MASH, a chronic and progressive form of fatty liver disease that until recently was known as NASH, affects millions of people in the United States, and its incidence continues to rise. In fact, MASH is now among the leading causes of liver transplantation in the United States. 89bio is developing an experimental therapy to target multiple disease mechanisms of the condition. We spoke to Rohan Palekar, CEO of 89bio, about what’s driving the prevalence of MASH, the limits of existing medicines, and how its experimental therapy targets both liver fibrosis and the underlying metabolic dysfunctions of the disease. Since recording this interview, Roche announced it would acquire 89bio for $14.50 a share and a contingent value right of $6 per share for up to a total of $3.5 billion.  

The average kidney transplant recipient experiences kidney failure within 10 to 12 years after a transplant, putting them on a cycle that ends with kidney failure and a need for a new transplant. This cycle adds to strains on transplant recipients, payers, providers, and the healthcare system and taxes the limited supply of organs for transplantation. Eledon Pharmaceuticals is seeking to extend the functional life of transplanted organs while reducing the side effects of current immunosuppressive treatments with its experimental, first-in-class immunosuppressive therapy, Tegoprubart. We spoke to Steve Perrin, president and chief scientific officer of Eledon Pharmaceuticals, about the need for innovative approaches to immunosuppression in organ transplantation, how its experimental therapy works, and why it may also have benefits in autoimmune and neurodegenerative diseases as well.

Antimicrobial resistance is projected to kill up to 10 million people a year by 2050. One particular area of concern is drug-resistant gonorrhea, where existing therapies are being exhausted. Taxis Pharmaceuticals is developing therapies to combat evolving superbugs by targeting their cellular infrastructure and disrupting the mechanisms that fuel antimicrobial resistance. We spoke to Greg Mario, president and CEO of Taxis, about the public health threat posed by drug-resistant gonorrhea, the approaches it’s taking to develop new antimicrobial treatments, and the need for new funding models to bring new therapies to market.

Brain tumors are difficult to treat in part because of the blood-brain barrier, the need to protect healthy and sensitive tissue surrounding tumors, and the limits of existing therapies. While there have been great advances in other types of cancer, there’s been relatively little progress in treating these CNS tumors. Plus Therapeutic is developing targeted radiotherapies that provide high doses of radiation directly into the tumor with a catheter. The approach enables the delivery of higher doses of radiation while minimizing exposure to healthy brain cells. We spoke to Marc Hedrick, president and CEO of Plus Therapeutics, about the challenges of treating brain tumors, the limitations of current therapies, and why the company’s targeted radiotherapies have the potential to create better outcomes for patients.

Macrocycles are complex compounds that can interact with targets that are often unreachable with traditional small molecules. Orbis Medicines is addressing the challenge with its nCycles, synthetic macrocycle drugs that are orally available but hit targets that would otherwise require biologic therapies. We spoke to Morten Graugaard, CEO of Orbis Medicines, about its class of synthetic macrocycles called nCycles, its platform technology to generate and screen these therapies, and how they can offer an orally-delivered alternative to biologics.

Animal testing for experimental therapies is slow, expensive, and an imperfect predictor for how a drug will act in humans. The Foundation for the National Institutes of Health in July announced a program to advance innovative laboratory technologies that model human biology, enabling faster, less expensive testing. We spoke to Stacey Adam, vice president of scientific partnerships for the FNIH and leader of the public-private partnership, about the new program, the technologies being explored, and what it will take to transform biomedical research with better disease models.

Many cancer patients are prescribed opioids to manage pain associated with their disease, but studies have shown that the use of these pain killers naturally mutes the immune response and can reduce the efficacy of immunotherapies. Glycyx Therapeutics is developing a drug it believes can allow opioids to relieve pain while preventing them from working against immunotherapies. We spoke to Lorin Johnson, chief scientific officer of Glycyx Therapeutics, about the effect of opioids on the immune system, the company’s  experimental therapy designed to mitigate the negative effects of opioids in cancer patients being treated with checkpoint inhibitors, and why its drug in development may promote gut health in these patients more broadly.

When Takeda in 2023 paid Nimbus Therapeutics $4 billion upfront and the potential for two additional $1 billion milestone payments for its experimental TYK2 inhibitor, the deal was an eye-popping validation of Nimbus’ approach. The company, an early innovator in a computational chemistry, has now integrated AI into its approach to drug discovery. And though it’s been an innovator in technology, it’s also been an innovator in its portfolio approach as an early example of an effective use of a hub-and-spoke business model. We spoke to Abbas Kazimi, CEO of Nimbus, about computational chemistry, how the company’s drug discovery approach has evolved with AI, and how its business model provides liquidity to investors and while making it easier to structure deals.

Despite the successes of immunotherapies to date, about 75 to 80 percent of cancer patients don’t respond to current immunotherapy treatments. Faron Pharmaceuticals is hoping to help change that with its experimental therapy bexmarilimab, which is in development to treat myelodysplastic syndrome. Bexmarilimab targets CLEVER-1, a checkpoint inhibitor found on macrophages, a type of myeloid cell that plays an essential role in the immune system. We spoke to Juho Jalkanen, founder and CEO of Faron, about how the tumor microenvironment can suppress macrophages, how the company’s macrophage checkpoint inhibitor works, and the challenges a Finland-based company faces accessing the capital markets.

There’s been a stunning lack of innovation around male contraceptives when it comes to the area of male contraceptives. Men have the choice between a vasectomy, a procedure innovated in the 19th century, or condoms, which date back to at least King Minos in Crete in 3000 BCE. Next Life Sciences is hoping to change that with its Plan A, an experimental hydrogel that is injected into the vas deferens and provides a barrier that prevents sperm from passing. Plan A, which is regulated as a medical device, is expected to be easily reversible. We spoke to Darlene Walley, CEO of Next Life Sciences, about Plan A, the need it is addressing, and why she expects men and women to see it as a welcome alternative to current choices.