I-Mab (NASDAQ: IMAB) is sharpening its focus on givastomig, a Claudin 18.2 ("CLDN18.2") x 4-1BB bispecific antibody, as its primary clinical program for treating first-line metastatic gastric cancers and other solid tumors. This strategic shift was announced alongside the pause of uliledlimab development to concentrate resources on advancing givastomig. The company anticipates key data readouts in the near future, with the goal of establishing givastomig as a leading treatment option.
Clinical Progress of Givastomig
Givastomig (TJ033721 / ABL111) is designed to target CLDN18.2-positive tumor cells and conditionally activate T cells through the 4-1BB signaling pathway within the tumor microenvironment. Phase 1 trials have demonstrated strong tumor-binding properties and anti-tumor activity, potentially due to the synergistic effect of interaction with CLDN18.2 and 4-1BB. This bispecific antibody is being developed for first-line metastatic gastric cancers, with potential applications in other solid tumors.
Data from a Phase 1 monotherapy dose escalation and dose expansion study, presented at ESMO 2024, showed an overall response rate (ORR) of 16.3% (7/43) with seven partial responses (PR) at doses between 5 mg/kg and 18 mg/kg. Notably, 71% of responders had received prior checkpoint inhibitor (CPI) therapy. The safety profile was favorable, with mainly grade 1 or 2 treatment-related adverse events (TRAEs), and no dose-limiting toxicities (DLTs) were observed.
A Phase 1b dose escalation study of givastomig in combination with nivolumab plus chemotherapy has completed enrollment (n = 17), with no maximum tolerated dose (MTD) reached and no DLTs to date. The company expects to present these data in the early second half of 2025. Based on encouraging early data, the dose expansion cohort is being expanded to include two dose cohorts, each evaluating 20 patients, for a total of 40 patients. Patients are being enrolled with tumors expressing CLDN18.2 as low as 1+ intensity in ≥1% of cells, regardless of PD-L1 expression. These data are expected in early 2026.
According to Phillip Dennis, MD, PhD, CMO of I-Mab, data from these studies will help establish the breadth of patients who might respond to this novel regimen, including those with low levels of CLDN18.2 expression, and help establish the recommended dose of givastomig for subsequent studies.
Strategic Portfolio Prioritization
I-Mab is pausing the development of uliledlimab (TJ004309), an antibody targeting CD73, to focus resources on advancing givastomig. This decision allows the company to prioritize its lead clinical program and await mature data from an ongoing China-only randomized study by TJ Biopharma evaluating uliledlimab with toripalimab in CD73-high NSCLC patients. I-Mab retains worldwide rights to uliledlimab outside of Greater China and may resume clinical development pending positive data.
Financial Outlook
As of September 30, 2024, I-Mab's cash balance was $184.4 million, which is expected to support operations into 2027. This financial stability, along with a strengthened U.S.-based leadership team and streamlined operating model, positions I-Mab to advance givastomig effectively.
Partnership with ABL Bio
The givastomig program is being jointly developed through a global partnership with ABL Bio, with I-Mab as the lead party, sharing worldwide rights (excluding China and South Korea) equally with ABL Bio.
I-Mab is also developing Ragistomig (TJ-L14B / ABL503), a bispecific, Fc-silent antibody designed to provide anti-PD-L1 activity and conditional 4-1BB-driven T-cell activation. ABL Bio reported promising objective responses in patients with various solid tumors that progressed or recurred after prior standard treatments, including PD-(L)1 inhibitors, at ASCO 2024. ABL Bio is continuing the Phase 1b study to increase the therapeutic index and identify appropriate tumor types for further development.
