IL-9

Combination of IL-15 and IL-21 robustly augments NK and CD8 T cell activity LA JOLLA, Calif.--(BUSINESS WIRE)-- $EQ -- 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, today announced that an abstract was accepted for poster presentation at the 39 th Annual Meeting of the Society for Immunotherapy of Cancer. The conference will take place at the George R. Brown Convention Center in Houston, Texas from November 6 to 10, 2024. Title: Interleukin (IL)-15 and IL-21 synergistically enhance NK and CD8+ T cell responses Presenting Author: Phoi Tiet, Senior Research Associate, Equillium, Inc. Abstract Number: 908 Location: Exhibit Halls A & B Date: Saturday, November 9, 2024 The abstract highlights that cytokines are a focus of anti-cancer therapeutic development due to their central role in regulating anti-tumoral immune responses, and that data demonstrates that IL-15 and IL-21 synergistically augment NK and CD8 T cells activities, which further enhanced their proliferation and cytolytic function. With the ability to rescue T cell dysfunction, this cytokine combination could be a promising treatment approach to stimulating anti-tumor immune responses. About Multi-Cytokine Platform and Multi-Cytokine Inhibitors EQ101 & EQ302 Our proprietary multi-cytokine platform generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. This approach is expected to avoid the broad immuno-suppression and off-target safety liabilities that may be associated with other therapeutic classes, such as Janus kinase inhibitors. Many immune-mediated diseases are driven by the same combination of dysregulated cytokines, and we believe identifying the key cytokines for these diseases will allow us to target and develop customized treatment strategies for multiple autoimmune and inflammatory diseases. Current platform assets include EQ101, a clinical stage, first-in-class, selective, tri-specific inhibitor of IL-2, IL-9, and IL-15 for intravenous and subcutaneous delivery and EQ302, a preclinical stage, first-in-class, selective, bi-specific inhibitor of IL-15 and IL-21 for oral delivery. 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. EQ101: a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15; recently announced positive results from a Phase 2 proof-of-concept clinical study of patients with alopecia areata. EQ302: an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21; currently in pre-clinical development. The multi-cytokine platform: generates rationally designed composite peptides that selectively block key cytokines at the shared receptor level targeting pathogenic cytokine redundancies and synergies while preserving non-pathogenic signaling. Itolizumab: a monoclonal antibody that targets the CD6-ALCAM signaling pathway which plays a central role in the modulation of effector T cells; currently under evaluation in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and exhibited positive results in a completed Phase 1b clinical study of patients with lupus/lupus nephritis in April 2024. Equillium acquired rights to itolizumab through an exclusive partnership with Biocon Limited and has entered a strategic partnership with Ono Pharmaceutical Co., Ltd., for the development and commercialization of itolizumab under an option and asset purchase agreement. For more information, visit . Forward Looking Statements Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. Because such statements are subject to risks and uncertainties, many of which are outside of Equillium’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Risks that contribute to the uncertain nature of the forward-looking statements include: Equillium’s ability to execute its plans and strategies; risks related to performing clinical studies; whether the results from clinical studies will validate and support the safety and efficacy of Equillium’s product candidates. These and other risks and uncertainties are described more fully under the caption “Risk Factors” and elsewhere in Equillium’s filings and reports, which may be accessed for free by visiting the Securities and Exchange Commission’s website at and on Equillium’s website under the heading “Investors.” Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. Equillium undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Contacts Investor Contact Michael Moore Vice President, Investor Relations & Corporate Communications 619-302-4431 ir@equilliumbio.com

细胞是机体的基本组成单位，其发生衰老会导致低能量效应、并驱动整体衰老，免疫细胞是衰老细胞的关键调节因子，其在衰老过程中也出现功能失调。 doi: 10.1038/s41392-023-01502-8. 造血干细胞（HSC） HSC衰老是免疫衰老的基础。衰老HSC会分化为各类功能失调的免疫细胞，导致免疫衰老。衰老HSC的主要特征是自我更新、分化偏向、能量代谢改变。HSC衰老特点细胞分化偏向 更偏向形成骨髓细胞，淋巴细胞减少，导致骨髓-淋巴失衡。 诱导偏向的细胞因子： IL-1/3/6； TNFα； IFN； G-CSF、M-CSF、GM-CSF。能量代谢改变 从无氧糖酵解转向氧化磷酸化。 由此产生ROS引起氧化应激，导致DNA损伤、细胞凋亡。自我更新减弱细胞周期活性降低。 中性粒细胞 年龄相关疾病与中性粒细胞功能降低相关，而中性粒细胞发育、数量的改变不大。中性粒细胞衰老特点功能降低 吞噬能力降低； 粘附性、趋化性异常； 细胞凋亡增加； NET释放异常； TLR功能异常。 中性粒细胞表达CXCR2可以响应CXCL1向炎症部位迁移，但衰老的中性粒细胞CXCR2表达下调，导致其迁移功能异常，不仅使抗炎作用降低，同时会引起非炎症部位损伤。 单核/巨噬 巨噬细胞功能恶化是免疫衰老的一个关键因素，其清除组织中衰老细胞的能力会随年龄增加而减弱，表现自噬水平降低、抵抗病毒感染的能力缺陷。巨噬细胞衰老特点SASP表型 IL-1β、IL-6、TNFα产生增加； IL-10产生减少，导致更易纤维化。代谢改变糖酵解、线粒体OXPHOS降低，导致能量不足，细胞功能受损。细胞周期异常细胞周期检查点p16INK4a、p21CIP1表达上调。 NK细胞 随年龄增长，外周血和骨髓中NK祖细胞数量未受影响，而NK总数增加，不过NK细胞增殖、杀伤能力下降。NK细胞衰老特点细胞比例改变 CD56（bright）NK减少（未成熟）； CD56（dim）NK增加（成熟）。NK激活受损NK激活受体NKp30、NKp46、DNAM1表达降低，免疫监视功能受损。细胞毒性减弱 穿孔素、颗粒酶、IFNα、IFNγ产生减少； IL-1/4/6/8/10、TNFα产生增加。 B细胞 生命周期中B细胞生成会持续进行，但虽年龄增长因骨髓生态位变化导致B细胞输出受影响。B细胞衰老特点比例改变 骨髓前体B细胞、浆细胞减少； 外周抗体反应性记忆B细胞减少，耗竭记忆B细胞增加。促炎 记忆B细胞产生促炎细胞因子： IL-1α、IL-1β、IL-6、TNFα。 B细胞与年龄相关的改变也是疫苗接种后抗体反应下降的主要原因。60~75岁人群接种流感疫苗的血清阳性保护率也仅为41~58%，75岁以上人群更低为29~46%。 同时B细胞多样性崩溃，各类自身抗体产生增加。 T细胞 正常情况下，T细胞数量靠胸腺输出和外周幼稚T细胞增殖来维持，而随年龄增长T细胞数量失衡；而且衰老与T细胞间的关系非常微妙，衰老会引起T细胞功能障碍，功能失调的T细胞又会释放多种炎症分子加速衰老。T细胞衰老特点数量改变Treg数量增加。 Th数量增加，其中CD4幼稚T细胞PU.1、BATF、IRF4转录因子网络诱导Th9分化偏好。 CD8循环初始T细胞数量减少； CD8效应T细胞增加，BATF、IRF4促进初始T细胞向效应T细胞转化，并上调效应功能相关转录因子（T-bet、Runx3、Blimp-1）。 效应功能减弱 炎症水平升高Treg虽然数量增加，但抑制能力减弱，间接诱导炎症。 Th1、Th2分泌细胞因子能力减弱，免疫防御功能下降； Th9通过产生IL-9参与自身免疫性和各类炎症性疾病过程。 记忆T细胞CD27、CD28共刺激分子丢失，出现耗竭表型； CD45RA+CD8+T细胞出现SASP表型，产生高水平IL-18、ADAM28，促进炎症。 小结 随着机体衰老，大多免疫细胞表现出衰老特征，内在表现为衰老/受损细胞清除效率降低，外在表现为免疫抵抗力减弱。 而且由细胞的衰老相关分泌表型（SASP）所引起的慢性炎症不仅是衰老的结果，也是促进衰老进一步发展的重要原因，由此上升到器官、组织，最终会导致各类疾病发生。 doi: 10.1038/s41392-023-01502-8. 参考资料 Li X et al. Inflammation and aging: signaling pathways and intervention therapies. Signal Transduct Target Ther. 2023;8(1):239. Published 2023 Jun 8. doi: 10.1038/s41392-023-01502-8. Yousefzadeh MJ et al. An aged immune system drives senescence and ageing of solid organs. Nature. 2021 Jun;594(7861):100-105.  Mogilenko DA, Shpynov O, Andhey PS, et al. Comprehensive Profiling of an Aging Immune System Reveals Clonal GZMK+ CD8+ T Cells as Conserved Hallmark of Inflammaging. Immunity. 2021;54(1):99-115.e12.  Hagen M, Derudder E. Inflammation and the Alteration of B-Cell Physiology in Aging. Gerontology. 2020;66(2):105-113.  本周好文推荐 如需转载请联系佰傲谷并在醒目位置注明出处 · · · · · · · ·

