BNZ-1

◆ IL-15的发现 白细胞介素15（IL-15）是一种关键性细胞因子，能够激活T细胞、B细胞以及NK细胞，并促进这些细胞的增殖与存活。IL-15于1994年被独立发现为T细胞生长的关键因子，这一重大突破，为后续深入研究IL-15的信号通路及其在肿瘤治疗中的应用奠定了坚实基础。 ◆ IL-15的信号通路 IL-15信号传导复杂，通过多种途径激活效应细胞，被受体抗体阻断。在一种情境下，IL-15会与抗原呈递细胞上高亲和力的IL-15Rα结合，随后这一复合物会进一步与IL-2/15Rβγ异二聚体相互作用。这一系列反应会导致效应细胞的激活，激活过程可能通过以下三种方式之一进行：一是涉及JAK/STAT的激活，二是通过Shc和Grb2的磷酸化作用激活下游信号；三是激活MAPK途径。 而在另一种情境下，特别是在肥大细胞中，IL-15会通过独特的IL-15RX受体链来发出信号，从而激活JAK2/STAT5途径。此外，IL-15还可以与常见的γ链结合，通过Tyk2/STAT6传递其信号。使用抗IL-15R抗体可以阻断IL-15与其受体的结合及信号传导。同时，靶向JAK/STAT途径的抑制剂能够防止STAT异二聚体的活化和细胞核转运。 ◆ IL-15在免疫系统中的作用 在免疫调节中，IL-15对多种免疫细胞的存活和增殖至关重要。 IL-15在免疫系统中扮演着关键角色，广泛调节T细胞，特别是NK细胞和记忆性CD8+T细胞的存活、增殖以及功能。 ◆ IL-15在抗肿瘤免疫中的作用 具有同名螺旋型细胞因子相似的促T细胞增殖和激活B细胞的特性。与IL-2同属螺旋型细胞因子家族，其结构颇为相似。这两种细胞因子都依赖于共同的受体成分，包括IL-2R/IL-15Rβ（CD122）和共同γc链（CD132），以及JAK1/JAK3/STAT5信号通路。因此，IL-15与IL-2在功能上具有诸多共性。 ◆ IL-2与IL-15的对比 两者作用不同，表现出独特性，IL-15在肿瘤治疗中的毒性较低。IL-2与IL-15的作用并非总是重叠，它们有时会展现出独特且往往相互竞争的效果。这种差异主要体现在Tregs细胞的激活、免疫应答的调节上。 ◆ IL-15的药物研发进展 国内SHR系列进入临床，国外有多个产品处在临床试验阶段。虽然国内尚无IL-15靶点产品上市，但恒瑞医药的SHR-1501（IL-15融合蛋白）已进入临床试验阶段。此外，SHR-1316与SHR-1501的联合治疗方案，为治疗失败的晚期恶性肿瘤患者带来了新的希望。 ◆ 国外IL-15研发动态 产品如ALT-803表现强有效性；BNZ-1在I/II期临床证明安全。国外多个IL-15靶点产品也正处于临床试验阶段，尤其值得注意的是，ALT-803作为IL-15的超级激动剂，已显示出显著的治疗潜力。 ◆ 真核表达系统应用 真核表达系统优于原核，提供结构与类似天然活性的蛋白。与原核表达系统相比，真核表达系统能够诱导高效表达，其表达的蛋白更接近天然活性，为药物研发提供了独特的优势。 ◆ 北京同立海源生物 专注于高质量真核蛋白研发，提供多项生物技术服务，并通过双认证。北京同立海源生物科技有限公司，是一家国家高新技术企业，专注于真核表达平台的研发与生产，其产品广泛服务于生物制药、细胞治疗研究等多个领域。 随着肿瘤免疫治疗的发展，免疫细胞因子如IL-6、IL-2的抑制剂已成为药物研发的热点。而IL-15，这一自发现以来便备受关注的细胞因子，其靶向抑制剂的研发仍在持续进行中。探索IL-15抑制的治疗潜力，无疑将为未来的药物研发带来更多可能。究竟谁能率先推出IL-15抑制的上市产品，我们拭目以待。

Itolizumab demonstrated clinical efficacy after 12 weeks of treatment, achieving a clinical remission rate of 23.3% compared to 20.0% for adalimumab and 10.0% for placebo Itolizumab achieved key secondary endpoint of endoscopic remission of 16.7% compared to 16.7% for adalimumab and 6.7% for placebo Itolizumab was generally well tolerated consistent with prior clinical experience LA JOLLA, CA, USA I February 06, 2025 I Equillium, Inc. (Nasdaq: EQ), a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders, and Biocon Limited (BSE code: 532523, NSE: BIOCON), an innovation-led global biopharmaceutical company, today announced positive topline results from the Phase 2 study evaluating itolizumab in the treatment of moderate to severe ulcerative colitis (UC). The double-blinded, placebo- and active-controlled Phase 2 clinical study evaluated the safety and efficacy of itolizumab in biologic-naïve patients with moderate to severe active UC. A total of 90 patients were randomized 1:1:1 to receive itolizumab (fixed dose of 140 mg), placebo, or adalimumab (a global standard of care biologic treatment used as an active control) every two weeks for an initial 12-week treatment period. The primary endpoint of the study was clinical remission as defined by Total Mayo Score, and secondary endpoints included the proportion of participants who achieved clinical response and endoscopic remission (evaluated by central endoscopy). The study was co-sponsored by Equillium and Biocon Limited and conducted at multiple clinical trial sites in India. The design and conduct of the trial were a collaborative effort, with input from the gastroenterology community and leading global clinical and scientific experts in the field of inflammatory bowel disease (IBD). “The CD6-ALCAM pathway is elevated in gastrointestinal inflammation and is associated with severity of disease in both ulcerative colitis and Crohn’s patients. As such, we are delighted with the strength of data across the primary and secondary endpoints of this Phase 2 study in moderate to severe ulcerative colitis patients,” said Dr. Stephen Connelly, chief scientific officer at Equillium. “Itolizumab was well tolerated and achieved a clinical remission rate of 23 percent despite an imbalance of more severe patients in the itolizumab arm compared to the other arms of the study. While these positive results add to itolizumab’s critical mass of safety and efficacy data across different patient populations, we are particularly encouraged by this data in the context of our Phase 3 EQUATOR study in acute graft-versus-host disease, where lower gastrointestinal pathogenesis is a key driver of mortality, with topline data expected this quarter.” “Itolizumab demonstrated proof of concept with a meaningful effect size – comparable to biologic standard of care adalimumab – in this Phase 2 study in