Monotherapy efficacy and safety profile provided backbone for clinical development strategy in 1L combination with nivolumab plus chemotherapy

ROCKVILLE, MD, June 30, 2025 (GLOBE NEWSWIRE) -- I-Mab (NASDAQ:IMAB) (the Company), a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer, today announced publication of the first-in-human monotherapy data for givastomig, a bispecific Claudin 18.2 x 4-1BB antibody, in Clinical Cancer Research, a journal of the American Association for Cancer Research (CCR), and a highly-ranked clinical oncology publication. The CCR paper¹ details promising clinical data showing that givastomig monotherapy achieved an objective response rate (ORR) of 16% in heavily pretreated Claudin 18.2-positive gastric cancer patients. The publication can be accessed HERE.

The CCR paper represents the first peer-reviewed manuscript publication of the Phase 1 monotherapy study of givastomig in heavily pre-treated solid tumor patients, after initial presentation of these data in poster form at the European Society of Medical Oncology (ESMO) Congresses in 2023 and 2024. The study evaluated a total of 75 patients with gastric cancers or other solid tumors, including 43 efficacy-evaluable patients with CLDN18.2-positive advanced or metastatic gastroesophageal carcinoma (GEC). Claudin 18.2 expression in responders ranged from 11% to 100%, demonstrating the activity of givastomig in tumors with low levels of Claudin 18.2 (CLDN18.2) expression. After the data cutoff, two additional patients were enrolled in the monotherapy study, resulting in an additional confirmed partial response (PR), leading to an increased ORR of 18% (8/45 patients). The Company anticipates sharing an updated monotherapy data set on the 45 patients in the fourth quarter of 2025 at a major medical meeting.

Monotherapy data indicate that givastomig is well tolerated and demonstrates single-agent activity in heavily pretreated patients. These findings support its development in combination with standard immunochemotherapy (nivolumab plus mFOLFOX6) as a first line (1L) treatment for gastric cancers. Data from the ongoing dose escalation combination study will be presented at a Mini Oral presentation at the ESMO Gastrointestinal (ESMO GI) Cancers Congress 2025 on July 2, 2025 in Barcelona, Spain.

"The CCR paper bolsters our confidence that givastomig has the potential to be a best-in-class, 1L treatment for Claudin 18.2-positive gastric cancers. Givastomig monotherapy demonstrated an ORR of ~18% in heavily pre-treated gastric cancer patients, across a wide range of Claudin 18.2 expression levels, with a 9.4-month median duration of response. This study helped us to further characterize givastomig's pharmacokinetic and pharmacodynamic profile to define the dosing cohorts being tested in the ongoing Phase 1b combination study," said Phillip Dennis, MD, PhD, Chief Medical Officer of I-Mab. "We believe givastomig has the potential to enhance the efficacy of combination regimens such as nivolumab plus chemotherapy, a cornerstone of gastric cancer care."

Dr. Dennis continued, "We believe givastomig's monotherapy data compare favorably to other Claudin 18.2 targeted agents that have less efficacy and/or greater toxicity. We believe givastomig's molecular structure is the key to its differentiated profile. Givastomig's unique bispecific design enables high binding affinity to Claudin 18.2-positive cancer cells across a wide range of Claudin expression levels, with finely tuned, localized T cell stimulation via 4-1BB. Through careful engineering, the Fc effector function that confers antibody-dependent cell-mediated cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) has been silenced, leading to less gastrointestinal toxicity than has been observed with other Claudin 18.2 assets with these functions intact. We look forward to presenting the initial combination data from the Phase 1b dose escalation cohort (n=17), at ESMO GI on July 2^nd in Barcelona, Spain."

Summary of Published Monotherapy Results:

A total of 75 patients received givastomig across nine sequential dose levels between 0.1 and 18 mg/kg. The 75 patients were comprised of 56 subjects from the United States and 19 subjects from China. Patients were heavily pretreated, with a median of three prior lines of therapy. 75% of patients were CLDN18.2-positive, by the trial definition.

Of the 43 efficacy-evaluable patients with CLDN18.2-positive advanced or metastatic GEC who received givastomig monotherapy at doses ranging from 5 to 18 mg/kg, PRs were observed in seven patients (one at 5 mg/kg, one at 8 mg/kg, four at 12 mg/kg, and one at 18 mg/kg) with an ORR of 16% (7/43 patients) for single agent givastomig. Five of the seven patients who had achieved a PR (71%) had previously received a checkpoint inhibitor. Stable disease (SD) was reported in 14 patients, which resulted in a disease control rate (DCR) of 49% (21/43 patients).

