February 19, 2020
-Phase 1 study demonstrated TERN-101 is safe and exhibits potent target engagement at all dose levels studied-
-Phase 2 studies of TERN-101 expected to begin in NASH patients in mid-2020-
Terns Pharmaceuticals, Inc., a global biopharmaceutical company focused on discovering and developing innovative therapies to treat non-alcoholic steatohepatitis (NASH) and cancer, today announced the completion of a Phase 1 clinical study of TERN-101, an investigational farnesoid X receptor (FXR) agonist, which demonstrated all dose levels were well tolerated and achieved potentially therapeutic-level target engagement.
The Phase 1 trial of TERN-101 was a randomized, double-blind, placebo-controlled study designed to evaluate safety, pharmacokinetics, pharmacodynamics, and plasma biomarkers of FXR pathway activation in 36 healthy participants who received placebo or TERN-101 at various dose levels for 7 days. Pharmacodynamic biomarkers of FXR target engagement, 7α‐hydroxy‐4‐cholesten‐3‐one (7α-C4), an intermediate in the biosynthesis of cholesterol to bile acids, and Fibroblast Growth Factor 19 (FGF19), a hormone produced after FXR activation in the intestine that regulates bile acid synthesis, as well as glucose and lipid metabolism, were measured in the serum of participants.
“These data showed strong target engagement with TERN-101 while avoiding any significant adverse event trends, supporting our strategy to target FXR in the liver while minimizing potential side effects through decreased drug exposure in other tissues. These results indicate that TERN-101 has best-in-class potential and gives us great confidence as we prepare to initiate Phase 2 clinical studies in NASH patients in mid-2020,” commented Erin Quirk, M.D., Chief Medical Officer of Terns.
The results showed reductions of serum 7α-C4 levels ranging from 74% to 91% across TERN-101 dose groups. Maximum increases from baseline in serum FGF19 levels between 6- to 8- fold were observed four hours after TERN-101 dosing and were not dose dependent.
There were no clinically relevant, dose-related trends in adverse events (AEs) or laboratory abnormalities in the study. AEs were mild in severity across all dose groups and were considered not related or unlikely to be related to study drug. No pruritus was reported by any subject, and no subjects prematurely discontinued study medication.
“The successful completion of the Phase 1 study of TERN-101 shows that we are able to execute rapidly on our strategy of developing novel medicines to treat NASH, while maintaining our focus on developing safe and effective combination regimens, which we believe are what will ultimately be required to control the disease,” said Weidong Zhong, Ph.D., President and Chief Executive Officer of Terns. “Many experts in the field believe that combining an FXR agonist with other experimental NASH therapeutics holds the most promise in driving higher response rates in NASH patients with fibrosis. Our pipeline is equipped to explore such combinations in the foreseeable future, and we look forward to continued progress with TERN-101 and the rest of our product pipeline.”
About TERN-101 and Farnesoid X Receptor (FXR) Agonism
TERN-101 is a potent, liver-selective non-bile acid FXR agonist being developed as a therapeutic for NASH. FXR is a nuclear receptor that is highly expressed in the liver and small intestine. Bile acids (BA) are natural ligands of FXR, and their binding with and activation of FXR is critical to the regulation of cellular pathways that modulate BA synthesis, lipid metabolism, inflammation, and fibrosis. FXR agonism and activation has demonstrated improvement over placebo in regression of histological liver fibrosis without progression to NASH in a late-stage study, demonstrating the potential for FXR agonists to be a new treatment modality for NAFLD and NASH. TERN-101 has been granted FastTrack Designation by the U.S. Food and Drug Administration (FDA) for the treatment of NASH.
Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD), which is caused by the accumulation of excess fat in the liver. NASH is associated with chronic liver inflammation and liver cell injury, and it can lead to fibrosis, cirrhosis, and eventually liver cancer or liver failure. Global rates of NAFLD and NASH are increasing rapidly, in tandem with rising rates of obesity. There is currently no approved medication for the treatment of NASH.
About Terns Pharmaceuticals
Terns Pharmaceuticals, Inc. is a clinical-stage pharmaceutical company that is focused on the discovery and development of medicines for chronic liver disease and cancer. Based in China and the United States, the company is advancing a pipeline of drug candidates for the treatment of non-alcoholic steatohepatitis (NASH) and cancer, across multiple modalities. Terns leverages world class expertise in disease biology, medicinal chemistry, and clinical development in order to bring promising new therapies to patients in China and other global markets.
For more information, visit www.ternspharma.com and www.ternspharma.com.cn