Nofazinlimab

中国苏州，2024年10月2日——基石药业（股票代码：2616.HK），一家专注于抗肿瘤药物研发的创新驱动型生物医药企业，今日宣布，其合作伙伴恒瑞医药近日启动了CS1002/SHR-8068（抗CTLA-4单抗）联合阿得贝利单抗及贝伐珠单抗一线治疗晚期肝细胞癌（HCC）的III期临床研究。 该研究将通过评估客观缓解率（ORR）及总生存期（OS），评价CS1002/SHR-8068联合阿得贝利单抗（抗PD-L1单抗）和贝伐珠单抗（试验组）对比信迪利单抗（抗PD-1单抗）联合贝伐珠单抗（对照组）一线治疗晚期HCC患者的有效性。 CS1002是由基石药业开发的在研抗CTLA-4单克隆抗体。区别于以往CTLA-4靶点药物的是，早期开发中测试了CS1002不同剂量给药方案，并且在三个适应症中展现出令人鼓舞的疗效和安全性，为CS1002作为肿瘤免疫联合疗法的重要地位提供了概念性验证。CTLA-4是由CTLA-4基因编码的一种跨膜蛋白质。CTLA-4可通过与其配体B7.1/B7.2分子结合后抑制T细胞激活，使肿瘤细胞免受T淋巴细胞攻击。因此，阻断CTLA-4通路可刺激T细胞的活化和增殖，从而诱导或增强抗肿瘤免疫反应。CTLA-4为人类多种癌症的治疗提供了一种新的免疫治疗方法。 2021年11月，基石药业与恒瑞医药就CS1002达成在大中华地区的战略合作暨独占许可协议。依据协议条款，基石药业有资格获得总计高达约两亿美金的首付款和潜在里程碑付款，以及两位数百分比的特许权使用费。恒瑞医药获得CS1002在大中华地区研发、注册、生产和商业化的独占授权。基石药业保留CS1002在大中华地区以外地区的开发和商业化权利。 2024年2月， CS1002首次人体研究的单药以及与nofazinlimab/CS1003（抗PD-1单抗）联合治疗晚期/转移性实体瘤的安全性和有效性数据在《癌症》杂志上发表。研究结果显示，CS1002无论作为单药治疗还是与nofazinlimab联合使用，均能展示出良好的耐受性和安全性。初步疗效数据也为进一步开发以CS1002为基础的联合疗法提供了有力的临床依据。 除针对HCC的III期研究之外，2024年1月，恒瑞医药获得中国国家药品监督管理局的IND批准，用于评估CS1002/SHR-8068联合阿得贝利单抗及化疗作为一线治疗晚期或转移性非鳞状非小细胞肺癌患者的疗效。 关于基石药业 基石药业（香港联交所代码: 2616）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，致力于满足中国和全球癌症患者的殷切医疗需求。截至目前，公司已成功上市4款创新药、获批15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抗体偶联药物（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。同时，基石药业拥有一支资深管理团队，“全链条”覆盖临床前探索、临床转化、临床开发、药物生产、商务拓展、商业运营等关键环节。 如需了解有关基石药业的更多信息，请访问： www.cstonepharma.com。  投资者关系: ir@cstonepharma.com  媒体关系: pr@cstonepharma.com  前瞻性声明 本文所作出的前瞻性陈述仅与本文作出该陈述当日的事件或资料有关。除法律规定外，于作出前瞻性陈述当日之后，无论是否出现新资料、未来事件或其他情况，我们并无责任更新或公开修改任何前瞻性陈述及预料之外的事件。请细阅本文，并理解我们的实际未来业绩或表现可能与预期有重大差异。本文内所有陈述乃本文章刊发日期作出，可能因未来发展而出现变动。 声明：仅供医疗卫生专业人士交流使用。

September 27, 2024 I Cereno Scientific (Nasdaq First North: CRNO B), a pioneering biotech developing innovative treatments for rare and common cardiovascular disease, today announced positive topline results from the Phase IIa trial of CS1 in Pulmonary Arterial Hypertension (PAH). The results demonstrate that CS1 is safe, well tolerated and has positive impact on clinically relevant parameters such as risk, functional class and hemodynamics. “ I am delighted to share the topline data from the Phase IIa trial of CS1 in PAH. Key results from the study demonstrate both that the primary endpoint was met with good safety and tolerability of CS1 in patients with PAH, and, in addition, we also show a positive impact already after 12 weeks on clinical parameters meaningful to patients and regulatory authorities. These results, together with our foundation of preclinical data, strengthen our conviction that CS1 is a disease-modifying therapy for PAH. We are excited to now move forward with the next development phase with CS1. Our mission is to deliver a drug addressing the pathological remodeling which is progressing the PAH disease and to provide a valuable addition to the PAH toolbox of therapeutics ”, said Sten R. Sörensen, CEO, Cereno Scientific. Pulmonary Arterial Hypertension PAH is a debilitating and fatal disease with no spontaneous improvement. Epigenetic mechanisms through histone deacetylase (HDAC) drive disease progression and continuous deterioration. The disease pathology is defined by endothelial dysfunction, inflammation, vasoconstriction, hypertrophy and remodeling of pulmonary small arteries, leading to poor lung function, right heart failure and ultimately death. Existing treatment alternatives are insufficient and do not address the root cause of the disease. The goal of PAH treatment is to improve risk score status (measured by amongst others REVEAL risk score), symptoms and physical capacity (measured by functional class) and hemodynamics (measured by mean Pulmonary Arterial Pressure, mPAP and Pulmonary Vascular Resistance, PVR), to ultimately improve both patients’ quality of life and extend survival. “ PAH is a rare and devastating disease for patients suffering from it. Despite advances in treatment options there is still a pronounced need for effective, safe and disease-modifying therapies for these patients. The results presented today with primary endpoints met