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, biology and CMC.

Preferred

• 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.

Work Environment

• Modern, collaborative office and adjacent BSL-1/BSL-2 laboratory space at our Alameda, CA campus.

• Routine handling of proteins, organic solvents, and cytotoxic linker-payloads under standard EH&S controls.

• Travel up to 10% for conferences, CRO/CDMO site visits and collaborations.

#LI-HG1

If you have a disability and need an accommodation in relation to the application and/or recruitment process, please email us at: recruiting@exelixis.com.

WORKING CONDITIONS:

Our office is a modern space that fosters collaboration and creativity. Teams work closely together, sharing ideas and solutions in a supportive atmosphere. We provide all necessary equipment, including dual monitors and ergonomic chairs, to ensure a comfortable workspace.

DISCLAIMER:
The preceding job description has been designed to indicate the general nature and level of work performed by employees within this classification. It is not designed to contain or be interpreted as a comprehensive inventory of all duties, responsibilities and qualifications required of employees assigned to the job.

We are an Equal Opportunity Employer and do not discriminate against any employee or applicant for employment because of race, color, sex, age, national origin, religion, sexual orientation, gender identity, status as a veteran, and basis of disability or any other federal, state or local protected class.