SC-0062

SHANGHAI, Nov. 4, 2024 /PRNewswire/ -- BioCity Biopharma (BioCity) announced late-breaking results of the 2-SUCCEED clinical trial of SC0062, a selective endothelin receptor type A (ETA) antagonist, for the treatment of IgA Nephropathy (IgAN). These results were presented at the Oral Abstract Session of American Society of Nephrology (ASN) Kidney Week 2024 and published simultaneously in the Journal of the American Society of Nephrology (JASN), a leading kidney journal worldwide. The 2-SUCCEED trial was designed as a multi-center, randomized, double-blind, placebo-controlled, two-cohort (IgAN and diabetic kidney disease [DKD]), Phase II study. The principal objective of the IgAN cohort was to evaluate the efficacy, safety, and optimal dose of SC0062 compared to placebo to determine SC0062's ability to reduce proteinuria in subjects at high risk of disease progression. The study allowed enrolment of subjects who were receiving sodium/glucose cotransporter 2 (SGLT2) inhibitors as a background therapy. Overall, 131 patients were randomized in a 1:1:1:1 ratio to 24 weeks of treatment with either SC0062 doses of 5 mg, 10 mg, or 20 mg or placebo once daily. A similar evaluation of SC0062 in the 2-SUCCEED cohort of subjects with DKD is ongoing. Key 2-SUCCEED Study Results Presented at ASN: SC0062 Met the Primary Endpoint of Reducing Urinary Protein Excretion in the IgAN Cohort: At week 12, subjects receiving SC0062 at doses of 5 mg, 10 mg, and 20 mg showed geometric mean reductions from baseline in 24-hour urine protein-to-creatinine ratio (UPCR) of 39.2%, 33.7%, and 48.3%, respectively, compared to 16.5% in the placebo group. SC0052 Met Secondary Endpoint 1: At week 12, the proportion of subjects achieving greater than a 30% reduction in UPCR was 48.5%, 62.5%, and 71.0% in those treated with SC0062 at doses of 5 mg, 10 mg, and 20 mg, respectively, compared to 33.3% in the placebo group. Respective reductions of UPCR by 40% were achieved in 45.5%, 37.5%, and 64.5% of subjects in SC0062 dose groups, respectively, compared to 18.2% in the placebo group. The respective proportions of subjects achieving a 50% reduction in UPCR were achieved by 33.3%, 21.9%, and 51.6% per SC0062 dose group versus 12.1% in the placebo group. SC0062 Met Secondary Endpoint 2: At week 24, subjects receiving SC0062 at doses of 5 mg, 10 mg, and 20 mg had geometric mean reductions from baseline in 24-hour UPCR of 39.5%, 46.1%, and 62.3%, respectively, compared to 22.1% in the placebo group. Subgroup Analysis: The proportion of subjects receiving SGLT2 inhibitors as background therapies in the four groups ranged from 46% to 47%. SC0062 at the various doses evaluated consistently reduced UPCR regardless of the use of SGLT2 inhibitors as background therapy or the magnitude of UPCR prior to treatment. Renal Function: In the early stage of treatment, no acute decline in the estimated glomerular filtration rate (eGFR) was observed in subjects receiving SC0062, and the eGFR values did not change significantly over 24-weeks of SC0062 treatment. Safety: SC0062 was well-tolerated, with no increase in the rate of peripheral edema or the risk of fluid retention, a common side effect of other IgAN treatments, compared to placebo. The rates of edema for placebo and SC0062 at 5 mg, 10 mg, and 20 mg were 15%, 6%, 3%, and 3%, respectively. Additionally, SC0062 treatment did not result in weight gain or an increase in NT-pro-BNP levels. The detailed results of the clinical trial can be obtained from the manuscript entitled "The Selective Endothelin Receptor Antagonist SC0062 in IgA Nephropathy: A Randomized Double-Blind Placebo-Controlled Clinical Trial" which was published in JASN（ASN.0000000538, October 26, 2024.）. SC0062 has been granted the Breakthrough Therapy Designation (BTD) by the Chinese regulatory agency National Medical Products Administration (NMPA) for the treatment of IgA Nephropathy with proteinuria. Dr. Hiddo Lambers Heerspink, a world-renowned expert in clinical trials for the treatment of chronic kidney disease (CKD), who presented the results of SC0062 at ASN, commented "The significant and sustained reduction in urine protein excretion with SC0062, along with its notable safety advantages compared to other treatments, support a larger and long-term clinical trial in subjects with various types of CKD including IgA nephropathy. We look forward to the results of further studies on this drug." About SC0062 SC0062 is a novel and unique ETA antagonist due to its high selectivity for ETA over endothelin receptor B (ETB). Its extraordinary selectivity for ETA suggests that it has a greater potential than non-selective ET antagonists for reducing progression of CKD while avoiding the side effects associated with nonselective medications in the same class for IgAN and other types of CKD. Preclinical studies have shown that SC0062 improves pathological scores in models of acute kidney injury and CKD. In a completed Phase I study, SC0062 demonstrated a favorable safety profile, good tolerability, and predictable pharmacokinetic characteristics. Fluid retention, an adverse event associated with non-selective ET antagonists due to undesirable ETB blockade, was not observed in the phase 1 trial and the risk was not increased compared to placebo in the IgAN cohort of the Phase 2 study. SC0062 is being developed by BioCity for IgAN, DKD, and other types of CKD as a potentially best-in-class ETA selective antagonist. The ongoing 2-SUCCEED Phase 2 clinical study is designed to evaluate the efficacy and safety of SC0062 in patients with CKD with proteinuria. It is a multi-center, randomized, double-blind, placebo-controlled study with two parallel cohorts (IgAN and DKD). The 2-SUCCEED study has fully enrolled all subjects in two cohorts. The primary endpoint in the IgAN cohort was met and based on this SC0062 has been granted Breakthrough Designation from NMPA, whereas the study results in the DKD cohort expected in the fourth quarter of 2024. About BioCity Founded in December 2017, BioCity is a clinical-stage biopharmaceutical company committed to developing