Ipilimumab

Givastomig data presented at ESMO 2024 and SITC 2024 highlights encouraging monotherapy data On track to dose first patient in randomized Phase 2 study of uliledlimab in first-line mNSCLC in 1H 2025 Appointed Dr. Sean Fu as permanent CEO effective November 1, 2024 Estimated cash runway into 2027, based on $184.4 million in cash and cash equivalents, and short-term investments as of September 30, 2024 ROCKVILLE, Md., Nov. 14, 2024 /PRNewswire/ -- I-Mab (NASDAQ: IMAB) (the "Company"), a U.S.-based, global biotech company, exclusively focused on the development of highly differentiated immunotherapies for the treatment of cancer, today announced financial results for the three and nine months ended September 30, 2024, and highlighted recent pipeline progress and business updates. "I-Mab is making excellent progress in advancing the development of our pipeline projects, supported by our strong cash balance, streamlined operating model, and a focused in-licensing strategy," said Dr. Sean Fu, CEO and Board Member of I-Mab. "In addition, Phase 1 data presented this year for uliledlimab, givastomig, and ragistomig at four international medical conferences highlight the strength of our early data sets for each program. These results have provided us with a strong foundation for advancing each molecule into expanded clinical trials, including Phase 2 studies, in the next year." Pipeline Overview and Potential Upcoming Milestones: Uliledlimab (CD73 antibody): Initiating a randomized Phase 2 combination study in first-line metastatic non-small cell lung cancer ("mNSCLC") Uliledlimab (TJ004309) is an antibody designed to target CD73, the rate-limiting enzyme critical for adenosine-driven immunosuppression in the tumor microenvironment. I-Mab owns worldwide rights to uliledlimab outside of Greater China. Pharmacokinetic/pharmacodynamic ("PK/PD") Phase 1 data presented at the 2024 World Conference on Lung Cancer ("WCLC 2024") in September showed that uliledlimab achieved full target engagement with a positive correlation between the overall response rate ("ORR") in patients with mNSCLC and uliledlimab exposure. The Company is on track to dose the first patient in the randomized Phase 2 study in patients with first-line mNSCLC testing multiple doses of uliledlimab in combination with pembrolizumab plus chemotherapy versus standard of care in 1H 2025. Givastomig (Claudin 18.2 x 4-1BB bispecific antibody): Ongoing Phase 1b escalation and expansion study in combination with nivolumab plus chemotherapy in first-line metastatic gastric cancer Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2 ("CLDN 18.2")-positive tumor cells that conditionally activates T cells via 4-1BB in the tumor microenvironment, with potential CLDN 18.2 specificity even in tumors with low levels of CLDN 18.2 expression. The program is being jointly developed with ABL Bio. Topline Phase 1 monotherapy dose escalation and dose expansion data presented at the European Society for Medical Oncology ("ESMO 2024") in September 2024 showed promising objective responses in patients with gastric cancers expressing CLDN 18.2 across low and high levels and defined the optimal monotherapy dose range (8-12 mg/kg). The study showed an ORR of 16.3% (7/43), including seven partial responses ("PR") at doses between 5 mg/kg and 18 mg/kg, with five of the seven patients (71%) having received prior checkpoint inhibitor therapy. Stable disease ("SD") was reported in 14 patients, with a disease control rate ("DCR") of 48.8% (21/43 patients). The safety profile was favorable, with mainly grade 1 or 2 treatment-related adverse events ("TRAEs") and no observations of dose-limiting toxicities ("DLTs") or identification of a maximum tolerated dose ("MTD"). I-Mab presented a poster highlighting Phase 1 pharmacokinetic modeling data for optimizing dose estimation of