CSO: Dr. Oshik Segev
A2i Therapeutics Ltd. is a joint venture of FutuRx and Atomwise, designed to utilize Atomwise’s AI platform, AtomNet® technology, to target ADAR1, a key protein involved in controlling the innate immune response, neurological disorders, metabolic diseases and potentially a key target for immuno-oncology and neurological homeostasis.
Scientific Approach
A2i Therapeutics is developing small molecule inhibitors of adenosine deaminase acting on RNA 1 (ADAR1). ADAR1 is an enzyme that deaminates the nucleotide adenosine to inosine in double stranded RNA (dsRNA), thus making dsRNA molecules unstable.
dsRNA molecules are uncommon in the cytoplasm of eukaryotic cells and trigger an innate immune response. Typically, the immune response to dsRNA is attenuated by the activity of ADAR1. ADAR1 efficiently neutralizes the immunogenicity of the endogenous dsRNAs, keeping the immune response in check.
Elevated ADAR1 activity has been reported in some cancers, and potentially allows cancer cells to exploit its activity to evade immune detection. Inhibition of ADAR1 could trigger an effect in two therapeutic arms: 1) directly kill a subset of cancers that have increased IFN signalling pathway activation; and 2) sensitize cancer cells to immunotherapy, through stimulation of cytotoxic T and NK cells and overcoming common mechanisms of resistance to immunotherapy.
Indications
The Company intends to initially target Non-Small Cell Lung Cancer (NSCLC) and triple-negative breast cancer (TNBC), as these tumors appear to be ADAR-dependent. The treatment landscape for patients with advanced NSCLC has evolved greatly with the advent of immune checkpoint inhibitors. However, many patients do not derive benefit from checkpoint blockade, developing either primary or secondary resistance, highlighting a need for alternative approaches to modulate immune function. Our approach is resisting the resistance with synergy; Inhibition of ADAR1 as a strategy for rendering tumors sensitive to immunotherapy and to overcome resistance to checkpoint blockade.
Dr. Oshik Segev, PhD: CSO
Dr. Segev holds a PhD in Biochemistry and molecular biology from the Tel Aviv University. Dr. Segev’s expertise include oncogenic protein analysis, isolation and structural analysis, especially interaction with small molecule drugs. Dr. Segev worked as senior scientist at Applied Immune Technologies Ltd. (now Adicet Bio Inc) in the development of a new therapeutics’ antibodies. Following which he served as an R&D project advisor for several pharma companies.