R1 Therapeutics is a California-based, (with presence in North Carolina and Boston) clinical-stage biotechnology company dedicated to transforming outcomes for patients living with chronic kidney disease. R1 is building a portfolio of differentiated therapies to address the interconnected complications of CKD—starting with hyperphosphatemia, where unmet need remains high and the standard of care has gone largely unchanged for decades.

The company’s lead asset, AP306, is a first-in-class pan phosphate transporter inhibitor with Phase 2a proof-of-concept and the potential to deliver meaningfully better efficacy with a lower pill burden. R1 launched in 2026 with a $77.5M Series A backed by Abingworth, F-Prime Capital, DaVita Venture Group, and U.S. Renal Care, and is advancing AP306 into Phase 2b with topline data expected in 2027.

Position Description

The Director, Drug Substance will lead all drug substance development and manufacturing activities at R1 Therapeutics, serving as the primary technical and operational owner for active pharmaceutical ingredient (API) development across the company’s pipeline. This role is responsible for defining and executing the drug substance strategy—from early process development through scale-up, tech transfer, and clinical supply—while ensuring regulatory compliance and supply continuity. The Director will manage external CDMO partnerships and work closely with the Head of CMC, regulatory affairs, and analytical development colleagues to advance AP306 into Phase 2b and beyond. This position reports to the Head of CMC.

Key Responsibilities

• Own and drive the drug substance development strategy for AP306 and future pipeline assets, including process development, optimization, and scale-up
• Lead technology transfer activities to CDMOs; serve as the primary technical point of contact for external drug substance manufacturing partners
• Oversee process characterization, process validation planning, and manufacturing readiness activities in alignment with regulatory requirements and program timelines
• Author and review drug substance CMC sections for regulatory submissions, including INDs, CTAs, and IND amendments; support NDA/BLA preparation as programs advance
• Ensure GMP compliance across all drug substance manufacturing operations; lead or support regulatory agency inspections and responses related to drug substance
• Manage API supply chain, including raw material sourcing, batch scheduling, and inventory planning to ensure uninterrupted clinical supply
• Collaborate with analytical development on the design and qualification of drug substance release and stability testing programs
• Track and communicate drug substance program status, risks, and timelines to the Head of CMC and broader leadership team
• Evaluate and recommend CDMO partners; contribute to contract negotiations and governance of external manufacturing relationships
• Support business development activities by providing drug substance technical assessments during due diligence

Education and Experience Requirements

• 10+ years of experience in drug substance/API development and manufacturing within the pharmaceutical or biotechnology industry
• Demonstrated hands-on expertise in small molecule process chemistry, API process development, and scale-up from lab to clinical manufacturing scale
• Experience managing CDMOs and executing technology transfers; strong understanding of CDMO oversight, quality agreements, and batch record review
• Solid regulatory knowledge, including authorship of drug substance CMC sections for IND and/or NDA filings; familiarity with ICH Q7, Q8, Q11 guidelines
• Working knowledge of GMP manufacturing requirements and experience supporting regulatory inspections
• Ability to work effectively in a lean environment with high ambiguity; hands-on, resourceful, and comfortable building processes without established infrastructure
• Strong written and verbal communication skills; ability to present complex technical content clearly to cross-functional audiences
• Advanced degree (PhD or MS) in chemistry, chemical engineering, pharmaceutical sciences, or a related discipline required

Why Join R1

• Opportunity to shape the strategy of a company redefining treatment for kidney disease
• Highly visible role with direct impact on company direction and growth
• Collaborative, mission-driven culture with a focus on innovation and urgency
• Ability to work at the forefront of science while driving meaningful business outcomes