givastomig at the Society for Immunotherapy of Cancer ("SITC 2024") on November 9, 2024, based on three clinical studies and additional nonclinical data. The studies demonstrated a dose-response relationship for givastomig and supported 8-12 mg/kg administered every two weeks ("Q2W") as the optimal monotherapy dose range for gastric cancer patients. Topline data from the on-going Phase 1b study evaluating givastomig in combination with nivolumab plus chemotherapy are expected in 2H 2025 in patients with treatment-naïve CLDN 18.2-positive metastatic gastric cancer. The primary endpoint is safety, with secondary endpoints including tumor response, PK/PD, and survival. Ragistomig (PD-L1 x 4-1BB bispecific antibody): Ongoing Phase 1 dose escalation and dose expansion in advanced and/or PD-L1 positive, solid tumors Ragistomig (TJ-L14B / ABL503) is a bispecific, Fc-silent antibody designed to provide anti-PD-L1 activity and conditional 4-1BB-driven T-cell activation in one molecule. The program is being jointly developed with ABL Bio. In October, the United States Patent and Trademark Office ("USPTO") issued a composition of matter patent for ragistomig, providing coverage through February 2039 before consideration of any potential patent term extensions. Additional dose schedules are being explored to maximize the therapeutic index in advanced and/or PD-L1-positive solid tumors. Significant Strategic Progress and Corporate Development Appointment of Dr. Sean (Xi-Yong) Fu, PhD, MBA, as Chief Executive Officer: Dr. Fu was appointed as the Company's permanent Chief Executive Officer ("CEO") effective November 1, 2024. Dr. Fu has served as the Company's Interim CEO since July 15, 2024. Dr. Fu will continue to serve as a member of the I-Mab Board of Directors. Dr. Fu has over 20 years of experience in the life sciences industry, leading and developing clinical-stage assets. Sanofi S.A. ("Sanofi") / TJ Biopharma ("TJ Bio") agreement for uliledlimab: On September 25, 2024, Sanofi and TJ Bio entered into a collaboration agreement to develop and commercialize uliledlimab in Greater China. The agreement includes an initial payment and near-term milestone payments totaling approximately €32 million, with the potential to receive up to €213 million in success-based milestone payments plus tiered royalties based on sales, with upside from potential expanded indications. I-Mab holds worldwide rights, excluding Greater China. Settlement of remaining repurchase obligations: I-Mab settled the remaining RMB equivalent of approximately $15 million in redemption obligations related to the divestiture of its China operations in mid-September 2024. As previously disclosed, in connection with the divestiture of I-Mab's China operations, certain non-participating shareholders of TJ Bio commenced arbitration against I-Mab Biopharma Hong Kong Limited. As reported in the Company's 1H 2024 business update, the RMB equivalent of $17.3 million related to the ongoing arbitration with certain non-participating shareholders was settled from funds previously placed into escrow, which was accounted for in prepayments and other current assets. I-Mab's ownership in TJ Bio post-settlement of the repurchase obligations is approximately 15%. As a result of the settlement of the redemption obligations, the corresponding put right liability was fully extinguished. Third Quarter 2024 Financial Results Cash Position As of September 30, 2024, the Company had cash and cash equivalents, and short-term investments of $184.4 million, compared to $311.0 million as of December 31, 2023. There was $10.8 million of cash classified as discontinued operations as of December 31, 2023. The Company expects its existing cash and cash related balances to be sufficient to fund its current operating plan into 2027. Shares Outstanding As of September 30, 2024, the Company