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Jobs · Analyst · California

Senior Principal Scientist (Antibody Drug Conjugate)

Exelixis · Alameda, CA · 2 days ago
On-siteAnalyst$170k–$240k/yrFull-time

SUMMARY/JOB PURPOSE

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.

ESSENTIAL DUTIES/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.

  • Scientific Leadership: 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.

  • Collaboration & Delivery: 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.

Education

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.

Experience

Required 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.

Preferred Experience

Preferred 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.

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