Head of DMPK

tl;dr General Proximity is a seed-stage startup developing the next generation of induced proximity medicines (IPMs). Our OmniTAC drug discovery engine furnishes molecules that co-opt existing cellular machinery to overcome therapeutic challenges, which have remained unapproachable to other modalities for decades. We are seeking a first-rate DMPK expert to help us pioneer this uncharted frontier of drug discovery. Our Story A long-standing challenge in drug discovery is the development of molecules capable of modulating difficult or "undruggable" targets. Disease-causing proteins can be dysfunctional in many different ways, but our armamentarium for fixing them is quite limited. The most common mechanism of action for FDA-approved drugs is inhibition [1] , but there are many other possible perturbation types whose potential remains unrealized. General Proximity is a seed-stage drug discovery company developing a novel platform technology to solve this problem. We make bifunctional drugs that induce the modification of drug targets by existing cellular machinery (rather than through direct modulation by the drug, the classical approach). Historically, the development of technologies that allow one to push new buttons in biology has been an incredibly fertile field for the discovery of new medicines[ 2 , 3 , 4 ], and our technology holds the same promise. The Position We are seeking an experienced Head of DMPK to lead and shape our drug metabolism and pharmacokinetics function. This is a high-impact leadership role in which you will own the DMPK strategy across our small molecule portfolio, build and mentor a growing team, and serve as the primary DMPK voice in cross-functional and external settings. You will set scientific direction, drive regulatory strategy, and play a pivotal role in advancing programs from lead optimization through IND and into clinical development. You will work closely with our medicinal chemistry, structural biology, pharmacology, and toxicology teams to translate DMPK science into actionable program decisions. The ideal candidate is a hands-on scientific leader who combines deep technical expertise in ADME, in vivo PK, and PK/PD modeling with the ability to build and inspire a high-performing team. This role is ideal for someone who has led DMPK at a pharma or biotech and now wants to build the function from the ground up at a mission-driven company working at the frontier of induced proximity medicine. Critically, this role demands familiarity with the unique DMPK challenges of induced proximity medicines and bifunctional molecules. These include non-linear and dose-dependent pharmacokinetics arising from ternary complex formation, linker and warhead metabolic soft spots, high molecular weight and physicochemical complexity affecting permeability and oral bioavailability, tissue distribution considerations for proteasome-engaging degraders, and the interpretation of hook-effect phenomena in in vitro and in vivo settings. Experience in TPD, molecular glue, PROTAC, or other bifunctional modality DMPK is a meaningful differentiator for this role. What You’ll Do In Vitro ADME Provide strategic oversight of in vitro ADME activities including metabolic stability, CYP inhibition/induction, plasma protein binding, permeability (Caco-2/MDCK), solubility, and transporter assays. Define and champion in vitro–in vivo correlation (IVIVC) strategies across programs to inform candidate selection and advance structure–activity/property relationships. Lead interpretation of metabolic soft spot and MetID data, integrating findings into actionable guidance for medicinal chemistry teams. Establish and manage CRO partnerships for outsourced ADME studies, including vendor qualification, scientific oversight, and data quality assurance. Bioanalytical Sciences Own or oversee bioanalytical strategy for the portfolio, including LC-MS/MS method development and validation for small molecules and their metabolites across biological matrices. Ensure GLP-compliant bioanalytical practices for IND-enabling studies; manage regulated bioanalysis timelines and data quality through CRO partners. Evaluate and deploy fit-for-purpose bioanalytical approaches for induced proximity molecules, including strategies for quantifying bifunctional compounds and target engagement biomarkers. In Vivo Pharmacokinetics Oversee and provide strategic direction for in vivo PK studies across rodent and non-rodent species, including study design, data interpretation, and cross-program learnings. Ensure high-quality PK data analysis (NCA and compartmental) using Phoenix WinNonlin or equivalent, setting standards for reporting and data integrity. Integrate PK data with pharmacology and toxicology readouts at a program level to shape candidate progression criteria and target product profiles. Manage and develop CRO relationships for in vivo studies, negotiating scope, timelines, and scientific deliverables. PK/PD Modeling & Simulation Lead PK/PD modeling and simulation strategy across the portfolio, including PBPK modeling (Simcyp, GastroPlus) and allometric scaling for robust human PK prediction. Drive quantitative pharmacology frameworks to support translational decision-making, FIH dose selection, and clinical dose range prediction. Champion the use of modeling and simulation internally to influence go/no-go decisions and communicate DMPK risk to leadership. Represent DMPK modeling expertise in cross-functional project teams, governance reviews, and external partnerships. Regulatory & IND-Enabling Work Own DMPK strategy and execution for IND-enabling programs, including study design, authoring of regulatory documents, and end-to-end data package delivery. Lead DMPK contributions to IND, CTA, and NDA/BLA submissions; serve as primary author and internal reviewer for relevant sections. Represent the company in interactions with FDA, EMA, and other regulatory agencies on DMPK matters, including briefing documents and agency meetings. Maintain expert-level knowledge of current regulatory guidance (DDI, MIST, bioanalytical method validation, ICH M9/M10) and proactively apply evolving standards. Leadership & Team Building Define and execute the long-term DMPK organizational strategy in alignment with company goals and pipeline evolution. Serve as a key member of the R&D leadership team, contributing to portfolio prioritization, resourcing decisions, and cross-functional planning. Represent DMPK in business development evaluations, partnering activities, and due diligence assessments. Support clinical pharmacology activities as programs advance through IND into Phase 1 and beyond, including FIH dose projections, DDI clinical risk assessment, and exposure–response analysis; serve as the primary DMPK liaison to clinical teams and contribute to clinical pharmacology sections of regulatory documents and eventual product labeling. Own the DMPK functional budget, including CRO spend planning, vendor contract negotiations, and resource forecasting in alignment with program milestones and company-wide R&D priorities. Author and present scientific findings externally through peer-reviewed publications, conference abstracts, and posters; contribute to General Proximity’s scientific credibility and platform visibility in the induced proximity field. About You High Agency. Initiative, independence, and self-accountability are some of our most valued traits. Enthusiastic. We love people who are excited about what they are doing and are generally attempting to build a high-energy team. Intensity and Grit. Early-stage startups are hard. Drug discovery is doubly so. We are looking for candidates who have a demonstrated ability to stick with complex problems for the long haul, with a team that has your back along the way. Prosocial. We are here to create life-saving medicines for the patients who need it most. You should be, too.