Principal Scientist, Protein Engineering
Drive protein engineering strategy for multispecific biologics programs, focusing on format design, biophysical screening, and candidate optimization.
About the role
As a Principal Scientist, you will guide protein engineering initiatives for complex multispecific biologics. Your role will encompass strategic format design, affinity optimization, and ensuring robust manufacturability standards are met prior to formal candidate nomination.
- Team: Protein-engineering group of 4 embedded with discovery biology and protein sciences
- Stage: Clinical-stage biologics company expanding earlier-stage discovery work
- Reporting line: VP, Therapeutic Discovery
- Rhythm: Hybrid role with consistent onsite collaboration in South San Francisco
Responsibilities
- Establish engineering parameters encompassing paratope optimization, binding valency, linker architecture, and Fc design.
- Evaluate potency, binding kinetics, expression levels, and biophysical stability data to recommend top lead series for advancement.
- Leverage structural modeling, epitope data, and empirical assays to propose targeted sequence optimizations.
- 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 in Protein Engineering, Structural Biology, Biophysics, or a related biologics discipline.
- Significant industry experience (10+ years) focusing on multispecifics, multi-domain proteins, or advanced therapeutic biologics.
- Comprehensive understanding of sequence design, transient expression workflows, purification, and advanced biophysical analysis.
- Demonstrated expertise utilizing assays such as SPR/BLI, SEC-MALS, DSC, CE-SDS, and LC-MS for molecular characterization.
- Proven track record of guiding lead selection decisions and interfacing effectively with CMC functions.
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
- 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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