IMG-007

Treatment with three doses of 300 mg (Cohort 1) and 600 mg (Cohort 2) IMG-007 over four weeks resulted in a dose-related clinical activity of hair regrowth.Patients in Cohort 2 showed a sustained improvement in Severity of Alopecia Tool (SALT) score, which did not plateau by Week 36, approximately eight months after the last dose: The mean reduction in SALT score at Week 36 was 21.7% in patients with baseline SALT score of 50 to 100, and 30.1% in the subset of patients with baseline SALT score of 50 to <95A durable inhibition of inflammatory markers of T helper (Th)1, Th2 and CD8+ T cells were observed at Week 16, approximately three months after the last dose IMG-007 was overall well-tolerated with no reports of pyrexia or chills SAN DIEGO, April 24, 2025 (GLOBE NEWSWIRE) -- Inmagene Biopharmaceuticals (“Inmagene” or the “Company”), a clinical-stage biotechnology company focused on developing innovative and differentiated therapies for immunological and inflammatory (“I&I”) diseases, today reports topline results from the Phase 2a trial of IMG-007 in patients with severe alopecia areata (“AA”). “AA is an I&I disease with tremendous unmet needs, especially for drugs with more favorable safety profiles,” said Jonathan Wang, Ph.D., founder, Chairman and CEO of Inmagene. “The marked and durable clinical and pharmacodynamic activities observed in Cohort 2 after a 4-week treatment, combined with a well-tolerated profile, suggest that blocking the OX40-OX40L signaling may be a novel approach to the treatment of AA.” The Phase 2a trial (NCT06060977) was a multiple ascending dose study evaluating the safety, pharmacokinetics, and efficacy of IMG-007 in adult AA patients with 50% or greater scalp hair loss, measured by the SALT score. A total of 29 patients were enrolled from 11 centers in the U.S. and Canada, including 6 patients in Cohort 1 who received up to three intravenous (IV) doses of 300 mg over four weeks (Baseline, Week 2 and 4) and 23 patients in Cohort 2 who received up to three IV doses of 600 mg over four weeks. Patients were followed up to Week 24. Sixteen patients in Cohort 2 also participated in an optional extended follow-up period up to Week 36. Key disease characteristics at baseline included a mean duration of current AA episode of 3.0 years and a mean SALT score of 80.4. Nine of 29 (31%) enrolled patients had baseline SALT scores of 95 or greater. Scalp biopsy samples were collected at Baseline and Week 16 for the evaluation of inflammatory biomarkers. Key study endpoints included safety and percentage change from baseline in SALT score over time. The four-week treatment resulted in a dose-related clinical activity of hair regrowth. Patients in Cohort 1 did not show a meaningful reduction from baseline (a mean of 1.1%) in SALT score at Week 24. Patients in Cohort 2 showed a mean reduction from baseline in SALT score of 14.3% at Week 24 and 21.7% at Week 36, which did not plateau by Week 36, approximately eight months after the last dose. At Week 36, 25% of patients in Cohort 2 achieved 30% or greater reduction from baseline in SALT score. In Cohort 2, patients who had a baseline SALT score of 50 to less than 95 showed a greater degree of improvement compared to those in the overall group (Table 1). Table 1. Improvement in SALT score in patients in Cohort 2 who had baseline SALT score of 50 to less than 95 Week 24 (n=17)Week 36 (n=11)Mean % reduction from baseline in SALT score20.1%30.1%Proportion of patients achieving ≥ 30% reduction from baseline in SALT score11.8%36.4% At baseline, patients showed activations of inflammatory markers of Th1, Th2, and CD8+ T