IL-38

Topline data for Phase 3 RINGSIDE trial of AL102 expected in first quarter of 2025 IM-1021 and IM-3050 IND filings expected in first quarter of 2025 Current cash expected to fund activities into 2026 BOTHELL, Wash.--(BUSINESS WIRE)-- Immunome, Inc. (Nasdaq: IMNM), a biotechnology company focused on developing first-in-class and best-in-class targeted cancer therapies, today announced financial results for the full year ended December 31, 2023, and provided an overview of recent developments. “2023 was a transformative year for Immunome as we closed the merger with Morphimmune, advanced our pipeline and expanded the company’s leadership team,” said Clay B. Siegall, Ph.D., President and Chief Executive Officer. “These accomplishments laid the groundwork for a productive start to 2024, including the acquisition of two promising assets and a successful financing.” Dr. Siegall continued, “We are focused on efficiently developing our four existing assets and expanding our pipeline. We expect to add novel antibody-drug conjugates (ADCs) and radioligand therapies (RLTs) to the pipeline through internal discovery efforts while continuing to evaluate opportunities to acquire high-quality assets on favorable financial terms. We are well-positioned to develop best-in-class or first-in-class therapies to improve the lives of cancer patients.” Pipeline Highlights The purchase of AL102 from Ayala Pharmaceuticals closed on March 25, 2024. Immunome expects to report topline data for the ongoing Phase 3 RINGSIDE Part B trial of AL102 in the first quarter of 2025. Ayala previously announced the full enrollment of RINGSIDE in February 2024. In parallel, Immunome is evaluating and performing additional manufacturing and pharmacology work required to support an NDA submission of AL102. Immunome’s preclinical pipeline includes IM-1021, a ROR1 ADC; IM-3050, a FAP-targeted RLT; and IM-4320, an anti-IL-38 immunotherapy candidate. Immunome anticipates submitting investigational new drug applications (INDs) for IM-3050 and IM-1021 in the first quarter of 2025. Anticipated timing for an IND for IM-4320 will be shared at a later date. Highlights from 2023 and early 2024 Successfully completed an underwritten offering of 11.5M shares priced at $20 per share for gross proceeds of $230.0M in February 2024, providing capital that is expected to support completion of the RINGSIDE trial and advancement of IM-1021, IM-3050 and IM-4320 into clinic. Immunome’s current cash runway is expected to extend into 2026. Acquired AL102, a Phase 3 gamma secretase inhibitor with best-in-class potential, from Ayala Pharmaceuticals in March 2024. Exclusively licensed IM-1021 (formerly known as ZPC-21), a preclinical ROR1 ADC with first-in-class potential, as well as the underlying ADC linker-payload technology, from Zentalis in January 2024. Nominated IM-3050 as a FAP RLT candidate with first-in-class potential in December 2023. Completed the acquisition of Morphimmune, Inc, a concurrent PIPE of $125 million, and the transition to Clay Siegall, Ph.D. as President and CEO in October 2023. Filled leadership positions