regarding safety and tolerability and supporting signs of clinical efficacy including improvement in risk score, improvement of functional class and impact on mean pulmonary pressure are promising,” said Dr. Raymond Benza, Network Director of Pulmonary Hypertension at Mount Sinai Icahn School of Medicine, New York; and Principal Investigator of the Phase IIa trial of CS1 . CS1 and the CS1-003 Phase IIa trial CS1 is an HDAC inhibitor that works through epigenetic modulation, being developed as a safe, effective and disease modifying treatment for PAH. CS1 targets the root cause of the disease, aiming to reverse the pathological vascular remodeling of the small lung arteries. CS1-003 is a Phase IIa trial evaluating the safety, tolerability, pharmacokinetics, and exploratory efficacy of CS1 on top of standard-of-care in patients with PAH. The study initially had as an objective to recruit 30 patients. In June, recruitment was stopped after the Study Clinical Steering Committee concluded that there was sufficient data for evaluating the next steps in development. The study, which was performed at 10 clinical sites in the US, randomized 25 patients to CS1 treatment, out of which 21 patients completed the treatment without protocol deviations. CS1 – Phase IIa safety data – Primary endpoint of safety and tolerability met successfully The primary endpoint of safety and tolerability was met successfully: CS1 Phase IIa – Compelling positive impact on exploratory clinical efficacy parameters Efficacy data from the three doses were pooled together due to therapeutic drug exposure (i.e. plasma concentration) also in the low dose group. CS1 showed compelling positive impact on exploratory clinical parameters already over a 12-week treatment period: “ I am very pleased with the positive outcomes we are seeing in our patients following treatment with CS1. Their improvements in health and well-being are encouraging and reflect the potential effectiveness of the therapy. The majority of my patients have expressed interest in enrolling into the Expanded Access Program. This progress reaffirms my commitment to advancing treatments that can make a meaningful difference in patients’ lives with PAH ,” said Dr. Jason Guichard , Advanced Heart Failure and Transplant Cardiology, Department of Medicine, Division of Cardiology, Prisma Health-Upstate, Assistant Professor of Medicine, University of South Carolina School of Medicine Greenville and investigator in the Phase IIa trial of CS1 in PAH. CS1 phase II a study clinical data, together with preclinical information, is consistent with reversing pathological remodeling An in-depth analysis made on a subgroup of patients with a remarkable response showed: The data from the CS1-003 trial, together with recently announced preclinical data from our HDAC inhibitor program, directly demonstrating our HDAC-inhibitor program’s dose-dependent positive impact on reverse vascular remodeling in small lung arteries, provide a basis for assuming that CS1 may act with a disease-modifying capacity in PAH. Clear path forward to develop a disease-modifying therapy for PAH​ Cereno will be initiating discussions with regulatory bodies based on these encouraging results and will progress pursuing a pivotal trial of CS1 in PAH. A comprehensive analysis of the complete CS1-003 data will be conducted, with the findings to be presented at upcoming medical conferences and published in a reputable medical journals. “ We are excited to take the next steps in our journey to make a meaningful impact for patients with PAH. Our plans include engaging with regulatory authorities to in pursuing a pivotal trial for CS1 and to continue enrolling patients in our Expanded Access Program . The CS1-003 trial demonstrated compelling signs of clinical efficacy already over a 12-week treatment period and we expect to see additional positive impact of CS1 with longer use of our drug in patients with PAH ” said Dr. Rahul Agrawal, CMO and Head of R&D, Cereno Scientific Webcast