Rivus' fat-trimming therapy nabs $35M to harness our own biology against a host of diseases

Fatty Liver
Fatty liver disease is one of a range of obesity-related diseases the biotech is going after. (Wikimedia Commons)

Rivus Pharmaceuticals is going after an alphabet soup of diseases: Type 2 diabetes, severe hypertriglyceridemia, nonalcoholic steatohepatitis (NASH) and heart failure with preserved ejection fraction.

These are just the start for the little biotech as it nabs $35 million for a big push into the clinic.

The series A for the Charlottesville, Virginia-based startup was co-led by Longitude Capital and Medicxi, with help from RxCapital, as it looks to push on with a new class of oral, once-daily, small-molecule drugs called controlled metabolic accelerators (CMAs).

These are designed to improve cellular metabolism and treat the underlying cause of metabolic and cardiovascular disease, including the blockbuster potential (but highly troubled) fatty liver disease NASH, as well as obesity and hypertension, among others.

RELATED: NGM's closely watched NASH prospect flops, cutting shares in half and spurring R&D rethink

“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,” said Allen Cunningham, President and CEO of Rivus Pharmaceuticals.

CMAs work as a new approach to triggering 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,” the biotech explained in a statement.

By turning this on, the idea is that it will not just lower built-up layers of fat, but also prevent more fat from being added to the body. And it’s not all preclinical either: Rivus is already working on a phase 2a clinical study with the lead CMA therapeutic known as HU6.

This drug has been through a phase 1 program, where 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 adviser at Medicxi.

The new cash drop will help with the phase 2 studies, which “will provide important insights into HU6's efficacy in specific metabolic and cardiovascular diseases with this very promising new therapy,” Grainger added.

RELATED: Hepion's NASH drug ready for phase 2b after clearing safety bar, dropping efficacy breadcrumbs

“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,” Cunningham said.

Rivus will have intense competition in the NASH market, with dozens of companies—big and small—trying to crack the difficult disease. Gilead and Novo Nordisk are one Big Pharma matchup in the game, while Eli Lilly has backed the small biotech Terns Pharmaceuticals and its two therapies. 

But as much as these clinical candidates suggest the indication is promising, the path has been littered with failures. Genfit and NGM Biopharmaceuticals have had high-profile failures.

Nevertheless, some analysts see tens of billions of dollars at stake for the companies that make the cut, even as the rocky path to approval has scaled back these forecasts.