Xilio Therapeutics has struck a deal with Merck to test its anti-CTLA-4 monoclonal antibody XTX101 in combination with Keytruda. The agreement sets Xilio up to show whether it can combine the checkpoint inhibitors without causing the toxicities associated with other cocktails that target CTLA-4 and PD-1.
Bristol Myers Squibb has racked up approvals in seven indications for its combination of CTLA-4 drug Yervoy and PD-1 inhibitor Opdivo on the strength of evidence the cocktail works better than either molecule alone in some indications. However, the Big Pharma has also linked the combination to a higher rate of certain grade 3 and 4 adverse events including increases in liver enzymes.
Xilio is trying to create a safer CTLA-4 inhibitor by linking the active molecule to a peptide. By pairing the antibody to the peptide, Xilio is aiming to keep it masked until it reaches the tumor, where the presence of proteases should cleave the link and thereby limit systemic exposure.
“Treatment with the combination of an anti-CTLA-4 mAb and PD-1 checkpoint inhibitor has been associated with challenging toxicities, preventing patients from receiving effective doses of the anti-CTLA-4 antibody. Based on data observed in preclinical studies, we believe [XTX101] could be an ideal CTLA-4-targeting candidate to combine with checkpoint inhibitors like Keytruda,” Marty Huber, M.D., chief medical officer at Xilio, said in a statement.
The Merck agreement gives Xilio a chance to assess whether its approach results in a safer combination therapy. Xilio plans to run a trial that will assess XTX101 as a monotherapy and in combination with Merck’s Keytruda in solid tumor patients. The biotech plans to file an IND in the second quarter and start the study promptly once it gets the green light from the FDA.
Xilio raised the money to enter the clinic earlier this year, when a syndicate featuring Rock Springs Capital, Bain Capital Life Sciences, Deerfield Management and RA Capital Management came together for a $95 million series C round.