Principal Scientist, Protein Engineering
Lead protein engineering for multispecific biologics designed to improve immune engagement in solid tumors.
About the role
The company is building multispecific antibody therapeutics that combine tumor targeting, immune-cell engagement, and developability requirements in formats that can move toward clinical testing. As a Principal Scientist, you will guide engineering decisions across format design, affinity tuning, expression and purification behavior, biophysical characterization, and the package needed to move a lead series toward candidate nomination.
- Team: Protein-engineering group of 4 embedded with discovery biology and protein sciences
- Stage: Clinical-stage biologics company expanding earlier multispecific discovery work
- Reporting line: VP, Therapeutic Discovery
- Experience: PhD with 10+ years in protein engineering, biologics discovery, or therapeutic protein design
- Rhythm: Hybrid role with consistent onsite collaboration in South San Francisco
Responsibilities
- Set the engineering strategy for paratope optimization, binding valency, linker architecture, Fc design, and developability trade-offs.
- Compare potency, binding kinetics, expression, purification behavior, aggregation risk, stability, and developability data to recommend lead series.
- Use structural models, epitope data, sequence analysis, and empirical assay results to propose targeted sequence or format changes.
- Collaborate directly with discovery biology, analytical sciences, and CMC teams to align molecular design with downstream requirements.
- Provide strategic scientific counsel during portfolio governance reviews, partner discussions, and patent filings.
Requirements
- PhD with 10+ years of industry experience in protein engineering, biologics discovery, structural biology, biophysics, or a related discipline.
- Direct experience engineering multispecifics, bispecifics, multi-domain proteins, Fc-containing biologics, or other non-standard therapeutic formats.
- Strong practical understanding of sequence design, transient expression, purification, developability screening, and biophysical characterization.
- Hands-on familiarity with assays such as SPR/BLI, SEC-MALS, DSC/DSF, CE-SDS, icIEF, or LC-MS for molecular characterization.
- Track record guiding lead selection decisions and working with discovery biology, protein sciences, analytical, or CMC partners.
Preferred qualifications
- Experience with half-life extension modalities, Fc engineering, or immune effector function tuning.
- Direct involvement in technical diligence, external collaborations, or extensive patent strategy activities.
Technical stack
- multispecific engineering
- bispecific format design
- structure-guided design
- purification screening
- SPR/BLI
- SEC-MALS
- DSC/DSF
- CE-SDS/icIEF
- intact-mass/LC-MS
- Rosetta/Schrödinger/PyMOL
What we offer
- Base salary: $215k - $250k
- Equity / upside: Senior-level equity package with annual refresh and bonus target.
- Benefits: Medical, dental, vision, 401(k), family support, and relocation where needed.
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