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.

There have been great advances in the treatment of hepatitis C with the advent of curative therapies, but hepatitis B has proven far more elusive. That’s due to differences in the way the virus replicates and how it creates a reservoir of viral DNA in the cells in the liver. nChroma Bio, the result of a merger between Chroma Medicine and Nvelop Therapeutics, thinks it has an answer. It’s developing a one-and-done epigenetic editing therapy that silences hepatitis B viral transcription. We spoke to nChroma Bio chief development officer Jenny Marlowe and chief scientific officer Melissa Bonner, about its experimental epigenetic editor for hepatitis B, the merger that brought together the two companies, and how it plans to leverage Chroma’s epigenetic editing platform with Nvelop’s programmable non-viral delivery technologies in future therapies.

Craig Lipset, advisor and founder of Clinical Innovation Partners, sits down with Nagaraja Srivatsan to discuss how AI can bring greater predictability to clinical trials, how organizations can adopt the technology effectively, and the importance of having a culture of experimentation.

While AI has been seductive in its promise for revolutionizing drug development, one of the constraints remains the quality of the data that is used by any given platform. BPG Bio, an early innovator in the application of AI to drug development as Berg, is taking what it calls a “biology-first” approach. It capitalizes on its proprietary biobank to conduct multi-omics analysis to understand the biological mechanisms of diseases. We spoke to Niven Narain, CEO of BPGbio, about how the company’s platform technology uncovers novel targets, its evolution from its start as Berg, and how the platform continues to provide insight into experimental therapies after they advance to the clinic.

Despite the market success of GLP-1 agonists to treat obesity, many patients suffer side effects such as nausea, diarrhea, and vomiting. These medicines also cause significant loss of muscle mass. And when someone discontinues use, they often regain the weight they lost. Skye Bioscience is developing nimacimab, an experimental therapy that has the potential to induce weight loss by inhibiting the CB1 receptor. Because of its different target, it may be able to be used in conjunction with GLP-1 agonists and lower the dose of those drugs to make them more tolerable, or combined with other therapeutic approaches. We spoke to Punit Dhillon, president and CEO of Skye Bioscience, about CB1 as a target for treating obesity, its experimental therapy nimacimab, and the potential to combine it with GLP-1 agonists and other therapeutic approaches.