Head of DMPK

<h3><span style="font-size: 14pt;"><strong>tl;dr</strong></span></h3> <p><span style="font-size: 10pt;">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.</span></p> <p><span style="font-size: 10pt;">We are seeking a <a href="https://www.youtube.com/watch?v=Uyzqmn8Azuo" target="_blank">first-rate</a>&nbsp;<span style="color: rgb(0, 0, 0);">DMPK</span> expert to help us pioneer this uncharted frontier of drug discovery.</span></p> <hr> <h3><span style="font-size: 14pt;"><strong>Our Story</strong></span></h3> <p><span style="font-size: 10pt;">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<a href="https://www.nature.com/articles/nrd.2016.230" target="_blank">[1]</a>, but there are many other possible perturbation types whose potential remains unrealized.</span></p> <p><span style="font-size: 10pt;">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).</span></p> <p><span style="font-size: 10pt;">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[<a href="https://www.nature.com/articles/nrd3410" target="_blank">2</a>, <a href="https://www.nature.com/articles/nrd.2016.213" target="_blank">3</a>, <a href="https://www.nature.com/articles/nrd.2016.211" target="_blank">4</a>], and our technology holds the same promise.</span></p> <h3>&nbsp;</h3> <h3><span style="font-size: 14pt;"><strong>The Position</strong></span></h3> <p><span style="font-size: 10pt;">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.</span></p> <p><span style="font-size: 10pt;">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.</span></p> <p><span style="font-size: 10pt;">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.</span></p> <p><span style="font-size: 10pt;">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.</span></p> <p><strong><span style="font-size: 10pt;">This is an on-site position with flexible working hours.</span></strong></p> <p>&nbsp;</p> <h1><span style="font-size: 14pt;">What You’ll Do</span></h1> <p><span style="font-size: 10pt;"><strong>In Vitro ADME</strong></span></p> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">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.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Define and champion in vitro–in vivo correlation (IVIVC) strategies across programs to inform candidate selection and advance structure–activity/property relationships.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Lead interpretation of metabolic soft spot and MetID data, integrating findings into actionable guidance for medicinal chemistry teams.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Establish and manage CRO partnerships for outsourced ADME studies, including vendor qualification, scientific oversight, and data quality assurance.</span></li> </ul> <p><span style="font-size: 10pt;"><strong>Bioanalytical Sciences</strong></span></p> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">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.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Ensure GLP-compliant bioanalytical practices for IND-enabling studies; manage regulated bioanalysis timelines and data quality through CRO partners.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Evaluate and deploy fit-for-purpose bioanalytical approaches for induced proximity molecules, including strategies for quantifying bifunctional compounds and target engagement biomarkers.</span></li> </ul> <p><span style="font-size: 10pt;"><strong>In Vivo Pharmacokinetics</strong></span></p> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">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.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Ensure high-quality PK data analysis (NCA and compartmental) using Phoenix WinNonlin or equivalent, setting standards for reporting and data integrity.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Integrate PK data with pharmacology and toxicology readouts at a program level to shape candidate progression criteria and target product profiles.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Manage and develop CRO relationships for in vivo studies, negotiating scope, timelines, and scientific deliverables.</span></li> </ul> <p><span style="font-size: 10pt;"><strong>PK/PD Modeling &amp; Simulation</strong></span></p> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Lead PK/PD modeling and simulation strategy across the portfolio, including PBPK modeling (Simcyp, GastroPlus) and allometric scaling for robust human PK prediction.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Drive quantitative pharmacology frameworks to support translational decision-making, FIH dose selection, and clinical dose range prediction.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Champion the use of modeling and simulation internally to influence go/no-go decisions and communicate DMPK risk to leadership.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Represent DMPK modeling expertise in cross-functional project teams, governance reviews, and external partnerships.</span></li> </ul> <p><span style="font-size: 10pt;"><strong>Regulatory &amp; IND-Enabling Work</strong></span></p> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Own DMPK strategy and execution for IND-enabling programs, including study design, authoring of regulatory documents, and end-to-end data package delivery.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Lead DMPK contributions to IND, CTA, and NDA/BLA submissions; serve as primary author and internal reviewer for relevant sections.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Represent the company in interactions with FDA, EMA, and other regulatory agencies on DMPK matters, including briefing documents and agency meetings.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Maintain expert-level knowledge of current regulatory guidance (DDI, MIST, bioanalytical method validation, ICH M9/M10) and proactively apply evolving standards.</span></li> </ul> <p><span style="font-size: 10pt;"><strong>Leadership &amp; Team Building</strong></span></p> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Define and execute the long-term DMPK organizational strategy in alignment with company goals and pipeline evolution.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Serve as a key member of the R&amp;D leadership team, contributing to portfolio prioritization, resourcing decisions, and cross-functional planning.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Represent DMPK in business development evaluations, partnering activities, and due diligence assessments.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">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.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Own the DMPK functional budget, including CRO spend planning, vendor contract negotiations, and resource forecasting in alignment with program milestones and company-wide R&amp;D priorities.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">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.