Senior Principal Scientist; Antibody Drug Conjugate

Senior Principal Scientist

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.

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 develop ability.
• Help design and interpret in vitro bio-functional assays (efficacy, bystander, catabolite/metabolite , 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:

• 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.

Knowledge, Skills and Abilities:

• 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.

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.

Compensation reflects the cost of labor across several U.S. geographic markets, and we pay differently based on those defined markets. The base pay range for this position is $169,500 - $239,500 annually. The base pay range may take into account the candidate's geographic region, which will adjust the pay depending on the specific work location. The base pay offered will take into account the candidate's geographic region, job-related knowledge, skills, experience and internal equity, among other factors.

In addition to the base salary, as part of our Total Rewards program, Exelixis offers comprehensive employee benefits package, including a 401k plan with generous company contributions, group medical, dental and vision coverage, life and disability insurance, and flexible spending accounts. Employees are also eligible for a discretionary annual bonus program, or if field sales staff, a sales-based incentive…