post-merger, including key members of the Executive Committee and five VP/SVP roles. Full-year 2023 Financial Results As of December 31, 2023, cash, cash equivalents and marketable securities totaled $138.1 million, which does not include gross proceeds of $230 million from the February financing. Research and development expenses for the year ended December 31, 2023 were $23.1 million. In-process research and development expenses for the year ended December 31, 2023 were $80.8 million. General and administrative expenses for the year ended December 31, 2023 were $19.7 million. Immunome reported a net loss of $106.8 million, or basic and diluted net loss per share attributable to common stockholders of $5.38, for the year ended December 31, 2023. About Immunome, Inc. Immunome is a biotechnology company dedicated to developing first-in-class and best-in-class targeted cancer therapies. Our portfolio pursues each target with a modality appropriate to its biology, including small molecules, ADCs, RLTs and immunotherapies. We believe that pursuing underexplored targets with appropriate drug modalities leads to transformative therapies. Our proprietary memory B cell hybridoma technology allows for the rapid screening and functional characterization of novel antibodies and targets. For more information, visit or follow us on Twitter and LinkedIn. Cautionary Statement Regarding Forward-Looking Statements Certain statements contained in this communication regarding matters that are not historical facts, are forward-looking statements within the meaning of Section 21E of the Securities and Exchange Act of 1934, as amended, and the Private Securities Litigation Reform Act of 1995 (the “PSLRA”). We use words such as “may,” “could,” “potential,” “will,” “plan,” “believe,” “goal,” “optimistic,” and similar expressions to identify these forward-looking statements that are intended to be covered by the safe-harbor provisions of the PSLRA. These forward-looking statements include, but are not limited to, statements regarding immunome’s expectation to add novel ADCs and RLTs to its pipeline; Immunome’s expectation to report topline data for the ongoing Phase 3 RINGSIDE Part B trial of AL102 in the first quarter of 2025; Immunome’s expected timeline for filing INDs for IM-3050 and IM-1021 in the first quarter of 2025; Immunome’s expectation that it will share a date for filing an IND for IM-4320; Immunome’s expectation that the funds from the February financing will support completion of the RINGSIDE trial and advancement of IM-1021, IM-3050 and IM-4320 into clinic; Immunome’s expected cash runway; and other statements regarding management’s intentions, plans, beliefs, expectations or forecasts for the future. No forward-looking statement can be guaranteed, and actual results may differ materially from those projected. Such forward-looking statements are based on Immunome’s expectations and involve risks and uncertainties; consequently, actual results may differ materially from those expressed or implied in the statements due to a number of factors, including, but not limited to, the risk