Xilio Therapeutics eyes the fast track to the clinic with $95M in investor cash to test redesigned IL-2, CTLA-4 meds
About three years after joining the search for IL-2 and CTLA-4 therapies without all those nasty side effects, Xilio Therapeutics has teed up $95 million to drive its two lead candidates into the clinic.
The Series C round was led by Rock Springs Capital, and should allow the small Waltham, Massachusetts-based biotech to file INDs for XTX101, its anti-CTLA-4 antibody, in Q2 and XTX202, its IL-2 agonist, in Q3.
Xilio got its start in 2018 under the name Akrevia with $30 million in launch money from Atlas and F-Prime. The 13-person shop was headed by scientist Tim Clackson, whose last job was running R&D at Ariad until Takeda bought it out. Clackson is now president and CTO.
The big idea — based on technology in-licensed from Thomas Jefferson University and City of Hope — was to take a set of antibodies, cytokines and chemokines that are either too dangerous or plagued with toxicity issues and redesign them.
Two years later, with CEO Rene Russo at the helm, the company bagged a $100.5 million Series B and rebranded to Xilio. The name was inspired by ex nihilo, a Latin term for creation or big bang.
“We view how our molecules work as completely off or dark when they’re circulating in the periphery,” Russo told Endpoints News at the time, “and this creation or big bang as efficacy in the tumor specifically.”
Xilio’s platform involves shielding the binding activity of molecules until they meet the proteases in the tumor. Then the blocking modules are removed, releasing the therapy just where it’s needed.
The biotech joins several others working on a new-and-improved IL-2, including Alkermes, which highlighted its first glimpse of efficacy at virtual ESMO 2020. Nektar, whose program with Bristol Myers Squibb’s Opdivo hit a snag back in 2018, announced earlier this month that it’s entering bempegaldesleukin in a Phase II/III trial with Keytruda. Sanofi struck a deal with Merck in October to pair Keytruda with a next-gen immuno-oncology candidate snagged in the Synthorx buyout. And back in July, Bright Peak Therapeutics launched out of Versant’s Ridgeline Therapeutics Discovery Engine with its own modified IL-2 molecule.
“In our view, agents like IL-2 and CTLA-4 have tremendous therapeutic potential, but have been really limited by their toxicity,” Russo said. “And our approach really aims to take advantage of what’s different inside the tumor microenvironment, namely high activity of MMPs, or matrix metalloproteinases, and then utilize that to really turn on the activity and concentrate it only in the tumors.”
The team, which has since grown to 45 staffers, is also working on IL-12 and IL-15 programs. However, it’s too soon to tell when those might be ready for IND submissions.
When asked if an IPO is on the horizon, Russo said: “We will be thinking carefully about that and what the right timing will be for us to maximize the development of these programs and to further advance the pipeline.”