</span></li> </ul> <h3>&nbsp;</h3> <h3><span style="font-size: 14pt;"><strong>About You</strong></span></h3> <p><span style="font-size: 10pt;"><strong>High Agency.</strong> Initiative, independence, and self-accountability are some of our most valued traits.</span></p> <p><span style="font-size: 10pt;"><strong>Enthusiastic.</strong> We love people who are excited about what they are doing and are generally attempting to build a high-energy team.</span></p> <p><span style="font-size: 10pt;"><strong>Intensity and Grit.</strong> 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.</span></p> <p><span style="font-size: 10pt;"><strong>Prosocial.</strong> We are here to create life-saving medicines for the patients who need it most. You should be, too.</span></p> <h3>&nbsp;</h3> <h3><span style="font-size: 14pt;"><strong>Qualifications &amp; Nice-To-Haves</strong></span></h3> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">PhD in Pharmacokinetics, Pharmaceutical sciences, or a related discipline</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;"><span style="text-decoration: underline;">A minimum of 10 years of industry experience in DMPK</span>, preferably in large pharma, spanning drug discovery and development, with a track record of advancing small molecule programs</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Demonstrated leadership experience, including managing scientists, building teams, and influencing cross-functional strategy</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Deep expertise in in vitro ADME and in vivo PK, with the ability to translate data into actionable drug discovery insights at a program level</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Expert-level proficiency in PK data analysis (Phoenix WinNonlin or equivalent) and PBPK/PK-PD modeling platforms (Simcyp, GastroPlus, or equivalent)</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Proven track record of leading IND-enabling DMPK programs and authoring regulatory submissions</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Extensive experience with FDA, EMA, and ICH guidance relevant to DMPK (DDI, MIST, M9/M10, bioanalytical validation)</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Exceptional communication and presentation skills, with the ability to distill complex DMPK science for diverse audiences including senior leadership and investors</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Demonstrated oversight of regulated bioanalytical activities, including LC-MS/MS method development and validation and GLP bioanalysis in support of IND-enabling programs</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Working knowledge of clinical pharmacology principles, including FIH dose projection, DDI risk assessment, and exposure–response analysis, sufficient to support drug development through early clinical stages<br><br></span></li> <li><span style="font-size: 10pt;"><strong>Nice to have:</strong></span> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Experience building a DMPK function from the ground up at a startup or early-stage biotech</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Track record of advancing at least one small molecule program through IND and into Phase 1/2 clinical trials</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Prior experience in business development, due diligence, or partnering activities involving DMPK assessment</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Familiarity with AI/ML-based ADME prediction tools and an interest in integrating computational approaches (e.g., ML-driven metabolic stability or permeability models, digital twins for PK simulation) into the DMPK workflow alongside established platforms such as Simcyp and GastroPlus</span></li> </ul> </li> </ul> <h3>&nbsp;</h3> <h3><a href="https://www.generalproximity.bio/benefits" target="_blank"><span style="font-size: 14pt;"><strong>Benefits</strong></span></a></h3> <ul> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Strong equity incentives. We are looking for candidates who will bring a strong sense of ownership to drive their project areas forward, and we believe that you deserve to be compensated accordingly.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Top tier medical, dental, and vision coverage + One Medical membership.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">401(k) retirement plans.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Education and health/fitness incentive programs.</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Meditation retreats—do a ten-day Vipassana retreat without counting towards vacation days.&nbsp;</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Reading budget! We will buy you books. 📚</span></li> <li style="font-size: 10pt;"><span style="font-size: 10pt;">Located in the MBC BioLabs at 135 Mississippi Street, an entrepreneurial hub full of the best scientists and operators the Bay Area has to offer. Our lab is a very short walk from the 22nd St Caltrain Station and a number of wonderful restaurants and cafés.</span></li> </ul> <h3>&nbsp;</h3> <h3><span style="font-size: 14pt;"><strong>About Us</strong></span></h3> <p><span style="font-size: 10pt;"><strong>Work Hard/Play Hard.</strong> We believe time is our most valuable commodity, so we strive to create a culture that reflects this. We won’t drag you through unnecessary meetings or email you at 7 PM on a Saturday. When we're at work, we're there to get things done, and when we're off, we're really off. 🌴</span></p> <p><span style="font-size: 10pt;"><strong>Strong Communication.</strong> We like well-written documents over PowerPoints, OKRs over vague mission statements, and weekly one-on-ones over yearly reviews.</span></p> <p><span style="font-size: 10pt;"><strong>Writing First.</strong> We have a "writing-first" culture. We believe that clarity of writing reflects clarity of thinking and that the benefits of well-written documentation in a scientific environment are innumerable: democratization of ideation and decision-making, increased reproducibility, quicker scaling and onboarding, and better company-wide alignment, to name a few.</span></p> <p><span style="font-size: 10pt;"><strong>Growth.</strong> As an early-stage startup, we value scientists with an independent, can-do attitude. The more hats you can wear, the better. Our job as employers is to put you in positive feedback loops so you can grow in the direction of your choosing.</span></p> <hr> <p><span style="font-size: 10pt;">Title and compensation commensurate with experience. Applications from candidates of diverse backgrounds, women, and members of underrepresented minority groups are particularly welcomed. We look forward to hearing from you. :)</span></p> <p>&nbsp;</p> <p><span style="font-size: 10pt;"><strong>More info at&nbsp;<a href="https://jobs.generalproximity.bio/">jobs.generalproximity.bio</a></strong></span></p> <p>&nbsp;</p>