[Hiring] Director, Computational DMPK @Deep Origin

Role Description

Deep Origin is building VHAT, the Virtual Human Avatars of Toxicology. VHAT takes a molecule, a dose, and a patient population and predicts organ-level human toxicity before a compound is synthesized or dosed. Metabolism sits at the heart of that chain. What a drug becomes, which enzymes act on it and how fast they act determine what each organ is exposed to, and every predicted metabolite is screened for its own off-target and organ liabilities. The Metabolism group builds four connected models: drug-metabolizing enzyme, site of metabolism, metabolite structure, and enzyme kinetics. As the group’s leader, you will own those models, mentor the team that builds them, and drive integration of their predicted parameters into the physiologically based pharmacokinetic (PBPK) model that governs exposure across the VHAT.

Qualifications

• A PhD in computational chemistry, cheminformatics, drug metabolism, computational biology, pharmacology or a related field.
• Deep, hands-on expertise in drug metabolism, including understanding of CYP and non-CYP enzymes, sites and products of metabolism, enzyme kinetics and clearance.
• A strong track record in computational modeling, including machine learning for molecular property or reactivity prediction, and mechanistic or kinetic modeling.
• Demonstrated rigor in model validation, including designing appropriate data splits and running external or blinded benchmarks.
• Experience leading a scientific team and delivering against milestones and deadlines.
• Clear written and spoken communication with scientists, partners, and funders.

Requirements

• This role owns the link between metabolism and whole-body exposure, so PBPK experience will weigh heavily in our decision.
• Hands-on experience building or parameterizing PBPK models in Simcyp, GastroPlus, PK-Sim, SimBiology or a custom ODE framework.
• Experience translating in vitro or predicted intrinsic clearance into in vivo hepatic clearance and human PK.
• Experience using PBPK to assess metabolic drug-drug interactions, such as CYP inhibition and induction.
• Experience combining machine learning predictions with mechanistic PK models.

Nice to have

• Experience with metabolomics or LC-MS metabolite identification data.
• Experience running data curation at scale, including annotation standards and quality control.
• Experience on government-funded research programs with milestone-based reporting.
• Exposure to regulatory science, such as FDA guidance on new approach methodologies.
• Familiarity with medicinal chemistry and how metabolism liabilities are addressed during lead optimization.

Responsibilities

• Lead a team of computational scientists and data curators across sites.
• Own the roadmap and release gates for the four metabolism models.
• Own the metabolism-to-PBPK integration.
• Design validation experiments that hold up to outside scrutiny.
• Set the data strategy for a field where high-quality labels are scarce.
• Extend coverage beyond CYP Phase I metabolism to Phase II enzymes and multistep metabolic networks.
• Manage external relationships with consortium partners, contract research organizations, and academic reviewers.
• Author technical milestone reports and present results to ARPA-H.
• Work with the modeling and integration teams to carry uncertainty from the metabolism models through PBPK.

What success looks like

• In the first 6 months, you will have taken ownership of the four models and the team.
• By 12 months, the metabolism models will have been tested by an independent validation team on held-out data.
• The team will be running on a roadmap you set, with each model's strengths and limits clearly documented.

Benefits

• Competitive compensation package with meaningful equity.
• Comprehensive health, dental, and vision coverage.
• A remote-friendly culture across the U.S. and Europe, with flexible, cross-time-zone working.
• Opportunity to shape the future of health, longevity, and our ability to simulate life.
• Annual team gatherings and company events.