cells in the AA lesional scalp, compared to the non-lesional scalp. A four-week treatment with three doses of 600 mg IMG-007 resulted in a marked inhibition of inflammatory markers of Th1, Th2 and CD8+ T cells at Week 16, approximately three months after the last dose. IMG-007 was generally well-tolerated, with no serious adverse events (SAEs). All treatment-emergent adverse events (TEAEs) were mild or moderate in intensity. TEAEs which occurred in at least 2 patients in any treatment group were headache (4 [13.8%]), nasopharyngitis (3 [10.3%]), hypertension (2 [6.9%]), and streptococcal infection (2 [6.9%]). There were no reports of pyrexia or chills. “Alopecia areata is a common chronic I&I disease affecting up to 2% of the population, including children. Currently, oral JAK inhibitors are the only systemic treatment options, but they require daily dosing and carry serious safety warnings, thus requiring routine clinical and laboratory monitoring. Safe and effective biologic therapies are desirable for the long-term management of this devastating disease,” said Yufang Lu, M.D., Ph.D., Chief Medical Officer of Inmagene. “The promising results from Cohort 2 in this study suggest that IMG-007 could be a potential biologic therapy for the long-term treatment of patients with AA.” Data from this study will be presented at an upcoming scientific conference. About Inmagene Inmagene is a global clinical-stage biotechnology company focused on developing novel therapeutics for immunological and inflammatory (“I&I”) diseases. The company has multiple drug candidates with best-in-class potential. The lead asset IMG-007, a nondepleting anti-OX40 monoclonal antibody with extended half-life, is in Phase 2 development for moderate-to-severe atopic dermatitis (AD) and alopecia areata (AA). IMG-004, a non-covalent reversible oral BTK inhibitor with an extended half-life and pharmacodynamic effect, enabling once-daily dosing potential, is ready for Phase 2 development. For more information, please visit www.inmagenebio.com. About IMG-007 IMG-007 is a humanized, non-depleting, subcutaneous-enabled, anti-OX40 IgG1 mAb with a silenced antibody-dependent cell-mediated cytotoxicity (ADCC) function and an extended half-life. The OX40-OX40L axis is important in T cell activation, expansion, and survival, thereby playing an important role in the pathogenesis of a spectrum of I&I diseases. In nonclinical studies, IMG-007 potently blocked the signaling between OX40 and OX40L. IMG-007’s SC formulation has demonstrated a half-life of 34.7 days which would support the potential for competitive dose regimens. In a Phase 2a study in patients with moderate-to-severe atopic dermatitis, IMG-007 demonstrated sustained clinical activity and a well-tolerated profile with no reports of pyrexia or chills. IMG-007 was originally discovered by HUTCHMED. Participants in the Solicitation This press release may be deemed to be solicitation material in respect of the previously announced proposed merger involving Ikena Oncology, Inc. (“Ikena”) and Inmagene. In connection with the proposed transactions, Ikena has filed and will file relevant materials with the Securities and Exchange Commission (“SEC”), including the Registration Statement on Form S-4 (File No. 333-285881) (the “Registration Statement”), initially filed by Ikena with the SEC on March 18, 2025, which contains a proxy statement (the “Proxy Statement”) and prospectus. This communication is not a substitute for the Registration Statement, the Proxy Statement or for any other document that Ikena may file with the SEC and or send to Ikena’s stockholders in connection with