novel and highly differentiated, modality-independent therapeutics for cancer and autoimmune disorders including CKD. BioCity has established a pipeline of more than 10 innovative drug candidates, including small molecules, monoclonal and bispecific antibodies, and antibody-drug conjugates (ADC). Currently, BioCity's SC0062, a highly selective ETA antagonist, is in Phase 2 clinical development for CKD and a global Phase 3 registration trial is being planned. In addition, BioCity has five core novel oncology assets in clinical development, including first-in-class CDH3- and GPC3-targeting antibody drug conjugates (ADCs), WEE1 and ATR inhibitors targeting the DNA damage response (DDR) pathway, and a monoclonal antibody targeting TIM-3. For more information, please visit Or LinkedIn BioCity Biopharma Contact: [email protected] [email protected] SOURCE BioCity Biopharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

▎药明康德内容团队报道 今日（10月29日），智康弘义宣布在美国肾脏病学会2024年度肾脏周（ASN Kidney Week 2024）的口头摘要环节（Oral Abstract Session）公布了SC0062胶囊治疗IgA肾病最新研究结果。该项研究结果已同步在ASN旗下肾脏病学杂志《美国肾脏病学会杂志》（Journal of the American Society of Nephrology，JASN）上发表。 SC0062是一种新型高选择性内皮素受体拮抗剂，正在开发用于治疗慢性肾脏病。据智康弘义新闻稿介绍，基于全新的分子设计和突出的临床表现，SC0062目前已被中国国家药监局药品审评中心（CDE）纳入突破性治疗品种，拟用于治疗伴有蛋白尿的IgA肾病。 IgA肾病是一种常见的原发性肾小球肾炎，常伴有严重的蛋白尿，与肾衰竭高度相关。内皮素-1（ET-1）是一种强效的血管收缩剂，在IgA肾病患者的单核细胞和肾组织中表达上调，IgA肾病患者的中性粒细胞会过度刺激间质细胞产生ET-1，ET-1的过表达将加快IgA肾病中慢性肾功能衰竭的进程。研究表明抑制A型内皮素受体可减少IgA肾病实验模型中的蛋白尿和肾组织学变化。 SC0062是一款内皮素受体A（ETA）小分子拮抗剂，针对慢性肾脏病进行了全新的分子设计，具有独特的ETA高选择性，目标在保证疗效的同时进一步提升药物安全性。 本次发表的项研究是一项多中心、随机、双盲、剂量探索、安慰剂对照的临床研究（n=131），旨在评估不同剂量（5mg、10mg、20mg）的SC0062与安慰剂相比，在减少高危IgA肾病患者蛋白尿方面的疗效、安全性，以及确定3期推荐剂量。 该研究不排除接受SGLT2抑制剂作为背景治疗的患者，研究将131名IgA肾病患者随机分成4组，3个组接受SC0062治疗，剂量分别为5mg（33人）、10mg (32人)、20mg (32人)，最后一组34人接受安慰剂给药，每日口服给药一次，连续给药24周，停药后随访时间为4周。该研究中女性患者占50%（66人），平均年龄为42岁。在接受安慰剂组及5mg、10mg、20mg剂量SC0062的患者的平均eGFR（mL/min/1.73m2）基线为71、74、72以及70；24小时UPCR（mg/g）的中位值为1.0（0.7，1.9）、1.1（0.9，1.5）、1.1（0.9，1.5）、1.3（1.0，1.6）；接受SGLT2抑制剂作为背景治疗的患者在四组中的比例为46~47%。 该项研究结果显示，与基线相比，接受5mg、10mg、20mg剂量的SC0062患者24小时尿蛋白/肌酐比值（UPCR）从第2周起至24周显著下降；SC0062在是否接受SGLT2抑制剂作为背景治疗的患者亚组、以及不同UPCR基线水平的患者亚组中均能持续降低UPCR。 主要终点：在第12周时，接受5mg、10mg、20mg剂量的SC0062及安慰剂各患者24小时尿蛋白/肌酐比值（UPCR）的几何平均比值降幅分别为39.2%、33.7%、48.3%和16.5%； 次要终点1：在第12周时，接受5mg、10mg、20mg剂量的SC0062及安慰剂组患者降低24小时尿蛋白/肌酐比值（UPCR）超过30%的比例为48.5%、62.5%、71.0%以及33.3%；超过40%的比例为45.5%、37.5%、64.5%以及18.2%；超过50%的比例为33.3%、21.9%、51.6%以及12.1%； 次要终点2：在第24周时*，接受5mg、10mg、20mg剂量的SC0062及安慰剂各患者24小时尿蛋白/肌酐比值（UPCR）的几何平均比值降幅分别为39.5%、46.1%、62.3%和 22.1%。（*截至口头报告及论文投稿截止日，24周的数据分析仍在进行中，本次会议中未及完整披露。现24周统计分析结果显示，疗效显著优于12周，此最终数据，后续将进一步发表公布。） 安全性：SC0062具有良好的安全性与耐受性，与安慰剂相比不增加体液潴留的风险，安慰剂组、5mg、10mg、20mg组发生水肿人数与比例为5（15%）、2（6%）、1（3%）、1（3%）。此外，SC0062不增加体重或NT-pro-BNP。 智康弘义新闻稿表示，SC0062显著地、持续地降低蛋白尿效果，以及突出的安全性优势将支持其进一步在慢性肾病（包括IgA肾病）患者中开展规模更大、时间更长的临床试验。智康弘义目前正在积极筹备该产品的中国国内及全球3期临床研究。 参考资料： [1]全球首发 | 智康弘义在ASN年会上公布SC0062治疗IgA肾病最新研究结果. Retrieved Oct 29, 2024. From https://mp.weixin.qq.com/s/CXn7G1v-YoEwCn5Jqg_SdA 本文由药明康德内容团队根据公开资料整理编辑，欢迎个人转发至朋友圈。转发授权及其他合作需求，请联系wuxi_media@wuxiapptec.com。 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。