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 coverage

ESPP

Job summary

Denali Therapeutics Inc. is a biotechnology company focused on delivering meaningful therapeutics across CNS diseases.

We seek a leader for the Oligonucleotide & Small Molecule CMC Analytical Development team to direct method development, testing, and characterization with hands-on lab leadership. You will oversee capabilities, external work, and regulatory documentation, collaborating across teams to meet program goals and timelines while maintaining data integrity and safety in a fast-paced

Qualifications

• PhD with 7+ years, or MS with 10+ years or BS with 12+ years in relevant industry.
• 5+ years hands-on analytical development supporting oligonucleotide and/or small-molecule drug substances and drug products.
• Demonstrated ability to lead and mentor a small team while balancing lab work and timely results.
• Deep expertise in chromatographic methods (HPLC/UPLC) and mass spectrometry; experience with GC, XRPD, DSC, TGA is desirable.
• Strong understanding of oligonucleotide synthesis, purification, impurity characterization, and analytical control strategies.
• Experience with method lifecycle activities, QC testing, stability programs, data integrity, and CMC regulatory expectations.
• Experience transferring analytical methods and providing oversight of CRO/CDMO activities.

Responsibilities

• Lead and mentor the analytical development team with hands-on involvement.
• Design, qualify, validate, transfer, test, and characterize analytical methods for oligonucleotide and small-molecule materials and products.
• Lead analytical activities for programs including impurity characterization and stability testing.
• Improve internal lab capabilities, instrumentation, data integrity, and safety.
• Analyze complex data and provide scientifically sound recommendations.
• Serve as the Analytical Development lead on cross-functional program teams.
• Plan and oversee work at CROs/CDMOs with technical guidance and data review.
• Prepare specifications, COAs, validation protocols, and regulatory CMC sections.

Skills

Analytical leadership

Chromatography (HPLC/UPLC)

Mass spectrometry

Laboratory management

Education

PhD in Analytical Chemistry

MS in Analytical Chemistry

BS in Chemistry

Tools

HPLC/UPLC

Mass spectrometry

GC

XRPD

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/careers

This 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.