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  • Met primary endpoint (liver fat reduction), multiple secondary endpoints (whole body, visceral, subcutaneous fat loss)
  • Significant fat selective weight loss while preserving muscle mass, without changes in diet or exercise
  • Amplified weight and fat loss in patients with elevated HbA1c
  • Improvement in key markers of insulin resistance and inflammation
  • Well tolerated across all studied doses

HU6 leads a pipeline of first-in-class, orally administered Controlled Metabolic Accelerators (CMAs) that accelerate fat metabolism and treat the underlying cause of type 2 diabetes, HFpEF, NASH, and other cardiovascular and metabolic diseases  

CHARLOTTESVILLE, Va., February 9, 2022 – Rivus Pharmaceuticals Inc., a biopharmaceutical company dedicated to improving cardio-metabolic health, today announced positive results from a Phase 2a clinical trial of HU6 in obese participants with elevated liver fat. In eight weeks, HU6 demonstrated significant reductions in liver, visceral, and total body fat while conserving skeletal muscle mass, leading to significant reductions in total body weight. Uniquely, the greatest reductions in weight and body fat were observed in patients who had high baseline HbA1c levels. Improvements were also observed in key metabolic parameters that drive the pathophysiology of type 2 diabetes, heart failure with preserved ejection fraction (HFpEF), and non-alcoholic steatohepatitis (NASH).  HU6 was well tolerated across all studied doses.

“We are highly encouraged by the Phase 2a clinical data evaluating HU6 to improve cardio-metabolic health. In this a relatively short study of 8 weeks, HU6 was able to achieve meaningful results safely in a high percentage of responders.  By reducing fat in the liver, and throughout the body, HU6 addresses the root cause of poor metabolic health and related diseases,” said Allen Cunningham, President and CEO of Rivus Pharmaceuticals.

HU6 Phase 2a Metabolic Trial Design and Results

The phase 2a metabolic trial of HU6 was a 61-day randomized, double-blind, placebo-controlled trial designed to assess the safety and efficacy of three dose levels of HU6 (150 mg, 300mg, and 450 mg) in obese participants (body mass index 28 to 45 kg/m2) with elevated liver fat (greater than 8%). Eighty (80) participants between ages 28 and 65 were randomly assigned to one of three HU6 treatment groups or the matched placebo group, stratified and blocked for HbA1c levels of 5.7% or greater, and dosed once daily (fasting). Participants were instructed to not change behavior with regard to diet or exercise. The Phase 2a trial met primary (liver fat reduction by MRI-PDFF) and secondary (body weight and fat reduction by abdominal MRI) endpoints. Key results and observations include:

  • Statistically significant (p<0.0001 by ANCOVA) reductions in liver fat at all three dose levels.
    • Relative reductions in liver fat were 33%, 43%, and 40% corresponding to responder rates (>30% relative reduction) of 40%, 71% and 72% at low, mid and high doses, respectively,  compared to placebo relative reduction in liver fat of 2% and responder rate of 5%.
  • Body weight reduction almost exclusively from loss of fat, sparing skeletal muscle mass at all dosing levels at eight weeks, without change in diet or exercise behavior.
    • Weight and fat loss showed a dose response with participants losing an average of 6 pounds (p<0.001, high dose vs. placebo).
    • Participants with elevated HbA1c levels experienced greater weight and fat loss, losing an average of 10 pounds (p<0.0001, high dose vs. placebo). 
    • Fat loss was observed in hepatic, visceral, and subcutaneous compartments by MRI.
  • Key cardiovascular and metabolic health indicators at all dosing levels including:
    • Signficant dose dependent reduction in glycated albumin, an indicator of glucose control and insulin function.
    • Significant dose dependent reduction in inflammation marker high sensitivity C-reactive protein (hsCRP), an important parameter of cardiovascular risk.
  • HU6 was well-tolerated at all dose levels with excellent compliance. No Serious Adverse Events or deaths were reported.  Intermittent diarrhea and transient flushing were the most commonly reported Treatment Emergent Adverse Events.  The majority of these events were mild; one participant discontinued HU6 for diarrhea in the low dose arm while no participant discontinued at the high dose. 

