twoXAR Pharmaceuticals, a drug discovery and development company focused on bringing first-in-class small molecules to market, today announced that two novel leads for the potential treatment of non-alcoholic steatohepatitis (NASH), TXR-611 and TXR-612, demonstrated significant efficacy and excellent tolerability in preclinical studies.
TXR-611 and TXR-612 represent two different novel mechanisms of actions. The overall timing to complete predictions, select hits and begin in vivo testing took a total of four weeks, significantly faster than traditional drug discovery processes. The data was presented at The Liver Meeting Digital Experience™ 2020, the Annual Meeting of the American Association for the Study of Liver Diseases (AASLD). The full poster is available here.
“In just a matter of weeks, we identified an initial set of 10 promising candidates, all with unique mechanisms of action, and selected TXR-611 and TXR-612 to advance our NASH program forward,” stated Anjali Pandey, Ph.D. Senior Vice President of Nonclinical R&D and Chemistry at twoXAR. “So far the data for these two lead candidates is very compelling and we’re thrilled to present our findings at this year’s AASLD annual meeting.”
NASH is a progressive disease and can lead to advanced fibrosis, cirrhosis, liver cancer and end-stage liver disease. It is difficult to diagnose and treat, with delays in management leading to poor patient outcomes. Currently, there are no FDA-approved treatments for NASH.
“NASH is a notoriously complex disease that is not yet fully understood and often associated with a poor prognosis,” stated Dr. Anna Mae Diehl, Florence McAlister Distinguished Professor of Medicine at Duke University. “The early data in TXR-611 and TXR-612 are promising because there is an urgent need to identify novel mechanisms of action that previously weren’t explored in order to make meaningful progress towards an approved treatment.”
In validation studies, discovery hits TXR-611 and TXR-612 modulated fibrosis associated gene and protein expression in primary human hepatic stellate cells similar to galunisertib, a well-accepted control treatment. In vivo efficacy with TXR-611 and 612 was evaluated using STAM™ mouse model where hits demonstrated good tolerability and significant decrease in liver weight, steatosis, ballooning, fibrillar collagen deposition, non-alcoholic fatty liver disease (NAFLD) activity score and efficacy compares favorably to telmisartan.
twoXAR is committed to advancing TXR-611 and TXR-612 and is continuing to research both promising leads in pharmacokinetic, pharmacodynamic, and additional CCl4-induced mouse efficacy studies.
Non-alcoholic steatohepatits (NASH) is an aggressive form of non-alcoholic fatty liver disease (NAFLD) that is progressive and can lead to advanced fibrosis, cirrhosis, liver cancer and end-stage liver disease. It is estimated that 25% of the patients with NAFLD have NASH.i NASH is often asymptomatic, making it difficult to diagnose and the underlying causes of the condition are not well understood. Currently, there are no FDA-approved treatments for NASH.
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This article first appeared on PR Newswire.