Allen Cunningham, Rivus

Rivus scores $132M to advance obesity drug, cardio-metabolic pipeline

Published: Sep 22, 2022

By Alex Keown

BioSpace

Rivus Pharmaceuticals announced Thursday it has raised $132 million in a Series B financing round. Proceeds will be used to advance the development of HU6, a new class of drug designed to treat cardio-metabolic disease by addressing obesity.

Rivus CEO Allen Cunningham told BioSpace the financing will enable it to advance HU6 deeper into the clinic and explore additional indications that impact millions of Americans.

HU6 is a Controlled Metabolic Accelerator (CMA), a new class of medicine that provides a novel, measured approach to activating mitochondrial uncoupling, a natural process by which the body generates heat. 

The therapy has demonstrated significant fat reduction while sparing muscle mass in clinical trials.

It also has the potential to treat a range of cardio-metabolic diseases, including heart failure, type 2 diabetes and Nonalcoholic fatty liver disease (NAFLD).

The CDC estimates the obesity rate in the United States to be about 42%. Obesity is a significant driver in multiple disease indications, including cardiac disease, diabetes and certain types of cancer.

According to company data, CMAs increase the oxidation of sugars and fats while at the same time maintaining the baseline production of adenosine triphosphate, which provides the energy that drives many cellular processes, such as muscle contraction. Triggering this process results in the reduction of accumulated fat and sugars throughout the body.

Cunningham noted there have been advancements made in the development of pharmaceuticals aimed at treating obesity. 

These include Novo Nordisk’s Wegovy, which received the green light from the FDA last year, and Eli Lilly’s Mounjaro (tirzepatide), a diabetes drug that causes weight reduction in patients.

While those drugs effectively reduce weight in patients, Cunningham said Rivus’ CMAs stand alone in their ability to significantly reduce fat while sparing muscle mass.

A Busy 15 Months 

The last 15 months have been busy for Rivus. The company officially launched in July 2021 with $35 million from a Series A financing round.

Earlier this year, Rivus announced positive data from a Phase IIa study assessing HU6 in obese patients. After eight weeks of treatment, HU6 generated significant reductions in liver, visceral and total body fat while maintaining skeletal muscle mass. This led to significant reductions in total body weight.

Shaharyar Khan_Rivus PharmaceuticalsShaharyar Khan, chief scientific officer of Rivus, noted this was an important revelation. He told BioSpace Wednesday that multiple diet plans focusing on reduced caloric intake negatively impact muscle mass. A loss of muscle mass hampers fat loss, which he said often causes a “yo-yo effect” where the weight goes up and down. 

For the Phase IIa study, Khan said patients were told not to change their habits when it came to eating or exercise. Rivus wanted to avoid introducing any new behavioral intervention that could skew the data. 

 After the eight weeks, patients who received HU6 recorded between a 2% and 2.5% loss of fat.

“Our patients were burning fat without any change in diet or behavior,” Khan said. “[They] were losing visceral fat, subcutaneous fat and liver fat. All these components were being seen while skeletal muscle mass was being preserved.” 

In a planned IIb study, Rivus will include dietary interventions alongside HU6. The study is expected to begin in 2023 and will consist of a subset of obese participants with type 2 diabetes. 

In the Phase IIa study, the most significant reductions in weight and body fat were observed in patients with high baseline HbA1c levels, Cunningham noted.

Rivus also intends to initiate another Phase IIa study in obese participants with heart failure with preserved ejection fraction (HFpEF).

Cunningham said patients in the early Phase IIa obesity study saw improvement in key cardiovascular and metabolic health indicators. This includes glycemic control, glycated albumin and HbA1c, reduction in blood pressure and inflammatory markers.

The Series B round was led by RA Capital Management and supported by Bain Capital Life Sciences, BB Biotech AG, as well as existing investors Longitude Capital, Medicxi and RxCapital. 

Source: BioSpace