presentation on Monday, September 30 Cereno Scientific will host a webcast including a Q&A session where CEO Sten R. Sörensen, CMO and Head of R&D Dr. Rahul Agrawal, CSO Dr. Björn Dahlöf and Head of Preclinical Development, Nicholas Oakes, will present the CS1-003 topline results. Date and time: Monday, September 30, 2024, at 14:00 CET How to join: https://ir.financialhearings.com/cereno-scientific-2024 The webcast and presentation will be available on the Company’s website after the webinar at: https://cerenoscientific.com/events-presentations/ About the CS1-003 trial The CS1-003 trial titled “A Phase II, Prospective, Randomized, Open-label, Blinded Endpoint, Multicenter Study to Investigate the Safety, Tolerability, Pharmacokinetics, and Exploratory Efficacy of 3 Doses of CS1 in Subjects With Pulmonary Arterial Hypertension ” (NCT05224531) randomized adult PAH patients with WHO Functional class II or III, stable on standard of care therapy for 90 days, to one of three total daily doses of CS1; 480 mg, 960 mg or 1920 mg. Subjects were enrolled for up to 22 weeks including a treatment period of 12 weeks. The trial was conducted at 10 specialist clinics in the US. 25 patients were randomized to CS1 treatment out of which 21 patients completed the treatment without protocol deviations. The study’s primary endpoint was to evaluate the safety and tolerability of CS1 treatment in patients with PAH. Other relevant standard endpoints used in previous studies of this patient group have been measured and evaluated in an exploratory fashion. A collaboration agreement with global healthcare company Abbott has allowed Cereno to use their cutting-edge technology CardioMEMS HF System in the trial, to measure mean Pulmonary Arterial Pressure (mPAP) and other hemodynamic parameters. CS1-003 is a Phase IIa trial that is not powered for statistically significant detection or exclusion of efficacy-related parameters. On June 28, 2024, Cereno announced the decision to close patient recruitment to the Phase IIa trial CS1-003 by July 1st, 2024, after the Study Clinical Steering Committee concluded that there was sufficient data for evaluating the next steps in development. About PAH Pulmonary Arterial Hypertension (PAH) is a rare disease and diagnosed with high blood pressure in the pulmonary circulation. Globally, the disease affects approximately 10 in 100,000 people. It is a severe, debilitating disease with no spontaneous improvement. The disease is characterized by a progressive narrowing of the pulmonary arterial vessels ultimately leading to right heart failure and death. Life expectancy is 2.5 years without therapy and 7.5 years on current standard of care. PAH has a major impact on quality of life and causes shortness of breath, fatigue, chest pains, reduced ability to work, unnatural swelling, fainting and heart palpitations. This has significant implications for a patient’s physical, mental, and social well-being. There is currently no cure available for PAH with the exception of lung transplantation, which patients are often too seriously ill to undergo. Current standard of care, mainly vasodilators, improves the patient’s symptoms and involves, at best, a moderate slowing of the disease progression. There is therefore a great need for safer therapies with disease-modifying capacity that address the root causes of PAH and that can give patients an increased opportunity for an improved quality of life and a longer life. About CS1 Drug candidate CS1 is an HDAC inhibitor that works through epigenetic modulation, being developed as a treatment for the rare disease PAH. CS1 holds the potential to be an effective, safe and disease-modifying drug, targeting the root cause of the disease by reverse remodeling. In preclinical cardiovascular disease models, HDAC inhibitors have shown disease-modifying potential through reverse pathological remodeling, as well as anti-fibrotic, anti-inflammatory, pulmonary pressure-reducing, and anti-thrombotic effects. CS1’s unique efficacy profile