that Immunome will not be able to realize the benefits of its strategic transactions, Immunome’s ability to grow and successfully execute on its business plan, including the development and commercialization of its pipeline; changes in the applicable laws or regulations; the possibility that Immunome may be adversely affected by other economic, business, and/or competitive factors; the risk that regulatory approvals for Immunome’s programs and product candidates are not obtained, are delayed or are subject to unanticipated conditions; the risk that pre-clinical data may not be predictive of clinical data; the risk that interim results of a clinical trial do not necessarily predict final results; potential delays in the commencement, enrollment and completion of clinical trials and the reporting of data therefrom; the risk that our product and development candidates fail to achieve their intended endpoints; the complexity of numerous regulatory and legal requirements that Immunome needs to comply with to operate its business; the reliance on Immunome’s management; the prior experience and successes of the Immunome’s management team not being indicative of any future success; uncertainties related to Immunome’s capital requirements and Immunome’s expected cash runway; the failure to obtain, adequately protect, maintain or enforce Immunome’s intellectual property rights; and other risks and uncertainties indicated from time to time described in exhibit 99.2 filed with Immunome’s Current Report on Form 8-K with Securities and Exchange Commission (“SEC”) on February 13, 2024, and in Immunome’s Annual Report on Form 10-K for the year ended December 31, 2023, being filed with the SEC later today, and in Immunome’s other filings with the SEC. Immunome cautions that the foregoing list of factors is not exclusive and not to place undue reliance upon any forward-looking statements which speak only as of the date made. Moreover, Immunome operates in a very competitive and rapidly changing environment. New risks emerge from time to time. Except as required by law, Immunome does not undertake any obligation to update publicly any forward-looking statements for any reason after the date of this press release to conform these statements to actual results or to changes in their expectations. Immunome, Inc. Consolidated Balance Sheets (in thousands, except share and per share amounts) December 31, 2023 December 31, 2022 Assets Current assets: Cash and cash equivalents $ 98,679 $ 20,323 Marketable securities 39,463 — Prepaid expenses and other current assets 6,561 2,326 Total current assets 144,703 22,649 Property and equipment, net 2,073 681 Operating right-of-use asset, net 1,564 284 Restricted cash 100 100 Deferred offering costs — 332 Other long-term assets 100 — Total assets $ 148,540 $ 24,046 Liabilities and stockholders’ equity Current liabilities: Accounts payable $ 3,311 $ 2,400 Accrued expenses and other current liabilities 8,025 4,931 Deferred revenue, current 10,493 — Total current liabilities 21,829 7,331 Deferred revenue, non-current 5,489 — Other long-term liabilities 1,340 62 