Principal Scientist, Late Phase and Commercial Analytical and Formulation Development

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

Benefits offered by this job

401k

Healthcare

ESPP

Other benefits

Job summary

Denali Therapeutics Inc. is seeking a Principal Scientist to provide strategic leadership in late-phase and commercial analytical development and extended characterization.

You will oversee control strategy development at CDMOs and deliver across CQAs, bridging, and validation activities while mentoring junior staff. You will develop and optimize MS- and chromatographic-based methods, perform in-depth physicochemical characterization, and drive regulatory-ready documentation for health authority

Qualifications

• PhD or equivalent with 10+ years in analytical development for protein therapeutics.
• Experience leading multidisciplinary analytical and quality teams to meet milestones.
• Experience with large molecule late phase and commercial analytical lifecycles.
• Hands-on development of analytical protein characterization and biophysical methods (HPLC, cIEF, CE, LC/MS, peptide mapping, spectrophotometry, SPR, light scattering).
• MS-based method development experience (intact/reduced MS, peptide mapping, glycosylation profiling).
• Experience with bioanalytical assays or MS characterization approaches is a plus.
• Strong DoE and data analysis skills; knowledge of GMP and regulatory guidance.
• Ability to collaborate across teams and with CDMOs to drive program timelines.
• Excellent written and oral communication; detail-oriented and problem-solving mindset.

Responsibilities

• Independently lead analytical development and product characterization for CMC late phase/commercial molecules, including CDMO management.
• Oversee method qualification/validation and transfer at CDMOs; support bridging and comparability studies.
• Define and execute overall biologics analytical development strategy for accelerated timelines.
• Provide hands-on lab work and mentorship to junior staff.
• Develop and optimize chromatography-, capillary-, spectroscopy-, and MS-based methods for product quality.
• Perform in-depth physical/chemical characterization of complex biologics.
• Lead CQAs assessments to support control strategies; support QA investigations with CMOs/CROs.
• Author/review development documents and sections of health authority filings.
• Establish state-of-the-art analytical capabilities to accelerate CMC development.
• Ensure rapid, cross-functional analytical support and timely deliverables.
• Maintain proficiency with latest analytical technologies and guidelines.
• Maintain accurate lab records per good documentation practices.
• Lead direct reports with goals, growth plans, and training compliance.

Skills

Analytical Development

CDMO Management

Mass Spectrometry

Biologic Characterization

DoE

GMP Knowledge

Cross-functional Leadership

Team Mentoring

Scientific Writing

Communication

Education

PhD in Analytical Chemistry

BS/MS with 14+ years experience

Tools

HPLC-based methods

cIEF

Capillary electrophoresis

LC/MS

Peptide mapping

Spectrophotometry

SPR

Light scattering

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. As Denali builds internal capabilities to support rapid process and formulation development for our diverse pipeline of large molecules, we are seeking a talented and motivated Principal Scientist to provide strategic technical leadership for late phase and commercial analytical development and extended characterization activities as well as oversight of control strategy development and implementation at contract development and manufacturing organizations (CDMOs).

Key Accountabilities / Core Responsibilities

• Independently lead analytical development and product characterization activities for one or more molecules in the CMC late phase/commercial space, including managing CDMO interactions and driving the development and implementation of overall analytical control strategy.
• Provide oversight of analytical method qualification, validation, and transfer activities at CDMOs, as well as method bridging, comparability, and extended characterization studies.
• Define execute overall biologics analytical development strategy to enable accelerated CMC development and commercial timelines.
• Hands‑on, technical execution in the laboratory while providing mentorship to junior colleagues.
• Develop and optimize chromatography-, capillary-, spectroscopy-, and mass spectrometry‑based analytical methods for product quality assessment.
• Perform in-depth physical/chemical characterization of complex biologics.
• Lead critical quality attributes (CQAs) assessments to support phase‑appropriate control system strategy.
• Provide technical guidance during testing‑related investigations at CMOs/CROs in collaboration with Quality.
• Author and review technical development documents and relevant sections of health authority filings.
• Drive the establishment of internal state‑of‑the‑art analytical capabilities to support accelerated CMC development.
• Ensure rapid and timely, cross‑functional analytical support. all relevant CMC‑related deliverables.
• Maintain proficiency in the latest analytical technologies and industry guidelines, as well as emerging analytical development strategies.
• Maintain timely and accurate lab records consistent with good documentation practices.
• Lead direct report(s) through annual goal setting, growth planning, adherence to company policies, maintain training compliance and provide ongoing feedback on growth, development and areas of improvement.

Qualifications/Skills

• PhD in Analytical Chemistry, Biochemistry, Chemical Engineering, Biophysics, or a related scientific discipline, plus a minimum of 10 years of analytical development experience for protein therapeutics in the biotech/biopharma industry; or BS/MS with a minimum of 14 years of relevant experience.
• Previous experience successfully managing multidisciplinary analytical and quality teams to meet program milestones and timelines.
• Previous experience with large molecule late phase and commercial analytical lifecycle activities, including leading/executing successful method transfers, method qualification and validation, bridging studies, comparability and characterization studies, and supporting Quality investigations, including familiarity with applicable GMP requirements.
• In‑depth knowledge and extensive hands‑on experience in developing a wide array of analytical protein characterization and biophysical methods (e.g. HPLC‑based methods, cIEF, capillary electrophoresis, LC/MS, peptide mapping, spectrophotometry, SPR, light scattering, etc.)
• Strong background in developing mass spectrometry‑based methods (Intact/reduced MS, peptide mapping, N‑/O‑glycosylation profiling, disulfide linkage determination, LC‑MS/MS analysis) for protein sequence confirmation, identification and characterization of product variants, and comparability evaluations considered highly preferable.
• Prior experience developing bioanalytical assays or advanced/specialized mass spectrometry characterization approaches, such as tandem mass spectrometry, quantitative analysis, and host cell protein analysis, is considered a plus.
• Strong grasp of statistical approaches for design‑of‑experiments (DoE) analytical method development, robustness testing, and data analysis.
• Strong grasp of relevant current industry guidelines (ICH, Pharmacopeia, FDA/EMA guidance) and best practices (BioPhorum or other consortia white papers).
• Demonstrated ability to work effectively and collaboratively with other scientists on cross‑functional projects teams as well as CDMOs.
• Ability to make thoughtful and meaningful recommendations and/or manage relationships in order to drive efficient advancement of the portfolio.
• Ability to balance competing priorities and thrive in a dynamic, fast‑paced environment.
• Excellent critical thinking, scientific problem‑solving, and organizational skills.
• Excellent oral and written communication skills.
• Motivated, detail‑oriented, scientifically driven individual with a creative approach to problem solving.

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.

"Life at Denali" is a living reflection of our values: trust, unity, grit and growth. These are not just words we share—they shape how we show up, collaborate and push boundaries together. From the lab to the community, across functions and milestones, our culture thrives on shared purpose and relentless pursuit.