“This trial provides compelling proof of clinical concept for the efficacy and safety of mitochondrial uncoupling with HU6, our first in class CMA. HU6 pharmacology which selectively reduces fat and weight without appetite suppression is highly differentiated. Given early indications that this biology may reverse insulin resistance and systemic inflammation, we can now explore whether reducing visceral and organ fat can provide clinical benefits to patients across a host of cardiometabolic diseases,” said Shaharyar Khan, Ph.D., Rivus’ Chief Scientific Officer.  

CMAs provide a new, measured approach to safely activating mitochondrial uncoupling, a process in the body that regulates and dissipates energy. By ferrying protons out of the mitochondrial intermembrane space, CMAs increase the oxidation of sugars and fats, while maintaining the same baseline production of adenosine triphosphate (ATP). Activating this process results in the reduction and the prevention of fat accumulation throughout the body.

In the first half of 2022, Rivus is continuing its HU6 clinical program with a Phase 2a study in heart failure with preserved ejection fracture (HFpEF) to be followed by Phase 2b studies in type 2 diabetes and non-alcoholic steatohepatitis (NASH).

About HU6

HU6 is a controlled metabolic accelerator (CMA) that provides a novel, measured approach to activating proton leak and mitochondrial uncoupling, a natural process in the body that regulates and dissipates energy. By ferrying protons out of the mitochondrial intermembrane space, CMAs cue the increased oxidation of sugars and fats, while maintaining the same baseline production of adenosine triphosphate (ATP). Activating this process results in the reduction of accumulated fat throughout the body.

About Rivus Pharmaceuticals

Rivus Pharmaceuticals, Inc., is dedicated to transforming the treatment of cardio-metabolic disease. Rivus’ first-in-class small molecule therapy, HU6, is a controlled metabolic accelerator (CMA) that addresses the underlying cause of cardio-metabolic disease by harnessing the body’s natural processes to improve cellular metabolism and selectively oxidize fat. Rivus’ therapy presents a tremendous opportunity to empower patients on their journey to better health when facing a broad range of cardio-metabolic conditions, including type 2 diabetes, heart failure with preserved ejection fraction (HFpEF), non-alcoholic steatohepatitis (NASH), and obesity. For more information, please visit www.rivuspharma.com.

HU6 was well tolerated and increased resting energy expenditure

 Dose dependent weight loss and an improvement in metabolic parameters were also observed, despite the study not being powered to demonstrate them

Enrollment for a Phase 2a Metabolic Trial of HU6 has completed with topline data expected in Q1 2022

HU6 leads a pipeline of first-in-class Controlled Metabolic Accelerators (CMAs), designed to harness the body’s natural processes to improve cellular metabolism and treat underlying causes of poor metabolic health and cardiovascular disease

CHARLOTTESVILLE, Va. November 1, 2021 – Rivus Pharmaceuticals Inc., a biopharmaceutical company dedicated to improving cardio-metabolic health, today announced positive results from both single and multiple ascending dose portions of its Phase 1 clinical trial of HU6. HU6, a first-in-class, orally administered Controlled Metabolic Accelerator (CMA) therapy, demonstrated robust and sustained target engagement with no apparent safety signals. Additionally, sustained effects on key biological parameters relevant to cardio-metabolic diseases including type 2 diabetes, heart failure with preserved ejection fracture (HFpEF), non-alcoholic steatohepatitis (NASH), and severe hypertriglyceridemia (SHTG) were observed. HU6 was well-tolerated at all studied doses, and there were no serious adverse events. Participants dosed with HU6 demonstrated an increase in resting energy expenditure, dose dependent weight loss and improvements in metabolic parameters.

