Director, Nonclinical Development - ADME/DMPK

Company Overview Rhythm is a global, commercial-stage biopharmaceutical company committed to transforming the lives of patients living with rare neuroendocrine diseases. We develop medicines for previously untreatable or undertreated diseases. We recognize the courage it takes for patients and their caregivers to begin their journey of advocacy to find the answers they need. Their courage inspires us to challenge convention, ask bold questions and seek answers for them. Every day, we strive for excellence through our willingness to adapt, learn, and our tenacity to overcome barriers, together. Opportunity Overview 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. Responsibilities and Duties 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 candi 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. Qualifications and Skills Required 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. Preferred 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. This role is based out of our corporate office in Boston, Massachusetts. Rhythm operates in a hybrid‑work model. Candidates applying must be willing and able to be in the Boston office in coordination with their department and business needs. This role may involvesome travel. The expected salary range for this position is $182,000 - $275,000. Actual pay will be determined based on experience, level, qualifications, geographic location, and other job‑related factors permitted by law. A discretionary annual bonus may be available based on individual and company performance. This role may be eligible for benefits and other compensation such as restricted stock units. More about Rhythm We are a dynamic and growing global team spanning more than a dozen countries. At Rhythm we are dedicated to transforming the lives of patients living with rare neuroendocrine diseases by rapidly advancing care and precision medicines that address the root cause. Our team is passionate about expanding access to reach more patients and developing novel therapies for other rare neuroendocrine diseases, including congenital hyperinsulinism. Our core values are: We are committed to advancing scientific understanding to improve patients’ lives We are inspired to tackle tough challenges and have the courage to ask bold questions We are eager to learn and adapt We believe collaboration and ownership are foundational for our success We value the unique contribution each individual brings to furthering our mission Inherent in our core values is the commitment to act ethically and with integrity in all we do. Rhythm is an equal employment opportunity employer and does not discriminate against any applicant because of race, creed, color, age, national origin, ancestry, religion, gender, sexual orientation, disability, genetic information, veteran status, military status, application for military service, or any other class protected by state or federal law. Headquartered in Boston, Rhythm is proud to have been named one of the Top Places to Work in Massachusetts. #J-18808-Ljbffr Rhythm Pharmaceuticals, Inc