SEATTLE--(BUSINESS WIRE)--Alpine Immune Sciences, Inc. (NASDAQ: ALPN), a leading clinical-stage immunotherapy company focused on developing innovative treatments for autoimmune and inflammatory diseases, today shared updated clinical data for povetacicept in IgA nephropathy (IgAN) which will be presented as a late breaking poster at the World Congress of Nephrology (WCN) April 13-16, 2024 in Buenos Aires, Argentina..

西雅图--（商业新闻短讯）--Alpine Immune Sciences，Inc.（NASDAQ:ALPN）是一家领先的临床阶段免疫治疗公司，专注于开发针对自身免疫性和炎性疾病的创新治疗方法，今天分享了IgA肾病（IgAN）中povetacicept的最新临床数据，该数据将于2024年4月13日至16日在阿根廷布宜诺斯艾利斯举行的世界肾脏病大会（WCN）上作为最新海报发布。。

Povetacicept is a potent dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, particularly antibody-secreting cells, as well as T cells and innate immune cells.

Povetacicept是BAFF（B细胞活化因子）和APRIL（增殖诱导配体）细胞因子的有效双重拮抗剂，它们通过其在B细胞的活化，分化和/或存活中的作用在多种自身免疫疾病的发病机制中起关键作用，特别是抗体分泌细胞，以及T细胞和先天免疫细胞。

RUBY-3 is a multiple ascending dose, multi-cohort, open label, phase 1b/2a study of povetacicept in autoimmune glomerulonephritis, including IgA nephropathy, where povetacicept is administered subcutaneously (SC) once every four weeks..

RUBY-3是一项针对自身免疫性肾小球肾炎（包括IgA肾病）的多剂量递增，多队列，开放标签的1b/2a期研究，其中每四周皮下注射一次povetacicept。。

Key Highlights Include:

主要亮点包括：

As of March 01, 2024, 41 patients with IgAN had received povetacicept 80 or 240 mg subcutaneously every 4 weeks. Treatment with povetacicept 80 mg SC Q4W has been associated with a clinically meaningful improvement in proteinuria, with a 64.1% reduction from baseline in urine protein to creatinine ratio (UPCR; n=6) at 36 weeks, associated with stable renal function as assessed by estimated glomerular filtration rate (eGFR).

截至2024年3月1日，41名IgAN患者每4周皮下注射80或240 mg povetacicept。用80 mg povetacicept SC Q4W治疗与蛋白尿的临床意义改善相关，36周时尿蛋白与肌酐比值（UPCR；n=6）比基线降低64.1%，与稳定的肾功能相关，通过估计的肾小球滤过率（eGFR）评估。

At this same time, 4/6 (67%) had achieved remission, as defined as UPCR < 0.5 g/g, ≥50% reduction in UPCR from baseline, and stable renal function (≤ 25% reduction in eGFR from baseline)..

与此同时，4/6（67%）达到缓解，定义为UPCR<0.5 g/g，UPCR比基线降低≥50%，肾功能稳定（eGFR比基线降低≤25%）。。

Resolution of hematuria, as defined as negative or trace/small hematuria in patients with non-negative/trace hematuria at baseline, was achieved in all (100%) patients with data available at 36 or more weeks (N=4).

在所有（100%）患者中，在36周或更长时间（N=4）的数据可用时，血尿的消退（定义为基线时非阴性/微量血尿患者的阴性或微量/小血尿）。

Treatment with povetacicept 240 mg SC Q4W has been associated with similar improvements in proteinuria, stable renal function, and remission, based on initial data through 12 (13 patients) and 24 (2 patients) weeks.

根据12（13名患者）和24（2名患者）周的初始数据，用波维他西普240 mg SC Q4W治疗与蛋白尿，肾功能稳定和缓解相似。

Treatment with both doses was associated with significant reductions in the key disease-related biomarker Gd-IgA1, with the 80 mg dose achieving a 68.9% reduction at 40 weeks, and the 240 mg dose achieving a 78.6% reduction at 20 weeks. Both doses achieved reductions in IgA/C3 and Gd-IgA1/C3 ratios, which are additional severity and prognostic biomarkers in IgAN..

