Happy new year, DLL3

If there were any doubts about the progress the DLL3 antigen made in 2024, emerging from obscurity to see its first approval, of Amgen's Imdelltra, in May, they were swept away as the year came to a close. On the first day of 2025 Roche licensed Innovent's anti-DLL3 ADC IBI3009, just three days after Ideaya ended 2024 by licensing a similarly acting ADC, Jiangsu Hengrui's SHR-4849. Both molecules use topoisomerase 1 inhibitor payloads, and the deals involve similar up-front payments: $75m from Ideaya and $80m in the case of Roche. However, SHR-4849 is further ahead in development, with Ideaya citing case reports from 11 evaluable SCLC patients given therapeutically active doses, while IBI3009 is effectively a preclinical asset, having only last month been dosed to the first patient in its first-in-human study. The two licensees' strategies likely differ too: Ideaya might be looking for combinations with its synthetic lethality-based small molecules, while Roche is likely shoring up its SCLC position, where Tecentriq is a standard of care. While Imdelltra's approval validated DLL3 at last, significant toxicity remains a problem, providing the impetus for the development of follow-on drugs.

Anti-DLL3 ADCs

Note: *this bispecific ADC targets B7-H3 as well as DLL3. Source: OncologyPipeline. This table has been updated.