Venetoclax has saved lives. Since the FDA approved it in 2016 for chronic lymphocytic leukemia, the BCL-2 inhibitor has become a pillar of modern blood cancer treatment. What most patients and even many clinicians don't know: a pediatric hematologist-turned-drug developer named Jorge DiMartino was in the room at Genentech when that drug's early clinical trajectory was being shaped. Same story with vismodegib - the first hedgehog pathway inhibitor approved for cancer. Same with enasidenib, the IDH2 inhibitor that changed outcomes in AML. Three different companies. Three different mechanisms. Three drugs on the market. One recurring name in the acknowledgments.
DiMartino didn't set out to become a serial drug architect. He trained as a physician first - pediatrics residency, then a fellowship in pediatric hematology/oncology at Lucile Salter Packard Children's Hospital at Stanford, followed by a post-doctoral stint in pathology at Stanford. His patients were children with blood cancers. His lab work was about how immune cells go wrong. The degrees accumulated: a B.A. in genetics from UC Berkeley, a Ph.D. in immunology from Cornell, an M.D. from UC San Diego. The arc was supposed to lead to an academic career. It didn't.
Three Drugs. Three Breakthroughs. One Career Thread.
The Genentech Years: Learning to Build
When DiMartino joined Genentech, it was as a founding member of their Exploratory Clinical Development group - a team designed to bridge the gulf between preclinical promise and clinical proof. That gulf is where most cancer drug programs fall apart. Genentech was betting that if you staffed the bridge right, more candidates would cross it. DiMartino became one of the people doing the staffing, the strategy, and the science simultaneously.
The BCL-2 program was a particularly instructive proving ground. BCL-2 proteins help cancer cells survive by suppressing apoptosis - programmed cell death. Inhibiting them was, for years, a theoretical goal with a graveyard of failed attempts behind it. The navitoclax-to-venetoclax journey required understanding not just mechanism but patient selection, dosing, toxicity management, and biomarker strategy. DiMartino led that program through its early clinical stages. Venetoclax is now standard of care in multiple settings. The lesson he took from it: the science has to be right, but so does everything around the science.
I am excited to leverage my background in oncology drug development to grow Plexium's clinical pipeline and realize the exciting potential of its platform.
- Jorge F. DiMartino, M.D., Ph.D., on joining Plexium (October 2024)Celgene and the Epigenetics Frontier
Celgene in the 2010s was one of the most ambitious drug development operations in oncology. When DiMartino joined in 2011 as Vice President of Translational Development, he stepped into an organization trying to understand how cancer hijacks the machinery that controls which genes get turned on and which stay silent. Epigenetics. Chromatin modifiers. Protein homeostasis. The language of the field was still being invented.
By 2014, DiMartino had been appointed Head of the Protein Homeostasis and Epigenetics Thematic Center of Excellence - an internal center designed to run vertically integrated research from drug discovery all the way through clinical proof-of-concept. He collaborated with Agios on IDH2 inhibitor enasidenib, which became the first approved drug in its class for AML. He worked with Epizyme on the DOT1L inhibitor pinometostat. These weren't passive partnerships. Celgene's model required its translational leaders to drive decisions across the full development axis - DiMartino's fingerprints were on target selection, biomarker strategy, trial design, and clinical execution.
At Celgene, DiMartino co-led research spanning drug discovery through clinical proof-of-concept - unusually broad scope for a single development leader, and rare training in the full drug-making arc.
Kronos Bio: Building from Zero
In December 2019, DiMartino made a different kind of move. He joined Kronos Bio as its Chief Medical Officer - stepping into a small company with a novel platform (Small Molecule Microarray screening) and no clinical machine yet. His job: build one.
Over the next five years, he constructed Kronos Bio's clinical and translational development group from scratch and led three clinical-stage programs through the pipeline - including KB-0742, a CDK9 inhibitor, and lanraplenib. The experience of standing up infrastructure rather than inheriting it is a different kind of education. You learn which systems are load-bearing and which are ceremony. You make tradeoffs under resource constraints that a larger organization never faces. That knowledge travels.
Plexium and the Undruggable Problem
When DiMartino joined Plexium in October 2024, he was walking into a company with a genuinely distinct theory of how cancer drugs should work. Plexium's DELTA Discovery platform uses ultra-high-throughput cell-based screening to find compounds that can degrade disease-causing proteins - not just inhibit them, but remove them from the cell entirely. The key insight: roughly 80% of proteins implicated in disease lack obvious small-molecule binding sites. They're considered "undruggable." Plexium's bet is that "undruggable" is a temporary designation, not a permanent fact.
Plexium Clinical Pipeline - Selected Targets (2024-2025)
The DELTA platform works differently from PROTACs, the bifunctional degrader molecules that have dominated the targeted protein degradation space. Plexium is developing "monovalent degraders" - single, smaller molecules that can engage the degradation machinery without the complexity or size of PROTAC constructs. At AACR 2025, DiMartino helped lead Plexium's two oral presentations on this approach, covering SMARCA2 and CDK2 programs. PLX-4545, a molecular glue degrader of IKZF2, had already entered first-in-human studies.
SMARCA2 is a compelling target. It's a component of the SWI/SNF chromatin remodeling complex, and cancers with SMARCA4 loss are selectively vulnerable to SMARCA2 degradation. CDK2 drives cell cycle progression and is implicated in resistance to CDK4/6 inhibitors - a significant unmet need given how many patients eventually progress on standard-of-care treatments. IKZF2 is a transcription factor involved in immune suppression within the tumor microenvironment. Each of these is a hard target. None has a straightforward inhibitor story. They are exactly the kind of problems DiMartino has spent two decades building the tools to solve.
The Career Arc: What It Actually Takes
The Pattern Worth Noticing
Look at the arc from a distance and a pattern emerges. DiMartino hasn't chased prestige or scale for its own sake. He joined Genentech's Exploratory Development group when exploratory development was risky and unfashionable. He went deep into epigenetics at Celgene before epigenetic targets were obviously druggable. He joined Kronos Bio when it was small and unproven. He joined Plexium when protein degradation was still in its early innings.
There's a consistent orientation toward problems that haven't been solved yet. Toward biology that is difficult, not convenient. Toward platforms that require you to build new tools rather than apply existing ones. And he has consistently done this as a physician-scientist - someone who came into the field having looked after patients, not just samples. That background shapes how you think about endpoints, about what a drug needs to do to matter, about the gap between a statistically significant result and a clinically meaningful one.
Plexium CEO Michael Martin put it plainly when DiMartino joined: he is "an important addition to our executive team, strengthening the abilities to optimally progress our product pipeline." The language is corporate. The context is real: you bring in someone with three marketed drugs in their history because the next ones are hard and you need someone who knows what hard looks like from the inside.