Principal Scientist

Alnylam Pharmaceuticals

2d•Onsite

About The Position

Alnylam is seeking an experienced Principal Scientist, Biotransformation & Metabolite Profiling to provide scientific leadership in characterizing drug metabolism and biotransformation across discovery and development programs. The role develops and executes integrated metabolite profiling and identification strategies using state-of-the-art LC-HRMS/MS approaches, supporting small molecules, peptides, RNAi, conjugated therapeutics, and other emerging modalities. The scientist serves as a subject-matter expert in metabolite identification and biotransformation and partners with DMPK, bioanalytical sciences, pharmacology, toxicology, research/biology, and other project functions to translate metabolite data into actionable understanding of drug disposition, efficacy, and safety. The position also provides staff coaching and career development, goal setting, and performance evaluation; represents bioanalytical sciences on responsible programs; and collaborates with Research and Development teams on project alignment, timelines, and data interpretation. The role conducts non-GLP sample analysis supporting Alnylam RNAi therapeutic development from candidate selection and CTA/IND-enabling work through later stages. It authors bioanalytical reports for in vitro and in vivo metabolite profiling used in IND filings and may support method transfers to CROs. The position may also support PK and PD analysis as needed.

Requirements

PhD in analytical chemistry, medicinal chemistry, pharmaceutical sciences, biochemistry, or drug metabolism.
At least 6 years of relevant industry research experience in small molecule, peptide, oligonucleotide, or RNAi development.
Extensive hands-on experience in drug metabolism, metabolite profiling, and metabolite identification for small molecules, peptides, oligonucleotides, ADCs, or RNAi compounds.
Strong expertise in LC-MS/MS and high-resolution mass spectrometry, including interpretation of complex MS/MS fragmentation data.
Demonstrated ability to elucidate metabolite structures and construct scientifically supported biotransformation pathways.
Strong understanding of drug metabolism, PK, tissue distribution, and mechanisms governing metabolite formation.
Detail-oriented, with exceptional organizational skills and the ability to handle multiple projects in a fast-paced, team-oriented environment.
Excellent verbal and written communication skills.

Nice To Haves

Track record in preparing conference presentations, publishing in peer-reviewed journals, or contributing to industry and regulatory white papers.

Responsibilities

Lead metabolite profiling and structural identification in plasma, urine, bile, tissues, and relevant in vitro biological matrices.
Support metabolite analysis across small molecules, peptides, RNAi, conjugated therapeutics, and other emerging modalities.
Apply LC-HRMS/MS approaches for metabolite detection, profiling, structural elucidation, and relative quantitation.
Use advanced mass-spectrometry data-processing platforms, including Thermo Scientific Compound Discoverer, BioPharma Finder, ProMass, Mass MetaSite, and other metabolite-profiling software.
Design biotransformation strategies using hepatocytes, liver subcellular fractions, lysosomal systems, serum/plasma, tissue preparations, and other fit-for-purpose models.
Characterize metabolic pathways, including oxidation, reduction, hydrolysis, conjugation, proteolysis, deconjugation, linker cleavage, and other modality-specific catabolic pathways.
Support PK and PD analysis as needed.
Establish relationships between in vitro metabolism, in vivo circulating metabolites, and tissue-specific metabolism and catabolism.
Identify major, disproportionate, persistent, or pharmacologically relevant metabolites and interpret their potential significance.
Interpret accurate mass, isotope patterns, charge states, MS/MS fragmentation, product-ion spectra, and chromatographic behavior to support metabolite assignments.
Evaluate and implement mass spectrometry technologies, software, and data-processing approaches that improve metabolite identification efficiency and confidence.
Conduct non-GLP sample analysis supporting RNAi therapeutic development from candidate selection and CTA/IND-enabling work through later stages.
Coach staff and support career development, goal setting, and performance evaluation.
Interact with research, eDEV, and clinical teams for responsible programs, build working relationships, and serve as the bioanalytical representative for those programs.
Collaborate with cross-functional Research and Development teams to align projects and timelines and aid data interpretation.
Author bioanalytical reports for in vitro and in vivo metabolite profiling used in IND filings and support method transfers to CROs as needed.