Senior Principal Scientist (Antibody Drug Conjugate)

Exelixis•Alameda, CA

30d•Onsite

About The Position

Exelixis is expanding its Antibody-Drug Conjugate (ADC) platform to advance a growing pipeline of oncology bioconjugates. We are seeking a Senior Principal Scientist with deep expertise in conjugation chemistry to serve as the technical anchor for ADC generation, from discovery-scale screening through early process development and IND-enabling tox supply. You will operate independently at the bench, shape platform strategy, and partner cross-functionally with antibody engineering, linker-payload chemistry, analytical development, DMPK, and CMC.

Requirements

BS/BA degree in Chemistry, Biochemistry, Chemical Biology or related discipline and a minimum of 13 years of related experience; or, MS/MA degree in Chemistry, Biochemistry, Chemical Biology or related discipline and a minimum of 11 years of related experience; or, PhD in Chemistry, Biochemistry, Chemical Biology or related discipline and a minimum of 8 years of related experience; or, Equivalent combination of education and experience.
Hands-on mastery of ADC conjugation chemistry from discovery through early CMC, with a track record of advancing molecules to development candidate nomination.
Demonstrated experience in DAR control, product homogeneity optimization and formulation of bioconjugates.
Working knowledge of linkers (cleavable and non-cleavable), payload classes and their MoA.
Fluency with HIC, SEC, RP-HPLC and LC-MS for conjugate characterization.
Rigorous scientific problem-solving, excellent written and oral communication; proven collaborator across chemistry, biology and CMC.
Excellent written and oral communication; proven collaborator across chemistry, biology and CMC.

Nice To Haves

Experience with site-specific conjugation platforms (e.g., engineered cysteine, THIOMAB, transglutaminase/AIICAP, glycan remodeling, sortase, click chemistry).
Experience with dual-payload conjugates, bispecific ADCs or AOCs.
Familiarity with early process development, tech transfer, and CDMO management for GLP/GMP supply.
Patents and peer-reviewed publications in bioconjugation.
Working knowledge of ADC IP landscape.

Responsibilities

Design, execute and optimize ADC conjugation reactions at mg-to-multigram scale to support discovery screening, in vivo pharmacology and early CMC deliverables.
Apply and advance both stochastic (interchain cysteine) and site-specific conjugation platforms (engineered cysteine, transglutaminase, sortase, glycan remodeling, unnatural amino acids, native disulfide re-bridging); contribute to the evaluation and adoption of new platforms.
Optimize stoichiometry, linker chemistry, conjugation reaction conditions and buffer systems to control drug-to-antibody ratio (DAR), homogeneity, and aggregation.
Purify conjugates via FPLC, TFF/UF-DF, and preparative chromatography; develop and validate formulation buffers for bioconjugate stability.
Characterize ADCs by HIC, SEC, RP-HPLC, LC-MS (intact & reduced), and UV-Vis; interpret data to inform process and molecular design decisions.
Partner with analytical development to establish critical quality attributes (CQAs) and in-process controls for lead candidates.
Serve as the Biotherapeutics group’s conjugation subject-matter expert (SME) on program teams; provide the go/no-go technical read on lead molecule DAR strategy, linker selection, and developability.
Help design and interpret in vitro bio-functional assays (efficacy, bystander, catabolite/metabolite ID, MoA studies) in collaboration with biology and DMPK teams to enable candidate selection.
Author technical reports, patents and manuscripts; present at program reviews and external scientific venues.
Track and integrate emerging conjugation technologies, linker-payload chemistries, and IP developments to shape platform investment.
Partner with Protein Science, ADC Chemistry, Analytical, DMPK, Toxicology and CMC/Process Development to deliver quality material on aggressive timelines.
Manage select CRO/CDMO relationships for outsourced conjugation, analytics or scale-up activities; support technology transfer.
Follow all IP, EH&S and laboratory compliance policies.