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, announced today that the Company presented new translational data for povetacicept (ALPN-303) at the SLEuro 14th European Lupus Meeting in Bruges, Belgium, March 19-22, 2024..

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疾病和炎症性疾病的创新治疗方法，今天宣布，该公司于2024年3月19日至22日在比利时布鲁日举行的第14届欧洲狼疮会议上提供了povetacicept（ALPN-303）的新翻译数据。。

Presentation Highlights Include:

演讲亮点包括：

BAFF- and APRIL-related genes are increased in myeloid and B cells in systemic lupus erythematosus (SLE) patients compared to healthy adults.

与健康成人相比，系统性红斑狼疮（SLE）患者的骨髓和B细胞中BAFF和APRIL相关基因增加。

Povetacicept significantly reduces multiple disease parameters in the NZB/W mouse model of lupus, more effectively than WT TACI-Ig or B cell depletion.

Povetacicept显着降低了NZB/W狼疮小鼠模型中的多种疾病参数，比WT TACI Ig或B细胞耗竭更有效。

Povetacicept exhibits greater distribution to multiple tissues – 19-fold higher in the kidney and 3-4-fold higher in the lung, skin, and brain – in normal mice, compared to WT TACI-Ig, potentially related to advantageous differences in molecular weight, target affinity and/or isoelectric point.

与WT TACI Ig相比，Povetacicept在正常小鼠的多个组织中表现出更大的分布-肾脏高19倍，肺，皮肤和大脑高3-4倍，这可能与分子量，靶亲和力和/或等电点的有利差异有关。

'We have long known that povetacicept possesses unique molecular attributes that were conferred by our discovery platform’s directed evolution process,” remarked Stanford Peng, MD, PhD, President and Head of Research and Development at Alpine. “At least one of these attributes is its ability to distribute to disease-relevant tissues to a greater extent than wild-type TACIs, which may explain its superiority in multiple preclinical or translational disease models.

“我们早就知道，povetacicept具有独特的分子属性，这是我们的发现平台的定向进化过程赋予的，”Alpine总裁兼研发负责人Stanford Peng博士说道。“这些属性中至少有一个是它比野生型TACI更能分布到与疾病相关的组织中，这可能解释了它在多种临床前或转化疾病模型中的优势。

These findings are particularly intriguing considering that these organs are of particular relevance to our lead indications, systemic lupus erythematosus and IgA nephropathy. These findings further support our intent to initiate both a pivotal trial in IgA nephropathy, RAINIER, as well as a phase 2 study in SLE, DENALI, later this year.”.

考虑到这些器官与我们的铅适应症，系统性红斑狼疮和IgA肾病特别相关，这些发现特别有趣。这些发现进一步支持了我们的意图，即在雷尼尔（RAINIER）的IgA肾病中启动关键试验，以及在今年晚些时候在德纳利（DENALI）的SLE中启动2期研究。”。

Table 1: Greater Tissue Distribution vs. WT TACI-Ig

表1：与WT TACI Ig相比，组织分布更大

Tissue

组织

% Positive (Mean ± SE)

%阳性（平均值±SE）

Fold Difference

折叠差异

(Povetacicept/Telitacicept)

（波韦他西普/Telitacicept）

Povetacicept

波韦他西普

Telitacicept

Telitacicept

Kidney

肾脏

1.9 ± 0.2

1.9 ± 0.2

0.1 ± 0.0

0.1 ± 0.0

19.0

19.0

Lung

肺

0.49 ± 0.13

0.49 ± 0.13

0.13 ± 0.05

0.13 ± 0.05

3.8

3.8

Skin

皮肤

2.7 ± 0.4

2.7 ± 0.4

0.8 ± 0.2

0.8 ± 0.2

3.4

3.4

Brain

大脑

0.10 ± 0.03

0.10 ± 0.03

0.03 ± 0.01

0.03 ± 0.01

3.3

3.3

Table 2: Molecular Attributes

表2：分子属性

Attribute

属性

Povetacicept

波韦他西普

Telitacicept

Telitacicept

MW (kDa)1

兆瓦（kDa）1

62.6

62.6

75.3-75.42

75.3-75.42

pI1

第1页

6.5-7.0

6.5-7.0

7.1-8.4

7.1-8.4

KD, BAFF

KD，BAFF

59 pM

下午59点

491 pM

下午491点

KD, APRIL

KD，四月

1 pM

下午1点

CNBD

CNBD

1

1

Theoretical, calculated by Expasy (web.expasy.org/compute_pi/), Prot pI (Protpi.ch/Calculator/Protein Tool), or at Alpine based on Anal. Biochem 179:319 (1989).

