HU6 / Rivus Pharma - LARVOL DELTA

Relative Bioavailability Study of HU6 (clinicaltrials.gov) - P1 | N=43 | Completed | Sponsor: Rivus Pharmaceuticals, Inc. | Recruiting ➔ Completed

Trial completion

Rivus Pharmaceuticals Expands Leadership Team and Establishes New San Francisco Bay Area Office Ahead of Phase 2 Read-Out in MASH (PRNewswire) - "Dr. Grainger will oversee the strategy, design and implementation of the clinical development for Rivus' pipeline of CMA drug candidates, including the company's lead investigational candidate, HU6." "

Clinical • Cardiovascular

Novel Controlled Metabolic Accelerator for Obesity-Related HFpEF: The HuMAIN-HFpEF Randomized Clinical Trial. (PubMed, JAMA Cardiol) - P2 | "Larger trials of longer duration are warranted to determine whether longer-term administration of HU6 can improve exercise function, quality of life, and cardiovascular outcomes in this increasingly common disorder. ClinicalTrials.gov Identifier: NCT05284617."

Clinical • Journal • Cardiomyopathy • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Obesity • CRP

Rivus Pharmaceuticals Announces Publication of Phase 2a HuMAIN Trial of HU6 in Patients with Obesity-Related Heart Failure in JAMA Cardiology (PRNewswire) - P2a | N=67 | HuMAIN (NCT05284617) | Sponsor: Rivus Pharmaceuticals, Inc.| "The published HuMAIN study results showed that HU6 resulted in a significantly greater reduction in body weight (-6.8 lbs vs -0.5 lbs, p=0.0026), total fat mass (-7.4 lbs vs. -0.88 lbs with placebo, p=0.0003), percent visceral fat (-1.5% vs. -0.2% with placebo, p=0.0028) and percent reduction in body fat percentage (-4.8% vs. -0.45% with placebo, p=0.0002) at 19 weeks compared with baseline. Other measures of body composition showed: No significant change in lean body mass or skeletal muscle mass with HU6 vs. placebo or with HU6 at 19 weeks compared with baseline. A reduction in abdominal visceral adipose tissue with HU6 vs. placebo (-0.19 L) in patients whose body composition was assessed by MRI; No significant differences in changes in cardiac safety parameters in participants who underwent a cardiac MRI or in resting heart rate or respiratory rate."

P2a data • Heart Failure • Obesity

A Novel Controlled Metabolic Accelerator For The Treatment Of Obesity-related Heart Failure With Preserved Ejection Fraction: Humain-hfpef Trial (HFSA 2024) - P2 | "Of the 66 participants randomized to HU6 or placebo (56% women, 17% Black), 65 were dosed, and 57 completed the study. Baseline characteristics were consistent with a population with obesity-related HFpEF (Table). The mean BMI and % body fat were 39 kg/m2 and 47%, respectively, and 68% of participants had Class II/III obesity."

Late-breaking abstract • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Inflammation • Obesity • CRP

Relative Bioavailability Study of HU6 (clinicaltrials.gov) - P1 | N=40 | Recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF (clinicaltrials.gov) - P2 | N=67 | Completed | Sponsor: Rivus Pharmaceuticals, Inc. | Active, not recruiting ➔ Completed

Trial completion • Cardiovascular • Congestive Heart Failure • Heart Failure • Obesity

Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Nonalcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=219 | Active, not recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Relative Bioavailability Study of HU6 (clinicaltrials.gov) - P1 | N=40 | Not yet recruiting | Sponsor: Rivus Pharmaceuticals, Inc.

New P1 trial

A novel controlled metabolic accelerator for the treatment of obesity-related heart failure with preserved ejection fraction: Rationale and design of the Phase 2a HuMAIN trial. (PubMed, Eur J Heart Fail) - "HuMAIN will test a promising novel agent for obesity-related HFpEF."

Clinical • Journal • P2a data • Cardiovascular • Congestive Heart Failure • Genetic Disorders • Heart Failure • Inflammation • Obesity

A Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-HU6 (clinicaltrials.gov) - P1 | N=8 | Completed | Sponsor: Rivus Pharmaceuticals, Inc. | Recruiting ➔ Completed

Trial completion

Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Nonalcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=204 | Recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Trial completion date: Nov 2024 ➔ Apr 2025 | Trial primary completion date: Sep 2024 ➔ Feb 2025

Trial completion date • Trial primary completion date • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

A Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-HU6 (clinicaltrials.gov) - P1 | N=8 | Recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open

A Study to Investigate the Absorption, Metabolism, and Excretion of [14C]-HU6 (clinicaltrials.gov) - P1 | N=8 | Not yet recruiting | Sponsor: Rivus Pharmaceuticals, Inc.

