Rivus Pharmaceuticals, a clinical-stage biopharmaceutical company focused on treating cardiometabolic diseases driven by obesity, announced today the expansion of its leadership team and the establishment of a new office in South San Francisco. The company has appointed David Grainger, Ph.D., as Chairman of Development and Meg Fitzgerald, J.D., as Chief Legal Officer as it prepares for the upcoming readout of its Phase 2b M-ACCEL study in metabolic dysfunction-associated steatohepatitis (MASH).
"We are thrilled to strengthen our management team with the addition of David, who has extensive expertise in drug discovery and development, and Meg, who has more than 20 years of legal experience in the biopharmaceutical industry," said Jayson Dallas, M.D., Chief Executive Officer of Rivus. "Together with our Bay Area team's move into dedicated office space in the biotech hub of South San Francisco, we are well positioned to drive forward the clinical development of our promising pipeline of controlled metabolic accelerators (CMAs) to treat obesity and obesity-related metabolic disorders."
Strategic Leadership Appointments
Dr. Grainger, who has served as an advisor to Rivus's Board of Directors since 2019, brings over 30 years of experience in the biopharmaceutical industry. He will oversee the strategy, design, and implementation of clinical development for Rivus' pipeline of CMA drug candidates, including the company's lead investigational candidate, HU6.
"I strongly believe that CMAs have the unique potential to transform the way we approach obesity and related cardiometabolic diseases and address widely acknowledged challenges with current therapeutic options," said Dr. Grainger. "I look forward to working more closely with the Rivus team as we approach the imminent readout of our Phase 2b M-ACCEL study in MASH and advance HU6 into the next pivotal phase of development."
Dr. Grainger's extensive background includes roles as co-founder and partner at Medicxi, one of Europe's largest life sciences venture capital groups, and Chief Innovation Officer at Centessa Pharmaceuticals. He has founded more than 30 biotech companies and holds over 150 patents and patent applications.
Ms. Fitzgerald joins Rivus with significant legal expertise in the biopharmaceutical sector. Prior to this appointment, she served as Chief Legal and Compliance Officer at Codexis, Inc., and held senior legal positions at Allakos, Inc., Aimmune Therapeutics, Inc., and ZS Pharma, Inc., where she played a key role in negotiations that resulted in the $2.7 billion sale to AstraZeneca.
"Rivus is at a pivotal point in its journey, and I am excited to join the San Francisco-based team as we continue to expand our local Bay Area footprint," said Ms. Fitzgerald. "I am energized by the team's upcoming milestones on the horizon, including the anticipated Phase 2b M-ACCEL readout."
Innovative Approach to Metabolic Disorders
Rivus is advancing a new class of investigational therapies called Controlled Metabolic Accelerators (CMAs) that aim to improve metabolic health for people with obesity and associated metabolic diseases. The company's CMAs are oral small molecules designed to increase resting metabolic rate, resulting in increased energy consumption, primarily from fat.
What distinguishes CMAs from other weight loss approaches is their mechanism of action. They leverage the natural metabolic process of mitochondrial uncoupling to increase metabolism in a manner that is consistent and imperceptible to patients. In preclinical studies, mitochondrial uncoupling was shown to account for 20% to 50% of daily energy expenditure.
Unlike caloric-restriction strategies that reduce energy input and often result in loss of muscle mass along with fat, initial human data has demonstrated that CMAs provide fat-selective weight loss while preserving muscle mass. They have also shown improved insulin sensitivity and significantly reduced oxidative stress and inflammation.
HU6: Lead Candidate with Promising Results
HU6, Rivus' lead CMA, is a novel, oral, once-daily investigational therapy designed to be a foundational monotherapy for cardiac, liver, diabetes, and obesity indications. To date, more than 400 patients have been treated with HU6 as part of the clinical development program.
The current clinical development of HU6 is focused on metabolic diseases with the most morbidity and greatest treatment needs: obesity-related heart failure with preserved ejection fraction (HFpEF) and metabolic dysfunction-associated steatohepatitis (MASH)/metabolic dysfunction-associated steatotic liver disease (MASLD).
Results from a Phase 2 metabolic study in patients with high body mass index (BMI) and MASLD showed that once-daily HU6 significantly reduced liver fat content and body weight with no loss of lean muscle mass. The treatment also improved key markers of systemic inflammation and metabolism. HU6 was well tolerated in this trial, with side effects mainly mild or moderate in severity.
Additionally, results from the Phase 2a HuMAIN study of HU6 in patients with obesity-related HFpEF showed the trial met its primary endpoint, demonstrating that treatment with HU6 resulted in statistically significant weight loss. The rationale for the use of HU6 in HFpEF and the design of the HuMAIN trial were published in the European Journal of Heart Failure in June 2024.
Looking Toward Future Development
With the imminent readout of the Phase 2b M-ACCEL study in MASH, Rivus is positioning itself for potential advancement of HU6 into pivotal trials. The expansion of its leadership team and establishment of a new office in the biotech hub of South San Francisco reflect the company's strategic growth plans and confidence in its innovative approach to treating obesity and related cardiometabolic diseases.
As obesity continues to drive a range of serious health conditions globally, Rivus' CMAs represent a potentially transformative approach that addresses the underlying metabolic dysfunction rather than simply restricting caloric intake. The company's progress will be closely watched by clinicians and patients seeking more effective and sustainable approaches to managing obesity and its complications.
