Principal Scientist, Analytical Development, Oligonucleotide & Small Molecule CMC

Denali Therapeutics•South San Francisco, CA

7d•$159,000 - $207,000

About The Position

Denali Therapeutics Inc. is a biotechnology company pioneering a new class of biotherapeutics designed to cross the blood-brain barrier (BBB) using its proprietary TransportVehicle™ platform. With the first FDA-approved biologic specifically designed to cross the BBB, a clinically validated delivery platform and a growing portfolio of therapeutic candidates across all stages of development, we are advancing toward our goal of delivering effective medicines to transform the lives of people living with neurodegenerative diseases, lysosomal storage disorders and other serious diseases. We invite you to consider an opportunity with Denali to help achieve our goal of delivering meaningful therapeutics to patients.

Requirements

Ph.D. in Analytical Chemistry, Chemistry, Pharmaceutical Sciences, or a related discipline with 7+ years of relevant industry experience; or M.S. with 10+ years or B.S. with 12+ years of relevant industry experience.
At least 5 years of hands-on analytical development experience supporting oligonucleotide and/or small-molecule drug substances and drug products, with demonstrated scientific leadership on development programs.
Demonstrated ability to lead and mentor a small team while balancing direct laboratory work, technical decision-making, delegation, and timely delivery of results.
Deep expertise in chromatographic methods, including HPLC/UPLC, and in mass spectrometry is expected.
Strong understanding of oligonucleotide synthesis and purification processes, impurity characterization, fate-and-purge assessments, and analytical control strategy development.
Working knowledge of method lifecycle activities, stage-appropriate QC testing, specifications, stability programs, data integrity, and CMC regulatory expectations from early clinical development through late-stage development.
Experience transferring analytical methods and providing technical oversight of CRO/CDMO activities, including review and interpretation of externally generated data.

Nice To Haves

Experience with relevant techniques such as GC, XRPD, DSC, TGA, and other physicochemical methods is desirable.

Responsibilities

Lead and mentor the Oligonucleotide & Small Molecule CMC Analytical Development team, developing talent, setting day-to-day priorities, reviewing data, and developing technical capabilities while maintaining a regular, hands-on presence in the laboratory.
Design, execute, troubleshoot, and oversee analytical method development, qualification, validation, transfer, testing, and characterization for oligonucleotide and small-molecule starting materials, intermediates, drug substances, and drug products.
Lead analytical activities for assigned programs, including impurity characterization, impurity fate and purge, reference standards, stability testing, specifications, and stage-appropriate analytical control strategies.
Establish, operate, and continuously improve internal analytical laboratory capabilities, including instrumentation, workflows, documentation, data integrity, safety, and laboratory readiness; identify and implement innovative technologies and practical improvements that strengthen laboratory and program performance.
Analyze and interpret complex data, integrating knowledge of oligonucleotide synthesis, purification, formulation, and degradation pathways to resolve technical issues and provide scientifically sound recommendations.
Serve as the Analytical Development lead on assigned cross-functional program teams, collaborating with discovery scientists, process chemists, formulation, quality, regulatory, and project teams to meet program goals and timelines.
Plan and oversee defined analytical work at CROs and CDMOs, including method transfer, technical guidance, data review, and troubleshooting.
Author and review specifications, Certificates of Analysis, validation protocols and reports, and relevant analytical CMC sections of regulatory submissions.