Senior Principal Scientist (Antibody Drug Conjugate)

SUMMARY/JOB PURPOSE (Basic purpose of the job):

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.

ESSENTIAL DUTIES/RESPONSIBILITIES:

• Bioconjugation & Process Innovation

  • 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.

• Analytical Characterization

  • 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.

  • Follow all IP, EH&S and laboratory compliance policies.

SUPERVISORY RESPONSIBILITIES:

• None.

EDUCATION/EXPERIENCE/KNOWLEDGE & SKILLS:

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 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.

Knowledge, Skills and Abilities:

Required

• 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,