On March 23, 2021 Asher Biotherapeutics, a biotechnology company developing precisely targeted immunotherapies for cancer and other diseases, reported its launch following a $55 million Series A financing led by Third Rock Ventures with participation from Boxer Capital of Tavistock Group, Invus, Y Combinator and MBC Biolabs (Press release, Asher Biotherapeutics, MAR 23, 2021, View Source [SID1234577014]). Asher Bio is pioneering a new approach to immunotherapy, called cis-targeting, which seeks to selectively activate only the immune cell-types that drive a desired immune response, thereby addressing the inherent limitations of immunotherapies attributable to their heterogenous effects on multiple cell-types.
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Jeffrey Tong, PhD, Partner at Third Rock Ventures said, "Following an exhaustive assessment of the cytokine immunotherapy landscape, Third Rock is excited to partner with Asher Bio and their unique approach, which we believe has breakthrough potential to generate multiple differentiated product candidates."
"Asher Bio has assembled a strong team, including two world-class academic founders in Ton Schumacher and Robert Schreiber, to execute on a big vision – to develop an entirely new biotherapeutic class to harness the therapeutic power of cytokine immunotherapies. The company is well positioned to bring its lead oncology program, AB248, into the clinic in 2022 while building out a pipeline of additional products across multiple disease areas," said Reid Huber, PhD, Partner at Third Rock Ventures.
Achieving high selectivity towards immune cell types with cis-targeting
"Therapeutics based on natural cytokines, costimulatory agonists, and checkpoint inhibitors 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," said Asher Bio academic co-founder, Ton Schumacher, PhD.
Craig Gibbs, PhD, Chief Executive Officer of Asher Bio, said, "Our founders had the insight to focus on designing immunotherapies that would only have their effect on defined immune cell subtypes rather than trying to localize the effect of inherently non-specific molecules. Our solution seeks to provide product candidates with superior selectivity and with broad applications across multiple tumor types, as well as treatment of infections and autoimmune diseases."
The company’s cis-targeted immunotherapies address the challenge of pleiotropy by requiring the engagement of two molecules in cis on the same cell for activation, an immunomodulatory receptor and a cell-type specific marker. Without both targets present on the same cell, the therapies are inactive, thereby reducing undesirable effects.
"We have implemented a systematic process to discover novel cis-targeted therapies that can be applied universally to multiple immunomodulatory molecules and target cell types," said Andy Yeung, PhD, co-founder and Chief Technology Officer of Asher Bio. "We first identify the immune cell subtype we want to target, next we attenuate the affinity of the immunomodulator towards receptors across all cell-types, then we create a fusion protein to direct the therapy only to the desired immune cell type, and finally we optimize the pharmacological properties."
Lead cis-targeted IL-2 program is followed by a diverse pipeline
The most advanced development candidate in Asher Bio’s pipeline is AB248, an engineered form of IL-2 designed to be specific to CD8+ effector T cells. Native IL-2 is a clinically approved immunotherapy whose use has been limited due to pronounced side effects.
"Recent insights have underscored that the anti-tumor efficacy of IL-2 is predominantly mediated via CD8+ effector T cells, whereas counter-productive and adverse activities are imparted via other IL-2 receptor-expressing cells, such as regulatory T cells, NK cells and endothelial cells. AB248, which was designed to target only CD8+ effector T cells, has demonstrated superior selectivity and efficacy in multiple preclinical models and is expected to enter trials for the treatment of solid tumors in 2022," said Ivana Djuretic, PhD, co-founder and Chief Scientific Officer of Asher Bio.
Beyond AB248, Asher Bio’s pipeline includes a cis-targeted IL-2 designed to specifically stimulate CAR-T cells, a T-cell cis-targeted STAT3 activating cytokine for cancer, and a Treg cis-targeted cytokine for the treatment of autoimmune disease.
Company founders and leadership
Asher Bio’s team of founders, management and board members brings together leaders with accomplished track records in academia and in the biotechnology industry and with deep drug discovery, development and commercialization experience from companies including Celgene, Celera, Forty Seven, Genentech, Gilead, GSK, Infinity, Incyte, Merck and Pfizer.
Craig Gibbs, PhD, MBA, Chief Executive Officer and Member of the Board
Ivana Djuretic, PhD, Co-Founder, Chief Scientific Officer and Member of the Board
Kyle Elrod, Chief Operating Officer
David Kaufman, MD, PhD, Interim Head, Clinical and Translational Research
Sheldon Okada, Vice President, Commercial and Business Strategy
Andy Yeung, PhD, Co-Founder and Chief Technology Officer
Robert Schreiber, PhD, Academic Co-Founder and Professor of Pathology and Immunology at Washington University School of Medicine.
Ton Schumacher, PhD, Academic Co-Founder and Senior Member at Netherlands Cancer Institute (NKI) and Professor of Immuno-technology at Leiden University
Reid Huber, PhD, Member of the Board and Partner at Third Rock Ventures
Jeffrey Tong, PhD, Member of the Board and Partner at Third Rock Ventures