Precision Signals

There is a sentence most physicians are trained never to say. Three words: I don't know. Thomas Clozel learned early — from Valentin Fuster at Mount Sinai — that those three words are not a confession of failure, but the beginning of discovery.Thomas is an oncologist, co-founder, and CEO of Owkin. He trained in Strasbourg, then crossed the Atlantic to work under Fuster in cardiology and alongside Olivier Elemento and Ari Melnick at Weill Cornell in computational biology. Ten years ago, he left clinical medicine to build a new kind of superhuman intelligence for biology — on a contrarian bet that chemistry was the confined, solvable problem, and that biology, the messy, causal, unsolved one, was where the real discovery lived.In this conversation, we trace that arc: from federated learning across the world's hospitals, to a mesothelioma study that surfaced categories of disease no human had ever named, to Owkin Pro — an AI scientist that, in Thomas's words, is beginning to have ideas of its own. We discuss why big pharma keeps missing the AI wave, why he thinks Anthropic could be the biggest pharma in five years, why the treatment for Alzheimer's might one day come from a fifteen-year-old in a garage, and what it will actually take for him to say, someday, that he has succeeded.

Sahir Ali’s career defies conventional paths. Trained as an engineer, he worked in quantitative finance, contributed to cancer research, built software companies, and ultimately founded Modi Ventures, where he developed the BioStack investment framework for technology-driven life sciences.In this conversation with Sean Khozin, Sahir explains how systems thinking, mathematics, and first-principles reasoning shaped his approach to investing. They discuss the evolution of artificial intelligence in medicine, the realities of drug discovery, founder psychology, venture capital, and why enduring innovation often comes from connecting ideas across disciplines rather than following trends.

In this episode of Precision Signals, we speak with Mike Krzyzewski, known to most of the world as Coach K, about leadership, trust, teams, cancer advocacy, and the human side of progress.Coach K is one of the defining figures in American sports. Over more than four decades at Duke, he built championship teams, led the United States to Olympic gold, and shaped generations of players and coaches whose lives extended far beyond basketball. But this conversation is not only about winning. It is about what allows people to come together, stay connected under pressure, and do difficult things in service of something larger than themselves.That question matters well beyond the court. In medicine and healthcare, progress depends on more than discovery, technology, or individual excellence. It depends on trust between people, coordination across institutions, and the ability to keep patients at the center when the system becomes complex. As we discuss leadership, teamwork, artificial intelligence, and the future of care, Coach K offers a perspective that is practical, human, and deeply relevant to the work of improving health.At its core, this conversation asks a simple question: how do we build the kind of trust and shared purpose that allows people to do hard things together?

Dr. Brian Druker helped change the course of modern oncology through his central role in the development of imatinib (Gleevec), a therapy that transformed chronic myeloid leukemia (CML) and helped establish the modern era of precision oncology.In this episode of Precision Signals, Dr. Sean Khozin speaks with Dr. Brian Druker about the scientific, clinical, and human story behind Gleevec, from the early search for a drug that could inhibit the abnormal signal driving CML, to skepticism around targeted therapy, to the first clinical trials and the broader impact on cancer medicine.The conversation also explores Dr. Druker’s path into oncology, the development of targeted therapies beyond CML, the limits of molecularly targeted drugs, the arrival of immunotherapy, the challenge of persistent leukemia cells, current work in AML, and how AI may help generate hypotheses while still requiring rigorous biological validation.This is a conversation about scientific persistence, translational medicine, precision oncology, and what meaningful progress in cancer research really requires.

In this episode of Precision Signals, Sean Khozin, MD, MPH sits down with Clifford A. Hudis, MD, FACP, FASCO, CEO of the American Society of Clinical Oncology (ASCO), to trace a career that began with a childhood memory of Brian Piccolo and Memorial Sloan Kettering, and now sits at the helm of the world's largest professional society in cancer care.Dr. Hudis reflects on his path from Northeast Philadelphia to an accelerated BA/MD program, to a transformative fellowship at MSK under Larry Norton, and through three decades building the modern breast cancer clinic. He shares what it has meant to lead ASCO through a period of profound change: the rise of AI and real-world evidence, the persistence of access and equity gaps, the evolving science of clinical trials, and the tension between precision and pragmatism at the bedside.Takeaways:Dr. Clifford A. Hudis reflects on his transformative journey from a modest upbringing to becoming the CEO of ASCO, illustrating the profound impact of early life experiences on career trajectory.The evolution of oncology, particularly in breast cancer treatment, is marked by significant advancements such as dose-dense chemotherapy and HER2-targeted therapies, reshaping patient outcomes.ASCO's guidelines are undergoing a revolutionary change towards dynamic, living guidelines, ensuring that oncologists have access to the most current and relevant treatment protocols.AI is positioned to become an integral component of clinical practice, enhancing decision-making and patient care, thereby allowing oncologists to focus more on patient relationships.The tension between science and societal perceptions of healthcare necessitates an ongoing dialogue to build trust and understanding, particularly in the face of misinformation and skepticism.Leadership in oncology requires not only clinical excellence but also an embrace of business acumen and a visionary outlook, fostering progress in a rapidly changing medical landscape.Companies mentioned in this episode:ASCOAmerican Society of Clinical OncologyMemorial Sloan KetteringGenentechMD AndersonDana FarberNCCNNIHNCIAACRACS