the proposed transactions. Ikena, Inmagene, and their respective directors and certain of their executive officers may be considered participants in the solicitation of proxies from Ikena’s stockholders with respect to the proposed transactions under the rules of the SEC. Information about the directors and executive officers of Ikena is set forth in its proxy statement, which was filed with the SEC on April 26, 2024, and in subsequent documents filed with the SEC. Additional information regarding the persons who may be deemed participants in the proxy solicitations and a description of their direct and indirect interests, by security holdings or otherwise, is included in the Registration Statement, the Proxy Statement and other relevant materials to be filed with the SEC when they become available. You may obtain free copies of these documents as described below. BEFORE MAKING ANY VOTING DECISION, INVESTORS AND SECURITY HOLDERS OF IKENA ARE URGED TO READ THE REGISTRATION STATEMENT, THE PROXY STATEMENT AND OTHER DOCUMENTS FILED WITH THE SEC CAREFULLY AND IN THEIR ENTIRETY WHEN THEY BECOME AVAILABLE BECAUSE THEY WILL CONTAIN IMPORTANT INFORMATION ABOUT IKENA, INMAGENE, THE PROPOSED TRANSACTIONS AND RELATED MATTERS. No Offer or Solicitation This communication does not constitute an offer to sell or the solicitation of an offer to buy any securities nor a solicitation of any vote or approval with respect to the proposed transactions herein or otherwise. No offering of securities shall be made except by means of a prospectus meeting the requirements of Section 10 of the U. S. Securities Act of 1933, as amended, and otherwise in accordance with applicable law. Forward-Looking Statements This press release contains “forward-looking statements” within the meaning of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995. Inmagene’s and Ikena’s actual results may differ from their expectations, estimates and projections and consequently, you should not rely on these forward-looking statements as predictions of future events. Words such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” “propose” or the negative of these terms, or other comparable terminology intended to identify statements about the future. Forward-looking statements contained in this press release include, but are not limited to, statements about: the proposed merger and related transactions; The potential of IMG-007 including as a biologic therapy for the long-term treatment of patients with AA; blocking the OX40-OX40L signaling may be a novel approach to the treatment of AA; the estimated patient population of AA; and the Company’s pipeline having best in class potential. These forward-looking statements involve significant risks and uncertainties that could cause the actual results to differ materially from the expected results. Most of these factors are outside Inmagene’s and Ikena’s control and are difficult to predict. Factors that may cause such differences include, but are not limited to the risk that the conditions to closing of the proposed merger or concurrent financing are not satisfied, including the failure to timely obtain shareholder approval for the merger agreement and the transactions contemplated thereby, if at all; uncertainties as to the timing of the consummation of the proposed merger; potential adverse reactions or changes to business relationships resulting from the announcement or completion of the proposed transactions; risks associated with the possible failure to realize certain anticipated benefits of the proposed transactions, including with respect to future financial and operating