The Fas signaling pathway plays a central role in activating cell death. As such, it is implicated in a range of conditions and has been associated with ophthalmic diseases. ONL Therapeutics is developing therapies that target Fas signaling to address a range of retinal conditions. We spoke to Connie Chang, chief operating officer for ONL Therapeutics, about the role Fas-signaling plays in cell death, how this underlies a number of retinal diseases, and the company’s experimental therapy to inhibit Fas signaling.

Antibody discovery is a long, costly, and complex process. LabGenius is reinventing that process by using its platform technology that combines AI with robotic systems capable of designing, conducting, and learning from its own experiments. Its platform not only has the potential to accelerate the drug discovery process but can generate high-performing molecules that likely would not have been found through conventional discovery methods. We spoke to James Field, founder and CEO of LabGenius, about the company’s use of generative AI to discover new therapeutic antibodies, its initial focus on immunotherapies, why he thinks the data the company is generating to train its AI system is a significant point of differentiation.

Opioid overdose, abuse, and addiction affect an estimated 3 million Americans and accounts for $35 billion in U.S. healthcare costs every year. Tris Pharma is developing the opioid Cebranopadol, as an effective pain management therapy without the addictive potential of FDA-approved opioids. We spoke to Ketan Mehta, founder and CEO of Tris Pharma, about Cebranopadol, how it modulates the addictive potential by targeting two receptors at once, and its potential to address the opioid crisis. An editor’s note: since recording this podcast, the National Institute on Drug Abuse, part of the National Institutes of Health, awarded Tris a five-year, $16.6 million grant to advance Cebranopadol.

With the rapid advances in cancer research, it can be difficult for physicians to stay on top of all of the emerging treatments in clinical development. Leal Health has developed an AI-powered platform that provides a personalized list of treatment options to match a patient’s precise diagnosis to advanced therapies in clinical testing. We spoke to Tzvia Bader, co-founder and CEO of Leal Health, about her own experience with cancer, how that led to the creation of Leal Health, and how it is harnessing AI to connect patients to clinical trials based on their exact diagnoses.  

Earlier this year, the venture capital firm SR One closed a $600 million fund, its second since spinning out from the pharmaceutical giant GSK. Despite the difficult investment landscape today for biotechs, it’s a reminder that significant capital is available to be deployed. We spoke to Simeon George, CEO and managing partner for SR One, about the firm’s investment approach, how the current landscape is causing venture capitalists and therapeutics developers to think differently, and what advice he’d offer entrepreneurs seeking to raise money today.  

Cytokines, which play an essential role in immune cell signaling, have long been recognized as having great therapeutic potential, but efforts to harness them have been hampered by their toxicity. Bonum Therapeutics is overcoming this limitation by engineering cytokines with a sensor domain that makes their activity dependent on their environment. While the company is focusing its efforts to develop regulated cytokine to treat cancer, it also has potential as an approach to autoimmune, metabolic, and other conditions. We spoke to Bonum Therapeutics Chief Scientific Officer Diane Hollenbaugh and Bonum Chief Business Officer Neela Patel about the therapeutic potential of cytokines, the challenges of using them as therapeutics, and why Bonum’s context-dependent cytokines may enable wider use of these proteins to treat a range of diseases

The Epstein-Barr virus is among the most common viruses associated diseases including multiple sclerosis and certain cancers. Atara Biotherapeutics is developing off-the-shelf, T-cell immunotherapies designed to target cancers and autoimmune conditions driven by the Epstein-Barr virus. It is also using its EBV T-cell platform to develop next-generation allogenic CAR T therapies to target a range of non-EBV associated diseases. We spoke to Pascal Touchon, president and CEO of Atara, about the role of the Epstein-Barr virus in certain cancers and autoimmune conditions, the company’s platform technology for allogenic CAR T therapies, and why it has implications beyond EBV-driven diseases.

Myeloid cells can stimulate anti-tumor effects in the body and recruit additional immune system cells to turn a cold tumor hot. Bolt Biotherapeutics is developing a new category of immunotherapies that combines the precision of antibody targeting with the strength of the innate and adaptive immune systems. By activating and recruiting myeloid cells, the company’s experimental therapies are designed to re-program the tumor microenvironment and invoke an anti-tumor immune response. We spoke to Randy Schatzman, CEO of Bolt Biotherapeutics, about the company’s immune-stimulating antibody conjugates, the case for activating both the innate and adaptive immune systems to fight cancer, and the company’s lead experimental therapy for HER2 positive cancers.

The development of mRNA-based vaccines has represented a major advance in the field of vaccine development. Rather than using weakened or inactivated viruses to stimulate an immune response to generate protective antibodies, mRNA-based vaccines provide a potentially safer and more effective approach. mRNA vaccines work by introducing a small piece of mRNA into the body, which encodes instructions to produce a specific viral protein for the cell to manufacture. This protein then triggers an immune response, leading to the production of antibodies that can protect against specific diseases. Combined Therapeutics has designed a modified mRNA-based vaccine platform that allows for the inhibition of protein expression in specific tissues, enabling targeted vaccine treatment and preventing off-target side effects. It’s designed to be adaptable and efficient, which makes possible rapid production of vaccines for a wide range of diseases and disease variants. We spoke to Thomas VanCott, chief scientific officer of Combined Therapeutics, about the company’s mRNA platform for vaccines, the advantages it provides, and its potential to use the same approach to train the immune system on specific mutations in a tumor.

Infectious diseases and microbial resistance represent major concerns in developing nations. The combination of globalization with the expanded use of antibiotics in resource-constrained environments is worsening the problem. In fact, hospital acquired infection rates in some regions are three times greater than in the United States and as much as 30 percent of all such infections are antimicrobial resistant. HDT Bio is developing immune activators and RNA-based vaccines to address this challenge with cost-effective and accessible medicines. We spoke to Chris Pirie, co-founder and chief operating officer of HDT Bio, about the problem the company is seeking to address, its platform technology for producing safe and stable RNA vaccines, and the potential to use the same platform to produce immunotherapies for cancer.