Epigenetics, the layer of chemical switches that controls how genes are turned on and off, can act like cancer’s operating system when a single epigenetic enzyme becomes essential for a tumor to survive. K36 Therapeutics is developing first‑in‑class medicines that block an epigenetic enzyme that helps certain multiple myeloma cells grow, change identity to escape treatment, and become resistant to today’s drugs. Terry Connolly, CEO of K36, discusses a new way to fight cancer by changing how cancer cells read their DNA instead of chasing one mutation at a time, how K36’s experimental therapies aim to re‑sensitize tumors to existing treatments, and the potential to create new options for people whose cancers have stopped responding.

Most marketed antibodies work as antagonists, simply shutting off a receptor, even though many immune, metabolic, and cancer pathways require more nuanced control. Metaphore Biotechnologies' function‑first platform combines live-cell experiments with machine learning to read how receptors and binding partners behave in living systems, distill those complex dynamics into the key functional features, and then design functional antibodies that agonize, bias, or multi-target pathways from the outset. Metaphore CEO Angela Hwang discusses how the company is using this approach to open up difficult or previously undruggable targets, generate medicines with better profiles, and give drug developers greater control over complex signaling than traditional drug development approaches allow.

Cells continuously sense their environment and in response to stressors, adapt, recover, or die. Soley Therapeutics uses its AI platform to capture thousands of intracellular features and map how cells sense, interpret, and respond to stress. The approach gives Soley the ability to pursue previously undruggable targets. It has generated more than 10 novel oncology programs in less than two years and advanced two first‑in‑class experimental small molecule therapies toward the clinic. Yerem Yeghiazarians, co-founder and CEO of Soley, discusses the science behind the company’s first-in-class lead candidate, the applicability of Soley’s platform to a broad set of diseases, and the capital efficiency of the company’s approach to drug development.

Promising drugs can become abandoned or underused because of tolerability issues, poor drug‑like properties, or other fixable limitations, even when there is already compelling human evidence that they work. PureTech Health starts with an unmet need and human pharmacology, then systematically dissects and solves the specific liabilities of discontinued drugs to unlock breakthroughs in an approach that has proved to be a highly efficient means of value creation. Eric Elenko, president and co‑founder of PureTech, discusses the company’s disciplined approach to drug innovation around rescuing promising but discontinued therapeutics, its hub‑and‑spoke structure, and how this model can neutralize emotional bias, enforce clear success criteria, and turn partially derisked assets into commercial successes.

Most cancer therapies hit one or a few pathways that tumors can escape by mutating, activating alternative survival routes, or pumping drugs out, leading to relapse and poor survival in indications such as liver, ovarian, and prostate cancer. Nuago is developing single-construct short RNAs that simultaneously silence many survival genes in cancer cells to achieve durable tumor cell killing with minimal toxicity to normal tissue. Nuago CEO Robert Schickel discusses the biology behind toxic RNA seeds and tumor-suppressive microRNAs; the company’s lead programs in liver, ovarian, and prostate cancer; and the implications if its cancer-agnostic RNA platform can live up to its preclinical promise.

Gout may be one of the oldest known forms of arthritis, but it remains widely misunderstood, undertreated, and a source of silent suffering for millions of people who are often blamed for their disease rather than offered effective care. Current therapies to lower urate levels suffer from limitations and safety challenges. Crystalys Therapeutics is in late-stage development of a next‑generation urate inhibitor that is already approved in Japan and China. Crystalys CEO James Mackay discusses the biology of gout, why standard therapies often fail to get uric acid to target levels, and how the company’s next‑generation URAT1 inhibitor may fill the treatment gap and change daily life for patients living with moderate to severe gout.

Small molecule drugs and monoclonal antibodies often fall short at addressing severe inflammatory and immune‑mediated diseases. Mesoblast has spent more than 15 years industrializing mesenchymal stromal cell therapies to treat these conditions. In late 2024, it won U.S. Food and Drug Administration approval for Ryoncil, the first mesenchymal stromal cell therapy approved in the United States. Ryoncil is approved to treat steroid‑refractory acute graft‑versus‑host disease in pediatric patients 2 months of age and older. Mesoblast founder and CEO Silviu Itescu discusses how this class of therapy can help dampen cytokine‑driven hyperinflammation, how the company is extending its platform into other high‑burden conditions, and what distinguishes its second‑generation cell therapy now in development from its first.

Most existing therapies for multiple sclerosis do a good job of reducing relapses and inflammatory activity, but they largely fail to stop the slow neurodegeneration that drives long-term disability, especially in progressive forms of the disease. Immunic Therapeutics is trying to reshape the treatment landscape for multiple sclerosis with its experimental once-daily oral therapy, designed not only to curb inflammation and relapses but also to tackle the neurodegeneration that silently drives disability progression in both relapsing and progressive forms of MS. Daniel Vitt, CEO of Immunic, discusses how the company’s experimental MS therapy works, how it may protect neurons from cell death, and the potential for its dual mechanism of action to change the treatment landscape.

The treatment of inflammatory bowel disease currently relies on immunosuppressive therapies that often lose effectiveness, carry infection risks, and drive high treatment cycling. Abivax is betting that fine-tuning, rather than suppressing, the immune system can reshape the treatment paradigm in IBD. Marc de Garidel, CEO of Abivax, discusses how a once-failed HIV candidate evolved into a late‑stage oral IBD therapy that may deliver durable remission, how it acts upstream of key inflammatory pathways, and its potential in a crowded but still underserved IBD market.

Many people with the genetic condition Lynch syndrome live with the near‑certainty that they will one day develop cancer and have few options beyond constant screening and, in some cases, preventive surgery. Nouscom is trying to change that by training the immune system to spot and destroy cancer cells before tumors ever form. We spoke to Marina Udier, CEO of Nouscom, about the company’s experimental cancer vaccines, how they work, and the broader potential for the company’s off‑the‑shelf cancer therapies.