Scientist III, Process Chemistry (Antibody-siRNA Conjugates)

Arrowhead Pharmaceuticals•Madison, WI

1d•$110,000 - $125,000

About The Position

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.

Requirements

PhD in Organic Chemistry, Bioconjugate Chemistry, Chemical Engineering, or a related field; or a Bachelor's/Master's degree with commensurate hands-on industry 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.

Nice To Haves

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.

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