CAMBRIDGE, MA, USA and SCHLIEREN, Switzerland I September 16, 2024 I Vivtex Corporation (“Vivtex” or “the Company”), a biotech company aiming to transform the development of oral biologic therapies for major diseases, announces that it has entered a research and licensing agreement with Equillium, Inc. (“Equillium”), a clinical-stage biotechnology company developing novel therapeutics to treat severe autoimmune and inflammatory disorders. The research collaboration is focused on the application of Vivtex’s unique and proprietary AI-enabled GI-ORIS™ screening and formulation platform technology to develop an optimized oral version of Equillium’s EQ302, a first-in-class bi-specific peptide inhibitor of IL-15 and IL-21 in development for the treatment of gastrointestinal (GI) inflammation. Under the agreement, Equillium has the option to enter into a license agreement under which Vivtex may be eligible for royalties and other payments. No financial terms are disclosed. EQ302 inhibits IL-15 and IL-21, two cytokines important in the pathophysiology of a range of GI disorders, including Inflammatory Bowel Disease (IBD), Celiac Disease and Eosinophilic Esophagitis. An optimized GI-targeted, oral formulation of EQ302 has the potential to revolutionize treatment options for patients suffering with GI disorders by combining a strong anti-inflammatory effect with improved convenience and patient compliance compared to current biologic therapies. Equillium is targeting a first-in-human Phase 1 trial to begin in 2H 2025. With a growing number of biotech and pharma collaborations, Vivtex is emerging as a leader in oral biologics delivery and has successfully delivered on multiple internal and external therapeutic programs. Vivtex’s technology has the ability to improve the oral bioavailability of peptides multiple fold beyond what current technologies can accomplish and is providing peptide drug developers with renewed hope to create oral therapeutics. Maureen Deehan, CEO of Vivtex , commented: “This collaboration with Equillium expands our portfolio of projects and speaks to the strength and potential of our GI-ORIS™ technology. Together, we are redefining what is possible with orally available peptides and are confident that this partnership will accelerate efforts to offer more effective, accessible, and less burdensome treatment options to patients.” “This partnership underscores our confidence in Vivtex’s ability to model complex gastrointestinal environments and provide critical insights to advance the development of EQ302 for oral delivery,” said Stephen Connelly, Chief Scientific Officer at Equillium. ### About Vivtex Corporation Vivtex was launched as a spin out from the labs of Robert Langer (MIT) and Giovanni Traverso (MIT, Harvard Medical School). The company is focused on transforming the market for biologic therapies through the development of novel oral biologics including enhanced, oral versions of existing high-value biologic candidates that can only be administered by injection or infusion. To achieve its mission, Vivtex is leveraging its proprietary and extensively validated AI-enabled high-throughput GI-ORIS™ screening and formulation platform through strategic partnerships and R&D collaborations with biotechnology and pharmaceutical companies. To find out more about Vivtex, please visit our website: www.vivtex.com and LinkedIn . 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. EQ101 is a selective tri-specific cytokine inhibitor targeting IL-2, IL-9, and IL-15 being developed for dermatological conditions, and EQ302 is an orally delivered, selective bi-specific cytokine inhibitor targeting IL-15 and IL-21 being developed for gastrointestinal conditions. The multi-cytokine platform generates rationally designed composite peptides. Itolizumab, a monoclonal antibody that targets the CD6-ALCAM signaling pathway, is in a Phase 3 clinical study of patients with acute graft-versus-host disease (aGVHD) and exhibited positive results in a completed Phase 1b clinical study of patients with lupus/lupus nephritis in April 2024. For more information, visit www.equilliumbio.com . SOURCE: Equillium