subjects with moderate to severe ulcerative colitis,” said Dr. Brian Feagan, Professor of Medicine at the Schulich School of Medicine & Dentistry at the University of Western Ontario. “Itolizumab represents a novel selective immune modifying mechanism of action with great potential in a treatment paradigm needing differentiation and improved outcomes for patients.” Summary of Key Study Results Baseline demographics of the study included a median age of 39 years, relatively equal proportions of male and female subjects evenly distributed among study arms, and a mean weight of 58 kilograms. Baseline disease severity of the study was greater in the itolizumab arm, where 23% of patients were classified as severe (Total Mayo Score of 11) versus 0% in the placebo and adalimumab arms, and 66% had left-sided colitis versus 30% and 43% in the placebo and adalimumab arms, respectively. The primary endpoint of the study was clinical remission, defined as Total Mayo Score of ≤ 2 with no individual sub-score greater than 1 at Week 12. Secondary endpoints included the proportion of participants who achieved clinical response (per Total Mayo Score) and endoscopic remission (evaluated by central endoscopy) at Week 12 and Week 24. Additional data is expected to be presented at a future scientific conference during 2025. * One patient from the adalimumab arm had ‘endoscopic remission,’ but was recorded as ‘not in clinical remission’ at week 12 due to missing sub-score data About Itolizumab Itolizumab is a clinical-stage, first-in-class immune-modifying monoclonal antibody that selectively targets the CD6-ALCAM signaling pathway to downregulate pathogenic T effector cells while preserving T regulatory cells critical for maintaining a balanced immune response. This pathway plays a central role in modulating the activity and trafficking of T cells that drive a number of immuno-inflammatory diseases. The blockade of CD6 with itolizumab has demonstrated a reduction in T effector cell proliferation and downregulation of several important pathways that contribute to T effector cell development. The downregulation of these pathways is accompanied by decreased secretion of the pro-inflammatory T effector cytokines IFN-γ, TNF-α, IL-6 and IL-17. Additionally, inhibiting the binding of ALCAM to CD6 modulates lymphocyte trafficking and results in reduced T effector cell infiltration into inflamed tissues. About Biocon Limited Biocon Limited, publicly listed in 2004, (BSE code: 532523, NSE Id: BIOCON, ISIN Id: INE376G01013) is an innovation-led global biopharmaceuticals company committed to enhance affordable access to complex therapies for chronic conditions like diabetes, cancer and autoimmune. It has developed and commercialized novel biologics, biosimilars, and complex small molecule APIs in India and several key global markets as well as Generic Formulations in the US, Europe & key emerging markets. It also has a pipeline of promising novel assets in immunotherapy under development. Website: www.biocon.com ; Follow-us on Twitter: @bioconlimited for company updates. About Equillium Equillium is a clinical-stage biotechnology company leveraging a deep understanding of immunobiology to develop novel therapeutics to treat severe autoimmune and inflammatory disorders with high unmet medical need. The company’s pipeline consists of the following novel first-in-class immunomodulatory assets and product platform targeting immuno-inflammatory pathways. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells that drive a number of immuno-inflammatory diseases. It is currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and has exhibited positive data from both a Phase 2 clinical study of patients with moderate to severe ulcerative colitis and a Phase 1b clinical study of patients with lupus/lupus nephritis. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited, who also provides commercial manufacturing for the product. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15, has exhibited positive results in both a Phase 2 proof-of-concept clinical study of patients with moderate to severe alopecia areata and a Phase 1/2 proof-of-concept clinical study of patients with cutaneous T cell lymphoma (CTCL). EQ302: an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21 at pre-clinical stage. For more information, visit www.equilliumbio.com . SOURCE: Equillium