VK2809 / Viking Therap, Ligand - LARVOL DELTA

Preclinical studies of a novel hydrolysis-based prodrug for treating metabolic dysfunction associated steatohepatitis (EASL 2025) - "Background and Aims: Approval of resmetirom for treating Metabolic dysfunction associated steatohepatitis validated thyroid hormone receptor beta (THR-b) as an effective therapeutic target. Our prodrugs showed a ~15-fold in vitro activity increase over VK-2809 in HepG2 assay. In vivo PK studies showed that they were barely detectable while the active metabolite was preferentially concentrated in the liver compared to VK-2809. The ratio of the active metabolite AUC between liver and heart was 116 (CG-025013), 158 (CG-025016) vs 63 (VK-2809)."

Preclinical • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Preclinical studies of a novel hydrolysis-based prodrug for treating metabolic dysfunction associated steatohepatitis (APASL 2025) - "Background: Approval of resmetirom for treating Metabolic dysfunction associated steatohepatitis validated thyroid hormone receptor beta (THR-b) as an effective therapeutic target. Our prodrugs showed a ~15-fold in vitro activity increase over VK-2809 in HepG2 assay. In vivo PK studies showed that they were barely detectable while the active metabolite was preferentially concentrated in the liver compared to VK-2809. The ratio of the active metabolite AUC between liver and heart was 116 (CG-025013), 158 (CG-025016) vs 63 (VK-2809)."

Preclinical • Dyslipidemia • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Viking Therapeutics Reports Fourth Quarter and Year-End 2024 Financial Results and Provides Corporate Update (PRNewswire) - "Initiation of Phase 3 Studies for Subcutaneous VK2735 for Obesity Planned for 2Q25. Phase 2 VENTURE-Oral Dosing Trial Evaluating VK2735 in Obesity Underway....The primary endpoint of the study is the percent change in body weight from baseline after 13 weeks of treatment....The company expects to report data from this study in 2H25....Best-in-Class Data from Phase 2b VOYAGE Trial in MASH Highlighted in Oral Late Breaker Presentation at The Liver Meeting 2024....Dual Amylin and Calcitonin Receptor Agonist (DACRA) Program Ongoing; IND Planned for 2025...Viking is evaluating an internally developed dual amylin and calcitonin receptor agonist (DACRA) program for the potential treatment of obesity."

IND • Late-breaking abstract • New P3 trial • P2 data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Obesity

Results From the 52-Week Phase 2b VOYAGE Trial of VK2809 in Patients With Biopsy-Confirmed Non-Alcoholic Steatohepatitis and Fibrosis: A Randomized, Placebo-Controlled Trial. (PubMed, Gastroenterol Hepatol (N Y)) - No abstract available

Journal • P2b data • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Thyromimetics and MASLD: Unveiling the Novel Molecules Beyond Resmetirom. (PubMed, J Gastroenterol Hepatol) - "Future clinical studies should thoroughly investigate THRβ agonists, including TG68, CS27109, MB07811, and KB-141."

Journal • Review • Cardiovascular • Endocrine Disorders • Fibrosis • Hepatology • Immunology • Inflammation • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease • Obesity

Viking Therapeutics Presents Results from Phase 2b VOYAGE Study of VK2809 in Biopsy-Confirmed NASH/MASH at the 75th Liver Meeting 2024 (PRNewswire) - P2b | N=248 | VOYAGE (NCT04173065) | Sponsor: Viking Therapeutics, Inc. | "Patients receiving VK2809 demonstrated statistically significant reductions in liver fat at Week 12, which was the primary endpoint in VOYAGE. Importantly, patients receiving VK2809 continued to demonstrate statistically significant reductions in liver fat content at Week 52, with the mean relative change from baseline ranging from 37% to 55%. The response rate in this study, defined as the proportion of patients experiencing reduction in liver fat ≥30%, ranged from 64% to 88% at Week 52, with all treatment arms demonstrating statistically significant improvement compared to placebo...On the secondary endpoint of NASH resolution with no worsening of fibrosis, VK2809-treated patients demonstrated NASH resolution ranging from 63% to 75%, compared with 29% for placebo (p<0.05 for each VK2809 treatment group). Across the combined VK2809 treatment groups, 69% achieved NASH resolution (p<0.0001 vs. placebo)."