had 187,452,500 ordinary shares issued and outstanding, representing the equivalent of 81,501,087 ADSs, assuming the conversion of all ordinary shares into ADSs. Research & Development Expenses Research and development ("R&D") expenses were $4.5 million and $15.7 million for the three and nine months ended September 30, 2024, respectively, compared to $5.1 million and $13.3 million for the three and nine months ended September 30, 2023, respectively. R&D costs for the three months ended September 30, 2024, were $0.6 million lower than the comparable period in 2023, primarily due to streamlined clinical pipeline activities. R&D costs for the nine months ended September 30, 2024, were $2.4 million higher than the comparable period in 2023, driven by higher clinical trial costs associated with the preparation of enrollment for the uliledlimab Phase 2 combination study and increased spend on the givastomig Phase 1b dose expansion study. These higher costs were partially offset by decreased share-based compensation expense. Administrative Expenses Administrative expenses were $7.9 million and $22.3 million for the three and nine months ended September 30, 2024, respectively, compared to $5.9 million and $19.9 million for the three and nine months ended September 30, 2023, respectively. The increase of $2.0 million and $2.4 million for the three and nine months ended September 30, 2024, respectively, were primarily driven by legal costs associated with the litigation against Inhibrx, Inc., partially offset by lower share-based compensation expense. Other Income (Expenses), Net Other income (expenses), net were $(10.5) million and $(5.0) million for the three and nine months ended September 30, 2024, respectively, compared to $2.4 million and $(9.1) million for the three and nine months ended September 30, 2023, respectively. The $12.9 million increase in other expenses for the three months ended September 30, 2024, was primarily driven by the settlement of the TJ Bio repurchase obligations. The $4.1 million decrease in other expenses for the nine months ended September 30, 2024, was primarily driven by a smaller impact from foreign exchange losses for the current period, partially offset by the settlement of the TJ Bio repurchase obligations. Net Loss from Continuing Operations Net loss from continuing operations was $(20.5) million and $(38.9) million for the three and nine months ended September 30, 2024, respectively, compared to $(8.2) million and $(45.3) million for the three and nine months ended September 30, 2023, respectively. About I-Mab I-Mab (NASDAQ: IMAB) is a U.S.-based, global biotech company, exclusively focused on the development of highly differentiated immunotherapies for the treatment of cancer. I-Mab has established operations in the U.S. in Rockville, Maryland, and Short Hills, New Jersey. For more information, please visit and follow us on LinkedIn and X. Exchange Rate Information As part of I-Mab's strategic transition to a US-based biotech, effective April 2, 2024, the Company changed its reporting currency from RMB to USD. As indicated in its interim financial results, reported on August 28, 2024, the Company applied this change retrospectively to its historical results of operations and financial statements, as if the Company had always used the U.S. dollar as its reporting currency. I-Mab Forward Looking Statements This announcement contains forward-looking statements. These statements are made under the "safe harbor" provisions of the U.S. Private Securities Litigation Reform Act of 1995. These forward-looking statements can be identified by terminology such as "will", "expects", "believes", "designed to", "anticipates", "future", "intends", "plans", "potential", "estimates", "confident", and similar terms or the negative thereof. I-Mab may also make written or oral forward-looking