Total liabilities 28,658 7,393 Commitments and contingencies (Note 8) Stockholders’ equity: Preferred stock — — Common stock 4 1 Additional paid-in capital 342,663 132,653 Accumulated other comprehensive income 22 — Accumulated deficit (222,807 ) (116,001 ) Total stockholders’ equity 119,882 16,653 Total liabilities and stockholders’ equity $ 148,540 $ 24,046 Immunome, Inc. Consolidated Statements of Operations (in thousands, except share and per share amounts) Year Ended December 31, 2023 2022 Collaboration revenue $ 14,018 $ — Operating expenses: In-process research and development 80,802 — Research and development 23,089 23,272 General and administrative 19,657 13,629 Total operating expenses 123,548 36,901 Loss from operations (109,530 ) (36,901 ) Other income: Interest income, net 2,724 5 Total other income 2,724 5 Net loss $ (106,806 ) $ (36,896 ) Deemed dividend arising from warrant modification — (622 ) Net loss attributable to common stockholders $ (106,806 ) $ (37,518 ) Per share information: Net loss per common share, basic and diluted $ (5.38 ) $ (3.09 ) Weighted-average common shares outstanding, basic and diluted 19,843,651 12,126,573 Comprehensive loss Net loss $ (106,806 ) $ (37,518 ) Unrealized gain on marketable securities 22 — Comprehensive loss $ (106,784 ) $ (37,518 )

细胞因子（Cytokine）是一类由免疫细胞或其他细胞产生的低分子量的可溶性蛋白，它们在免疫系统中起着桥梁和调节器的作用，能够促进免疫反应的启动和调节。细胞因子在炎症过程中起着重要作用，它们参与了病毒和细菌感染以及许多疾病的发展，包括癌症、自身免疫疾病、神经退行性疾病、动脉粥样硬化以及与细胞治疗相关的细胞因子风暴等。研究细胞因子的功能和调控机制有助于进一步理解免疫系统的工作原理，为新药物的研发和治疗策略的改进提供指导。细胞因子根据结构和功能主要分为：白细胞介素、肿瘤坏死因子、干扰素、生长因子、趋化因子、集落刺激因子。它们在免疫和炎症反应的调控中发挥着重要作用。白细胞介素白细胞介素简称白介素（ILs），主要由巨噬细胞和淋巴细胞产生，它能够增强T细胞、B细胞等免疫细胞的杀伤力，从而提高机体的免疫功能。白介素还具有抗肿瘤、抗病毒的功效，并且能够促进干扰素因子和其他细胞因子的分泌。白介素超家族涵盖了大量的细胞因子，目前所发现的白介素至少有38种（IL-1~IL-38），每种IL还可进一步拆分为几个亚型，如IL-1可分为IL-1α、IL-1β等，不同亚型之间具有相似的基因结构。不同的白介素作用也不完全相同，例如IL-6主要由巨噬细胞、T淋巴细胞、B淋巴细胞产生的多效细胞因子，它可以根据其浓度水平反馈炎症反应，可以调节多种细胞的生长分化、免疫应答、急性期反应以及造血功能，并在机体抗感染免疫中发挥重要作用。IL-6在急性炎症反应中处于中心地位，多种感染性疾病可导致血清IL-6水平升高。IL-6激活时间短、恢复时下降快、幅度大，是早期炎症、脓毒症，感染严重程度及预后评估的关键指标。IL-2则主要是由活化T细胞产生，可作用于多种免疫细胞，它具有促进免疫细胞的增殖和生长、增强免疫细胞的功能、促进抗体产生、调节免疫应答和平衡等作用。它能够增强和调节免疫细胞的功能，促进T细胞和B细胞的生长和活性，并增强它们对病原体的识别和攻击能力。可以用于治疗如黑色素瘤和肾细胞癌等疾病，在器官移植、自身免疫性疾病等领域中发挥重要作用，主要作用于人体免疫系统。肿瘤坏死因子肿瘤坏死因子（TNFs）是通过胞外蛋白水解或裂解从细胞膜上释放出来后作为细胞因子发挥作用，常见的分为两种类型：TNFα和TNFβ，TNFα来源于单核细胞和巨噬细胞，TNFβ则由T细胞产生，TNFα能够直接杀伤肿瘤细胞而对正常细胞无明显毒性，是在细胞内组装，形成一个非共价连接的同源三聚体，并在细胞表面进行表达。TNFα参与正常炎症反应和免疫反应，可以通过协同调节其它细胞因子的产生、细胞存活和死亡来协调组织的稳态。TNFβ与TNFα的类型结构有所区别，但生物学活性比较相似，两者都有引起肿瘤组织坏死和杀伤的作用，均能引起抗感染的炎症反应，可以促进免疫细胞的调节和诱生。干扰素干扰素（IFNs）主要分为IFNα、IFNβ、IFNγ三种类型。其中IFNγ也被称为T细胞产生的干扰素或免疫球蛋白2，主要由激活的T细胞、自然杀伤细胞（NK细胞）和某些淋巴细胞产生。IFNγ能够调节免疫细胞的功能，增强它们对病原体的杀伤能力，并调节炎症反应。此外，IFNγ还能够抑制病原体的复制和生长，增强细胞的抗病毒能力。因此，IFNγ在抵抗感染、抗肿瘤免疫和自身免疫性疾病的治疗中发挥着重要的调节作用。总之，细胞因子是评估免疫反应和炎症反应的重要指标。虽然细胞因子的靶向治疗在临床阶段仍需要克服许多障碍，但是细胞因子的研究对于剖析免疫系统功能和疾病机制至关重要，因此深入研究细胞因子的作用机制将为免疫疾病治疗领域带来更多可能性。诺唯赞作为一家拥有可控上游技术开发能力的原料供应商，推出了Add&Read®人细胞因子定量检测试剂盒，帮助客户更快速地完成检测，促进细胞因子相关研究的进展，加速新药研发。 诺唯赞Add&Read®人细胞因子定量检测系列试剂盒 诺唯赞Add&Read®人细胞因子定量检测试剂盒依托于诺唯赞自主研发的Add&Read®（免洗ELISA）技术，基于TR-FRET原理（时间分辨-荧光共振能量转移）的快速均相检测方法学。系列产品采用夹心法，用于检测细胞上清中细胞因子含量。1.产品优势✦均相的检测体系，操作简单，加样-孵育-检测，无需包被-洗板，节省人力、时间；✦试剂盒中包含了检测所需的标准品、标签抗体以及Buffer，无需调试即可直接使用，简单方便；✦节省样本（只需16 ul），适合高通量检测（兼容96孔板，384孔板）。