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Precision Cancer Immunotherapy Biotech Underway

T-cells and cancer cells

Killer T-cells surround a cancer cell (NICHD, Flickr)

23 Mar. 2021. A new company is beginning work on a safer form of cancer immunotherapy that avoids toxic off-target effects, and raising $55 million in venture funds. Asher Biotherapeutics in South San Francisco, California is based on research by its scientific founders that apply computational genomics to more precisely direct the immune system to attack tumors.

Asher Biotherapeutics is designing cancer immunotherapies that address a continuing problem from pleiotropy, a condition where changes in a single gene can affect multiple human traits. In cancer immunotherapies, pleiotropy can cause unintended changes in cells and tissue other than the tumors, when the treatment’s cancer targets are attacked. The company’s technology is based on studies by its scientific founders, immunologist Ton Schumacher at Netherlands Cancer Institute in Amsterdam and pathology/immunology professor Robert Schreiber at Washington University in St. Louis.

Schumacher and Schreiber investigate neoantigens, unique sets of mutations expressed in cancer patients’ tumors, as cancer targets. Schreiber and colleagues design precise genomic techniques for targeting neoantigens characteristic of specific tumors, while Schumacher’s lab uses high-throughput genomic analysis to better target tumor neoantigens with T-cells in the immune system. Schumacher is also a serial entrepreneur who founded the company Neogene Therapeutics Inc. in Amsterdam in September 2020, as reported by Science & Enterprise.

“Therapeutics based on natural cytokines, costimulatory agonists, and checkpoint inhibitors,” says Schumacher in an Asher Bio statement, “have demonstrated meaningful efficacy, but are often limited by pleiotropic effects: antagonistic signaling and systemic toxicities due to their interaction with receptors on a wide range of cell types.”

Better targeting for IL-2

Asher Bio’s technology, called cis-targeting, addresses receptor proteins at two sites on surfaces of a single immune system cell, the therapeutic antigen target and a separate receptor that simulates immune responses, called an immunomodulator. The company applies computational techniques to screen immune system cells and sub-types for therapeutic benefits, but also for possible unintended toxicities or reverse effects that block the therapy. Asher Bio then engineers selected immune system cells to produce cytokine enzymes that bind only on specific tumor targets and boost their potency.

The company’s first product, code-named AB248 is an engineered protein that addresses receptor pathways for cancer-killing CD8+ T-cells in the immune system for interleukin-2 or IL-2 cytokines. Various IL-2 forms are already approved for treating some metastatic solid tumor cancers, but because of pleiotropy, IL-2 can also stimulate other unintended immune system cell types. And, because of its short active lifetime, IL-2 is needed in high doses, which can be toxic, causing heart and blood damage.

Asher Bio says AB248 is designed to selectively expand CD8+ T-cells to attack solid tumor cancer cells, but avoid promoting regulatory T-cells and natural killer cells in the immune system. “AB248, which was designed to target only CD8+ effector T cells,” notes company co-founder and chief scientist Ivana Djuretic, “has demonstrated superior selectivity and efficacy in multiple preclinical models and is expected to enter trials for the treatment of solid tumors in 2022.”

Asher Bio was formed and incubated by science and technology venture investor Third Rock Ventures in Boston, which led the company’s first venture funding round, raising $55 million. Taking part in the round are Boxer Capital of Tavistock Group, Invus, Y Combinator, and MBC Biolabs.

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