Computational scientists design a new IL-2 cancer drug and spin it out into a biotech startup

One of the Holy Grails in the booming immuno-oncology research field right now involves finding an IL-2 drug that can be used safely and effectively to combat cancer, without the immense toxicity that has largely sidelined the original IL-2 Proleukin. Bristol-Myers Squibb paid Nektar $1.85 billion in upfront cash to partner on NKTR-214 — which has since come under a cloud of uncertainty over flailing response rates in their key demonstration study combining it with Opdivo.

Now a group of scientists at the University of Washington says they built an IL-2 protein therapy all their own, and they’ve launched a new biotech — Neoleukin — to take it forward from mouse studies toward the clinic.

Umut Ulge

Describing their work to a writer at UW Medicine, the group says they designed their protein to bind specifically to IL-2  beta and gamma receptors to whip up a more potent T cell response to cancer while steering clear of CD25 to circumvent the toxic reaction. By doing that they created a lab model of the drug that the scientists were able to ratchet up the dose on without the lethal reaction.

They also added a complementary component for IL-15 to increase the efficacy and dubbed the drug Neo-2/15, describing it as particularly small and stable. And the game plan is to continue to use their computational skills to improve the drug.

“Neo-2/15 has therapeutic properties that are at least as good as or better than naturally occurring IL-2, but it was computationally designed to be much less toxic,” said Umut Ulge, one of the lead authors of a paper published in Nature.

An illustration depicting how the new protein, in red, binds only to the beta and gamma receptors, and not to cells with a third kind of receptor. (UW MEDICINE)

Neoleukin, though, is hardly the only rival to the throne that Nektar and Bristol-Myers Squibb have been striving for. Laura Shawver’s Synthorx has also been angling for the clinic — in H1 of this year — with their drug candidate Synthorin IL-2, backed by Orbimed and Medicxi. The biotech $THOR went public just a few weeks ago, raising $150 million.

Last November Nektar Therapeutics $NKTR managed to add 1 more patient out of its 38 evaluable stage 4 melanoma patients to the win column with its closely-watched 3-month update on Opdivo/NKTR-214’s objective response rate. That managed to nudge up the ORR from 50% — a figure that routed Nektar’s stock at ASCO — to 53%. But the scientists also pushed up the complete response rate to 24%, maintaining they were satisfied with the improved response they were seeing.