2.检测原理 图1 Add&Read® Human cytokine assays原理示意3.检测步骤在待测样本处理后，将荧光供受体预混加入待测样本中，孵育完成后即可进行检测（图2）。图2 Add&Read® Human cytokine assays流程示意4.应用示例以IL2和IFNγ试剂盒为例，在PBMC细胞体系上进行细胞因子的释放实验，使用PMA和不同浓度的Lonomycin联合刺激细胞产生细胞因子IL2和IFNγ。分别使用Vazyme Cytokines Kit和同类方法学Competitor对应产品进行细胞上清样本检测，检测结果一致性良好，如图3、图4所示。图3、图4 诺唯赞Add&Read® Human IL2 Kit检测结果展示（左图），诺唯赞Add&Read® Human IFNγ Kit检测结果展示（右图）5.产品列表更多产品信息，可登录诺唯赞生物医药官网查看https://www.vazymebiomed.com/index.html研发动力加满，好书与您相伴为回馈新老粉丝，诺唯赞将好书送上抽取20位读者，免费获得《詹韦免疫生物学》参与方式1.关注【诺唯赞药物研发】公众号2.输入框发送：“细胞因子”3.获取链接，登记信息，即可参与抽奖活动时间3月4日-3月10日活动对象Vazyme终端客户奖品发放奖品将在活动结束两周内由诺唯赞销售员送出或快递至所预留地址识别微信二维码，添加生物制品圈小编，符合条件者即可加入生物制品微信群！请注明：姓名+研究方向！版权声明本公众号所有转载文章系出于传递更多信息之目的，且明确注明来源和作者，不希望被转载的媒体或个人可与我们联系(cbplib@163.com)，我们将立即进行删除处理。所有文章仅代表作者观点，不代表本站立场。

关注并星标CPHI制药在线          白细胞介素（IL）是由多种细胞产生并作用于多种细胞的一类细胞因子，因最初由白细胞产生、在白细胞间发挥作用而得名。IL是先天性及适应性免疫细胞以及非免疫细胞与组织间的通讯手段，在传递信息，激活与调节免疫细胞，介导细胞活化、增殖与分化及在炎症反应中起重要作用。此外，IL与多种癌症的发生和发展也密切相关。       IL是目前发现种类最多，调控作用最为广泛的一类细胞因子，已发现成员至少有38个，分别命名为IL-1~IL-38。研究发现，IL是自身免疫性疾病、炎性疾病和肿瘤药物研发的重要靶点。其中IL-1、IL-4、IL-5、IL-6、IL-13、IL-17、IL-18、IL-22、IL-23、IL-31、IL-33、IL-36等是自身免疫性疾病药物研发的潜力靶点，IL-2、IL-7、IL-8、IL-15、IL-25、IL-30等是肿瘤药研发的潜力靶点。IL-10、IL-11、IL-12、IL-21等是自身免疫性疾病和肿瘤药物研发的潜力靶点。       六款IL靶向药入围2022年全球药品销售额TOP200       IL靶点在自身免疫性疾病领域的潜力已经显现，目前全球已批准多款IL靶向药，详见下表。       从作用靶点来看，治疗自身免疫性疾病的IL靶点主要是IL-5、IL-6、IL-17、IL-23。适应症上，上述药物主要被批准用于治疗银屑病、银屑病关节炎、特应性皮炎等。值得一提的是，上述药物中多款进入重磅行列，并入围2022年全球药品销售额TOP200。其中Dupixent表现最好，2022年销售额高达87.31亿美元。Skyrizi排名第二，2022年销售额达51.65亿美元。Consentyx排名第三，2022年销售额达47.88亿美元。Actemra/RoActemra排名第四，2022年销售额达28.34亿美元。Tremfya排名第五，2022年销售额达26.68亿美元。Taltz排名第六，2022年销售额达24.82亿美元。       多款新药进入临床后期       自身免疫性疾病药物市场规模庞大，据弗若斯特沙利文测算，2022年全球自免疾病药物市场规模总体预计达到1323亿美元。IL作为自身免疫性疾病药物开发的潜力靶点，目前全球还有多款新药处于临床后期，详见下表。       这些处于临床后期的IL靶向药主要是单抗，作用靶点主要集中在IL-4R、IL-17A。与上述已获批的IL靶向药不同，处于临床后期的IL靶向药大多是国产创新药。       具体品种和靶点上看，康诺亚的司普奇拜单抗是一款针对IL-4Rα的高亲和力、人源化抗体，今年11月其用于治疗外用药控制不佳或不适合外用药治疗的成人中重度特应性皮炎的上市申请在国内被CDE纳入优先审评。       优时比的olokizumab是针对IL-6的一款新型单抗，其治疗类风湿性关节炎的上市申请正在美国接受审查。       智翔金泰的Xeligekimab和恒瑞医药的Vunakizumab均是IL-17A靶向重组人源化单抗，今年3月和4月这两款药物的上市申请先后获CDE受理。其中Xeligekimab是首款申请上市的国产抗IL-17A单抗，其治疗中重度斑块型银屑病和放射学阳性中轴型脊柱关节炎的临床试验均处于3期阶段。Vunakizumab是一款起效很快的IL-17单抗，两周内平均PASI评分可下降50%，相较而言，司库奇尤单抗需要3-4周，Vunakizumab的半衰期更长。       丽珠单抗与鑫康合联合开发的LZM012是国内首个国产创新IL-17A/F双靶向药物。目前国内还没有IL-17A/F双靶向药物获批上市，已完成的3期临床试验（BE RADIANT）结果显示：LZM012对中重度斑块型银屑病疗效优于IL-17A靶向的司库奇尤单抗。       此外，还有多款治疗自身免疫性疾病的在研IL靶向药处于1期临床、2期临床。整体来看，IL-4、IL-13、IL-17三个靶点竞争相对比较激烈，不过这三个靶点在研药物适应症侧重有所不同。IL-4、IL-13靶向药主要被开发用于治疗特应性皮炎、哮喘，IL-17靶向药主要被开发用于治疗银屑病。       总结       TNF、JAK、BTK、CD20、IL等是自身免疫性疾病药物布局的热门靶点，且均有多款药物获批上市。目前，全球获批治疗自免疾病的IL靶向药主要为单抗，且靶点相对集中，主要在IL-6、IL-17、IL-23。鉴于多款重磅IL靶向药在自身免疫性疾病领域取得可喜战绩，越来越多的药企开始布局IL靶点。值得国民骄傲的是，多款国产创新IL靶向药进入临床后期。期待越来越多的IL靶向药被批准用于治疗自身免疫性疾病。       参考资料：      1.《靶点黑马IL-4，有望进军慢阻肺》.药研网.2023-03-24       2.《研发 | 从礼来Lebrikizumab惨遭FDA拒批，浅谈IL-13靶向药进展》. CPHI制药在线.2023-10-09       3.《自免明星靶点：IL-17》.同写意Biotech.2023-07-18       作者简介：@忆，医院药师，关注国内外新药研发动态，期望在不断的输入和输出中提升自己，和医药自媒体共同成长。智药研习会12月线上课程报名来源：CPHI制药在线声明：本文仅代表作者观点，并不代表制药在线立场。本网站内容仅出于传递更多信息之目的。如需转载，请务必注明文章来源和作者。投稿邮箱：Kelly.Xiao@imsinoexpo.com▼更多制药资讯，请关注CPHI制药在线▼点击阅读原文，进入智药研习社~