The HU6 Phase 1 program consisted of a double blind, placebo controlled, randomized single ascending dose (SAD) as well as a multiple ascending dose (MAD) trial. In the SAD portion of the program, 50 healthy volunteers received doses of HU6 ranging from 30 to 1400mg. In the MAD portion of the program, 24 subjects with high BMI (35-45) received doses of 200, 400, and 550 mg over 14 days of oral, once daily (QD) dosing. HU6 was well-tolerated at all dose levels. The limit to tolerability was not reached at any of the doses studied in the trial. 

“We are highly encouraged by Phase 1 clinical trial results for HU6, which demonstrate a compelling, positive impact on multiple key indicators of cardio-metabolic disorders. The data overwhelmingly support the continued development of HU6 to deliver novel and effective treatment to the millions people who live with poor metabolic health and cardiovascular disease,” said Allen Cunningham, President and CEO of Rivus Pharmaceuticals. “While many existing cardio-metabolic therapies address downstream effects of these diseases, we’ve designed CMAs to address the underlying cause.”

CMAs provide a new, measured approach to activating proton leak and mitochondrial uncoupling, a natural process in the body that regulates and dissipates energy. By ferrying protons out of the mitochondrial intermembrane space, CMAs cue the increased oxidation of sugars and fats, while maintaining the same baseline production of adenosine triphosphate (ATP). Activating this process results in the reduction of accumulated fat and the prevention of additional fat accumulation throughout the body.

The company also announced it has completed enrollment for a double blind, placebo controlled, randomized Phase 2a clinical metabolic study of HU6 in cohorts of participants with high BMI (28-45 kg/m2). Topline data are expected in Q1 2022.

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About Rivus Pharmaceuticals

Rivus Pharmaceuticals, Inc., is dedicated to transforming the treatment of cardio-metabolic disease.  Rivus’ first-in-class small molecule therapy, HU6, is a controlled metabolic accelerator (CMA) that addresses the underlying cause of cardio-metabolic disease by harnessing the body’s natural processes to improve cellular metabolism.  Rivus’ therapy presents a tremendous opportunity to empower patients on their journey to better health when facing a broad range of cardio-metabolic conditions, including type 2 diabetes, hypertension, non-alcoholic steatohepatitis (NASH), dyslipidemia and obesity.  For more information, please visit www.rivuspharma.com.

Advancing a pipeline of first-in-class Controlled Metabolic Accelerators (CMAs) to harness the body’s natural processes to improve cellular metabolism and treat the underlying causes of poor metabolic health and cardiovascular disease

Initial programs to focus on type 2 diabetes, severe hypertriglyceridemia (SHTG), non-alcoholic steatohepatitis (NASH), heart failure with preserved ejection fraction (HFpEF)

CHARLOTTESVILLE, Va., July 20, 2021 /PRNewswire/ — Rivus Pharmaceuticals, Inc., a biopharmaceutical company dedicated to improving cardio-metabolic health, today announced the completion of a $35 million Series A financing. Rivus is advancing a new class of oral, once daily, small molecule therapeutics called Controlled Metabolic Accelerators (CMAs), designed to improve cellular metabolism and treat the underlying cause of highly-prevalent metabolic and cardiovascular diseases. The round was co-led by Longitude Capital and Medicxi and RxCapital also participated.

“More than 40 million people in the U.S. alone are living with cardio-metabolic disorders, conditions that adversely impact a person’s health and quality of life, as well as place significant cost burdens on healthcare systems. While many existing therapeutic options address the downstream effects of metabolic disease, they do little to address the underlying cause – greater consumption of energy than is required by the body, which over time results in inefficient cellular metabolism and the excess accumulation of fat,” said Allen Cunningham, President and CEO, Rivus Pharmaceuticals. “Our CMAs are designed to effectively target the root cause of these diseases by improving cellular metabolism with the potential to halt the progress of, or even reverse, these diseases.”