No dose-limiting toxicity was reported up to 15 mg/kg dosed every two weeks (Q2W), and 18 mg/kg dosed every three weeks (Q3W), and a maximum tolerated dose (MTD) was not identified
The most common treatment-related adverse events (TRAEs) were mainly Grade 1 or 2
Givastomig exhibited linear pharmacokinetics (PK) at doses ≥5 mg/kg, and showed a dose-dependent increase in soluble 4-1BB levels, reaching a plateau at doses ranging from 8 to 18 mg/kg
CLDN18.2 expression in responders ranged from 11% to 100%

_{¹ CCR Paper Citation}

_{Geoffrey Ku, Lin Shen, Farshid Dayyani, Jeremy Kratz, Xinjun Liang, Funan Liu, Zhenning Wang, Laura Feller, Eugenia Girda, Hongming Pan, Sunnie Kim, Yanhong Deng, Ting Deng, Tianshu Liu, John Powderly, Kristen Spencer, Reva Schneider, Jordan Berlin, Claire (Cong) Xu, Christoph M. Ahlers, Xuejun Liu, Jou-Ku Chung, Peter Sabbatini, Jinyoung Park, Yangmi Lim, Juyeun Jeon, Yuan Meng, Samuel J. Klempner; A First-in-Human Study of Givastomig, a CLDN18.2 and 4-1BB Bispecific Antibody, as Monotherapy in Patients with CLDN18.2-Positive Advanced or Metastatic Solid Tumors. Clin Cancer Res 2025; https://doi.org/10.1158/1078-0432.CCR-24-4280}

About Givastomig

Givastomig (TJ033721 / ABL111) is a bispecific antibody targeting Claudin 18.2 (CLDN18.2)-positive tumor cells. It conditionally activates T cells through the 4-1BB signaling pathway in the tumor microenvironment where CLDN18.2 is expressed. Givastomig is being developed for first line (1L) metastatic gastric cancers, with further potential in other solid tumors. In Phase 1 trials, givastomig has shown promising anti-tumor activity attributable to a potential synergistic effect of proximal interaction between CLDN18.2 on tumor cells and 4-1BB on T cells in the tumor microenvironment, while minimizing toxicities commonly seen with other 4-1BB agents.

An ongoing Phase 1b study is evaluating givastomig for the treatment of gastric cancer in the 1L setting in combination with standard of care, nivolumab (an anti-PD-1 checkpoint inhibitor) plus chemotherapy, in dose escalation and dose expansion cohorts. Dose escalation is complete, and enrollment in the first dose expansion cohort (n=20) finished ahead of schedule. Enrollment continues to progress ahead of schedule in the second dose expansion cohort (n=20). The study builds on positive Phase 1 monotherapy data.

Givastomig is being jointly developed through a global partnership with ABL Bio, in which I-Mab is the lead party and shares worldwide rights, excluding Greater China and South Korea, equally with ABL Bio.

About I-Mab

I-Mab (NASDAQ:IMAB) is a U.S.-based, global biotech company, focused on the development of precision immuno-oncology agents for the treatment of cancer. The Company's differentiated pipeline is led by givastomig, a potential best-in-class, bispecific antibody (Claudin 18.2 x 4-1BB) designed to treat Claudin 18.2-positive gastric cancers. Givastomig conditionally activates T cells via the 4-1BB signaling pathway in the tumor microenvironment where Claudin 18.2 is expressed. Givastomig is being developed for first-line metastatic gastric cancers, with additional potential in other solid tumors. In Phase 1 trials, givastomig was observed to maintain strong tumor-binding and anti-tumor activity, attributable to a potential synergistic effect of proximal interaction with Claudin 18.2 and 4-1BB, while minimizing toxicities commonly seen with other 4-1BB agents.

For more information, please visit www.i-mabbiopharma.com and follow us on LinkedIn and X.

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 clinical development of I-Mab's drug candidates, including givastomig; the projected advancement of the Company's portfolio and anticipated milestones and related timing; the Company's expectations regarding the impact of data from ongoing and future clinical trials; the timing and progress of studies and trials (including with respect to patient enrollment); the potential benefits of givastomig; and the availability of data and information from ongoing studies and trials. 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 annual report on Form 20-F filed with the SEC on April 3, 2025, as well as the 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

PJ Kelleher
LifeSci Advisors
+1-617-430-7579
pkelleher@lifesciadvisors.com
IR@imabbio.com

I-Mab Announces Publication of Givastomig Monotherapy Data in Clinical Cancer Research