Engineering T-Cell Engagers for Solid Cancers

Pain is one of medicine’s most common complaints, yet finding effective alternatives to opioids has proved remarkably difficult. Latigo Biotherapeutics is developing experimental medicines that target NaV1.8, a sodium channel involved in transmitting pain signals through peripheral nerves, with the goal of relieving pain without the addiction risk and other side effects associated with opioids. We spoke with Nima Farzan, CEO of Latigo, about the science behind the company’s approach to treating pain, what its clinical results suggest about the potential to reduce opioid use after surgery, and what clinicians and insurers will need to see beyond regulatory approval.

Biotech investors have long considered scientific uncertainty, clinical setbacks, and commercial risk when making investments. John Stanford, founder and executive director of the policy advocacy organization Incubate argues that the life sciences venture capital firms he represents need to pay increasing attention to Washington due to instability at the U.S. Food and Drug Administration, competitive threats from China’s emergence as an innovation powerhouse, and reduced federal investment in research. Stanford discusses how drug-pricing policy and FDA leadership turnover influence which companies get funded, why he sees the Inflation Reduction Act’s treatment of small-molecule drugs as a particular problem, and why protecting American leadership requires supporting the entire drug-development ecosystem.

For patients with metastatic breast cancer, successive treatments can lose effectiveness as tumors evolve and resistant cancer cells survive, leaving those who have received multiple therapies with limited options. BriaCell is seeking to address that problem with an experimental, off-the-shelf, cell-based immunotherapy designed to stimulate the immune system against multiple cancer-associated targets rather than a single target. Its lead candidate, Bria-IMT, is being studied in combination with a checkpoint inhibitor in a phase 3 trial, while its next-generation programs aim to offer personalized treatment using off-the-shelf cells. William Williams, CEO of BriaCell, discusses how its therapies work, what earlier clinical findings suggest, and the development path forward.

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.

T-cell engagers have delivered important advances in blood cancers, but extending their success to solid tumors has proved considerably more difficult. Physical barriers, immunosuppressive tumor microenvironments, and the risk of attacking healthy tissue have constrained the field. Deck Bio is developing multi-target T-cell engagers to address these limitations. Jack Silberstein, the company’s CEO, discusses Deck Bio’s efforts to create therapies that reach more cancer cells, reduce the likelihood that tumors will evade treatment, and minimize harm to healthy tissue.

For people with severe allergies and mast cell diseases, the risk of a dangerous reaction can shape everyday decisions about food, activities, and family routines. Current treatments generally manage symptoms or lower the likelihood of a reaction, rather than directly targeting the immune cells thought to drive the disease. Allergene AI Therapeutics is developing an in vivo mRNA CAR-T therapy intended to address that underlying biology. The approach aims to temporarily program a patient’s own T cells to target mast cells, with the goal of eliminating sensitized cells and enabling the immune system to rebuild a less reactive mast cell population. Sid Kerkar, founder and CEO of Allergene AI Therapeutics, discusses the scientific rationale for this proposed immune reset, the potential for mRNA and lipid nanoparticle delivery to simplify and broaden access to CAR-T therapy, and the work needed to move the approach from early research into clinical testing.