HU6 / Rivus Pharma - LARVOL DELTA

Rivus Pharmaceuticals Announces New Data from Phase 2 M-ACCEL Trial of HU6 in MASH in Late-Breaker Oral Presentation at AASLD The Liver Meeting 2025 (The Manila Times) - "Liver fat reduction: Primary endpoint met as HU6 showed a statistically significant reduction in liver fat compared to placebo (by least-squares mean difference -29.4%, -31.2%, -27.0% for 150, 300, and 450 mg doses, respectively, versus -6.7% with placebo; Responder rate: Majority of patients achieved ≥30% liver fat reduction, with 57%, 58%, and 50% of patients achieving a response following 150, 300, and 450 mg doses, respectively, versus 22% for placebo."

P2 data • Metabolic Dysfunction-Associated Steatotic Liver Disease

Rivus Pharmaceuticals to Present Clinical Data from Phase 2a M-ACCEL Trial of HU6 in MASH as Late-Breaker Oral Presentation at AASLD The Liver Meeting 2025 (PRNewswire)

Late-breaking abstract • P2a data • Metabolic Dysfunction-Associated Steatohepatitis • Metabolic Dysfunction-Associated Steatotic Liver Disease

Phase 1, Open-Label, Randomized, Study of the Safety and Pharmacokinetics of HU6 (clinicaltrials.gov) - P1 | N=108 | Recruiting | Sponsor: Rivus Pharmaceuticals, Inc. | Not yet recruiting ➔ Recruiting

Enrollment open • Obesity

Phase 1, Open-Label, Randomized, Five-Part Study of the Safety and Pharmacokinetics of HU6 (clinicaltrials.gov) - P1 | N=108 | Not yet recruiting | Sponsor: Rivus Pharmaceuticals, Inc.

New P1 trial • Obesity

Rivus Pharmaceuticals Announces Positive Topline Results from Phase 2 M-ACCEL Trial of HU6 Showing Significant Reductions in Liver Fat in Patients with MASH (PRNewswire) - P2 | N=219 | M-ACCEL (NCT05979779) | Sponsor: Rivus Pharmaceuticals, Inc. | "Rivus Pharmaceuticals...announced that its Phase 2 M-ACCEL clinical trial of HU6 in patients with metabolic dysfunction-associated steatohepatitis (MASH) met its primary endpoint, with statistically significant reductions in liver fat content at 6 months compared with placebo (p<0.01) in each of the three treatment groups. The proportion of responders, defined as experiencing a greater than 30% reduction in liver fat, was also statistically significant (p<0.01) in all treatment groups...The study also met a number of secondary endpoints despite not being powered to do so, including reductions in body weight, visceral fat mass, blood pressure and hemoglobin A1c, which is consistent with HU6 having a broadly beneficial profile to address the dysmetabolism in MASH....HU6 was well tolerated, and the safety profile was consistent with previous studies, with no treatment-related serious adverse events."

P2 data • Metabolic Dysfunction-Associated Steatohepatitis

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