TERN-201 / Terns Pharma - LARVOL DELTA

AVIATION Study: A Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TERN-201 in Patients With Non-Cirrhotic Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P1 | N=52 | Completed | Sponsor: Terns, Inc. | Phase classification: P1b ➔ P1

Phase classification • Hepatology • Metabolic Dysfunction-Associated 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

AVIATION Study: A Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TERN-201 in Patients With Non-Cirrhotic Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P1b | N=52 | Completed | Sponsor: Terns, Inc. | Active, not recruiting ➔ Completed

Trial completion • Hepatology • Non-alcoholic Steatohepatitis • AOC3

Favorable safety profile of TERN-201, a highly selective inhibitor of vascular adhesion protein-1, in the nonalcoholic steatohepatitis phase 1b AVIATION study (EASL-ILC 2022) - P1b | "TERN-201 was well-tolerated with a safety profile similar to placebo in patients with BL multiparametric MRI and LS values indicating NASH with at least stage 2 fibrosis. While 10 mg TERN-201 led to near complete inhibition of plasma VAP-1 activity and decreased levels of the hepatic fibrogenesis marker TIMP1, no statistically significant differences were observed between TERN-201 and placebo on markers of liver inflammation and injury following 12 weeks of treatment. Overall, these data support further assessment of safety and activity of 20 mg TERN-201 in the ongoing Part 2 of the AVIATION Trial in phenotypic NASH."

Clinical • P1 data • Fibrosis • Hepatology • Immunology • Inflammation • Non-alcoholic Steatohepatitis • AOC3 • KRT18 • TIMP1

TERN201-1007: AVIATION Study: A Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TERN-201 in Patients With Non-Cirrhotic Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P1b | N=60 | Active, not recruiting | Sponsor: Terns, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Non-alcoholic Steatohepatitis • AOC3

When Being Antagonistic Is a Good Thing: Using Memantine as Salvage Therapy for Catatonia From NMDA-Receptor Encephalitis (APA 2022) - "Due to significant ongoing catatonic symptoms, he was given a one-time infusion of Rituximab and started on oral Memantine 5 mg daily with reduction in BFS to 10-17. Memantine was later uptitrated to 5 mg twice a day - while lorazepam was weaned down - with continued improvement in catatonic symptoms...First, catatonia has a medical etiology in up to 46% of cases (Stern 2018), and this rate increases with age and level of care (Oldham 2018)...In turn, many clinicians are hesitant to prescribe memantine for such cases, with scant evidence to refute this. This is a unique case that demonstrates memantine’s utility and safety profile in cases of NMDA-R encephalitis-induced catatonia through a patient who was falsely assumed to have a primary psychiatric illness due to demographic factors."

Bipolar Disorder • Cardiovascular • CNS Disorders • Germ Cell Tumors • Immunology • Mental Retardation • Psychiatry • Testicular Seminoma • Urology

TERN201-1007: AVIATION Study: A Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TERN-201 in Patients With Non-Cirrhotic Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P1b | N=60 | Recruiting | Sponsor: Terns, Inc. | Active, not recruiting ➔ Recruiting

Enrollment open • Hepatology • Non-alcoholic Steatohepatitis • AOC3

[VIRTUAL] ECC0509, A NOVEL PERIPHERALLY DISTRIBUTED AND SELECTIVE SEMICARBAZIDE-SENSITIVE AMINO OXIDASE (SSAO) INHIBITOR FOR NASH TREATMENT (AASLD 2021) - "The clinical development of SSAO inhibitor BI 1467335 for NASH was discontinued due to interference with brain monoamine oxidase B (MAO-B)...In addition, ECC0509 has less inhibition to DAO compared to TERN-201, suggesting unlikelihood of interference with histamine metabolism . ECC0509 is a potential best-in-class SSAO inhibitor and currently in phase I clinical trial ."

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

TERN201-1007: AVIATION Study: A Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TERN-201 in Patients With Non-Cirrhotic Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P1b; N=60; Active, not recruiting; Sponsor: Terns, Inc.; Recruiting ➔ Active, not recruiting; Trial completion date: Aug 2022 ➔ Nov 2022

Clinical • Enrollment closed • Trial completion date • Hepatology • Non-alcoholic Steatohepatitis • AOC3 • MRI

A Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TERN-201 in Patients With Non-Cirrhotic Non-Alcoholic Steatohepatitis (clinicaltrials.gov) - P1b; N=60; Recruiting; Sponsor: Terns, Inc.; Not yet recruiting ➔ Recruiting

Enrollment open • Hepatology • Non-alcoholic Steatohepatitis • AOC3

A Safety, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy Study of TERN-201 in Patients With Non-Cirrhotic Non-Alcoholic Steatohepatitis (NASH) (clinicaltrials.gov) - P1b; N=60; Not yet recruiting; Sponsor: Terns, Inc.

