Senior Scientist, Large Molecule Formulation Development

Neurodegenerative diseases are one of the largest medical challenges of our time. Denali Therapeutics is a biotechnology company dedicated to developing breakthrough therapies for neurodegenerative diseases through our deep commitment to degeneration biology and principles of translational medicine. Denali is founded on the collaboration of leading scientists, industry experts, and investors who share the vision that scientific discovery energetically applied to translational medicine is the key to delivering effective therapies to patients.

We invite you to consider an opportunity with Denali to help achieve our goal of delivering meaningful therapeutics to patients.

The Opportunity

We are seeking a talented and motivated Sr. Scientist with an extensive knowledge of therapeutic protein formulation strategies and potential protein degradation mechanisms, including experience developing high concentration protein formulations.  The candidate must have a strong knowledge of protein biochemistry & biophysics; familiarity with biologic drug product characterization & control strategies; and experience developing drug product manufacturing processes including lyophilization and/or combination products.  The candidate will join a broader process development group with opportunities to closely collaborate on all aspects of analytical, formulation, and process development across a broad range of novel large molecules including oligonucleotide-protein conjugates and knob-in-hole Fc-fusion proteins.

Key Responsibilities

• Independently drive formulation and drug product development activities for one or more of Denali’s large molecule biotherapeutics including:
• Developing an understanding of key mechanisms of degradation for each potential therapeutic
• Designing and executing appropriate formulation development studies to identify clinical and commercial formulation & dosage form, establish in-use compatibility, and support comparability
• Oversee drug product process development activities
• Develop stress comparability strategies to support process changes and scale-up
• Hands-on biophysical and biochemical characterization of protein therapeutics in the laboratory using chromatography-, capillary-, spectroscopy-based analytical methods with a focus on evaluating product stability, compatibility, and comparability.
• Translate understanding of critical quality attributes (CQA) and key mechanisms of degradation into robust, stable formulations and dosage forms that ensure product quality and efficacy
• Perform rigorous risk assessments of the impact of drug product manufacturing and storage conditions on product quality
• Author technical documents including formulation development reports, ICH-compliant stability protocols, and relevant sections of regulatory filings to support external QC partners and regulatory submissions.
• Oversee formulation and drug product manufacturing activities at external contract manufacturing organizations (CMO) including review of stability protocols, DP process development studies, tech transfer activities, review of drug product analytical control system specifications and DP-specific analytical method transfer and qualification protocols/reports.
• Lead troubleshooting activities and serve as subject matter expert (SME) for Quality investigations at CMOs
• Participate and be actively engaged in cross-functional technical decision-making including collaborating with Discovery Biotherapeutics, Bioprocess Development, Analytical Development and Quality
• Contribute to establishing internal state-of-the-art formulation capabilities to support accelerated CMC development

Requirements

• Ph.D. in Biochemistry, Biophysics, Chemical/Biochemical Engineering, Pharmaceutical Sciences, or related scientific discipline with a minimum of 3 years of experience in formulation development for protein therapeutics in the biotech/biopharma industry (protein-oligo conjugates, Fc-fusion proteins, enzymes, ADC’s, monoclonal antibodies) or B.S. with a minimum of 10 years or M.S. with a minimum of 8 years of formulation development experience in similarly relevant environment.
• In-depth knowledge and extensive hands-on experience in designing and executing formulation development, in-use compatibility, formulation comparability, and ICH-compliant stability studies.  Experience with high concentration formulation development considered a plus.
• Hands-on experience with chromatography-, capillary-, spectroscopy-based analytical methods to evaluate product quality.  Experience using advanced particulate analysis techniques (e.g. flow microscopy, FTIR/RAMAN, NTA, etc.) considered a plus.
• Familiarity with regulatory expectations, compe