Director, Medicinal Chemistry

Centessa Pharmaceuticals, a wholly owned subsidiary of Eli Lilly and Company, is a clinical-stage company developing orexin receptor 2 (OX2R) agonists as a new class of medicines for the treatment of narcolepsy and potentially other sleep-wake disorders. Centessa’s lead investigational candidate – cleminorexton (formerly ORX
750) – is being developed for narcolepsy type 1, narcolepsy type 2, and idiopathic hypersomnia. Centessa's OX2R agonist portfolio includes additional clinical and preclinical-stage assets with potential utility across a broader range of neurological, neurodegenerative, and neuropsychiatric conditions. Headquartered in Boston, Massachusetts, Centessa was recognized as a Great Place to Work® in 2026.

We are seeking a Director, Medicinal Chemistry who will lead the medicinal chemistry component of a multi-disciplinary team within a CNS GPCR drug discovery program. This is a hands-on leadership role responsible for guiding a virtual, geographically distributed organization — including internal chemistry staff (some based at remote sites), a CRO-based synthetic chemistry team, consultants, and partners — through the identification and progression of small-molecule and other modality candidates from hit-to-lead through IND-ready status.

Success in this role requires strong scientific leadership, sound judgment, and the ability to build effective working relationships across a geographically dispersed team.

• Lead and manage internal chemistry resources — including staff based at remote sites — alongside dedicated synthetic chemistry teams within CROs, setting priorities, resolving synthetic challenges, and directing the groups toward IND-ready candidate molecules.
• Serve as the chemistry leader within the broader multi-disciplinary project team, building strong working relationships and effective communication with colleagues, partners, consultants, and CROs to jointly identify the best path forward.
• Use all available resources to creatively design new molecules which address the target product profile, establish new intellectual property, and progress the project toward time-based goals
• Make substantial contributions to the development of a chemistry strategy that secures a robust intellectual property position for the company in each area of work
• Analyse SAR within weekly pharmacology & ADME data to identify opportunities for improved molecules, and translate these into tractable designs for molecules with drug-like properties
• Maintain awareness of competitor activities and current medicinal chemistry developments, and use this effectively to advance internal programs
• Communicate regularly with synthetic team, maintain awareness of all ongoing chemistry and look for opportunities to maximise throughput of test compounds
• Effectively utilise in-house structure-based drug design knowledge
• Use compound property computational predictive tools to refine designs
• Present data and clearly articulate ideas for next steps at both chemistry-focused and cross-functional TCs, and at ad hoc F2F meetings
• Use evidence from SAR and literature precedent to defend proposed designs, and also be receptive to alternative suggestions
• Express ideas clearly and professionally in written and verbal interactions within the context of project teams and senior management

• BS/MS Chemistry. PhD Strongly preferred.
• 10+ years designing small molecules as a medicinal chemistry team leader within a biotech and/or pharmaceutical company
• Expert, enthusiastic command of synthetic chemistry and medicinal chemistry principles, combined with solid working knowledge of pharmacology, ADME, pharmaceutical sciences, IP protection, and candidate selection criteria
• Experience of…