两种剂量的治疗均与关键疾病相关生物标志物Gd-IgA1的显着降低相关，80 mg剂量在40周时降低68.9%，240 mg剂量在20周时降低78.6%。两种剂量均降低了IgA/C3和Gd-IgA1/C3比率，这是IgAN中额外的严重程度和预后生物标志物。。

Both doses have been well tolerated in IgAN, with no instances of IgG < 3 g/L and no severe infections.

两种剂量在IgAN中均具有良好的耐受性，没有IgG<3 g/L的情况，也没有严重感染。

“These updated findings for povetacicept are highly promising and continue to support the potential for the program as an important new therapy in IgA nephropathy,” noted Jonathan Barratt, M.D., the Mayer Professor of Renal Medicine and Honorary Consultant Nephrologist and IgA Nephropathy Rare Disease Group Lead, University of Leicester.

莱斯特大学梅耶肾脏医学教授、名誉顾问肾病学家和IgA肾病罕见病小组负责人乔纳森·巴拉特（JonathanBarratt，M.D.）指出：“波维他西普的这些最新发现非常有前景，并继续支持该计划作为IgA肾病重要新疗法的潜力。”。

“The marked and clinically meaningful improvement in UPCR and stable eGFR observed with a monthly dosing regimen at 36 weeks are particularly impressive, as are the deep reductions in Gd-IgA1, a key disease-related biomarker, and resolution of hematuria in patients. The lack of serious adverse events with longer duration of treatment and higher dose is also notable and, together with povetacicept’s disease modifying potential and substantial patient experience, strongly supports the rapid advancement of povetacicept into a pivotal study for IgA nephropathy.”.

“在36周的每月给药方案中观察到的UPCR和稳定eGFR的显着和临床意义的改善尤其令人印象深刻，关键疾病相关生物标志物Gd-IgA1的深度降低以及患者血尿的消退也是如此。缺乏治疗持续时间更长和剂量更高的严重不良事件也是值得注意的，加上波维他西普的疾病缓解潜力和丰富的患者经验，强烈支持波维他西普迅速发展成为IgA肾病的关键研究。”。

“Despite advancements in IgA nephropathy, there remains an urgent need for safe and convenient therapies that effectively treat the underlying cause of the disease,” said James Tumlin, M.D., Professor of Medicine at Emory University School of Medicine, Founder and CEO of NephroNet Clinical Trials Consortium.

埃默里大学医学院医学教授、NephroNet Clinical Trials Consortium创始人兼首席执行官詹姆斯·图姆林（JamesTumlin）医学博士说：“尽管IgA肾病取得了进展，但仍然迫切需要安全方便的疗法来有效治疗疾病的根本原因。”。

“Dual APRIL/BAFF inhibition is a potent inhibitor of Galactose Deficient IgA1 (Gd-IgA1) production which is closely linked to the pathogenesis and progression of IgA nephropathy. Monthly administration of povetacicept has been shown to be well-tolerated at both the 80mg and 240 mg doses with clinical responses including Gd-IgA1, urine protein levels and eGFR stabilization within 3 months.

“双重APRIL/BAFF抑制是半乳糖缺陷型IgA1（Gd-IgA1）产生的有效抑制剂，与IgA肾病的发病机制和进展密切相关。每月服用泊维他西普在80mg和240mg剂量下均表现出良好的耐受性，临床反应包括Gd-IgA1，尿蛋白水平和3个月内eGFR稳定。

These data strongly support the inhibition of APRIL/BAFF pathways by povetacicept and its efficacy in the treatment of IgAN as well as the need for further clinical development. If approved, povetacicept could be used a front-line disease modifying treatment in IgAN.”.

