Asher Biotherapeutics joins search for a better IL-2 sans the toxicities
Can IL-2 therapies — which can be powerful against cancer but infamous for their toxic side effects — be made inherently more specific? For Asher Biotherapeutics, that’s the $55 million question.
Ivana Djuretic and Andy Yeung left their jobs in cancer immunology and protein engineering at Pfizer in 2019 to start Asher with the idea that they could improve the efficacy of immunotherapies. More specifically, they wanted to know if restricting the activity of a cytokine to only the cells that matter would counterintuitively result in better therapeutics.
They decided to start with IL-2, what Djuretic called “one of the most exciting challenges today.” And that work, she said, led them to an “aha moment.”
“We sort of realized that we could … modulate specific immune cell subsets in many contexts, not only IL-2, not only CD8,” through a process called cis-targeting, Djuretic said. Cis-targeting is an engineering approach that works by requiring the simultaneous engagement of two receptors on the same immune cell for activation.
Djuretic and Yeung ran into Third Rock at an early 2020 meeting in Boston, and the rest is history. Washington University professor Robert Schreiber and Netherlands Cancer Institute top scientist Ton Schumacher, who were involved with Third Rock, hopped on board as co-founders. And on Tuesday morning, the company unveiled a $55 million Series A to take its lead oncology program, AB248, to the clinic next year.
“So a lot of people are trying to target IL-2 spatially to the site of the tumor, but it’s an inherently nonspecific molecule. So we think there’s only a limited amount of specificity we can get out of that,” CEO Craig Gibbs said. “What we’re trying to do is make IL-2 inherently specific, so it only binds CD8+ T cells, which is the ones that we want, and not to T regs which are going to be immunosuppressive, and not to NK cells which just cause toxicity, and not to endothelial cells which cause vascular leak.”
Gibbs left his job as CBO at Forty Seven to join Asher last summer, after the former was bought by Gilead for nearly $5 billion. That September, he was “gratified” by some “really stellar” data from Schreiber’s lab. In vitro and monkey studies have shown a “much larger expansion” of CD8 cells, without the activation of regulatory T cells or NK cells, he said.
In addition to oncology, the Asher team believes the platform could have applications in autoimmunity and infectious disease.
The Series A was led by Third Rock with participation from Boxer Capital of Tavistock Group, Invus, Y Combinator and MBC Biolabs.