Principal Scientist / Associate Director, Medicinal Chemistry

Role Overview

We are seeking an experienced medicinal chemist at the Principal Scientist or Associate Director level to contribute to and lead the design of the next generation of radioligand therapeutics. This role owns medicinal chemistry strategy and execution for one or more discovery programs, from hit validation through lead optimization to development candidate nomination. Target chemical matter sits firmly beyond the rule of 5: linear and macrocyclic peptides, constrained and bicyclic scaffolds in both peptide and small molecule space, and the novel linker architectures that join them to a radionuclide chelator. Success in this role therefore depends on genuine fluency in bRo5 design and property optimization, not on classical small molecule experience alone. The ideal candidate is a hands-on designer and a decisive project leader, is adept at interpersonal communication, and enjoys working in a fast-paced environment with a multidisciplinary team of Chemists, Biologists, and Engineers. Title and level will be commensurate with experience. This position is on-site in Salt Lake County, so US work authorization is needed.

Key Responsibilities

• Own the medicinal chemistry strategy and design output for one or more radioligand therapy programs, from hit validation through lead optimization to development candidate nomination.

• Design linear and macrocyclic peptides, constrained and bicyclic scaffolds, and peptide–small molecule hybrids, using structure-based and property-based design to balance target affinity, selectivity, plasma and metabolic stability, and clearance.

• Drive fast, well-instrumented DMTA cycles: build and interpret SAR across multiple chemical series simultaneously, and set explicit go/no-go criteria for each iteration.

• Solve the beyond-rule-of-5 property problem directly — conformational control, intramolecular hydrogen bonding, N-methylation and backbone modification, macrocyclization strategy, solubility, proteolytic stability and permeability in molecules well outside Ro5 space.

• Design and optimize targeting ligand–linker–chelator constructs for matched diagnostic and therapeutic radionuclide pairs, in close partnership with radiochemistry, and optimize tumor uptake, retention, and normal-tissue clearance.

• Select, contract, and technically direct external CRO partners for solid-phase and solution-phase synthesis, purification, and analytical characterization, holding them to timeline, quality, and cost.

• Work as an integrated member of several project teams and partner closely with Computational Chemistry, DMPK, Biology, and Translational Sciences to convert modeling and in vitro / in vivo data into the next design cycle.

• Mentor and develop junior chemists, and contribute to the recruitment and technical evaluation of new team members as the chemistry organization scales.

• Author patent applications, technical reports, and IND-enabling documentation, and present work to project teams, senior leadership, and external partners in the form of written updates, PowerPoint presentations, and ad hoc communications and meetings.

Qualifications

• Ph.D. in organic chemistry with 4+ years of relevant industry experience.

• Required: a substantive track record in at least one of the following modalities — (a) peptide-drug conjugates, (b) linear peptide therapeutics, (c) macrocyclic, cyclic, constrained, or bicyclic peptides, or (d) targeted protein degraders such as PROTACs, molecular glues, or other bifunctional constructs.

• Deep working knowledge of bRo5 property optimization and its trade-offs, including passive permeability, aqueous solubility, conformational behavior, proteolytic and metabolic stability, and the design levers used to control them.

• Demonstrated personal ownership of a chemical series through lead optimization, evinced by compounds advanced and design decisions the candidate can speak to directly.

• Hands-on synthetic expertise, including solid-phase peptide synthesis on manual and automated systems, multi-step solution-phase synthesis, and purification and characterization by preparative HPLC, LC-MS, and NMR.

• Proven experience selecting and managing external CRO partners, including peptide CROs, and coordinating workstreams across partners and time zones.

• Fluency in structure-based drug design and the ability to work productively with computational chemists, interpreting docking, MD, and FEP output and translating structural hypotheses into compounds.

• Proven track record of successfully supporting drug discovery efforts as evinced by presentations, publications, granted patents, or a preclinical or clinical asset.

• Strong written and oral communication skills, and comfort operating with limited infrastructure in an early-stage company.

Preferred Qualifications

• Experience in radiopharmaceuticals or radioligand therapy, including chelator selection and design (DOTA, DOTAGA, macropa, and related systems) and conjugate design for radiometals such as Lu-177, Ac-225, and Ga-68.

• Experience working with and designing peptide drug conjugates.

• Experience with peptide-drug conjugate or antibody-drug conjugate linker design and payload attachment chemistry.

• Experience taking a peptide or bRo5 program through IND-enabling studies, and working with CMC and process chemistry colleagues on scale-up.

• Working familiarity with cheminformatics tools.

• Prior line management or formal mentorship responsibility for synthetic chemists.