Clinical • New P1 trial • Hepatology • Non-alcoholic Steatohepatitis • AOC3

[VIRTUAL] MULTIPLE ASCENDING DOSES OF TERN-201, A NOVEL SELECTIVE SEMICARBAZIDE-SENSITIVE AMINE OXIDASE (SSAO) INHIBITOR, FULLY SUPPRESSES PLASMA SSAO ACTIVITY IN A PHASE 1 STUDY (AASLD 2020) - "In this multiple ascending dose trial, TERN-201 was safe and well tolerated in healthy subjects when administered up to 10 mg QD for 14 days. Steady state levels of TERN-201 were achieved after 7 days of dosing, supporting a QD dosing regimen. Near complete inhibition of plasma SSAO amine oxidase activity was seen after a single dose and inhibition was sustained up to 2 weeks after cessation of dosing."

P1 data • Addiction (Opioid and Alcohol) • Hepatology • Non-alcoholic Steatohepatitis

[VIRTUAL] PHARMACOKINETICS AND TISSUE DISTRIBUTION OF TERN-201, A NOVEL INVESTIGATIONAL SSAO/VAP-1 INHIBITOR, IN PRECLINICAL SPECIES (AASLD 2020) - "TERN-201 shown good tissue distribution in the liver, which allows for a robust direct effect on the target SSAO in the liver, as demonstrated in PK and tissue distribution studies in preclinical species. Additionally, TERN-201 distribution to the lung, kidney and eyes suggest the potential use of TERN-201 to target other chronic inflammatory diseases such as diabetic nephropathy, inflammatory and diabetic retinopathy. Taken together, PK and tissue distribution of TERN-201 support its continued clinical development for NASH."

PK/PD data • Preclinical • Cholangiocarcinoma • Diabetic Nephropathy • Diabetic Retinopathy • Hepatology • Immunology • Inflammation • Nephrology • Non-alcoholic Steatohepatitis • Renal Disease • Retinal Disorders • Solid Tumor • AOC3

[VIRTUAL] Single doses of TERN-201, a novel selective semicarbazide-sensitive amine oxidase (SSAO) inhibitor, are safe, well-tolerated, and result in sustained reduction of SSAO activity in healthy participants (EASL-ILC-I 2020) - "Inhibition of plasma SSAO amine oxidase activity and dose-dependent increases in plasma MMA were sustained up to 1 week after single doses of TERN-201, suggesting potent, covalent target engagement and supporting once daily dosing despite a short plasma half- life. All TERN-201 dose levels were well-tolerated. Additional studies are warranted to further investigate TERN-201 for the treatment of NASH."

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

[VIRTUAL] Anti-inflammatory and anti-fibrotic activity of TERN-201, a semicarbazide-sensitive amine oxidase inhibitor, in a rat choline-deficient high-fat diet non-alcoholic steatohepatitis model (EASL-ILC-I 2020) - "TERN-201 strongly inhibited liver inflammation in a rat model of NASH. A reduction in liver fibrosis markers was also seen, supporting the further development of this drug in patients with NASH."

Preclinical • Addiction (Opioid and Alcohol) • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Liver Failure • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • AOC3

Single doses of TERN-201, a novel selective semicarbazide-sensitive amine oxidase (SSAO) inhibitor, are safe, well-tolerated, and result in reduced plasma SSAO activity in healthy participants (APASL 2020) - No abstract available

Clinical

Single doses of tern-201, a novel selective semicarbazide-sensitive amine oxidase (ssao) inhibitor, are safe, well-tolerated, and result in sustained reduction of ssao activity in healthy participants (EASL-ILC 2020) - No abstract available

Clinical

Anti-inflammatory and anti-fibrotic activity of tern-201, a semicarbazide-sensitive amine oxidase inhibitor, in a rat choline-deficient high-fat diet non-alcoholic steatohepatitis model (EASL-ILC 2020) - No abstract available

Preclinical

"James Novak, @HFNephrology TPD and #NSMC intern 2018. No COI." (@JamesNovakNeph)

A novel semicarbazide-sensitive amine oxidase inhibitor, TERN-201, reduces NAS and fibrosis in rodent models of non-alcoholic steatohepatitis (EASL-ILC 2019) - "TERN-201 is a potent SSAO inhibitor effective in rodent models of NASH and fibrosis. Daily dosing of TERN-201 reduced the NAFLD activity score in a diet-induced obese mouse model of NASH, primarily through a reduction in hepatocyte ballooning. TERN-201 reduced liver inflammation and fibrosis in a rat CCL4 model of liver fibrosis."

Preclinical

Die Zeitschrift für Rheumatologie dankt den Gutachtern 2018. (PubMed, Z Rheumatol) - No abstract available.

Journal

Medizinische Klinik – Intensivmedizin und Notfallmedizin dankt den Gutachtern 2018. (PubMed, Med Klin Intensivmed Notfmed) - No abstract available.

Journal