理论上，由Expasy（web.Expasy.org/compute\u pi/），Prot pi（Protpi.ch/Calculator/Protein Tool）或基于Anal的Alpine计算。生物化学179:319（1989）。

2

2

MW reported as 80.24 kDa in J Clin Pharmacol 56:948 (2016)

《临床药理学杂志》56:948（2016）报道的分子量为80.24 kDa

SLEuro 14th European Lupus Meeting Poster Presentation Details

SLEuro第14届欧洲狼疮会议海报展示细节

Date: Thursday, March 21, 2024

日期：2024年3月21日，星期四

Poster Title: The Enhanced Dual BAFF/APRIL Inhibitor Povetacicept (TACI vTD-Fc; ALPN-303) More Potently Reduces Disease Activity in Murine Lupus Compared to CD20 Depletion and WT TACI-Ig, Associated with Greater End-Organ Distribution

海报标题：与CD20耗竭和WT TACI Ig相比，增强的双重BAFF/APRIL抑制剂Povetacicept（TACI-vTD-Fc；ALPN-303）更有效地降低了小鼠狼疮的疾病活动，这与更大的终末器官分布有关

Poster Number: Tour 2, P104

海报编号：Tour 2，P104

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. 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。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 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. For more information, visit www.alpineimmunesciences.com. Follow @AlpineImmuneSci on X and LinkedIn..

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。有关更多信息，请访问www.alpineimmunesciences.com。在X和LinkedIn上关注@AlpineImmuneSci。。

Forward-Looking Statements

前瞻性声明

This release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, Section 21E of the Securities Exchange Act of 1934 and the Private Securities Litigation Reform Act of 1995. These forward-looking statements are not based on historical fact and include statements regarding our platform technology and potential therapies; the timing of and results from clinical trials and preclinical development activities; clinical and regulatory objectives and the timing thereof; expectations regarding the sufficiency of cash, including cash equivalents and restricted cash, and investments to fund our planned operations into 2026; our ability to achieve additional milestones in our collaborations and proprietary programs; the progress and potential of our development programs; future development plans and clinical and regulatory milestones and objectives, including the timing and achievement thereof; the efficacy of our clinical trial designs; anticipated enrollment in our clinical trials and the timing thereof; expectations regarding the anticipated reporting of data from our ongoing and planned clinical trials and potential publication of future clinical data; our ability to potentially advance povetacicept directly into a pivotal trial in the second half of 2024 as well as a phase 2 study in systemic lupus erythematosus, pending engagement with and approval of the Food and Drug Administration; and the potential efficacy, safety profile, addressable market, regulatory success and commercial or therapeutic potential of our product candidates.

本新闻稿包含《1933年证券法》第27A节、《1934年证券交易法》第21E节和《1995年私人证券诉讼改革法》所指的前瞻性声明。这些前瞻性声明不是基于历史事实，包括关于我们平台技术和潜在疗法的声明；临床试验和临床前开发活动的时间和结果；临床和监管目标及其时间安排；对现金充足的预期，包括现金等价物和限制性现金，以及为2026年的计划运营提供资金的投资；我们在合作和专有项目中实现额外里程碑的能力；我们发展计划的进展和潜力；未来发展计划以及临床和监管里程碑和目标，包括时间安排和实现；我们的临床试验设计的功效；预计参加我们的临床试验及其时间安排；对我们正在进行和计划中的临床试验数据的预期报告以及未来临床数据的潜在发布的期望；我们有能力在2024年下半年将povetacicept直接推进关键试验，以及系统性红斑狼疮的2期研究，等待食品和药物管理局的参与和批准；以及我们候选产品的潜在功效，安全性，可寻址市场，监管成功以及商业或治疗潜力。

Forward-looking statements generally include statements that are predictive in nature and depend upon or refer to future events or conditions and include words such as “may,” “will,” “should,” “woul.

前瞻性陈述通常包括预测性陈述，取决于或提及未来事件或条件，并包括“可能”、“将”、“应该”、“将会”等词语。