Principal Scientist, Analytical Development, Oligonucleotide & Small Molecule CMC

Denali Therapeutics; South San Francisco (CA); On-site; USD 159,000 - 207,000; Full time

Benefits offered by this job

401k

Healthcare

ESPP

Job summary

Denali Therapeutics is seeking an experienced leader to head the Oligonucleotide & Small Molecule CMC Analytical Development team in South San Francisco. You will mentor staff, drive method development, and ensure robust analytical control strategies across drug substances and products.

The role requires deep chromatographic and MS expertise, proven program leadership, and collaboration with discovery, formulation, quality, and regulatory teams to advance programs for CNS indications.

Qualifications

• Ph.D. in Analytical Chemistry or related discipline with 7+ years of industry experience; or MS/BS with extensive industry experience.
• Hands-on analytical development experience supporting oligonucleotide and/or small-molecule drug substances and products.
• Expertise in chromatographic methods (HPLC/UPLC) and mass spectrometry; knowledge of GC, XRPD, DSC, TGA desired.

Responsibilities

• Lead and mentor the analytical development team, setting priorities and reviewing data.
• Design, troubleshoot, and oversee analytical method development, validation, transfer, and testing.
• Lead analytical activities for programs including impurity characterization and stability testing.
• Establish and improve internal lab capabilities, instrumentation, and data integrity.
• Collaborate with cross-functional teams to meet program goals and timelines.
• Oversee CRO/CDMO method transfers and provide technical guidance.

Skills

HPLC/UPLC

Mass spectrometry

Oligonucleotide synthesis

Impurity characterization

Method transfer

Data interpretation

Education

Ph.D. in Analytical Chemistry or related field

Experience in oligonucleotide and/or small-molecule development

Job description

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.Lead and mentor the Oligonucleotide & Small Molecule CMC Analytical Development team while providing hands-on scientific leadership in analytical method development, testing, and characterization. Oversee laboratory capabilities, external analytical work, and regulatory documentation, collaborating across teams to resolve technical challenges and advance development programs.Key Accountabilities / Core Job 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.Qualifications / Skills :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; experience with relevant techniques such as GC, XRPD, DSC, TGA, and other physicochemical methods is desirable.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.Salary Range: $159,000.00 to $207,000.00 . Compensation for the role will depend on a number of factors, including a candidate’s qualifications, skills, competencies, and experience. Denali offers a competitive total rewards package, which includes a 401k, healthcare coverage, ESPP and a broad range of other benefits. Learn more at https://www.denalitherapeutics.com/careersThis compensation and benefits information is based on Denali’s good faith estimate as of the date of publication and may be modified in the future.Denali is committed to its core company value of unity by creating a diverse and inclusive environment. We are proud to be an equal opportunity employer and do not discriminate against any employee or applicant for employment because of race, color, sex, age, national origin, religion, sexual orientation, gender identity and/or expression, status as a veteran, basis of disability, or any other federal, state, or local protected class.