results; the potential for the occurrence of any event, change or other circumstance or condition that could give rise to the termination of the merger agreement and any agreements entered into in connection therewith; risks associated with the clinical development and regulatory approval of product candidates; risks related to the inability of the combined company to obtain sufficient additional capital to continue to advance these product candidates; uncertainties in obtaining successful clinical results for product candidates and unexpected costs that may result therefrom; ; clinical results may not be indicative of results that may be observed in the future; Inmagene’s ability to successfully commercialize IMG-007 and any future product candidates, if approved, the rate and degree of market acceptance of IMG-007 and any future product candidates and the favorability of pricing regulations, reimbursement practices from third-party payors or healthcare reform initiatives in the United States and abroad; developments and projections relating to Inmagene’s competitors, its industry or the market opportunities for IMG-007 or any future product candidates; regulatory, political, environmental and public health developments in the United States and foreign countries; and the ability of Inmagene to maintain and protect its intellectual property rights. Actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. These and other risks and uncertainties are more fully described in periodic filings with the SEC, including the factors described in the section titled “Risk Factors” in the Registration Statement and in Ikena’s Annual Report on Form 10-K for the year ended December 31, 2023, filed with the SEC on March 6, 2025, and in other filings that Ikena makes and will make with the SEC in connection with the proposed merger, including the Proxy Statement described below under “Additional Information and Where to Find It.” You should not place undue reliance on these forward-looking statements, which are made only as of the date hereof or as of the dates indicated in the forward-looking statements. Inmagene and Ikena expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward-looking statements contained herein to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statements are based. This press release does not purport to summarize all of the conditions, risks and other attributes of an investment in Ikena or Inmagene. Additional Information and Where to Find It Investors and security holders will be able to obtain free copies of the Registration Statement, the Proxy Statement and other documents filed by Ikena with the SEC through the website maintained by the SEC at http://www.sec.gov. Copies of the documents filed by Ikena with the SEC will also be available free of charge on Ikena’s website at www.ikenaoncology.com, or by contacting Ikena’s Investor Relations at rcohen@ikenaoncology.com. For further information, please contact:Inmagene:Anna Vardanyan, MD, PhDSVP of Corporate and Business Developmentpublic.relations@inmagenebio.com Investor Relations:Bruce MackleLifeSci Advisors, LLCbmackle@lifesciadvisors.com

