Senior​/Principal Scientist, Medicinal Chemistry

Senior / Principal Scientist - Medicinal Chemistry

Axonis is seeking a Senior / Principal Scientist, Medicinal Chemistry to join its growing team. Axonis is a Boston-based biotechnology company advancing breakthrough drug discoveries to treat neurological disorders. Our lead program is a portfolio of first- and best-in-class oral small molecule drugs targeting KCC2, the chief CNS-specific chloride transporter essential for neuronal inhibition, to treat epilepsies, chronic pain and other neurological disorders.

This full-time role will report to the Senior Director of Medicinal Chemistry and the position will be located within the UK.

The Senior / Principal Scientist, Medicinal Chemistry will play a key role in advancing small molecule discovery and lead optimization efforts across Axonis’ KCC2-targeted therapeutic programs. This role contributes to medicinal chemistry strategy from hit identification through candidate nomination and is responsible for driving structure–activity relationship (SAR) design and execution in close collaboration with cross-functional partners.

Working closely with in vitro biology, in vivo pharmacology, and DMPK, the Senior / Principal Scientist will design and progress differentiated, CNS-penetrant small molecules. This individual will contribute scientific insight, data interpretation, and hands‑on chemistry leadership to advance programs toward candidate selection.

• Design and advance compounds across one or more discovery‑stage programs.
• Develop and execute SAR strategies to optimize potency, selectivity, exposure, safety margins, and CNS penetration.
• Progress compounds from hit identification through lead optimization, contributing to candidate nomination activities.
• Evaluate and prioritize chemical series based on multi‑parameter optimization criteria.
• Integrate physicochemical, ADME, pharmacology, and safety data into compound design decisions.
• Work collaboratively with the Senior Director of Medicinal Chemistry to design the overall medicinal chemistry strategy of the programs.

• Partner with in vitro biology to align compound design with mechanistic insights.
• Collaborate with DMPK to optimize exposure, clearance, and PK/PD relationships.
• Work with in vivo pharmacology to interpret exposure–efficacy data and guide compound progression.
• Contribute to safety and toxicology strategy by ensuring compounds meet advancement criteria.

• Interface with external medicinal chemistry CRO partners to support compound synthesis and optimization.
• Contribute to experimental planning, data review, and milestone tracking with vendors.
• Ensure high standards of data integrity, documentation, and reproducibility.

• Present program data and recommendations at internal governance meetings.
• Provide scientific input into portfolio discussions from a chemistry perspective.
• Thorough, meticulous, and detail‑focused approach to data handling and documentation (including contributions to compiling patent applications)
• Contribute to a collaborative, high‑rigor discovery culture.

• PhD in Organic Chemistry or related discipline.
• Significant industry experience in small molecule drug discovery (>5 years).
• Demonstrated contribution to programs progressing through lead optimization; experience supporting candidate nomination preferred (required at Principal Scientist level).
• Strong SAR expertise, ideally including CNS-focused projects.
• Solid understanding of medicinal chemistry principles for oral small molecules.
• Experience integrating DMPK, pharmacology, and safety data into compound design.
• Experience working with external CRO chemistry teams preferred.
• Strong written and verbal communication skills.

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Axonis Therapeutics is a neuro-focused biotechnology company developing first‑ and best‑in‑class medicines targeting KCC2, the critical mediator of inhibition within the brain, by translating breakthrough discoveries spun out from Boston…