposure and half-life findings supportive of daily dosing. Topline data show a dose dependent increase in Cmax and AUC0-24 up to the 400 mg target dose. The average half-life is approximately 12 hours suggesting that OV888/GV101 capsule may be well suited for once daily dosing. Laboratory results. In the study period, there were two asymptomatic laboratory findings rated Grade 2 or higher, which occurred in at least 5% of treated subjects relative to placebo. Increases in total bilirubin without direct hyperbilirubinemia were reported in 30% of participants. These elevations were clinically insignificant and are consistent with the understood effect of ROCK2 inhibition on UGT1A1 enzyme. Importantly, no concurrent liver enzyme elevations were observed. Creatine phosphokinase elevations without muscle pain or weakness were reported in 7% of participants. There were no reported related clinical impacts for either laboratory finding, and all participants normalized during the study period. Ovid and Graviton expect to initiate a Phase 2 proof-of-concept study in people living with CCMs in the second half of 2024. Additionally, under the collaboration agreement between Ovid and Graviton, the parties have agreed to develop an intravenous formulation of OV888/GV101 for undisclosed neurological indications. About Cerebral Cavernous Malformations CCMs are one of the most common vascular malformations in the central nervous system (CNS), with a prevalence of approximately 400,000 symptomatic individuals in the seven major markets. CCMs are clusters of abnormal mulberry-shaped blood vessels with thin walls. CCMs can cause blood to leak into the brain, resulting in a variety of symptoms, including: headaches, seizures, and other focal neurological deficits. Surgical resection is the only recommended treatment for CCM hemorrhage, as there are no approved pharmacological treatments. However, surgical intervention is dependent on the location of the lesion and is not an option for many individuals with CCM. About OV888/GV101 Capsule OV888/GV101 capsule is a highly selective and potent inhibitor of ROCK2. Proper regulation of ROCK2 pathway has been shown to be important for vascular endothelial function, as abnormal activation of this pathway has been demonstrated to be a key component of CCM pathogenesis, including bleeding and formation of lesions in the brain and the spinal cord. In preclinical studies, OV888/GV101 capsule has been shown to be blood-brain-barrier penetrant and highly selective for ROCK2. OV888/GV101 capsule has the potential to be a first- and best-in-class oral therapy for CCM and other rare CNS diseases. About Graviton Bioscience Corporation Graviton Bioscience Corporation is a clinical-stage drug discovery and development company, dedicated to engineering and developing best-in-class therapeutics for treating CNS, autoimmune, fibrotic, and other serious diseases where ROCK2 and its other therapeutic compounds play a pivotal role in pathology. Graviton's first drug candidate, GV101, is in clinical studies, with additional assets advancing through the preclinical pipeline. Leading Graviton is Dr. Samuel Waksal, the founder, and former Chairman and CEO of Kadmon Pharmaceuticals (acquired by Sanofi). Dr. Waksal is also the founder and former CEO of ImClone Systems (acquired by Eli Lilly) and a founder of MeiraGTx. For more information, please visit . About Ovid Therapeutics Ovid Therapeutics Inc. is a New York-based biopharmaceutical company that is dedicated to meaningfully improving the lives of people affected by certain epilepsies and brain conditions with seizure symptoms. The Company is advancing a pipeline of novel, targeted small molecule candidates that modulate the intrinsic and extrinsic factors involved in neuronal hyperexcitability causative of seizures and other neurological symptoms. Ovid is developing: OV888/GV101 capsule, a potent and highly selective ROCK2 inhibitor capsule, for the potential treatment of cerebral cavernous malformations and other rare CNS diseases; OV329, a GABA-aminotransferase inhibitor, a potential therapy for treatment-resistant seizures; and OV350, a direct activator of the KCC2 transporter, for the potential treatment of epilepsies and other psychiatric conditions. For more information about these and other Ovid research programs, please visit . Forward-Looking Statements This press release includes certain disclosures by Ovid that contain “forward-looking statements,” including, without limitation: statements regarding the potential opportunity OV888/GV101 capsule, including its potential first-in-class status and the ability to become the first oral treatment for CCM; the timing of initiation and data readouts of Ovid’s Phase 2 clinical program studying OV888/GV101 capsule in CCM; expectations concerning the relationship with Graviton and the benefits thereof; the potential safety and or tolerability of OV888/GV101 capsule; the timing of potential Phase 2 studies, regulatory discussions and filings and/or regulatory decisions for OV888/GV101 capsule, and Ovid’s potential future business development opportunities and statements regarding the potential use and development of OV888/GV101 capsule, OV329, and OV350 and compounds from Ovid’s library of direct activators of KCC2. You can identify forward-looking statements because they contain words such as “advances,” “anticipates,” “could,” “demonstrates,” “expects,” “intends,” “may,” “plan,” “potential,” “promise,” and “progress,” and similar expressions (as well as other words or expressions referencing future events, conditions or circumstances). Forward-looking statements are based on Ovid’s current expectations and assumptions. Because forward-looking statements relate to the future, they are subject to inherent uncertainties, risks and changes in circumstances that may differ materially from those contemplated by the forward-looking statements, which are neither statements of historical fact nor guarantees or assurances of future performance. Important factors that could cause actual results to differ materially from those in the forward-looking statements include, without limitation, uncertainties inherent in the preclinical and clinical development and regulatory approval processes, risks related to Ovid’s ability to achieve its financial objectives, the risk that Ovid may not be able to realize the intended benefits of its technology or its business strategy, or risks related to Ovid’s ability to identify business development targets or strategic partners, to enter into strategic transactions on favorable terms, or to consummate and realize the benefits of any business development transactions. Additional risks that could cause actual results to differ materially from those in the forward-looking statements are set forth under the caption “Risk Factors” in Ovid’s Quarterly Report on Form 10-Q filed with the Securities and Exchange Commission (“SEC”) on May 14, 2024, and in future filings Ovid makes with the SEC. Any forward-looking statements contained in this press release speak only as of the date hereof, and Ovid assumes no 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. Ovid Contacts Investor Relations Garret Bonney 617-735-6093 IR@ovidrx.com Media Raquel Cabo 646-647-6553 RCabo@ovidrx.com Graviton Bioscience Contact Julia Balanova Corporate Strategy and Communications Julia.Balanova@gravitoncorp.com