在自免药物领域，OX40靶点正掀起一场颠覆性变革。安进、赛诺菲凭III期临床领跑，创响/和黄以非耗竭性抗体突围，共撼度普利尤单抗在自免领域的“药王”地位，推动免疫治疗升级。作者｜momo  01  OX40赛道研发竞速OX40是肿瘤坏死因子受体超家族成员，主要在活化后的T细胞上表达，包括初级效应Th2细胞和其他T细胞亚群如Th1、Th17和Th22，而不在幼稚CD4+或CD8+T细胞上表达，其配体OX40L主在抗原呈递细胞上表达，OX4与配体OX40L连接后激活下游免疫应答，刺激效应CD4+和CD8+T细胞群的克隆扩增，上调促炎细胞因子的表达，并促进T细胞的存活（图1）。图1.OX40/OX40L作用机制针对OX40靶点的药物研发主要集中在两个方面：OX40激动剂主要开发用于肿瘤治疗，其作用机制是通过激活肿瘤特异性效应T细胞的免疫应答，从而显著增强对肿瘤细胞的清除能力；OX40/OX40L拮抗剂则被广泛应用于自身免疫疾病的治疗，其通过特异性阻断OX40与OX40L的相互作用，有效抑制过度激活的免疫反应。由于OX40通路位于免疫调控网络的上游，使得OX40/OX40L拮抗剂能够广泛抑制多条自免相关信号通路。这种独特的作用特点使其具有更持久的治疗效果，是极具潜力的自免疾病靶点。表1.全球特应性皮炎的OX40/OX40L靶点主要在研管线数据来源：公开资料整理据不完全统计，截至目前，全球针对OX40/OX40L靶点的特应性皮炎生物制剂主要有7个在研项目，其中安进/协和麒麟的 Rocatinlimab 和赛诺菲的Amlitelimab全球进展最快，均处于临床III期阶段。国内进度较快的企业主要有创响生物/和黄医药、百奥泰和信达生物等，目前均已进入临床阶段（表1）。其中，Rocatinlimab最初由协和麒麟研发，2021年安进斥资12.5亿美元获得其日本以外的全球市场权益；Amlitelimab由Kymab开发，2021年赛诺菲斥资14.5亿美元收购Kymab将其纳入囊中；IMG-007则是由创响生物在2024年从和黄医药引进。2024年，达必妥（度普利尤单抗）以141.79亿美元的销售额超越修美乐（阿达木单抗）加冕新一代“自免药王”。尽管已获批7项适应症，其百亿美元市场规模的基石仍在于特应性皮炎（AD）领域的统治地位。然而，随着OX40赛道的研发竞速，直指度普利尤单抗的统治地位，推动OX40单抗成为免疫治疗新焦点。  02  安进Rocatinlimab三期告捷赛诺菲Amlitelimab前途未定Rocatinlimab（KHK4083）是协和麒麟研发的一款靶向共刺激受体OX40的全人源单抗，用于治疗特应性皮炎，已进入临床III期阶段，并有望用于治疗其他自身免疫疾病如哮喘等。3月8日，安进（Amgen）和协和麒麟（Kyowa Kirin）共同宣布Rocatinlimab治疗特应性皮炎的两项III期研究（ROCKET-IGNITE和ROCKET-SHUTTLE）达到主要终点（图2）。图2.Rocatinlimab治疗特应性皮炎的两项III期研究达到主要终点该药物是全球首款顺利完成III期研究的抗OX40单抗，并且已经连续在3项III期研究中取得积极结果（图3），有望成为全球首个上市的OX40单抗。ROCKET-IGNITE研究评估了每月给药一次的低剂量和高剂量 OX40 抑制剂的效果。结果显示，治疗第24周，低剂量组和高剂量组分别有19.1%和23.6%的患者达到vIGA-AD 0/1且较基线至少降低2分，与安慰剂组之间的差异分别为10.3%（p=0.002）和14.9%（p<0.001）；低剂量组和高剂量组分别有36.3%和42.3%的患者达到EASI 75，与安慰剂组之间的差异分别为23.4%（p<0.001）和29.5%（p<0.001），达到主要终点，且安全性良好。图3.Rocatinlimab在特应性皮炎的临床III期研究布局ROCKET-SHUTTLE研究评估了Rocatinlimab联合局部皮质类固醇药物或钙调磷酸酶抑制剂（TCS/TCI）的效果。研究显示，治疗第24周，低剂量组和高剂量组分别有25.8%和26.1%的患者达到vIGA-AD 0/1且较基线至少降低2分，与安慰剂组之间的差异分别为13.5%（p<0.001）和13.8%（p<0.001）；低剂量组和高剂量组分别有54.1%和52.3%的患者达到EASI 75，与安慰剂组之间的差异分别为30.4%（p<0.001）和28.7%（p<0.001）。此前，Rocatinlimab已经在2024年9月顺利完成了其第一项III期研究（ROCKET-HORIZON）。综合三项III期研究的结果，Rocatinlimab有望成为特应性皮炎患者的全新治疗选择。然而，赛诺菲的Amlitelimab却因治疗哮喘的II期研究（TIDE-Asthma）未达主要终点，为这款潜在重磅药物的前程增加了几分不确定性。Amlitelimab是一款靶向OX40L的全人源非清除性单克隆抗体，能够阻断OX40L，相比直接作用于OX40具备优势（图4）。该药目前在特应性皮炎和哮喘适应症上处于临床IIb期阶段。图4.Amlitelimab的作用机制4月15日，赛诺菲宣布Amlitelimab治疗哮喘的II期TIDE-Asthma研究未达到主要终点（年化恶化率未降低），但披露关键亚组数据后调整策略。TIDE-Asthma研究评估了Amlitelimab对比安慰剂作为附加治疗用于治疗中重度哮喘成人患者的效果。初步结果表明，高剂量组第48周的年化发作率未达到主要终点，但中等剂量组相比安慰剂组显示出“统计学显著且具有临床意义”的哮喘发作次数降低。此外，在60周时，高剂量组患者的哮喘年化发生率降幅更大。图5.Amlitelimab研发进度在亚组分析中，amlitelimab在异质性炎症哮喘患者群体中展现出“令人信服的疗效”。若后续研究能验证这一发现，可能为这一长期缺乏有效疗法的患者群体带来突破性治疗方案。基于该积极结果，赛诺菲表示将按计划推进amlitelimab的Ⅲ期临床试验（图5）。与此同时，赛诺菲还在推进该药物在特应性皮炎、化脓性汗腺炎、系统性硬化症等多项适应症的临床研究，其中特应性皮炎适应症已进入临床Ⅲ期，有望成为下一个度普利尤单抗，共同捍卫赛诺菲在免疫炎症领域的王者地位。  03  和黄/创响黑马亮剑同一赛道，中国药企创响生物自主研发的IMG-007在特应性皮炎患者中的临床IIa期研究中取得积极顶线结果（图6）。IMG-007是目前全球唯一处于临床期、非耗竭性抗OX40的单克隆抗体，以独特的方式靶向OX40受体，不清除T细胞，并且半衰期长，具有同类最佳的潜力。IMG-007最初由和黄医药发现，创响生物负责从药物候选阶段进行全球开发至今，拥有IMG-007的全球权利的独家选择权。IMG-007在特应性皮炎患者中的临床IIa期研究（NCT05984784）评估了IMG-007静脉注射给药在成人中重度AD患者中的安全性、药代动力学（PK）和有效性。研究共纳入了来自美国和加拿大6家研究中心的13例患者。图6.IMG-007在特应性皮炎患者中的临床IIa期研究中取得积极顶线结果研究结果显示，经IMG-007 治疗第16周，EASI评分较基线平均下降了77%，并且54%的患者达到了EASI-75的改善标准。该疗效表现与其他靶向OX40/OX40L的研究性单克隆抗体在较长治疗周期中的疗效相当。此外，研究中还观察到IMG-007对多种辅助性 T 细胞 （包括 Th1、Th2 和 Th17 细胞） 的血清炎症标志物有持续时间长达 24 周的抑制作用。且研究中并未发生严重不良事件 （SAE）, 未报告导致研究药物停药的不良事件，且未报告与研究药物相关的不良事件。无患者报告发热或寒颤。值得注意的是，创响生物还开展了一项评估IMG-007皮下注射制剂在16名健康受试者中的安全性和PK特征的1期临床研究（NCT06304740）。研究结果显示，其药代动力学特征与静脉注射剂型相似，在预期有效剂量下，18 周内血清药物浓度可阻断 OX40/OX40L 信号传导。该制剂平均消除半衰期达 34.7 天，长于同类临床开发药物。此外，IMG-007 SC 耐受性和安全性良好，常见不良事件为轻度注射部位反应，且发生率低于安慰剂组。创响预计在2025年启动在IMG-007皮下注射剂在中重度特应性皮炎患者中的Phase 2b剂量探索研究。作为中国药企自主研发的成果，IMG-007 正以黑马之姿，向特应性皮炎治疗的现有格局发起冲击，有望打破度普利尤单抗的垄断局面，引领特应性皮炎治疗领域进入全新的竞争时代。  结语  OX40靶点的崛起，标志着自免治疗从“下游通路抑制”转向“上游免疫调控”。“中外双雄”共同构成了对度普利尤单抗的围剿之势。若OX40药物能在长期安全性和患者依从性上持续验证，或将重塑特应性皮炎治疗格局，开启自免领域“去IL-4Rα化”的新时代。参考资料[1]https://www.sanofi.com/en/media-room/press-releases/2025/2025-04-15-05-00-00-3061368[2]https://www.amgen.cn/cn/media/news-release.html[3]https://inmagenebio.com/press-release/inmagene-reports-positive-topline-results-of-img-007-a-nondepleting-anti-ox40-monoclonal-antibody-with-an-extended-half-life-for-the-treatment-of-atopic-dermatitis/[4]华创研究研报、平安证券研报、各种公开资料共建Biomedical创新生态圈！如何加入BiG会员？