aligns well with the underlying mechanisms of PAH, positioning it to address the critical unmet need for more effective treatment options. The goal of CS1’s development is to improve quality of life and extend survival for patients with PAH. CS1 is part of Cereno’s HDACi portfolio, untapping the potential of epigenetic modulation in CVD. CS1 has been granted orphan drug status in both the US and EU. Since January 30, 2024, CS1 is approved by the FDA for Expanded Access, as an extension of the ongoing Phase IIa trial CS1-003 evaluating CS1 in PAH. The EAP gives patients that have completed the Phase IIa trial the opportunity to, after being judged suitable and to benefit from CS1 treatment by investigators, continue CS1 treatment of PAH when no comparable or satisfactory alternative therapy options are available. The EAP allows Cereno to, under a formal FDA-approved protocol, collect safety and efficacy data from long-term exposure to CS1 in patients with PAH. As such, this initiative not only supports the treatment of PAH patients but also enables Cereno to gather additional CS1 usage documentation for regulatory discussions and Phase IIb/III pivotal study design planning. On August 30, 2024, the Company announced that the first patient had been dosed under the EAP. About Cereno Scientific AB Cereno Scientific develops innovative treatments for rare and common cardiovascular disease. The lead drug candidate, CS1, is an HDAC (histone deacetylase) inhibitor that acts as an epigenetic modulator with pressure-reducing, reverse-remodeling, anti-inflammatory, anti-fibrotic and anti-thrombotic properties. A Phase IIa trial evaluating CS1’s safety, tolerability, and exploratory efficacy in patients with the rare disease pulmonary arterial hypertension (PAH) demonstrated that CS1 was safe, well-tolerated and showed a positive impact on exploratory clinical efficacy parameters. CS1 study data, together with preclinical information, is consistent with reversing pathological remodeling. A collaboration agreement with global healthcare company Abbott allowed Cereno to use their cutting-edge technology CardioMEMS HF System in the trial. Since January 2024, we are delighted that the FDA´s Expanded Access Program will enable patients with PAH, a serious life-threatening disease condition, to gain access to CS1 where no comparable alternative therapy options are available. Cereno’s pipeline comprises two additional programs in development through research collaborations with the University of Michigan CS014 is a new chemical entity with a multi-fold mechanism of action as an epigenetic modulator – regulating platelet activity, fibrinolysis, and clot stability for the prevention of thrombosis without an increased risk of bleeding as documented in preclinical trials. The drug candidate has also demonstrated a favorable profile in preclinical models of other cardiovascular diseases, such as PAH, with reverse remodeling of pulmonary arterial vessels and effects on vascular fibrosis. On 28th of June, 2024, Cereno initiated a first-in-human Phase I trial of CS014. Preclinical candidate CS585 is an oral, highly potent and selective prostacyclin (IP) receptor agonist that has demonstrated the potential to significantly improve disease mechanisms relevant to cardiovascular disease. While CS585 has not yet been assigned a specific indication for clinical development, preclinical data indicates that it could potentially be used in indications like Pulmonary Hypertension and thrombosis prevention without increased risk of bleeding. CS585 was in-licensed from the University of Michigan in 2023. The Company is headquartered in GoCo Health Innovation City, in Gothenburg, Sweden, and has a US subsidiary; Cereno Scientific Inc. Based in Kendall Square, Boston, Massachusetts, US. Cereno is listed on the Nasdaq First North (CRNO B). The Certified Adviser is Carnegie Investment Bank AB, certifiedadviser@carnegie.se. More information is on www.cerenoscientific.com. SOURCE: Cereno Scientific