Regeneron’s Met bet falls short

Regeneron’s bispecific efforts haven’t gone smoothly recently, and now the company has discontinued a bispecific ADC, REGN5093-M114, after it flunked its early-stage trial.

The group confirmed the development to ApexOnco after REGN5093-M114 was seen to be missing from its most recent quarterly results presentation. Regeneron still has a Met x Met bispecific antibody, davutamig, in phase 1/2, although that project hasn’t impressed so far.

Met x Met

Davutamig hits two distinct epitopes on the Met protein, a feature designed to prevent the Met-mediated signalling that has held back previous attempts to develop Met-targeting antibodies. Davutamig was also the backbone for the ADC REGN5093-M114, which employed a maytansinoid payload.

REGN5093-M114 was in a phase 1/2 trial in Met-overexpressing NSCLC that had been expected to yield data last year. However, after appearing in Regeneron’s third-quarter 2024 earnings presentation in October, the project was missing from its fourth-quarter update this month.

A spokesperson for Regeneron confirmed to ApexOnco that the group had abandoned REGN5093-M114, adding that it “didn’t see a significant enough signal to warrant continuing the programme”. She declined to give further details.

However, this might not be the end for Regeneron’s efforts here. At last year’s ESMO meeting the group’s head of translational sciences for oncology, Israel Lowy, told ApexOnco that REGN5093-M114 was a “first-generation ADC”, and that the group might be bringing other ADCs forward. 

One possibility is that Regeneron might develop a similarly acting project using a different payload, though no such asset is currently listed in its pipeline.

Disappointing

Moreover, davutamig itself has hardly been a runaway success. At ESMO a phase 1/2 trial in Met-altered NSCLC produced an ORR of just 12% with a 2,000mg dose. Regeneron was left relying on subgroup analyses, and saw the best results in patients with the highest Met protein overexpression, IHC 3+ at ≥90%. Here the ORR was 31% among 13 patients.

The only other company developing a Met x Met bispecific antibody, according to OncologyPipeline, is KYinno biotechnology, whose KA-3005 had preclinical data at last year’s AACR meeting. At the time, the project was said to have potential to be developed as an ADC.

Meanwhile, there are plenty of regular Met-targeting ADCs in development, including AbbVie’s telisotuzumab vedotin and telisotuzumab adizutecan, Mythic's MYTX-011 and RemeGen’s RC108. Others are developing ADCs against EGFR x Met, including Genmab, whose ProfoundBio-originated GEN1286 recently went into the clinic, and AstraZeneca, with the phase 1 AZD9592.

Regeneron’s Met-targeting efforts

Source: OncologyPipeline & company communications.