# Principal Scientist, Protein Engineering

Live page: https://affinitytalent.bio/jobs/principal-protein-engineer-multispecifics

## Role summary

- Clinical-stage multispecific therapeutics company
- South San Francisco, CA, US
- Hybrid · Specialist
- Compensation: $215k - $250k + equity + annual bonus

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.

## Role details

- 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
- Business goal: Advance multispecific antibody formats that balance tumor biology, immune engagement, developability, and manufacturability
- Near-term deliverable: Refine the engineering strategy and lead-selection package for two active multispecific programs.

## Responsibilities

- Lead multispecific design strategy: Set the engineering strategy for paratope optimization, binding valency, linker architecture, Fc design, and developability trade-offs.
- Drive lead selection: Compare potency, binding kinetics, expression, purification behavior, aggregation risk, stability, and developability data to recommend lead series.
- Structural and epitope modelling: Use structural models, epitope data, sequence analysis, and empirical assay results to propose targeted sequence or format changes.
- Cross-functional alignment: Collaborate with discovery biology, analytical sciences, and CMC teams to align molecular design with downstream requirements.
- Technical leadership: Provide scientific counsel during portfolio 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 SPR/BLI, SEC-MALS, DSC/DSF, CE-SDS, icIEF, or LC-MS.
- Track record guiding lead selection decisions with discovery biology, protein sciences, analytical, or CMC partners.

## 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/Schrodinger/PyMOL.