Scientist III, Process Chemistry (Antibody-siRNA Conjugates)

About the role

Arrowhead Pharmaceuticals is seeking a motivated Scientist III to join our Process Chemistry team, focused on the development and scale-up of conjugated RNAi therapeutics. This role centers on process development for antibody-siRNA conjugates (AOCs/ARCs), a key expansion of Arrowhead's TRiM platform into targeted extrahepatic delivery. The successful candidate will span the full development continuum—taking discovery-stage conjugation protocols, optimizing them for robustness and reproducibility, and developing them into GMP, kilogram-scale manufacturing processes. This is a hands-on role at the bench combined with oversight of external CRO/CDMO partners.

Responsibilities

• Optimize discovery-stage conjugation protocols for antibody-siRNA conjugates, improving yield, reproducibility, and product quality to enable scale-up.
• Develop GMP-ready, kilogram-scale conjugation processes, including site-specific and stochastic conjugation strategies, linker chemistry, and payload attachment.
• Work hands-on in the laboratory to design, execute, and optimize conjugation reactions, purification (chromatography, TFF/UF-DF), and analytical control strategies.
• Oversee and direct CROs/CDMOs executing process development and manufacturing activities, including setting technical direction, reviewing data, and ensuring timelines and quality standards are met.
• Characterize conjugates for DAR/siRNA-to-antibody ratio, aggregation, charge heterogeneity, and stability using relevant analytical methods (e.g., HIC, SEC, IEX, LC-MS, AEX).
• Lead technology transfer to internal and external manufacturing partners, authoring process descriptions, batch records, and development reports.
• Troubleshoot process and analytical challenges; design experiments to define process parameters, ranges, and robustness for kilogram-scale operation.
• Collaborate cross-functionally with discovery chemistry, linker/conjugation chemistry, analytical development, and CMC teams.

Requirements

• PhD in Organic Chemistry, Bioconjugate Chemistry, Chemical Engineering, or a related field with some relevant industry experience; or a Master's degree in a related field with 10+ years of relevant experience.
• Demonstrated hands-on experience in siRNA conjugation development is required.
• Working knowledge of oligonucleotide and/or antibody chemistry, linker design, and bioconjugation methods.
• Familiarity with purification and analytical characterization of conjugates.
• Strong problem-solving, documentation, and communication skills.

Preferred

• Experience with antibody-oligonucleotide conjugates (AOCs) or antibody-drug conjugates (ADCs).
• Experience developing and scaling processes to GMP/kilogram scale and managing CRO/CDMO relationships.
• Knowledge of site-specific conjugation technologies (e.g., engineered cysteines, enzymatic/click chemistry).
• Experience with tech transfer and CMC/GMP environments.

Pay

Wisconsin pay range $110,000–$125,000 USD