Lilly drops PD-L1/TIM-3 bispecific from clinical pipeline

Eli Lilly has dropped (PDF) a PD-L1/TIM-3 bispecific antibody from its clinical pipeline. The asset moved into a phase 1 advanced solid tumor trial late last year but was culled from the pipeline before delivering final data.

Lilly, Roche, Novartis, Tesaro and other companies have progressed anti-TIM-3 drugs into the clinic in recent years on the strength of evidence that the co-inhibitory molecule marks exhausted T cells in the tumor microenvironment. As T-cell exhaustion limits responses to PD-1/L-1 drugs, the function of TIM-3 raised hopes that the target can help overcome primary and acquired resistance to checkpoint inhibitors.  

Those hopes led Lilly to design a PD-L1/TIM-3 bispecific and start testing it in humans last year. Lilly and its collaborators discussed the trial last month at the 2019 American Society of Clinical Oncology annual meeting. But over the following weeks, Lilly decided to dump the molecule, leading to its removal from its pipeline in a R&D update today.

The move seemingly signals the end for the PD-L1/TIM-3 bispecific at Lilly, but the company retains an interest in the concept that attracted it to the molecule. Lilly began testing an anti-TIM-3 antibody, LY3321367, in humans in 2017, putting it ahead of the bispecific in development. A phase 1 trial of LY3321367 as a monotherapy and in combination with a PD-L1 antibody is continuing. 

Most of the other companies with anti-TIM-3 drugs in the clinic are pursuing similar combination strategies to Lilly. Roche is one of the notable exceptions. The Swiss pharma moved its PD-1/TIM-3 drug, RO7121661, into the clinic around the same time Lilly began enrolling subjects in a trial of its now-axed bispecific.

Lilly disclosed the removal of the drug from its pipeline alongside news of the axing of another bispecific. The second drug to get the chop was an IL-23/CGRP bispecific antibody that Lilly saw as a potential treatment for autoimmune diseases such as inflammatory bowel disease and psoriatic arthritis.