statements in its periodic reports to the U.S. Securities and Exchange Commission (the "SEC"), in its annual report to shareholders, in press releases and other written materials and in oral statements made by its officers, directors or employees to third parties. Statements that are not historical facts, including statements about I-Mab's beliefs and expectations, are forward-looking statements. Forward-looking statements in this press release include, without limitation, statements regarding: the Company's pipeline and capital strategy; the projected advancement of the Company's portfolio and anticipated milestones and related timing; the market opportunity and I-Mab's potential next steps (including the potential expansion, differentiation, or commercialization) for uliledlimab, givastomig and ragistomig; the Company's expectations regarding the impact of data from ongoing and future clinical trials; the Company's financial condition and results of operations; the Company's expectations regarding its cash runway; timing and progress of studies and trials (including with respect to patient enrollment); the availability of data and information from ongoing studies and trials; and the patent protection available for the Company's product candidates. Forward-looking statements involve inherent risks and uncertainties that may cause actual results to differ materially from those contained in these forward-looking statements, including but not limited to the following: I-Mab's ability to demonstrate the safety and efficacy of its drug candidates; the clinical results for its drug candidates, which may or may not support further development or New Drug Application/Biologics License Application (NDA/BLA) approval; the content and timing of decisions made by the relevant regulatory authorities regarding regulatory approval of I-Mab's drug candidates; I-Mab's ability to achieve commercial success for its drug candidates, if approved; I-Mab's ability to obtain and maintain protection of intellectual property for its technology and drugs; I-Mab's reliance on third parties to conduct drug development, manufacturing and other services; and I-Mab's limited operating history and I-Mab's ability to obtain additional funding for operations and to complete the development and commercialization of its drug candidates, as well as those risks more fully discussed in the "Risk Factors" section in I-Mab's most recent annual report on Form 20-F, as well as discussions of potential risks, uncertainties, and other important factors in I-Mab's subsequent filings with the SEC. All forward-looking statements are based on information currently available to I-Mab. I-Mab undertakes no obligation to publicly update or revise any forward-looking statements, whether as a result of new information, future events, or otherwise, except as may be required by law. I-Mab Investor & Media Contacts Notes: (1) Includes share-based compensation expense of $0.6 million and $0.9 million for the three and nine months ended September 30, 2024, respectively, compared to $0.6 million and $2.3 million for the three and nine months ended September 30, 2023, respectively. (2) Includes share-based compensation expense of $(0.3) million and ($3.7) million for the three and nine months ended September 30, 2024, respectively, compared to $1.5 million and $6.2 million for the three and nine months ended September 30, 2023, respectively. The period ended September 30, 2024 includes forfeitures as a result of the divestiture of China operations and organizational changes. (3) Includes share-based compensation expense of $0.0 million and ($0.7) million for the three and nine months ended September 30, 2024, respectively, compared to $0.1 million and $0.7 million for the three and nine months ended September 30, 2023, respectively. The period ended September 30, 2024 includes forfeitures as a result of the divestiture of China operations. (4) Includes share-based compensation expense of $0.0 million and ($11.5) million for the three and nine months ended September 30, 2024, respectively, compared to $2.7 million and $14.8 million for the three and nine months ended September 30, 2023, respectively. The period ended September 30, 2024 includes forfeitures as a result of the divestiture of China operations. (5) Each 10 ADSs represents 23 ordinary shares. SOURCE I-Mab Biopharma WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

