There is no shortage of companies working to deliver the therapeutic benefits of cytokines without their nasty side effects, from Synthekine and Nektar Therapeutics to Synthorx, which Sanofi bought for $2.5 billion in 2019. The latest entrant to the arena is Asher Bio, a biotech engineering immunotherapies, such as cytokines, that only affect specific immune cell targets.
Cytokines have long held promise as cancer treatments, but their use has been limited as they affect many different cells, causing unwanted effects. That’s because they interact with receptors on multiple cell types. Asher Bio launches with $55 million to advance a suite of immunotherapies, including cytokine treatments, that only activate a targeted cell type.
The series A round, drawn from Third Rock Ventures, Boxer Capital, Invus, Y Combinator and MBC Biolabs, will advance its lead asset, an engineered interleukin-2 (IL-2) for the treatment of cancer, into the clinic and support preclinical work for its other programs.
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Rather than try to limit the effects of molecules that are, by nature, nonspecific, Asher Bio focuses on designing immunotherapies that only affect the target immune cells. It uses a protein engineering approach called cis-targeting to build its treatments. Cis-targeting drugs engage two molecules on the same cell, unlike trans-targeting drugs, which interact with targets on two different cells.
“It’s different than fusing the cytokine to a tumor-targeting antibody, which requires two different cells: a cancer cell and an immune cell,” said Asher Bio co-founder and Chief Scientific Officer Ivana Djuretic, Ph.D.
Asher Bio’s treatments target an immunomodulatory receptor and a marker found only in the immune cells it wants to activate. Its lead program, AB248, is designed to activate CD8+ killer T cells while leaving other immune cells such as regulatory T cells, natural killer cells and endothelial cells alone. It plans to start clinical trials for AB248 in 2022.
The company starts by identifying the type of immune cell it wants to target, said Asher Bio co-founder and Chief Technology Officer Andy Yeung, Ph.D., in a statement. This involves figuring out which immune cell types and which immunotherapies bring about the desired effect.
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It then dials down the activity of the cytokine across all cell types by reducing its affinity toward its immunomodulatory receptor, Djuretic said.
“[Then] we create a fusion protein to direct the therapy only to the desired immune cell type, and finally we optimize the pharmacological properties,” Yeung said in the statement.
Asher Bio’s treatments can be given systemically because they don’t activate the immune cell unless it’s bound to a cell type-specific antigen. Systemic delivery doesn’t work for trans-targeting cytokines because the cytokine can interact with all manner of immune cells before it arrives at the tumor, said Asher Bio CEO Craig Gibbs, Ph.D.
“On the way to the tumor, you have a fully active cytokine in systemic circulation,” he said.
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Besides its lead program, Asher Bio has unveiled two cancer programs: an IL-2 designed to stimulate CAR-T cells and a T-cell-activating cytokine that targets STAT3, a pathway through which some cytokines signal. It is also working on a cytokine that targets regulatory T cells, or Tregs, for the treatment of autoimmune disease.
“Our hope would be to improve the expansion of CAR-T cells following infusion, which correlates with long-term complete responses,” Gibbs said. “It may also allow you to infuse fewer cells, which could potentially save on manufacturing costs or potentially reduce the amount of conditioning you need.”
Moving forward, Asher Bio wants to see how broadly it can apply its technology in CAR-T targeting, Treg targeting and cell therapy. Partnering will naturally fall into the mix.
“It makes sense to look at partnering on a CAR-T therapy because it’s not a product you can just buy in a pharmacy,” Gibbs said. And partnering will become important for indications that aren’t in Asher Bio’s wheelhouse.
Between Djuretic and Yeung’s immunotherapy experience at Pfizer and Gibbs’ decades at Gilead and tenure as Forty Seven’s chief business officer, the team has great expertise in immuno-oncology and oncology drug development, Gibbs said.
“Our sweet spot may not be multiple sclerosis, rheumatoid arthritis or lupus. It would perhaps make sense for a strategic partnership,” he said.