P2b data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Viking Therapeutics to Present Data from Phase 2b VOYAGE Study of VK2809 in Patients with Biopsy-Confirmed NASH/MASH at the 75th Liver Meeting 2024 (PRNewswire) - "Viking Therapeutics, Inc...announced that results from the company's Phase 2b clinical trial of VK2809, the company's novel liver-selective thyroid hormone receptor beta agonist, in patients with biopsy-confirmed non-alcoholic steatohepatitis (NASH; also referred to as metabolic dysfunction associated steatohepatitis, MASH) will be highlighted in an oral late breaker presentation at the 75th Liver Meeting 2024, the annual meeting of the American Association for the Study of Liver Disease (AASLD)."

P2b data • Metabolic Dysfunction-Associated Steatohepatitis

Viking Therapeutics Reports Third Quarter 2024 Financial Results and Provides Corporate Update (PRNewswire) - P2b | N=248 | VOYAGE (NCT04173065) | Sponsor: Viking Therapeutics, Inc. | "Successful Phase 2b VOYAGE Trial in NASH/MASH Reported in 2Q24; Data to be Featured in Oral Late Breaker Presentation at The Liver Meeting 2024....On the secondary endpoint of NASH/MASH resolution without worsening of fibrosis, VK2809-treated patients demonstrated NASH/MASH resolution rates ranging from 63% to 75%, compared with 29% for placebo. On the secondary endpoint evaluating the proportion of patients demonstrating at least a one-stage improvement in fibrosis with no worsening of NASH/MASH, the proportion of VK2809-treated patients demonstrating improvements in fibrosis ranged from 44% to 57%, compared with 34% for placebo."

P2b data • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

VOYAGE: A Study to Assess the Efficacy and Safety of VK2809 for 52 Weeks in Subjects With Biopsy Proven NASH (clinicaltrials.gov) - P2 | N=248 | Completed | Sponsor: Viking Therapeutics, Inc. | Active, not recruiting ➔ Completed | Phase classification: P2b ➔ P2 | Trial completion date: Jun 2024 ➔ Jan 2024

Biopsy • Phase classification • Trial completion • Trial completion date • Fibrosis • Hepatology • Immunology • Metabolic Dysfunction-Associated Steatohepatitis

Viking Therapeutics Announces Positive 52-Week Histologic Data from Phase 2b VOYAGE Study of VK2809 in Patients with Biopsy-Confirmed Non-Alcoholic Steatohepatitis (NASH) (PRNewswire) - P2b | N=248 | VOYAGE (NCT04173065) | Sponsor: Viking Therapeutics, Inc. | "Viking Therapeutics, Inc...today announced positive 52-week histologic data from its Phase 2b VOYAGE study of VK2809....As previously reported, the study successfully achieved its primary endpoint, with patients receiving VK2809 experiencing statistically significant reductions in liver fat content from baseline to Week 12 as compared with placebo. The results announced today highlight achievement of secondary endpoints evaluating histologic changes assessed by hepatic biopsy after 52 weeks of treatment with VK2809....On the secondary endpoint of NASH resolution with no worsening of fibrosis, VK2809-treated patients demonstrated NASH resolution ranging from 63% to 75%, compared with 29% for placebo (p<0.05 for each VK2809 treatment group). Across the combined VK2809 treatment groups, 69% achieved NASH resolution (p<0.0001 vs. placebo)."

P2b data • Fibrosis • Metabolic Disorders • Metabolic Dysfunction-Associated Steatohepatitis

Viking Therapeutics Reports First Quarter 2024 Financial Results and Provides Corporate Update (PRNewswire) - "Histology Results for Phase 2b VOYAGE Study Evaluating VK2809 for the Treatment of NASH and Fibrosis Expected in 2Q24."

P2b data • Metabolic Dysfunction-Associated Steatohepatitis

THE NOVEL THYROID HORMONE RECEPTOR BETA AGONIST VK2809 SIGNIFICANTLY REDUCES LIVER FAT IN PATIENTS WITH NASH AND FIBROSIS, RESULTS FROM THE PRIMARY ENDPOINT OF THE ONGOING PHASE 2b VOYAGE STUDY (AASLD 2023) - "VK2809 produced significant reductions in liver fat after 12 wks of dosing in patients with biopsy confirmed NASH and fibrosis. Dosing in the study continues and patients will be assessed by hepatic biopsy after 52 wks of treatment."