点击蓝字 关注我们 编者按 免疫治疗已改变了不可切除肝细胞癌（HCC）的治疗格局。目前，阿替利珠单抗联合贝伐珠单抗（atezo-bev）和度伐利尤单抗联合tremelimumab在许多国家已获得监管部门的批准，作为HCC患者的一线治疗选择。此外，也有数据支持其他免疫治疗组合的使用，如纳武利尤单抗联合伊匹木单抗（nivo-ipi）、卡瑞利珠单抗联合瑞戈非尼和信迪利单抗联合贝伐珠单抗生物类似药。但是，对于在一线免疫治疗后疾病仍出现进展的HCC患者而言，如何确定最佳后续治疗方案成为了一个治疗难题和亟待满足的临床需求。 当前国际指南普遍倾向于推荐在免疫治疗后采多激酶抑制剂（MKI）药物（诸如索拉非尼或仑伐替尼），这一建议主要基于以下几点考量：这些药物在一线治疗中的疗效与安全性已得到证实；这些药物具有广泛的可用性；同时，其作用机制也被认为是合理的。然而，需要注意的是，在此特定情境下，这些推荐尚缺乏直接基于确凿证据的支持。 因此，香港中文大学威尔斯亲王医院临床肿瘤科的Landon L.Chan博士、加州大学旧金山分校Helen Diller家庭综合癌症中心的Robin K Kelley博士、香港中文大学香港癌症研究所邵逸夫爵士癌症中心转化肿瘤学国家重点实验室的Stephen L. Chan博士回顾了近日发布的前瞻性和回顾性研究数据，总结出了一套在晚期HCC患者一线免疫治疗后出现疾病进展后的治疗方法。 从左到右依次为：Dr. Landon L.Chan、Dr. Robin Katie Kelley、Stephen L. Chan 一、免疫治疗进展后应用MKI的前瞻性研究数据 1.卡博替尼 最近一项在亚洲进行的多中心Ⅱ期研究证明了卡博替尼在免疫治疗失败后患者中的疗效和安全性，这是该领域的第一项前瞻性证据。 该研究纳入了47例接受过1种或多种前期免疫治疗的患者。总体中位无进展生存期（mPFS）为4.1个月，中位总生存期（mOS）为9.9个月。当仅限于二线治疗环境时，卡博替尼的mPFS为4.3个月，mOS为14.3个月。值得注意的是，这些数值与索拉非尼和仑伐替尼在二线环境中的真实世界疗效相当，mPFS在3~6个月之间，mOS在12~18个月之间。安全性特征与以往研究相似，最常见的不良反应包括手足皮肤反应、疲劳和腹泻。尽管如此，3级或更高级别的毒性反应并不常见，最常见的3级或更高级别的毒性反应是血小板减少症。 2.瑞戈非尼 在2024年美国临床肿瘤学会胃肠道肿瘤研讨会（ASCO GI）上，另一种MKI药物瑞戈非尼被评估作为一线阿替利珠单抗联合贝伐珠单抗治疗后疾病进展的不可切除HCC患者的二线治疗方案。该研究是在韩国进行的一项前瞻性Ⅱ期临床研究，共入组40例患者，所有患者先前均接受过至少2个周期的阿替利珠单抗联合贝伐珠单抗治疗。在疗效方面，患者的mPFS为3.5个月，mOS为9.7个月，ORR为10%，疾病控制率（DCR）为82.5%。在安全性方面，高级别治疗相关不良事件（TRAEs）不常见，最常见的3~4级TRAEs包括血小板减少症（5.0%）、手足皮肤反应（2.5%）和疲劳（2.5%）。 3.瑞戈非尼联合帕博利珠单抗 在2024年ASCO年会上，瑞戈非尼联合帕博利珠单抗被评估为另一种治疗一线免疫治疗失败后疾病进展的晚期HCC患者的治疗选择。在这项国际Ⅱ期研究中，共入组了95例患者，其中先前接受过阿替利珠单抗联合贝伐珠单抗治疗的患者组成队列1（68例），先前接受过其他免疫治疗的患者组成队列2（27例）。在68例先前接受阿特珠单抗联合贝伐珠单抗治疗后疾病进展并接受瑞戈非尼联合帕博利珠单抗联合治疗的患者中，mPFS为2.8个月，ORR为5.9%。在其余27例一线接受其他免疫治疗的患者中，mPFS为4.2个月，ORR为11.1%。由于随访时间相对较短（中位7.1个月），两个队列均未达到mOS。两队列中分别有37%和3%的患者观察到3级或4级药物相关治疗期不良事件，1例患者因治疗发生5级事件（心脏骤停）。对治疗无应答患者的相关性生物标志物分析显示，瑞戈非尼联合帕博利珠单抗降低了巨噬细胞水平和血管生成标志物，但未激活T细胞、减少调节性T细胞或改变非应答者中T细胞耗竭标志。 二、免疫治疗进展后继续应用免疫治疗的获益 上述3项研究为基于免疫治疗的方案后MKI在HCC治疗中的应用提供了初步前瞻性证据，尽管帕博利珠单抗是免疫治疗基石，但是与瑞戈非尼联合使用似乎并未比单独使用MKI带来更多获益。此外，回顾性队列研究表明，在一线免疫治疗失败后，将抗CTLA-4药物添加到抗PD-L1/抗PD-1抑制中可能具有潜在益处。在10例先前接受阿替利珠单抗联合贝伐珠单抗治疗后接受纳武利尤单抗联合伊匹木单抗联合治疗的患者中，3例（30%）患者观察到确认的客观缓解。在另一项纳入32例先前接受抗PD-L1/抗PD-1治疗随后接受纳武利尤单抗联合伊匹木单抗联合治疗的小规模研究中，ORR为22%（7/32）。因此，在一线免疫治疗进展后继续免疫治疗是否有益仍不明确。一项正在进行的Ⅲ期试验（IMbrave251；NCT04770896）也试图回答这个问题，方法是将在使用阿替利珠单抗联合贝伐珠单抗治疗后疾病进展的患者随机分配接受阿替利珠单抗联合仑伐替尼或索拉非尼治疗，或仅接受仑伐替尼或索拉非尼单药治疗。 三、免疫治疗后寡进展应用放疗及其他局部区域治疗的获益 寡进展是指经系统治疗后残留病灶有限或仅有少量病灶（通常为3~5个）开始进展。该现象在肺癌、结直肠癌和前列腺癌中常见，但在HCC中描述较少。考虑到潜在的第二原发肿瘤可能因肝脏损伤的基础场效应和转移时的基因组差异而出现，所以对寡进展进行治疗可能在HCC中特别有益，这提示不同疾病克隆对免疫治疗的反应可能不同，为部分患者进行局部治疗提供了理论依据。 最近的一项回顾性研究报道了54例对免疫治疗有初步持久反应并随后进展的晚期HCC患者的进展模式。其中，2/3的患者在接受免疫治疗后出现寡进展。对于出现寡进展的患者，又有2/3的患者接受了某种形式的局部区域治疗。接受局部区域治疗的患者mOS长于未接受局部区域治疗的患者（46.2 vs. 22.2个月）。 综上所述，3项前瞻性Ⅱ期临床研究探索了在免疫治疗进展后应用MKI方案的疗效，并取得了初步成果。此外，新兴的回顾性研究还表明，对于寡进展患者，加用抗CTLA-4或局部区域治疗可能有益。因此，在总结上述最新证据的基础上，研究者总结出了在晚期HCC患者一线免疫治疗后出现疾病进展后的治疗方法（图1），以供大家参考。 图.1 晚期HCC患者免疫治疗进展后的拟治疗方法 四、前瞻性数据仍缺乏，多学科诊疗是关键 当前关于一线免疫治疗失败后不可切除HCC的治疗决策，前瞻性数据仍然有限，但各方向上的证据正在涌现，如改用二线MKI、替代基于免疫治疗的方案（如抗CTLA-4联合方案）以及为寡进展添加局部区域治疗。多项Ⅱ期研究正在进行中，以测试一线免疫治疗失败后这些策略的有效性（表1）。 但是，当前由于前瞻性数据仍然稀缺，多学科诊疗仍然是确定每例患者最佳治疗的关键。当然，我们也非常需要生物标志物研究，包括肿瘤微环境分析以及原发性和获得性基因组异质性分析，以便为HCC患者在日益增多的治疗选择中，精准选择最有效的治疗策略。 表1. 免疫治疗进展后系统治疗的在研研究 参考资料： https://dailynews-ascopubs-org.libproxy1.nus.edu.sg/do/systemic-therapy-hepatocellular-carcinoma-s-next-after-immunotherapy （来源：肿瘤瞭望消化时讯） 声 明 凡署名原创的文章版权属《肿瘤瞭望》所有，欢迎分享、转载。本文仅供医疗卫生专业人士了解最新医药资讯参考使用，不代表本平台观点。该等信息不能以任何方式取代专业的医疗指导，也不应被视为诊疗建议，如果该信息被用于资讯以外的目的，本站及作者不承担相关责任。