The Bio Report

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.

Antibody-drug conjugates have established themselves as an important cancer-treatment modality, but their effectiveness and tolerability in solid tumors can be constrained by inadequate tumor delivery, incomplete internalization, and off-target toxicity. NEOK Bio is seeking to overcome those challenges with its bispecific ADC platform that uses dual-antigen targeting, engineered antibodies, and next-generation linker technology. Mayank Gandhi, co-founder and CEO of NEOK Bio, discusses the company’s bispecific ADC platform, its two clinical programs, and its strategy to develop more selective therapies for patients with advanced solid tumors.

Alzheimer’s disease remains one of medicine’s most intractable challenges. While existing therapies may address individual features of the disease, such as amyloid or tau, they have yet to reverse the progressive cognitive decline, inflammation, and neurodegeneration that characterize it. Evinco Therapeutics is developing nanoscale, natural killer cell-derived particles that carry proteins and microRNAs to target the neuroinflammation underlying Alzheimer’s. Alan Trounson, founder and CEO of Evinco Therapeutics, discusses the company’s multifaceted therapeutic approach, how these particles are designed to cross the blood-brain barrier, and their potential to modulate neuroinflammation, support the brain’s immune cells, and promote amyloid clearance.

Gilead today stands at an inflection point. Its HIV and broader virology business still account for roughly two-thirds of total revenue, even as oncology has grown into a mid–single-digit billion-dollar franchise and inflammation and immunology remain earlier-stage bets. The company is tackling the strategic challenge of diversifying beyond HIV while preserving its leadership in virology. Chief Medical Officer Dietmar Berger discusses how the company is raising the bar for mechanistic understanding before making major investments, using targeted acquisitions to build platform-based franchises, and bringing in differentiated therapies and platforms that can be applied across solid tumors, autoimmune diseases, and even future viral threats.

Ischemic stroke remains one of the most devastating and resource‑intensive emergencies in medicine, with the physical removal of a clot, the current gold-standard care, still leaving more than half of patients with poor outcomes at 90 days. Revalesio is developing a next‑generation, oxygenated saline infusion designed to protect the brain during and after clot removal by stimulating mitochondrial function, reducing reperfusion injury, and limiting the spread of damage to surrounding tissue. Revalesio president Greg Archambeau discusses how the company’s experimental therapy may reshape the trajectory of stroke recovery, shorten hospital stays, and change the economics of stroke centers.

Type 1 diabetes is still a disease we manage day‑to‑day rather than prevent, and today’s approaches do little to stop the immune system from attacking beta cells in the first place. Zag Bio is trying to change that by turning the thymus, the body’s training ground for T cells, into a therapeutic engine for immune tolerance, using thymus‑homing antibodies to program long‑lived, antigen‑specific Tregs against type 1 diabetes and other autoimmune diseases. Zag Bio CEO Jason Cole discusses type 1 diabetes, how the company’s thymic training platform fits into the emerging tolerance landscape alongside cell therapies and nanoparticle approaches, and the potential to extend this strategy to a broader set of autoimmune diseases.

Most small molecule drugs and biologics miss a large group of important receptors in the body. These receptors, known as GPCRs, play big roles in major diseases, but they are unusually hard to target in a precise and safe way. Skape Bio is trying to change that by using artificial intelligence to design an emerging class of therapies known as mini proteins that can fit these receptors snugly and control them in ways traditional drugs often can’t. Christoffer Norn, co‑founder and CEO of Skape Bio, discusses how mini proteins share strengths of both small molecules and biologics while avoiding some of their weaknesses, why the company’s approach could open up new therapeutic opportunities, and how Skape Bio is building a broad pipeline of differentiated GPCR‑targeting therapies.

AI’s promise in drug discovery is being held back by a simple but stubborn problem: the field doesn’t have enough of the right kind of lab-generated data to train good models. Public databases and scattered studies give a patchy view of how proteins interact, mostly showing successful interactions and using different methods and conditions, which makes it hard for AI systems to learn broad rules or understand what doesn’t work. A-Alpha Bio tackles this data gap with AlphaSeq, a lab platform that can test around a million protein pairs in one experiment under the same conditions, producing rich, consistent information on both hits and misses that’s well suited for AI. David Younger, co-founder and CEO of A-Alpha Bio, talks about why far more lab data and infrastructure will be needed than most people expect, why current public datasets fall short, and why the company’s business model is built around providing data and services rather than developing its own drugs.

Multi-specific antibodies promise to unlock complex biology that conventional monoclonals can’t touch, but their added mechanisms of action also introduce safety and developability risks. These antibodies—especially T‑cell engagers—behave differently from traditional monospecific antibodies, and seemingly minor architectural tweaks can cause disproportionate shifts in potency, selectivity, and cytokine release. LabGenius is trying to turn multi-specific design from an intuition-driven art into a genuine engineering discipline by generating proprietary data at scale and feeding them back into machine learning models. Angus Sinclair, chief scientific officer of LabGenius, discusses why many safety failures in early solid-tumor T‑cell engagers were effectively locked in at design, how the company’s AI platform engineers multi-specific T‑cell engagers that are both potent and selective in solid tumors, and where AI is actually adding value in multi-specific design today.

Acute ischemic stroke is both ubiquitous and undertreated. Only a small fraction of patients currently receive clot-busting drugs or mechanical thrombectomy because of the small treatment window. That’s because existing therapies require rapid presentation to specialized centers and carry nonreversible bleeding risks that make clinicians hesitant to use them. Basking Biosciences is developing a first-in-class, reversible thrombolytic that targets von Willebrand factor to expand access to safe, effective treatment. Basking Biosciences CEO Julia Owens and co-founder and chief scientific officer Shahid Nimjee discuss the tension between restoring blood flow and causing irreversible intracranial hemorrhage that clinicians face in treating ischemic stroke, the narrow treatment window for existing therapies, and how modulating von Willebrand factor may open a much larger treatment window across a broader range of care settings.

Plasma gelsolin is an abundant, endogenous regulator of inflammation that is consumed during severe inflammatory insults. When levels fall too low, patients are at higher risk of organ damage and death, particularly in settings like acute respiratory distress syndrome where a dysregulated inflammatory response floods the lungs with fluid and leaves patients dependent on ventilatory support with no approved therapies today. BioAegis Therapeutics is working to turn recombinant human plasma gelsolin into a pipeline-in-a-product. Susan Levinson, CEO of BioAegis, discusses recombinant human plasma gelsolin as a potential first-in-class treatment for ARDS and other inflammasome-driven conditions, how it modulates cytokine storms without suppressing the immune system, and its potential in other conditions including neurodegenerative diseases.

A chronic shortage of high‑quality targets remains one of the biggest constraints in drug discovery, even as therapeutic tools become more powerful and diverse. Regeneron is tackling that problem with its Regeneron Genetics Center, which has built a genetics‑driven discovery engine that integrates human genetics with rich clinical data, large‑scale proteomics, and AI‑driven analytics. Aris Baras, head of the Regeneron Genetics Center, discusses how proteomics is reshaping RGC’s view of risk prediction, how AI helps his team sift through hundreds of millions of variants, and what it really takes to scale this kind of effort and translate it into more successful, transformative therapies for patients.