这些数据强烈支持povetacicept对APRIL/BAFF途径的抑制及其在IgAN治疗中的功效以及进一步临床开发的需要。如果获得批准，povetacicept可以用于IgAN的一线疾病缓解治疗。”。

“These data indeed continue to further our enthusiasm for the potential of povetacicept in IgAN and other autoimmune diseases,” remarked Stanford Peng, MD PhD, President and Head of Research and Development at Alpine. “We are pleased to have completed our successful end of phase 2 meeting with FDA, enabling advancement to a registrational trial in IgAN (RAINIER) later this year.

Alpine总裁兼研发主管Stanford Peng博士表示：“这些数据确实继续激发我们对povetacicept在IgAN和其他自身免疫性疾病中潜力的热情。”。“我们很高兴成功地完成了与FDA的第二阶段会议，从而能够在今年晚些时候在IgAN（RAINIER）进行注册试验。

In addition, we plan to continue to explore povetacicept’s potential in multiple other autoimmune diseases via the ongoing RUBY-3 and RUBY-4 studies, and via the initiation of a phase 2 study (DENALI) in systemic lupus erythematosus later this year.”.

此外，我们计划通过正在进行的RUBY-3和RUBY-4研究，以及今年晚些时候启动的系统性红斑狼疮2期研究（DENALI），继续探索povetacicept在多种其他自身免疫性疾病中的潜力。”。

World Congress of Nephrology Late-Breaking Poster

世界肾脏病大会最新海报

Date/Time: Monday, April 15, 2024, 5:45 pm local time (GMT-3) /4:45 pm ET/1:45 pm PT

日期/时间：2024年4月15日，星期一，当地时间下午5:45（GMT-3）/东部时间下午4:45/太平洋时间下午1:45

Poster Title: Updated Results from the RUBY-3 study of Povetacicept, an Enhanced Dual BAFF/APRIL Antagonist in IgA Nephropathy

海报标题：RUBY-3对Povetacicept的研究的最新结果，Povetacicept是IgA肾病中增强的双重BAFF/APRIL拮抗剂

Poster Number: MON-304

海报编号：MON-304

Session Name: Poster Session 3 (Late Breaking)

课程名称：海报课程3（晚休息）

Location: Exhibition Hall and Main Foyer, Buenos Aires Convention Center, Buenos Aires, Argentina

地点：阿根廷布宜诺斯艾利斯布宜诺斯艾利斯会议中心展厅和主门厅

Presenter: James Tumlin, M.D., Professor of Medicine at Emory University School of Medicine, Founder and CEO of NephroNet Clinical Trials Consortium

主持人：詹姆斯·图姆林（JamesTumlin），医学博士，埃默里大学医学院医学教授，NephroNet临床试验联盟创始人兼首席执行官

Alpine will host an investor call and webcast to discuss the data update as well as provide a corporate update.

Alpine将主持投资者电话和网络广播，讨论数据更新以及提供公司更新。

The link to the webcast is available in the investor relations section of the Company’s website at https://ir.alpineimmunesciences.com/events and a replay will be available on the Company's website for 90 days following the live event.

该网络广播的链接可在公司网站的投资者关系部分获得，网址为https://ir.alpineimmunesciences.com/events现场活动结束后，公司网站将提供90天的重播。

About Povetacicept (ALPN-303)

关于Povetacept（ALPN-303）

Povetacicept (ALPN-303) is a dual antagonist of the BAFF (B cell activating factor) and APRIL (a proliferation inducing ligand) cytokines, which play key roles in pathogenesis of multiple autoimmune diseases via their roles in the activation, differentiation and/or survival of B cells, particularly antibody-secreting cells, as well as T cells and innate immune cells.

Povetacicept（ALPN-303）是BAFF（B细胞活化因子）和APRIL（增殖诱导配体）细胞因子的双重拮抗剂，它们通过其在B细胞（特别是抗体分泌细胞）以及T细胞和先天免疫细胞的活化，分化和/或存活中的作用在多种自身免疫性疾病的发病机制中起关键作用。

Based upon an engineered TACI (transmembrane activator and CAML interactor) domain, povetacicept has exhibited greater potency in preclinical studies versus other inhibitors of BAFF and/or APRIL alone and B cell depletion and has demonstrated initial activity in patients with IgA nephropathy. Povetacicept is in development for multiple autoimmune diseases, including IgA nephropathy and other autoimmune kidney diseases, systemic lupus erythematosus, and autoimmune cytopenias..

