TERN-101 / Terns Pharma - LARVOL DELTA

Change in cT1 following interventions in metabolic dysfunction-associated steatotic liver disease: a systematic review and meta-analysis (EASL 2025) - "By treatment type, fibroblast growth factor (FGF) analogues (aldafermin; pegozafermin), glucagon-like peptide (GLP)-1 receptor agonists (pemvidutide; tirzepatide) and farnesoid X receptor (FXR) agonists (vonafexor; ocaliva; TERN-101), cT1 had a mean change of -79ms [95% CI: -90, - 68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively... Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform current and future study designs for investigational therapies for liver disease and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice."

Retrospective data • Review • Hepatology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

Change in cT1 following interventions in MASLD: A systematic review and meta-analysis (APASL 2025) - "By treatment type, fibroblast growth factor (FGF) analogues (aldafermin; pegozafermin), glucagon-like peptide (GLP)-1 receptor agonists (pemvidutide; tirzepatide) and farnesoid X receptor (FXR) agonists (vonafexor; ocaliva; TERN-101), cT1 had a mean change of -79ms [95% CI: -90, -68], -68ms [95% CI: -77, -58] and -62ms [95% CI: -74, -49], respectively... Evidence to-date supports a significant treatment-induced reduction in cT1 as compared to minimal changes in the placebo group. Our findings could inform current and future study designs for investigational therapies for liver disease and support monitoring of treatment response in individuals with MASLD in clinical trials and clinical practice. Table and Figure:Figure 1.Figure."

Retrospective data • Review • Hepatology • Metabolic Dysfunction-Associated Steatotic Liver Disease • FGF

DUET Study: A Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy and in Combination With TERN-101 in Noncirrhotic Adults With Presumed Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=162 | Completed | Sponsor: Terns, Inc. | Phase classification: P2a ➔ P2

Monotherapy • Phase classification • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

TOPLINE RESULTS FROM A 12- WEEK PHASE 2a TRIAL (DUET) EVALUATING TERN-501, A HIGHLY SELECTIVE THYROID HORMONE RECEPTOR (THR)BETA AGONIST, EITHER AS MONOTHERAPY OR IN COMBINATION WITH TERN-101, A NONSTEROIDAL FARNESOID X RECEPTOR (FXR) AGONIST, DEMONSTRATED SIGNIFICANT REDUCTIONS IN MRBASED LIVER FAT CONTENT AND FIBROINFLAMMATION IN PATIENTS WITH PRESUMED MASH (AASLD 2023) - "12wks TERN-501 treatment significantly improved LFC and fibroinflammation in MASH pts and was well tolerated with no GI or CV AE concerns. This first placebo-controlled MASH combination trial of a THRβ and an FXR agonist met all key endpoints without additional safety findings. The compelling overall efficacy/tolerability/combinability profile of TERN-501 warrants further investigation for MASH."

Clinical • Combination therapy • Late-breaking abstract • Monotherapy • P2a data • Cardiovascular • Diabetes • Fibrosis • Gastrointestinal Disorder • Immunology • Inflammation • Metabolic Disorders • Type 2 Diabetes Mellitus • APOB

DUET Study: A Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy and in Combination With TERN-101 in Noncirrhotic Adults With Presumed Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2a | N=162 | Completed | Sponsor: Terns, Inc. | Active, not recruiting ➔ Completed

Combination therapy • Monotherapy • Trial completion • Hepatology • Non-alcoholic Steatohepatitis

A stepwise screening approach using noninvasive tests to identify phenotypic nonalcoholic steatohepatitis (NASH) patients with fibrosis for clinical trials (EASL-ILC 2023) - "LIFT and AVIATION were double-blind, placebo- controlled studies in adults with non-cirrhotic NASH evaluating TERN-101, a potent, nonsteroidal farnesoid X receptor (FXR) agonist with enhanced liver distribution, and TERN-201, a highly specific vascular adhesion protein-1 (VAP-1) inhibitor, respectively. A stepwise screening approach first using clinical assessments, laboratory tests and VCTE with CAP allowed for screening of patients that were more likely to meet the MRI eligibility criteria. As a result, this reduced the number of MRI assessments that were required which reduced costs and the need for patients to be scheduled for a separate imaging visit. These NIT-guided studies recruited efficiently and enrolled subjects likely to have presumed NASH."

Clinical • Fibrosis • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis • AOC3

Combination therapy of TERN-501, a selective agonist of thyroid hormone receptor (THR) beta with TERN-101, a farnesoid X receptor (FXR) agonist improves nonalcoholic steatohepatitis (NASH) in a GAN diet-induced and biopsy-confirmed mouse model (EASL-ILC 2023) - "Treatment with the THR-beta agonist TERN-501 in combination with the FXR agonist TERN- 101 led to greater NAS and fibrosis improvements from baseline compared with single agent treatments, likely driven by increased anti-steatotic activity. These data suggest that combining the robust anti-steatotic effects of a selective THR-beta agonist with an FXR agonist may provide a superior therapeutic benefit for NASH over either agent alone. The use of AI-digital pathology can provide granularity in NASH drug development during the preclinical phase, which may be translated to current use in NASH clinical trials."

