GSK has bet up to $750 million on a Chimagen Biosciences trispecific T-cell engager (TCE), positioning the Big Pharma to start phase 1 development of the multiple myeloma drug candidate next year.
The deal comes two years after GSK paid China’s Chimagen $300 million upfront for a trispecific lupus prospect. Neither party has disclosed the targets of the new candidate, but GSK shed some light on the rationale for the trispecific design.
TCEs have shown “transformational efficacy in multiple myeloma but have been associated with difficult tolerability profiles,” GSK said. Chimagen designed its candidate to overcome the limitations of existing TCEs by targeting two tumor-associated antigens while also binding to T cells.
The FDA has approved several bispecific TCEs in multiple myeloma. Johnson & Johnson's Tecvayli, Pfizer’s Elrexfio and Regeneron’s Lynozyfic all engage BCMA on cancer cells and CD3 on T cells. J&J’s Talvey is a GPRC5DxCD3 bispecific. All four TCEs carry boxed warnings for cytokine release syndrome and neurologic toxicity.
GSK licensed the Chimagen candidate believing it could trigger deeper, more durable responses than existing TCEs while having improved tolerability. A product with the target profile may be used more broadly than existing TCEs and be adopted earlier in the treatment pathway. The current TCEs are approved for monotherapy use in patients who have received at least four prior lines of therapy.
Multiple companies have identified the trispecific design as a way to create better TCEs for multiple myeloma. Last year, AbbVie paid Ichnos Glenmark Innovation $700 million upfront for a trispecific antibody that targets CD38, BCMA and CD3. The deal represented a big bet that targeting CD38, as well as BCMA, will make the drug candidate more potent than the bispecifics Tecvayli, Elrexfio and Lynozyfic.
J&J is also investing in trispecifics, launching phase 3 trials of a drug candidate that binds CD3 on T cells and BCMA and GPRC5D on myeloma cells. The company sees the trispecific design as a way to achieve a more sustained immune response in recurrent multiple myeloma. J&J’s phase 3 program includes a trial comparing the trispecific to a BCMAxCD3 TCE.
While trispecifics are promising, the modality can be complex to manufacture, suffer pharmacokinetic limitations and cause immunogenicity-related toxicities. Chimagen’s efforts to overcome the challenges have spawned a pipeline of tri- and multispecific programs in immunology and oncology.