Clinical • Late-breaking abstract • P2b data • Diabetes • Fibrosis • Hepatology • Immunology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Type 2 Diabetes Mellitus • APOB

Viking Therapeutics Reports Third Quarter 2023 Financial Results and Provides Corporate Update (PRNewswire) - "The results for the primary endpoint of the VOYAGE Phase 2b study have been selected for poster presentation at the upcoming meeting of the American Association for the Study of Liver Diseases (AASLD). Abstract 48541...will be presented at the Late Breaking Poster Session, scheduled for Monday, November 13 at 1:00 pm ET....Phase 2b VOYAGE Study Evaluating VK2809 for the Treatment of NASH and Fibrosis Ongoing; Histology Results Expected 1H24."

P2b data • Fibrosis • Non-alcoholic Steatohepatitis

Development and validation for bioanalysis of VK2809, its active metabolite VK2809A and glutathione-conjugated metabolite MB06588 in rat liver using LC-MS/MS. (PubMed, J Pharm Biomed Anal) - "Subsequently, several factors were investigated such as the use of 60% acetonitrile for homogenization to stabilize the analytes, the addition of 20 mM glutathione for the derivation of VK2809B, and the protein precipitation with methanol containing Sobetirome as the internal standard (IS). This method is suitable for the bioanalysis of VK2809 and its metabolites and has been successfully applied to the study of intrahepatic exposure in rats. It is expected to be further practiced in drug design, optimization, and metabolism study in the following research."

Journal • Preclinical • Hepatology • Non-alcoholic Steatohepatitis

Two Experimental Therapies Show Promise for NASH (Hep) - "'These data are amongst one of the most consistent data sets for drugs in clinical development for NASH with a parallel improvement in both MRI-PDFF and ALT and bodes well for the likelihood of success in the upcoming Phase III program,' said lead investigator Rohit Loomba, MD..."

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VOYAGE: A Study to Assess the Efficacy and Safety of VK2809 for 52 Weeks in Subjects With Biopsy Proven NASH (clinicaltrials.gov) - P2b | N=248 | Active, not recruiting | Sponsor: Viking Therapeutics, Inc. | Recruiting ➔ Active, not recruiting | Trial completion date: Dec 2023 ➔ Jun 2024 | Trial primary completion date: Dec 2022 ➔ May 2023

Biopsy • Enrollment closed • Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis

VOYAGE: A Study to Assess the Efficacy and Safety of VK2809 for 52 Weeks in Subjects With Biopsy Proven NASH (clinicaltrials.gov) - P2b | N=337 | Recruiting | Sponsor: Viking Therapeutics, Inc. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Jun 2022 ➔ Dec 2022

Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis

Thyroid hormones as a disease modifier and therapeutic target in nonalcoholic steatohepatitis. (PubMed, Expert Rev Endocrinol Metab) - "Unselective TR targeting can be accompanied by negative side effects due to high TRβ expression in other organs and TRα-mediated effects. Recent advances in drug development and the introduction of liver-targeted thyromimetics selectively activating TRβ such as Resmetirom (MGL-3196) and VK2809 bring new hope of translating the knowledge on local TH effects into effective hepatic lipid-clearing therapies against NASH."

Journal • Fibrosis • Hepatology • Immunology • Liver Cirrhosis • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis

"$VKTX completion of Enrollment in Phase 2b VOYAGE Study of VK2809 in Biopsy-Confirmed NASH Expected in 2H'22. 🥱" (@BioStocks)

P2b data • Hepatology • Non-alcoholic Steatohepatitis

VOYAGE: A Study to Assess the Efficacy and Safety of VK2809 for 52 Weeks in Subjects With Biopsy Proven NASH (clinicaltrials.gov) - P2b; N=337; Recruiting; Sponsor: Viking Therapeutics, Inc.; Trial primary completion date: Dec 2021 ➔ Jun 2022

Clinical • Trial primary completion date • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • MRI

