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 groups 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

Our compensation reflects the cost of labor across severalU.S. geographic markets and we pay differently based on those defined markets. The base pay range for this positionis $169500 - $239500 annually. The base pay range may take into account the candidates geographic region which will adjust the pay depending on the specific work location. The base pay offered will take into account the candidates 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 plan. Exelixis also offers employees the opportunity to purchase company stock and receive long-term incentives 15 accrued vacation days in their first year 17 paid holidays including a company-wide winter shutdown in December and up to 10 sick days throughout the calendar year.

If you have a disability and need an accommodation in relation to the recruiting process please email us at: .

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.