Biopsy • Combination therapy • Preclinical • Fibrosis • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis • Obesity

DUET Study: A Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy and in Combination With TERN-101 in Noncirrhotic Adults With Presumed Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2a | N=162 | Active, not recruiting | Sponsor: Terns, Inc. | Recruiting ➔ Active, not recruiting

Combination therapy • Enrollment closed • Monotherapy • Hepatology • Non-alcoholic Steatohepatitis

TRIAL IN PROGRESS: THE FIRST 12-WEEK, RANDOMIZED, CONTROLLED PHASE 2a STUDY OF A THYROID HORMONE RECEPTOR-ΒETA AGONIST (TERN-501) ADMINISTERED AS MONOTHERAPY OR IN COMBINATION WITH A FARNESOID X RECEPTOR AGONIST (TERN-101) IN PATIENTS WITH NASH (AASLD 2022) - "This is the first trial assessing safety and efficacy of a THR-β and FXR agonist combination in NASH patients. The factorial design will allow evaluation of the potential additive effects of TERN-501+TERN-101 combination compared to each agent and to placebo using noninvasive biomarkers."

Clinical • Combination therapy • Monotherapy • P2a data • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis

DUET Study: A Clinical Study to Evaluate the Safety, Efficacy, Pharmacokinetics and Pharmacodynamics of Orally Administered TERN-501 as Monotherapy and in Combination With TERN-101 in Noncirrhotic Adults With Presumed Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P2a | N=140 | Recruiting | Sponsor: Terns, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Non-alcoholic Steatohepatitis

Terns Pharmaceuticals Highlights Clinical Data from Multiple NASH Programs in Five Presentations at the EASL International Liver Congress 2022 (GlobeNewswire) - "A second clinical presentation titled 'Favorable lipid and pruritus profile of liver-distributed farnesoid X receptor agonist TERN-101 at clinically efficacious doses in non-alcoholic steatohepatitis phase 2a LIFT study' will be delivered by Kris Kowdley, M.D....A fourth clinical presentation titled 'TERN-101, a farnesoid X receptor agonist, demonstrated similar safety and efficacy in non-alcoholic steatohepatitis patients with coronavirus disease of 2019 (COVID-19) exposure compared to those with no COVID-19 exposure in phase 2a LIFT study' will be presented by Kris Kowdley."

Media quote

Liver-distributed farnesoid X receptor agonist TERN-101 demonstrates potent target engagement with a favorable exposure-response profile in nonalcoholic steatohepatitis patients (EASL-ILC 2022) - P2a | "TERN-101 resulted in significant FXR target engagement in the liver relative to the intestine, as evidenced by sustained decreases in C4 at the 10 and 15 mg doses and transient increases in FGF19. Higher exposures of TERN-101 were associated with greater decreases in cT1, a marker of fibroinflammation improvement in NASH patients. These analyses support further development of TERN- 101 for the treatment of NASH, either alone or in combination with other agents."

Clinical • Addiction (Opioid and Alcohol) • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis • FGF19

Favorable lipid and pruritus profile of liver-distributed farnesoid X receptor agonist TERN-101 at clinically efficacious doses in nonalcoholic steatohepatitis phase 2a LIFT study (EASL-ILC 2022) - P2a | "LDL and HDL mean changes, and proportion of patients with lipid changes by specified thresholds, were similar for 5 and 10 mg TERN-101 and placebo atWeek 12. Pruritus AEswere not dosedependent and did not lead to treatment discontinuation. These data support an overall differentiated and favorable safety and tolerability profile for TERN-101 at potentially efficacious dose levels."

Clinical • P2a data • Addiction (Opioid and Alcohol) • Dermatology • Dyslipidemia • Hepatology • Non-alcoholic Steatohepatitis • Pruritus

TERN-101, a farnesoid X receptor agonist, demonstrated similar safety and efficacy in nonalcoholic steatohepatitis patients with coronavirus disease of 2019 (COVID-19) exposure compared to those with no COVID-19 exposure in phase 2a LIFT study (EASL-ILC 2022) - P2a | "NASH patient recruitment and retention in the LIFT Study was feasible during the COVID-19 pandemic with successful implementation of COVID-19 testing. The TERN-101 safety profile and cT1 responses were similar between the subset of patients with COVID-19 exposure and those without."

Clinical • P2a data • Hepatology • Infectious Disease • Non-alcoholic Steatohepatitis • Novel Coronavirus Disease • Respiratory Diseases

A Phase 2a Clinical Study to Evaluate the Safety, Efficacy, PK and PD of Orally Administered TERN-501 as Monotherapy and in Combination With TERN-101 in Noncirrhotic Adults With Presumed (NASH) (clinicaltrials.gov) - P2a | N=140 | Not yet recruiting | Sponsor: Terns, Inc.