What’s in the Pipeline for NAFLD and NASH Treatment? - "A study by Zobair Younossi, MD, MP...found that NAFLD/NASH is responsible for 26% of liver-related deaths in the United States, second only to alcoholic liver disease....Stephen Harrison, MD...evaluated aldafermin (NGM282), a genetically engineered fibroblast growth factor (FGF19) analogue from NGM Biopharmaceuticals....The consistency and durability of efficacy reported with VK2809 in this trial regardless of therapeutic dose, baseline patient characteristics or underlying NASH risk factors is encouraging,' Loomba said in a Viking press release. 'Particularly noteworthy is that VK2809-treated patients with NASH risk factors, including elevated baseline ALT, obesity and hypertension, experienced reductions in liver fat that were significantly greater than observed among patients receiving placebo.'"

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Physiological Role and Use of Thyroid Hormone Metabolites - Potential Utility in COVID-19 Patients. (PubMed, Front Endocrinol (Lausanne)) - "It appears that i) the more potently-acting molecules T3 and triiodoacetic acid have shorter half-lives than the less potent antagonists 3-iodothyronamine and tetraiodoacetic acid; ii) reverse T3 and 3,5-diiodothyronine may serve as indicators for metabolic dysregulation and disease, and iii) Nanotetrac may be a promising candidate for treating cancer, and resmetirom and VK2809 for steatohepatitis. Further, the use of L-T3 in the treatment of severely ill COVID-19 patients is critically discussed."

Clinical • Journal • Review • Hepatology • Infectious Disease • Metabolic Disorders • Novel Coronavirus Disease • Oncology

VOYAGE: A Study to Assess the Efficacy and Safety of VK2809 for 52 Weeks in Subjects With Biopsy Proven NASH (clinicaltrials.gov) - P2b; N=337; Recruiting; Sponsor: Viking Therapeutics, Inc.; Trial completion date: Nov 2021 ➔ Dec 2022; Trial primary completion date: Mar 2021 ➔ Dec 2021

Clinical • Trial completion date • Trial primary completion date • Fibrosis • Hepatology • Immunology • Non-alcoholic Steatohepatitis • MRI

Regulation of gene transcription by thyroid hormone receptor β agonists in clinical development for the treatment of non-alcoholic steatohepatitis (NASH). (PubMed, PLoS One) - "In this study, we tested three THRβ-agonism-based NASH treatment candidates, GC-1 (sobetirome), MGL-3196 (resmetirom), and VK2809, and compared their selectivity for THRβ and their ability to modulate the expression of genes specific to cholesterol and fatty acid biosynthesis and metabolism in vitro using human hepatic cells and in vivo using a rat model. MGL-3196 treatment resulted in concentration-dependent decreases in total and low-density lipoprotein cholesterol with corresponding increases in liver gene expression, but the compound was significantly less potent than T3. In conclusion, we have implemented a strategy to rank the efficacy of THRβ agonists by quantifying changes in the transcription of genes that lead to metabolic alterations, an effect that is directly downstream of THR binding and activation."

Clinical • Journal • Addiction (Opioid and Alcohol) • Dyslipidemia • Hepatology • Non-alcoholic Steatohepatitis

[VIRTUAL] CHARACTERIZATION OF THYROID HORMONE RECEPTOR (THR) AGONISTS FOR THE TREATMENT OF NON-ALCOHOLIC STEATOHEPATITIS (NASH) BY QUANTIFICATION OF GENE TRANSCRIPTION IN HUMAN HEPATOCYTES (AASLD 2020) - "Here, we compared the ability of three THR agonists, GC-1, MGL-3196, and VK2809, to modulate the expression of genes specific to cholesterol and fatty acid biosynthesis and metabolism in vitro using human hepatocytes and in vivo using a rat model. Many studies report changes in cholesterol and triglyceride levels in animal models when profiling NASH therapeutic candidates, but in vitro testing of compounds in human hepatocytes offers information faster and with higher throughput. We have implemented a strategy to rank the efficacy of THR agonists by quantifying changes in the transcription of genes that lead to metabolic alterations, directly downstream of THR binding and activation. Using human-derived hepatocytes provides more biologically relevant data compared to biochemical or non-hepatocyte screening assays."

Dyslipidemia • Hepatology • Non-alcoholic Steatohepatitis