Director, Nonclinical Development - ADME/DMPK

Rhythm Pharmaceuticals•Boston, MA

1d•$182,000 - $275,000•Hybrid

About The Position

We are seeking an experienced Director of Nonclinical Development, ADME/DMPK to provide strategic scientific leadership and execution of drug metabolism and pharmacokinetics (DMPK) strategies across our portfolio. This individual will serve as the ADME/DMPK subject matter expert and will be accountable for driving integrated, cross‑functional nonclinical development strategies and workstreams supporting small molecule and peptide therapeutics from IND‑enabling development through late‑stage clinical development and registration. The Director will play a critical role in understanding and predicting drug disposition, exposure‑response relationships, metabolite characterization, drug‑drug interaction risk, and translational science, including the application of PBPK and other modeling approaches. This individual will lead the nonclinical inputs to first‑in‑human dose selection and dose escalation strategy and will serve as a key scientific voice in internal first‑in‑human and dose‑selection reviews. Success in this role requires strong scientific judgment, the ability to operate comfortably in a fast‑paced environment, and the confidence to contribute an independent scientific perspective in a collaborative and constructive manner. This individual will be an independent self‑starter who thrives in a highly collaborative cross‑functional team environment. This is a highly visible role that requires an exceptional scientific communicator. The Director will be expected to distill complex scientific and technical information into clear, actionable messages and to communicate strategic priorities, data interpretation, and risk cross‑functionally and to senior leadership with clarity and confidence. This is an individual contributor role with significant cross‑functional leadership scope; the Director will lead through influence across program teams rather than through direct reports. This role will contribute to portfolio-level decision making, development prioritization, and governance discussions by providing expert scientific assessment of program opportunities, development risks, and translational strategies across the pipeline.

Requirements

PhD or equivalent advanced degree in Pharmacokinetics, Drug Metabolism, Pharmaceutical Sciences, Pharmacology, or a related scientific discipline.
10+ years of industry experience in DMPK/ADME and nonclinical development within pharmaceutical or biotechnology organizations.
Small molecule drug development experience is required with a proven track record advancing candidates from discovery through IND-enabling and clinical-stage development.
Deep expertise in ADME, DMPK, translational science, and model-informed drug development approaches including hands‑on experience with PK/PD and PBPK modeling.
Demonstrated experience translating nonclinical PK/PD and exposure data into human dose projections and first‑in‑human dosing strategy.
Demonstrated ability to set and drive nonclinical strategy and to lead cross‑functional workstreams through influence, with clear accountability for delivery.
Proven experience delivering nonclinical DMPK packages supporting IND‑enabling and clinical‑stage development programs.
Extensive experience designing and managing outsourced ADME, DMPK, and bioanalytical studies and working effectively with CRO partners.
Strong understanding of global regulatory expectations related to ADME/DMPK, drug‑drug interactions, and metabolite characterization.
Experience supporting health authority interactions involving first-in-human dose selection, drug-drug interaction strategy, metabolite qualification, pediatric extrapolation, or related translational development topics.
Demonstrated authorship or major contribution to key regulatory documents, including INDs and Investigator’s Brochures, and participation in health authority interactions.
Exceptional written and verbal communication skills, with a demonstrated ability to synthesize complex data and communicate scientific and strategic concepts clearly to cross‑functional teams and senior leadership.

Nice To Haves

Experience supporting nonclinical development for Phase 2/3 clinical programs and beyond, including NDA submissions and post‑approval life‑cycle activities.
Experience with peptide therapeutics, conjugated peptides, or novel modalities in addition to small molecules.
Advanced proficiency with PBPK platforms (e.g., Simcyp, GastroPlus) and population PK/PD approaches.
Experience supporting nonclinical ADME/DMPK strategies for pediatrics extrapolation and rare disease indications.
Exposure to global regulatory submissions or interactions (e.g., EMA, PMDA).
Prior experience working in an early‑stage or startup biotech environment.

Responsibilities

Own and drive integrated ADME/DMPK strategies supporting programs from candidate selection and IND‑enabling development through Phase 2/3 development, registration, and life‑cycle management.
Partner with Discovery and Medicinal Chemistry teams to evaluate developability, optimize candidate properties, and inform candidate selection.
Serve as the DMPK representative and strategic Nonclinical Development partner on cross‑functional program teams, contributing to program strategy, risk assessment, translational planning, and key development decisions.
Accountable for the planning, prioritization, and delivery of cross‑functional Nonclinical Development workstreams, including timelines, budgets, and interdependencies with Clinical, Regulatory, CMC, and other functions.
Lead the nonclinical PK/PD and exposure‑based analyses that underpin first‑in‑human starting dose selection, dose escalation design, and exposure caps, including NOAEL‑ and MABEL‑based approaches, and present these recommendations in internal first‑in‑human and dose‑selection review forums.
Design, oversee, and interpret nonclinical ADME and DMPK studies, including pharmacokinetics, mass balance and disposition, metabolite identification and profiling, in vitro and in vivo ADME assessments, drug‑drug interaction and transporter evaluations, species selection, translational PK analyses, and bioanalytical strategy.
Lead model informed (MIDD) approaches including PBPK and translational PK/PD modeling and simulation, to project human pharmacokinetics, inform dose projection, and assess DDI and special‑population risk.
Lead exposure‑based assessments to support toxicology study design, safety margin determination, and registration planning.
Partner seamlessly with Clinical Pharmacology to establish cohesive translational PK/PD strategies, support FIH protocol development, and facilitate smooth transition into clinical development.
Evaluate nonclinical data packages to identify gaps and development risks and propose mitigation strategies aligned with ICH guidelines and evolving global regulatory expectations.
Provide scientific oversight of external CROs and bioanalytical laboratories, including protocol review, study execution, data interpretation, reporting, timelines, and budget management.
Author, review, and substantially contribute to nonclinical pharmacokinetic and ADME sections of regulatory submissions, including INDs, Investigator’s Brochures, briefing packages, NDAs, and other global filings.
Support health authority interactions and responses related to DMPK, drug disposition, metabolite qualification, and clinical pharmacology strategy (e.g., FDA, EMA, PMDA).
Communicate complex ADME/DMPK findings and strategic recommendations clearly and persuasively to development teams, senior leadership, and other partners.
Operate effectively in a dynamic, growing environment and contribute to continuous improvement of non-clinical development standards, scientific capabilities, and external partnerships.