Combination therapy • Monotherapy • New P2a trial • Hepatology • Non-alcoholic Steatohepatitis

LIVER-DISTRIBUTED FXR AGONIST TERN-101 DEMONSTRATES FAVORABLE SAFETY AND EFFICACY PROFILE IN NASH PHASE 2A LIFT STUDY (NASH-TAG 2022) - "TERN-101 was overall safe and well-tolerated, with no discontinuations due to AEs. Treatment resulted in significant decreases in ALT, cT1, and MRI-PDFF. Future investigation of TERN-101 is warranted."

Clinical • P2a data • Dermatology • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • Pruritus

LIVER-DISTRIBUTED FXR AGONIST TERN-101 LEADS TO CORRECTED T1 (CT1) RESPONSE AND A POPULATION SHIFT TO LOWER CT1 RISK CATEGORIES IN NASH PHASE 2A LIFT STUDY (NASH-TAG 2022) - "TERN-101 treatment resulted in a higher proportion of patients with cT1 decline ≥80 msec and a study population shift to cT1 lower risk categories vs placebo. Improvements in cT1 may serve as a TERN-101 treatment response biomarker and may reflect the impact of this FXR agonist on fibroinflammation."

Clinical • P2a data • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Steatohepatitis

Terns Pharmaceuticals Highlights Positive Clinical Data from Multiple NASH Programs at AASLD The Liver Meeting Digital Experience 2021 (GlobeNewswire) - "Terns Pharmaceuticals, Inc...today announced that multiple presentations of positive results from clinical trials of TERN-101 and TERN-501 will be delivered at The Liver Meeting Digital Experience 2021....clinical presentation titled 'Liver-distributed FXR Agonist TERN-101 Leads to Corrected T1 (cT1) Response and a Population Shift to Lower cT1 Risk Categories in NASH Phase 2a LIFT Study' will be delivered by Eric Lawitz, M.D., director of the Texas Liver Institute and Clinical Professor of Medicine at University of Texas Health Science Center."

[VIRTUAL] LIVER-DISTRIBUTED FXR AGONIST TERN-101 DEMONSTRATES FAVORABLE SAFETY AND EFFICACY PROFILE IN NASH PHASE 2a LIFT STUDY (AASLD 2021) - "TERN-101 was overall safe and well-tolerated, with no discontinuations due to AEs . Treatment resulted in significant decreases in ALT, cT1, and MRI-PDFF. Future investigation of TERN-101 is warranted."

Clinical • P2a data • Dermatology • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • Pruritus • MRI

Data on TERN-101 Show Promise for NASH Treatment (Gastroendonews) - "'However, only a handful of molecules have shown a potential of entering into phase 3 clinical trials,' Dr. Singal said. 'Further, the field in the last few years has recognized that a multifaceted pathophysiology of NASH and NAFLD would best be tackled using a combination approach targeting different pathophysiological pathways. The promising results of this LIFT study favorably fit the current NASH landscape, and are critical in designing a larger phase 3 clinical trial.'"

Media quote

[VIRTUAL] LIVER-DISTRIBUTED FXR AGONIST TERN-101 LEADS TO CORRECTED T1 (cT1) RESPONSE AND A POPULATION SHIFT TO LOWER cT1 RISK CATEGORIES IN NASH PHASE 2a LIFT STUDY (AASLD 2021) - "TERN-101 treatment resulted in a higher proportion of patients with cT1 decline ≥80 msec and a study population shift to cT1 lower risk categories vs placebo . Improvements in cT1 may serve as a TERN-101 treatment response biomarker and may reflect the impact of this FXR agonist on fibroinflammation."

Clinical • P2a data • Fibrosis • Hepatology • Immunology • Inflammation • Liver Cirrhosis • Non-alcoholic Steatohepatitis • MRI

"Add to the list of "Surgery Intern 101" pearls: This... 👇" (@brakenridge_md)

LIFT Study: A Safety, Tolerability, Efficacy, and Pharmacokinetics Study of TERN-101 in Subjects With Non-Cirrhotic Non-Alcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P2a; N=101; Completed; Sponsor: Terns, Inc.; Active, not recruiting ➔ Completed

Trial completion • Hepatology • Non-alcoholic Steatohepatitis • MRI

Safety, Pharmacokinetics, Pharmacodynamics, and Formulation of Liver-Distributed Farnesoid X-Receptor Agonist TERN-101 in Healthy Volunteers. (PubMed, Clin Pharmacol Drug Dev) - "There was no significant effect of food on exposure. The overall safety, PK, and PD profiles of TERN-101 support its further evaluation for the treatment of NASH."

Clinical • Journal • PK/PD data • Dermatology • Hepatology • Non-alcoholic Steatohepatitis • Pruritus

Q&A: TERN-101 may be tolerable in patients with NASH (Healio) - "Healio Gastroenterology spoke with Rohit Loomba...about the phase 2a trial take-aways and the next step in research on TERN-101."

Interview