Rivus Pharmaceuticals Striving for Fundamental Change in Cardio-metabolic Disorders

Allen Cunningham

Rivus Chief Executive Officer, Allen Cunningham/Photo Courtesy of Rivus Pharmaceuticals. 

They are conditions that personally impact scores of people around the world. Type 2 diabetes, heart failure, non-alcoholic steatohepatitis (NASH) – all are highly prevalent in America, and this morning, Rivus Pharmaceuticals, Inc. launched with a novel approach to solving them.

While many therapeutic options already exist to help patients manage the symptoms caused by these cardio-metabolic disorders, Rivus is focused on developing an entirely new class of small molecule therapeutics called Controlled Metabolic Accelerators (CMAs). Their intention is to accelerate metabolism to reduce cardiovascular risk and mortality.

“We’re really one of the first companies to address this fundamental problem of energy excess, a problem that hasn't been addressed previously in metabolic disease, and we're focused on treating the root cause of dysmetabolism, rather than the downstream effects,” said Rivus Chief Executive Officer, Allen Cunningham.

Thanks to a $35 million Series A led by Longitude Capital and Medicxi, with participation from RxCapital, Rivus now has ample funds to propel its initial pipeline out of the starting gate. This includes the company’s lead compound, HU6, which holds promise in Type 2 diabetes, severe hypertriglyceridemia (SHTG), NASH, and heart failure with preserved ejection fraction (HFpEF).

Rivus recently completed its phase I clinical study of HU6 and is now conducting a phase IIa metabolic study which will lead to phase IIb trials in the first three illnesses, and a phase IIa study in HFpEF.

“The problem that all of these conditions have in common is one of energy excess, where there's an imbalance of energy intake and energy expenditure. Our controlled metabolic accelerators are designed to increase energy expenditure, restore balance and good metabolic health,” Cunningham said.

He added that these disease areas share a number of conditions of dysmetabolism, including diabetes, hypertension, and dyslipidemia.

Rivus’ CMAs are designed to overcome these illnesses by activating the body’s natural process of mitochondrial uncoupling. Once triggered, this process leads to the reduction of accumulated fat and the prevention of additional fat accumulation.

“We are utilizing this very potent pharmacology of uncoupling, where you've uncoupled the activities of electron transport from complex five, and in the process, you can significantly increase the amount of caloric expenditure and address the energetic disbalance that exists,” explained Rivus Chief Scientific Officer, Shaharyar Khan, PhD.

The approach is rooted in the groundbreaking work of Peter D. Mitchell, a British biochemist who was awarded the Nobel Prize for Chemistry in 1978 for his development of the chemiosmotic theory, which explained the mechanism by which mitochondria generate energy by converting ADP to ATP.

The theory was initially met with resistance when Mitchell first proposed it in 1961, but the scientific establishment came around in the 1970s, leading to the coveted award and, nearly 50 years later, to Rivus Pharmaceuticals.

“Our western diets and lifestyles have poised us in this epidemic of energy excess, and this is one of the most potent ways the body disposes of energy. So, to be able to do that, we think will have far-reaching implications,” Khan said. “Importantly, it's not that we're inhibiting a process; we are helping the body to utilize its inherent mechanisms to expend energy. We’re helping the mitochondria do its job.”

Cunningham added that while Rivus’ initial focus is on leveraging CMAs to treat metabolic disease, its long-range plans are even more ambitious.

“Our CMAs have potential application in neurodegeneration and cancer. In addition to clinical development of our lead program, HU6, we have an ongoing R&D effort to identify additional CMAs with our discovery platform that we can bring into the clinic,” he said.

So far, Rivus has identified close to 100 CMAs and is actively seeking additional clinical candidates.

“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.”

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