Sunil Verma, SVP and Global Head of Oncology at AstraZeneca, has lived a life defined by reinvention. Born in Zambia, raised across Africa, India, and Canada, he was accepted to medical school at 19, became one of the most respected breast cancer oncologists in Canada, built a cancer center in Calgary from the ground up, and then left academia entirely to help write the next chapters of oncology at AstraZeneca alongside the late Jose Baselga.In this conversation, Sean Khozin and Sunil explore the formative experiences that shaped his worldview and leadership philosophy, what it means to build healthcare infrastructure around the concept of healing, and how AstraZeneca's oncology portfolio expanded from a single asset into one of the most consequential in the world.They go deep on the science and strategy behind antibody-drug conjugates (ADCs), the frontier of ADC and immunotherapy combinations, and a distinction Sunil considers the true next frontier of the field: the difference between precision medicine and genuinely personalized medicine, where patient values are matched to therapeutic value.

As cancer treatments become more powerful and precise, the field of oncology is entering a new era. We are moving beyond the question of "Can we extend life?" to "How do we live with the biology these therapies unleash?"In this episode of Precision Signals, host Sean Khozin is joined by Dr. Afreen Shariff (Director of the Endocrine Neoplasia Program at Duke University) and Jon McDunn (President of Project DataSphere) to discuss the complexities of immune-related adverse events (irAEs). While immune checkpoint inhibitors have revolutionized outcomes for various cancers, they can also trigger inflammatory conditions affecting the thyroid, heart, and nervous system. Our guests explore the "double-edged sword" of immunotherapy and how data science, AI, and clinician-led innovation are bridging the gap between clinical trials and real-world patient care. In this episode, we discuss: The "Next HIV": Why Dr. Shariff believes cancer care is reaching a similar turning point in long-term management. The Gap in Data: Why traditional clinical trial reporting often fails to capture the nuances physicians see at the bedside. AI & Triage: How unique e-consult models and AI tools are helping oncologists manage complex side effects more efficiently. The Future of Oncology: Predictions on patient-driven care and the push for greater data accessibility to drive innovation.

In this episode of Precision Signals, Sean Khozin sits down with Dr. David Fajgenbaum — physician, scientist, patient, and founder of Every Cure — to explore one of the most extraordinary stories in modern medicine. As a third-year medical student, David developed idiopathic multicentric Castleman disease, a rare inflammatory disorder that led to multi-organ failure. He was read his last rites five times. Facing a condition with no clear therapeutic roadmap, he began banking his own blood, performing proteomic analyses, and identified an mTOR pathway signal that led to a life-saving repurposed transplant drug. He has now been in remission for over a decade. But survival was only the beginning. David went on to found the Castleman Disease Collaborative Network and later co-founded Every Cure, a nonprofit using AI and computational pharmacophenomics to systematically evaluate every approved drug against every known disease. This episode is about moving from serendipity to strategy in medicine — and what it will take to build systems that leave no patient behind.

Sean Khozin in a conversation with Sushil (Sush) Patel, CEO of Replimune, discussing advancements in cancer immunotherapy, particularly the use of oncolytic viruses. They explore how engineered viruses can turn tumors into targets for the immune system, representing a shift in oncology towards reprogramming tumor biology. Sush shares insights from his extensive career, including challenges faced at Genentech and the regulatory hurdles from the FDA regarding Replimune's clinical trials. They examine the dual mechanism of oncolytic viruses and the complexities of treating diverse patient populations, advocating for collaborative efforts to refine regulatory frameworks. Sush also highlights the potential of future therapies, including advancements in gene editing and AI, while emphasizing the need for cautious optimism in integrating these technologies into cancer treatments.

Most people know Sean Parker as the prodigy behind Napster and Facebook. Far fewer know why he chose to take on one of the hardest problems in science: cancer. In this clip from Precision Signals, we explore the founding insight behind the Parker Institute for Cancer Immunotherapy—that the greatest barrier to progress in cancer research isn’t talent or ideas, but how science is funded. Despite more than $300 billion spent on cancer R&D in the U.S. alone, progress has been slowed by systems that reward safety, incrementalism, and short-term wins—rather than bold, high-risk, potentially curative science. In conversation with Karen Knudsen, CEO of the Parker Institute, we unpack why embracing risk and accepting failure aren’t flaws in science—they’re prerequisites for real breakthroughs.