New P1 trial

Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF (clinicaltrials.gov) - P2 | N=62 | Active, not recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Recruiting ➔ Active, not recruiting

Enrollment closed • Cardiovascular • Congestive Heart Failure • Heart Failure • Obesity

Phase 2a Study of HU6 in Subjects With Elevated Liver Fat and High BMI Volunteers (clinicaltrials.gov) - P2 | N=80 | Completed | Sponsor: Rivus Pharmaceuticals, Inc. | Phase classification: P2a ➔ P2

Phase classification • Hepatology • Metabolic Dysfunction-Associated Steatohepatitis

Exploratory Ph 2A, Double-Blind, Placebo-Controlled Dose Escalation Study of Safety, Tolerability, PD, & PK of HU6 for Subjects With Obese HFpEF (clinicaltrials.gov) - P2 | N=62 | Recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Phase classification: P2a ➔ P2 | Trial completion date: Oct 2023 ➔ Jun 2024 | Trial primary completion date: Sep 2023 ➔ May 2024

Phase classification • Trial completion date • Trial primary completion date • Cardiovascular • Congestive Heart Failure • Heart Failure • Obesity

Ph 2a Study of HU6 on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function in Subjects Who Are Overweight or Obese With Type 2 Diabetes (clinicaltrials.gov) - P2 | N=0 | Withdrawn | Sponsor: Rivus Pharmaceuticals, Inc. | N=48 ➔ 0 | Recruiting ➔ Withdrawn

Enrollment change • Trial withdrawal • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Ph 2a Study of HU6 on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function in Subjects Who Are Overweight or Obese With Type 2 Diabetes (clinicaltrials.gov) - P2 | N=48 | Recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting | Phase classification: P2a ➔ P2

Enrollment open • Phase classification • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Safety and efficacy of once-daily HU6 versus placebo in people with non-alcoholic fatty liver disease and high BMI: a randomised, double-blind, placebo-controlled, phase 2a trial. (PubMed, Lancet Gastroenterol Hepatol) - P2a | "HU6 could be a promising pharmacological agent for treating patients with obesity and NAFLD and its metabolic complications."

Journal • P2a data • Genetic Disorders • Hepatology • Non-alcoholic Fatty Liver Disease • Obesity

Ph 2a Study of the Effects of HU6 on Energy Metabolism, Muscle and Liver Substrate Metabolism, and Mitochondrial Function in Subjects Who Are Overweight or Obese With Type 2 Diabetes (clinicaltrials.gov) - P2a | N=48 | Not yet recruiting | Sponsor: Rivus Pharmaceuticals, Inc.

New P2a trial • Diabetes • Genetic Disorders • Metabolic Disorders • Obesity • Type 2 Diabetes Mellitus

Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Obese Subjects With Type 2 Diabetes at Risk of Nonalcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=280 | Recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity • Type 2 Diabetes Mellitus

Phase 2a Study of HU6, Rivus Pharmaceuticals' Investigational Controlled Metabolic Accelerator, Demonstrates Clinical Benefit in Patients with High Body Mass Index and Nonalcoholic Fatty Liver Disease (BioSpace) - P2a | N=80 | NCT04874233 | Sponsor: Rivus Pharmaceuticals, Inc. | "'The positive efficacy and safety results of this Phase 2a metabolic clinical trial of HU6 give us confidence that this first-in-class therapy has the potential to provide an effective, well-tolerated treatment for a broad range of cardiometabolic diseases associated with obesity,' said Mazen Noureddin...'A broad range of investigational therapies have been studied in patients with NAFLD/MASLD, but there are still not many options that are able to effectively manage this disease in patients with obesity and elevated liver fat. The significant reductions in liver fat, coupled with greater than expected reductions in inflammatory markers, make HU6 a promising new approach.'"

P2a data

Phase 2a Study of HU6, Rivus Pharmaceuticals' Investigational Controlled Metabolic Accelerator, Demonstrates Clinical Benefit in Patients with High Body Mass Index and Nonalcoholic Fatty Liver Disease (PRNewswire) - P2a | N=80 | NCT04874233 | Sponsor: Rivus Pharmaceuticals, Inc. | "Rivus Pharmaceuticals...announced publication in The Lancet Gastroenterology & Hepatology of the results of a Phase 2a metabolic study of HU6...in patients with nonalcoholic fatty liver disease (NAFLD)....Liver fat content (primary endpoint): A significant decrease from baseline to day 61 as assessed by MRI-PDFF was observed with all HU6 doses compared with placebo (p30% reduction in liver fat: Overall, 61% of study participants treated with any dose of HU6 had at least a 30% reduction in liver fat from baseline to day 61 as assessed by MRI-PDFF. Among the HU6 150 mg, 300 mg and 450 mg dosing groups, the percentages were 40%, 71% and 72%, respectively, versus 5% of those receiving placebo; all p<0.0001)....HU6 300 mg and 450 mg were associated with significant weight loss at day 61..."

P2a data • Non-alcoholic Steatohepatitis

Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Obese Subjects With Type 2 Diabetes at Risk of Nonalcoholic Steatohepatitis (clinicaltrials.gov) - P2 | N=280 | Not yet recruiting | Sponsor: Rivus Pharmaceuticals, Inc.

New P2 trial • Diabetes • Genetic Disorders • Hepatology • Metabolic Disorders • Non-alcoholic Fatty Liver Disease • Non-alcoholic Steatohepatitis • Obesity • Type 2 Diabetes Mellitus