CMAs provide a new, measured approach to activating mitochondrial uncoupling, a natural process in the body that regulates and dissipates energy. By ferrying protons out of the mitochondrial intermembrane space, CMAs cue the increased oxidation of sugars and fats, while maintaining the same baseline production of adenosine triphosphate (ATP).  Activating this process results in the reduction of accumulated fat and the prevention of additional fat accumulation throughout the body. Rivus is currently conducting a Phase 2a clinical study with its lead CMA therapeutic, HU6. The Series A financing will enable Rivus to advance a pipeline of CMA therapies to treat a range of metabolic conditions including type 2 diabetes, severe hypertriglyceridemia (SHTG), non-alcoholic steatohepatitis (NASH), as well as cardiovascular diseases such as heart failure with preserved ejection fraction (HFpEF).

“We are very encouraged by early clinical results of HU6 and the potential for CMAs to deliver a new and highly-effective approach to improving metabolic health,” said Patrick Enright, Managing Director at Longitude Capital. “There is tremendous global potential for CMAs to fundamentally change the therapeutic landscape across a variety of difficult to manage chronic diseases related to metabolic health.”

“Rivus has recently completed its Phase 1 program for HU6, and the results exceeded our expectations, demonstrating an early positive impact on key metabolic parameters, while being well-tolerated,” said David Grainger, Ph.D., Chief Scientific Advisor at Medicxi. “Phase 2 studies will provide important insights into HU6’s efficacy in specific metabolic and cardiovascular diseases with this very promising new therapy, and we are excited to advance these programs in partnership with Rivus.”

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About Rivus Pharmaceuticals

Rivus Pharmaceuticals, Inc., is dedicated to transforming the treatment of cardio-metabolic disease. Rivus’ first-in-class, small molecule therapy, HU6, is a controlled metabolic accelerator (CMA) that addresses the underlying cause of cardio-metabolic disease by harnessing the body’s natural processes to improve cellular metabolism. Rivus’ therapy presents a tremendous opportunity to empower patients on their journey to better health when facing a broad range of cardio-metabolic conditions, including type 2 diabetes, hypertension, non-alcoholic steatohepatitis (NASH), dyslipidemia and obesity. For more information, please visit www.rivuspharma.com.

About Longitude Capital

Longitude Capital is a leading healthcare venture capital firm that invests in transformative biotechnology, medical technology and health solutions companies seeking to improve clinical outcomes, enhance quality of life, and drive efficiency of healthcare delivery. Founded in 2006, Longitude Capital invests in both privately held and publicly traded companies through a variety of investment approaches. Longitude Capital has offices in Menlo Park, CA, Greenwich, CT, and Boston, MA. For more information, please visit www.longitudecapital.com or LinkedIn.

About Medicxi

Medicxi is an international investment firm with the mission to create and invest in companies across the full healthcare continuum. Medicxi was established by the former Index Ventures life sciences team and invests in both early stage and late stage therapeutics with a product vision that can fulfill a clear unmet medical need. GlaxoSmithKline, Johnson & Johnson Innovation – JJDC, Inc., Novartis and Verily (an Alphabet company) are investors in Medicxi funds.

Medicxi’s team has been investing in life sciences for over 20 years. Globally, it has invested in 91 innovative biopharma companies and achieved 32 exits through IPO and M&A, including Genmab, PanGenetics (sold to AbbVie), Cellzome (sold to GSK), Micromet (sold to Amgen), Molecular Partners, XO1 (sold to Janssen Pharmaceuticals, Inc.), Minerva Neurosciences, Padlock Therapeutics (sold to Bristol-Myers Squibb), Gadeta (structured transaction with Gilead), Impact BioMedicxines (sold to Celgene) and Adaptive Biotechnologies. Medicxi is also the founding investor of Centessa Pharmaceuticals. Please see https://www.medicxi.com/ for more information.

About RxCapital
RxCapital is the venture capital arm of RxCelerate, a leading international out-sourced drug discovery platform based in Cambridge, UK.  RxCapital invests in early-stage biotechnology companies with transformative capability and, unlike many CROs, there is no requirement for portfolio companies to use RxCelerate services.  RxCapital will invest in any geography, following an asset-centric investment model, deploying up to £1million per investment.  For further information, please contact Nick Tait, Chief Financial Officer of RxCelerate Group: nick@rxcelerate.com.