In this episode of Precision Signals, Sean Khozin speaks with Dan McHugh, investor at Yosemite, about the systems that mediate between scientific discovery and patient impact. Dan’s path runs from Stanford bioengineering and the Greenleaf Lab to Bain & Company, Emerson Collective, and the co-founding of Tune Therapeutics. Across these roles, he has operated at the boundary between deep biological science and the capital and policy structures that determine whether that science ultimately reaches patients. The conversation examines how incentives, reimbursement, and regulation shape the fate of cancer therapies, sometimes in rather unpredictable ways. It also explores Yosemite’s founding by Reed Jobs, Dan’s longstanding friendship with him, and how trust, time horizon, and shared mission have shaped a hybrid model that combines venture investment with grant-based risk-taking. This is a discussion about cancer, but it is equally a discussion about architecture: how systems are designed and what they reward.

Dr. Karen Knudsen, CEO of the Parker Institute for Cancer Immunotherapy (PICI), joins Dr. Sean Khozin to dissect the science and business of curing cancer. From her upbringing as a self-described "nomad" and "army brat" to leading the American Cancer Society, Karen shares her journey from the lab bench to the boardroom.In this episode, we explore the Parker Institute's unique model of "venture philanthropy." Karen explains how PICI uses shared intellectual property to de-risk early-stage science and spin out venture-ready companies like Dispatch and Orbital Therapeutics. We also discuss the challenges of modernizing a historic non-profit with "no product" to sell , the intersection of AI and biomarkers with companies like ArteraAI , and PICI's massive data project, "Radiohead".Karen is candid about her leadership philosophy: she is not a "keep the trains running" executive, but a leader built for transformation.

In Episode 4 of Precision Signals, Dr. Sean Khozin sits down with Daniel Arbess—investor, social entrepreneur, and healthcare innovator—to explore why the limiting factor in solving cancer and neurodegenerative diseases isn't breakthrough science, but institutional innovation.Daniel Arbess has built a career on questioning foundational assumptions across multiple domains: from analyzing Cold War nuclear policy to restructuring post-Soviet industries as the youngest-ever partner at White & Case, to founding Xerion Capital, a hedge fund that delivered over 25% annualized returns through the 2008 financial crisis. Now, he's applying that same lens to healthcare transformation.

In this episode of Precision Signals, Dr. Sean Khozin speaks with Dr. James Gulley, Chief of the Medical Oncology Service and Co-Director of the Center for Immuno-Oncology at the National Cancer Institute.Dr. Gulley is one of the world’s leading figures in immuno-oncology. He helped bring immune-based cancer therapies from an era of skepticism into a clinical mainstay, shaping both the science and the clinical frameworks that define the field today.Their conversation explores the critical frontiers of immunotherapy: the limits of predictive biomarkers, the biological opacity of treatment resistance, and the shortcomings of current trial designs. They discuss adaptive clinical trials, new endpoints, and the integration of AI into clinical research. Emerging tools such as digital pathology, wearable monitoring, and continuous physiologic data capture are highlighted, including recent work detecting CAR-T toxicity before it becomes clinically evident.

Dr. Michelle Longmire, physician-scientist, technologist, and CEO, cofounder of Medable; shares how early lessons in science and systems design shaped her mission to fix one of medicine’s most persistent bottlenecks: slow, fragmented, and inaccessible clinical trials.We discuss her path from autoimmune skin disease research at Stanford to building Medable into a global clinical trial infrastructure platform operating across 14 therapeutic areas, and what it takes to align technology, AI, and scientific rigor with the needs of patients, regulators, and researchers.

What does it take for AI to move from technical innovation to real-world adoption in oncology?In the first episode of Precision Signals, Dr. Sean Khozin speaks with Dr. Cora Sternberg and Dr. Olivier Elemento—two leaders at the intersection of clinical trials, precision medicine, and computational biology.Together, they unpack the central paradox of medical AI: why so many tools are technically validated, yet so few are clinically trusted. Topics include:Why randomized clinical trials—not just retrospective benchmarks—are essential for AI adoptionThe limitations of current training data and the risks of treating clinical guidelines as ground truthThe evolving role of real-world data, EHRs, and multimodal inputs in building more adaptive AI systemsWhat physicians actually need to trust and use AI in everyday cancer careThis is a candid conversation about evidence, trust, and what it will take to build AI that earns a place in the oncology clinic, grounded in insights from the participants’ recent review published in NEJM AI: https://ai.nejm.org/doi/abs/10.1056/A...