Senior/Principal Scientist, DMPK

Flagship Pioneering, Inc.•Cambridge, MA

64d•Onsite

About The Position

We are seeking an innovative and collaborative Senior / Principal Scientist in Drug Metabolism and Pharmacokinetics (DMPK) to help shape the next generation of covalent small-molecule therapeutics for previously undruggable targets. The successful candidate will have a proven track record of guiding small molecule drug discovery programs, including experience with both mono- and bi-functional modalities. You will be a key architect in translating molecular design into human pharmacology - applying deep ADME/PK science and modeling insights to accelerate discovery, inform development candidate selection and support IND-enabling studies. We're assembling the founding DMPK team - an extraordinary opportunity to operate at the intersection of chemoproteomics, quantum chemistry, and generative AI. You'll work with the world's most advanced chemoproteomics platform focused on undruggable targets and a deeply integrated AI-driven quantum chemistry engine to redefine what's possible in modern drug discovery. This role sits at the interface of chemistry, biology, formulation, pharmacology, toxicology and machine learning, working closely with program teams to drive decisions from first-in-class concept to IND.

Requirements

Ph.D. in Pharmacokinetics, Drug Metabolism, Pharmaceutical Sciences, or related discipline
(or M.S. with ≥10 years of directly relevant biotech/pharma experience)
8-12+ years of experience in DMPK or ADME, ideally spanning discovery through IND enablement.
Demonstrated impact on compound design and optimization through integration of DMPK science (mono- and bi-functional modalities).
Hands-on experience with in-vitro ADME assays, in-vivo PK studies, in-vitro-in-vivo correlation building and generating human dose projections.
Strong understanding of enzyme kinetics, transporters, and biotransformation mechanisms.
Proficiency in PK-PD modeling, PBPK, and simulation approaches to support preclinical and clinical translation.
Familiarity with regulatory expectations for ADME/PK characterization and drug-drug interaction assessment.
Experience managing external collaborations and CRO partnerships.

Nice To Haves

Think from first principles
Value cross-disciplinary exploration, from chemistry to computation to translational biology.
Approach others collaboratively.
Are excited helping to build frameworks and platforms, not just running assays.
Communicate complex data clearly, connecting mechanistic insight to program strategy.
Enjoy fast-moving, hypothesis-driven environments.
Are excited by the idea helping to build a first-in-class company that is redefining the future of drug discovery.

Responsibilities

Design and guide in-vitro and in-vivo ADME/PK studies to characterize absorption, distribution, metabolism, and excretion for small molecules (mono- and bi-functional modalities).
Apply and advance modeling and simulation tools (PBPK, compartmental, and empirical) to interpret complex datasets and guide clinical pharmacology design.
Integrate DMPK thinking early in discovery-connecting mechanistic data to compound design, structure-activity relationships, and developability.
Shape translational PK-PD strategy, including in-vitro-in-vivo extrapolation, human dose projection, and species selection for efficacy and safety studies.
Collaborate cross-functionally with medicinal chemistry, biology, pharmacology, toxicology and machine learning to inform compound prioritization and drive program progression.
Author and critically review DMPK and modeling components of IND-enabling packages, investigator brochures, and regulatory filings.
Leverage and manage CRO partners, ensuring scientific excellence, data integrity, and rapid execution of external studies.
Communicate insights with clarity and conviction-translating data into actionable hypotheses for multidisciplinary teams and senior leadership.
Collaboratively implement a strong customer focus with the ability to have robust discussions with project leaders and other stakeholders to ensure that project, scientific and resource demands are aligned