Our Clinical Trial
We are currently conducting a Phase 1/2a, multi-center, open-label, dose escalation and dose expansion study to evaluate the safety, pharmacokinetics (PK) and preliminary efficacy of our lead program ATRN-119, an inhibitor of ataxia telangiectasia and Rad3-related, or ATR, in patients with advanced solid tumors having mutations in one or more defined DNA damage response-related (DDR) genes.
DNA damage response-related gene mutations
Cells are continuously exposed to endogenous and exogenous stress that can lead to DNA damage. To counter this lethal threat, cells have mechanisms to detect DNA damage, activate the appropriate repair pathway or, if irreparable, induce cell cycle arrest or apoptosis (cell death). These DDR processes are vital for cell survival.
Cancer cells rely on various alternative pathways to repair and resist DNA damage and replication stress. Many of these DDR-related genes are mutated across cancers, as loss of the DDR pathway allows cancer cells to rapidly evolve and grow out of control. Notably, functional loss of these pathways also creates a vulnerability in these cancers because mutation or loss of some DDR genes increases reliance on other DDR genes to support continued cancer cell growth. When mutation or loss of function of two DDR genes leads to cell death, the interplay between these genes is synthetic lethality. Importantly, selective targeting of specific members of the DDR pathway represents an attractive potential therapeutic approach for the treatment of cancer. Furthermore, because genes that are mutated in cancers continue to function normally in healthy tissues, this treatment approach can potentially reduce drug-induced toxicity while maintaining anti-cancer activity.
We are currently enrolling patients in the U.S. in our clinical trial of ATRN-119. Please visit gov (NCT04905914) for more information on the study and site locations.