The Bio Report

GLP-1 medicines have transformed obesity treatment, but what happens when patients stop taking them? For Fractyl Health, the challenge of preventing weight regain has become the focus of its development strategy. The company is advancing Revita, an experimental outpatient procedure designed to regenerate the lining of the duodenum and potentially change how the body regulates weight and blood sugar. Harith Rajagopalan, co-founder and CEO of Fractyl Health, discusses the company’s shift from focusing on type 2 diabetes to maintaining weight loss after patients stop taking GLP-1 medicines, the biology behind its approach, and what it takes to turn the promise of a metabolic reset into a treatment option.

Cardiovascular disease remains the world's leading cause of death, yet many patients still face substantial risks even after conventional factors such as LDL cholesterol and blood pressure are controlled. Rezera is developing its experimental therapy ruvonoflast, an NLRP3 inhibitor, to address this residual inflammatory risk. The therapy is designed to suppress chronic, tissue-based inflammation while preserving the immune system's ability to respond to infection. Rezera CEO Geoff McDonough discusses the role of inflammation in heart disease, the company’s phase 3 trial of ruvonoflast in peripheral artery disease, and its next-generation, brain-penetrant NLRP3 inhibitor in development for neuroinflammatory conditions.

Many cancer treatments fail not because immune cells can’t recognize a tumor, but because the hostile environment surrounding it can prevent them from doing their job. Dyve Biosciences is seeking to address that problem by targeting tumor acidity, which the company says can suppress T-cell activity, promote immune evasion, and contribute to resistance to checkpoint inhibitors and other therapies. Its solution is a transdermal drug-delivery platform designed to move a buffering agent through the skin and into systemic circulation. The company’s lead oncology candidate, DYV 800, is intended to raise extracellular tumor pH and thereby make the tumor microenvironment more hospitable to immune attack. Ryan Beal, CEO of Dyve Biosciences, discusses why the company sees acidity as an overlooked but foundational target in oncology, how its delivery technology may overcome the limitations of oral bicarbonate dosing, and indications beyond cancer that the company is pursuing.

For people with non-muscle-invasive bladder cancer, treatment can involve repeated procedures, a high risk of tumor recurrence, toxic therapies and, in some cases, removal of the bladder. Hamlet Biopharma is developing Alpha1H, a synthetic peptide inspired by a protein complex found in human breast milk. Catharina Svanborg, chair of Hamlet Biopharma, discusses how Alpha1H is designed to selectively target bladder tumor cells while sparing healthy tissue, the science that led to the program, and the clinical-development path ahead.

GLP-1 therapies have dramatically reshaped obesity care, but the next generation of medicines may be judged by more than how much weight patients lose. A central question is whether treatments can selectively reduce the visceral fat associated with cardiometabolic disease while maintaining the muscle needed for physical function, metabolic health, and durable weight management. Erik Ingelsson, chief scientific officer of Wave Life Sciences, discusses the biology behind a new RNA-based approach designed to remove a natural brake on fat breakdown, how the company is thinking about clinical endpoints and patient populations, and why precision approaches to fat loss could change the definition of success in obesity treatment.