Scientist III, Process Chemistry (Antibody-siRNA Conjugates)

Arrowhead Pharmaceuticals, Inc. (Nasdaq ARWR) is a commercial stage biopharmaceutical company that develops medicines that treat intractable diseases by silencing the genes that cause them. Using a broad portfolio of RNA chemistries and efficient modes of delivery, Arrowhead therapies trigger the RNA interference mechanism to induce rapid, deep, and durable knockdown of target genes. RNA interference, or RNAi, is a mechanism present in living cells that inhibits the expression of a specific gene, thereby affecting the production of a specific protein. Arrowhead’s RNAi-based therapeutics leverage this natural pathway of gene silencing. Arrowhead is focused on developing innovative drugs for diseases with a genetic basis, typically characterized by the overproduction of one or more proteins that are involved with disease. The depth and versatility of our RNAi technologies enables us to potentially address conditions in virtually any therapeutic area and pursue disease targets that are not otherwise addressable by small molecules and biologics. Arrowhead is leading the field in bringing the promise of RNAi to address diseases outside of the liver, and our clinical pipeline includes disease targets in the liver and lung with a promising pipeline of preclinical candidates. Arrowhead’s corporate headquarters is in Pasadena, CA with research and development teams in Madison, WI & San Diego, CA, and a state of the art manufacturing facility in Verona, WI. Our employees are nimble, science-driven innovators who are collaborating to bring new therapies to patients in need. 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. 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; 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. 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. Wisconsin pay range

$110,000—$125,000 USD