基于工程化的TACI（跨膜激活剂和CAML相互作用物）结构域，与其他单独的BAFF和/或APRIL抑制剂和B细胞耗竭相比，povetacicept在临床前研究中表现出更高的效力，并且在IgA肾病患者中表现出初始活性。波维他西普正在开发多种自身免疫性疾病，包括IgA肾病和其他自身免疫性肾脏疾病，系统性红斑狼疮和自身免疫性血细胞减少症。。

About RUBY-3

关于RUBY-3

RUBY-3 (NCT05732402) is a multiple ascending dose, multi-cohort, open label, phase 1b/2 study of povetacicept in autoimmune glomerulonephritis, including IgA nephropathy, primary membranous nephropathy, lupus nephritis, and renal ANCA-associated vasculitis, where povetacicept is being administered subcutaneously for up to 104 weeks.

RUBY-3（NCT05732402）是一项针对自身免疫性肾小球肾炎（包括IgA肾病，原发性膜性肾病，狼疮性肾炎和肾ANCA相关性血管炎）的多剂量递增，多队列，开放标签，1b/2期研究，其中povetacicept皮下给药长达104周。

Key endpoints include proteinuria, eGFR, renal response, and disease-related autoantibodies..

关键终点包括蛋白尿，eGFR，肾脏反应和疾病相关的自身抗体。。

About RUBY-4

关于RUBY-4

RUBY-4 (NCT05757570) is a multi-cohort, open label study of povetacicept in autoimmune cytopenias, including immune thrombocytopenia, autoimmune hemolytic anemia, and cold agglutinin disease, where povetacicept is being administered subcutaneously for up to 48 weeks. Key endpoints include respective blood cell counts, durable responses, as well as disease-related autoantibodies..

RUBY-4（NCT05757570）是一项针对自身免疫性血细胞减少症（包括免疫性血小板减少症，自身免疫性溶血性贫血和冷凝集素病）的多队列开放标签研究，其中povetacicept皮下给药长达48周。关键终点包括各自的血细胞计数，持久反应以及与疾病相关的自身抗体。。

About RAINIER

关于雷尼尔

RAINIER is an upcoming, randomized, double-blind, placebo-controlled, pivotal phase 3 study to evaluate the safety and efficacy of povetacicept in patients with IgA nephropathy at risk of progression to kidney failure.

RAINIER是一项即将进行的随机，双盲，安慰剂对照，关键性的3期研究，旨在评估波维他西普对有进展为肾衰竭风险的IgA肾病患者的安全性和有效性。

About DENALI

关于DENALI

DENALI is an upcoming, randomized, double-blind, placebo-controlled phase 2 study to evaluate the safety and efficacy of povetacicept in patients with active systemic lupus erythematosus.

DENALI是一项即将进行的随机双盲安慰剂对照2期研究，旨在评估波维他西普在活动性系统性红斑狼疮患者中的安全性和有效性。

About Alpine Immune Sciences

关于阿尔卑斯免疫科学

Alpine Immune Sciences is committed to leading a new wave of immune therapeutics. With world-class research and development capabilities, a highly productive scientific platform, and a proven management team, Alpine is seeking to create first- or best-in-class multifunctional immunotherapies via unique protein engineering technologies to improve patients’ lives.

阿尔卑斯免疫科学致力于引领新一波免疫疗法。凭借世界一流的研发能力、高效的科学平台和久经考验的管理团队，Alpine正在寻求通过独特的蛋白质工程技术创造一流或一流的多功能免疫疗法，以改善患者的生活。

Alpine has entered into strategic collaborations with leading global biopharmaceutical companies and has a diverse pipeline of clinical and preclinical candidates in development.

Alpine已与全球领先的生物制药公司进行战略合作，并在开发中拥有多种临床和临床前候选药物。