I-Mab has begun the new year with a pipeline pivot, pausing work on an asset Sanofi bought into last year to focus on its play for the congested CLDN18.2 space.
Uliledlimab is the asset I-Mab has put on the back burner. The anti-CD73 antibody was the biotech’s lead candidate. But rather than advance into a phase 2 lung cancer trial, as I-Mab proposed in November, the company is pausing development to focus resources on its new lead program. I-Mab left the door open to further development of uliledlimab if the molecule impresses in studies run by its partners in China.
For now, I-Mab is focused on the CLDN18.2x4-1BB bispecific givastomig. The biotech shared phase 1 monotherapy data on the candidate last year, reporting results management said suggest the asset hits the sweet spot for efficacy and tolerability.
I-Mab reported a 16.3% response rate in 43 patients who received one of two monotherapy doses in a phase 1 trial. The biotech now has early tolerability data from a study that is testing givastomig with Bristol Myers Squibb’s checkpoint inhibitor Opdivo. I-Mab is yet to see dose-limiting toxicities or reach the maximum tolerated dose in the combination study.
Encouraged by the data, the biotech is growing the dose-expansion stage of the study. The trial will now enroll 40 patients across two dose cohorts. People with tumors that express CLDN18.2 at 1+ intensity in 1% or more cells are eligible for the trial. Astellas’ anti-CLDN18.2 antibody Vyloy is approved for use in patients with moderate-to-strong, 2+ to 3+ intensity, membranous staining in at least 75% of tumor cells.
Showing efficacy in CLDN18.2-low patients would differentiate givastomig from Vyloy, potentially helping I-Mab overcome Astellas’ head start. I-Mab is far from the only company gunning for Vyloy, though. The CLDN18.2 race features a clutch of bispecifics and antibody-drug conjugates (ADCs) aimed at the target.
Activating T cells through the 4-1BB pathway differentiates givastomig from CLDN18.2xCD3 bispecifics such as AstraZeneca’s AZD5863. Other 4-1BB drugs have been associated with toxicities, but givastomig’s design—which limits activation to places where CLDN18.2 is expressed—could minimize those problems.
I-Mab is pitching givastomig as a candidate that is more effective and tolerable than Vyloy and free from the cytokine release syndrome associated with T-cell engagers. Developers of ADCs such as AstraZeneca’s CMG901 have seen higher response rates offset by more grade 3 or worse adverse events.
The risk-benefit profile could limit ADCs to later lines of use. I-Mab wants to take givastomig into first-line settings. The biotech is pulling back from other programs to pursue that vision, ensuring its existing cash will keep it going beyond dose-expansion readouts next year and into 2027.
I-Mab’s decision to sacrifice uliledlimab, at least temporarily, to advance givastomig comes months after Sanofi paid $36 million for Chinese rights to the anti-CD73 antibody. TJ Biopharma, an I-Mab spinout, inked the deal with Sanofi.