Ex nihilo: Takeda leads $100M+ round to fund biotech's sneak attack on tumors, propelling new IL-2, CTLA-4 drugs to clinic
Since emerging out of stealth in 2018 with $30 million in launch money from Atlas and F-Prime, Akrevia has kept a relatively low profile, hammering away at its platform technology to design immunotherapies with all their potency but little of their side effects. With an official CEO in place for almost a year — and now a new name — the biotech is ready to step up with another $100.5 million to bring its two lead compounds into the clinic.
Meet Xilio, a 35-strong team working out of Waltham, MA. Whereas the original name had been derived from the Greek word for precision, Xilio draws inspiration from 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,” CEO Rene Russo told Endpoints News, “and this creation or big bang as efficacy in the tumor specifically.”
Xilio’s protein engineering approaches shield the binding activity of molecules while they are travelling around the body, explained Tim Clackson, president and head of R&D. Once they meet the proteases in the tumor, the blocking modules are removed, releasing the therapy just where it’s needed.
Under Clackson, who ran the R&D shop at Ariad before Takeda acquired it, the team went straight for IL-2 and CTLA-4, two well-known targets each with approved therapies. Considering the significant toxicities associated with the first-generation treatments — Proleukin and Yervoy both have black box warnings on their labels — many patients can’t tolerate the full dose. Xilio promises to change that with their recombinant IL-2 and CTLA-4 inhibitor.
They are not the only ones latching on to IL-2, but Clackson maintains that theirs is a fundamentally different approach to those taken by rivals such as Synthorx (now Sanofi), Neoleukin and Alkermes — which have generally focused on binding to specific receptors. The troubles Nektar has run into with its once-high-flying NKTR-214 after Bristol-Myers Squibb paid $1.85 billion upfront to partner on it underscore the difficulty of balancing efficacy and safety.
Beyond IL-2, Clackson sees “clear untapped potential” for cytokines as a class. Xilio has two programs for tumor-selective IL-12 and tumor-selective IL-15 in the lead optimization phase.
The Series B, led by Takeda Ventures and featuring SV Health Investors, MRL Ventures Fund (a venture arm of Merck), RiverVest Venture Partners, Bay City Capital, Solasta Ventures, M Ventures and Ipsen Ventures as well as the two original backers, gives them the firepower to steer the lead programs to INDs by next year while moving the others forward.
Jayson Punwani, partner at Takeda Ventures, is joining the board alongside Mike Ross of SV Health Investors, Peter Dudek of MRL Ventures Fund and Nancy Hong of RiverVest Venture Partners.