Principal Scientist

Alnylam Pharmaceuticals; United States; On-site; USD 180,000 - 240,000; Full time

Job summary

Alnylam Pharmaceuticals seeks a Principal Scientist, Biotransformation & Metabolite Profiling to provide scientific leadership in drug metabolism and biotransformation characterization across discovery and development programs.

You will develop and execute integrated metabolite profiling strategies using state-of-the-art LC-HRMS/MS approaches and collaborate with DMPK, bioanalytical, pharmacology, toxicology, and other project teams to translate data into actionable insights on drug disposition

Qualifications

• PhD in analytical chemistry, medicinal chemistry, pharmaceutical sciences, biochemistry, or drug metabolism with 6+ years of industry experience.
• Hands-on experience in drug metabolism, metabolite profiling, and metabolite identification for small molecules, peptides, RNAi, or related modalities.
• Expertise in LC-MS/MS and high-resolution mass spectrometry with capability to interpret complex MS/MS data.
• Ability to elucidate metabolite structures and biotransformation pathways; strong PK and tissue distribution understanding.

Responsibilities

• Lead metabolite profiling and structural identification across plasma, urine, bile, tissues, and in vitro matrices.
• Apply LC-HRMS/MS approaches for detection, profiling, elucidation, and relative quantitation of metabolites.
• Conduct advanced MS data processing with Compound Discoverer, BioPharma Finder, ProMass, Mass MetaSite, and related software.
• Design biotransformation strategies using hepatocytes, liver fractions, lysosomal systems, serum, and tissues.
• Collaborate with DMPK, bioanalytical sciences, pharmacology, toxicology, and other functions to translate data into disposition insights.
• Coach staff, set goals, and evaluate performance; support IND-enabling activities and CRO method transfers as needed.

Skills

Metabolite profiling

LC-MS/MS

Data interpretation

Biotransformation

Team leadership

Strategic planning

Education

PhD in analytical chemistry or related field

Tools

Thermo Compound Discoverer

BioPharma Finder

ProMass

Mass MetaSite

LC-HRMS/MS workflows

Job description

Overview:

We are seeking an experienced and highly motivated Principal Scientist, Biotransformation & Metabolite Profiling to provide scientific leadership in the characterization of drug metabolism and biotransformation across discovery and development programs.

The successful candidate will develop and execute integrated metabolite profiling and identification strategies using state-of-the-art LC-HRMS/MS approaches. The role will support a range of therapeutic modalities, including small molecules, peptides, RNAi, conjugated therapeutics, and other emerging modalities.

The scientist will serve as a subject-matter expert in metabolite identification and biotransformation, partnering closely 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.

Key Responsibilities:

• Lead metabolite profiling and structural identification in plasma, urine, bile, tissues, and relevant in vitro biological matrices.
• Support a range of therapeutic modalities, including small molecules, peptides, RNAi, conjugated therapeutics, and other emerging modalities.
• Apply LC-HRMS/MS approaches for metabolite detection, profiling, structural elucidation, and relative quantitation.
• Extensively and proficiently conduct advanced MS data processing platforms, specifically Thermo Scientific Compound Discoverer, BioPharma Finder, ProMass, Mass MetaSite and other metabolite profiling software.
• Design appropriate 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.
• May 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 provide scientific interpretation of 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 new mass spectrometry technologies, software, and data-processing approaches that improve metabolite identification efficiency and confidence.
• Conduct non-GLP sample analysis to support all Alnylam's RNAi therapeutic development from DC selection and CTA/IND enabling to late stages.
• Responsible for staff coaching/career development, goal setting, and performance evaluation.
• Interact with research, eDEV, and clinical teams for the responsible programs and build strong working relationships via teamwork. Serve as BA representative for the responsible programs.
• Collaborate with cross-functional teams within Research and Development to align projects and timelines, and aid in interpretation of data.
• Author BA reports for in vitro and in vivo metabolite profiling used in IND filings, and support method transfers to CROs, as needed.

Qualifications:

• PhD in analytical chemistry, medicinal chemistry, pharmaceutical sciences, biochemistry, drug metabolism with 6+ years of relevant industry research experience in small molecule, peptide, oligonucleotide, RNAi development.
• Extensive hands-on experience in drug metabolism, metabolite profiling, and metabolite identification for small molecules, peptide, oligonucleotide, ADC, 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.
• Track record in preparing conference presentations, publications in peer reviewed journals, or industry and regulatory white papers.
• Detail-oriented with exceptional organizational skills, the ability to handle multiple projects, and thrive in a fast-paced, team-oriented environment.
• Possesses excellent verbal and written communication skills.

About Alnylam

We are the leader in RNAi therapeutics- a revolutionaryapproach with the potential to transform the lives of people with rare and common diseases. Built on Nobel Prize-winning science, Alnylam has delivered the breakthroughs that made RNAi therapeutics possibleand are just at the beginning of what is possible. Our deep pipeline, late-stage programs, and bold vision reflect our core values: fierce innovation, passion for excellence, purposeful urgency, open culture and commitment to people. We're proud to be a globally recognized top employer, wherean authentic, inclusive culture and breakthrough thinkingfuel one another.

At Alnylam, we commit to an inclusive recruitment process and equal employment opportunity. Qualified applicants will receive consideration for employment without regard to their sex, gender or gender identity, sexual orientation, race, color, ethnicity, national origin, ancestry, citizenship, religion, creed, physical or mental disability, pregnancy status or related conditions, genetic information, veteran or military status, marital or familial status, political affiliation, age, or any other factor protected by federal, state, or local law. Alnylam is an E-Verify Employer.

Before applying, please review Alnylam's Candidate Privacy Notice regarding how Alnylam handles Personal Data you provide with your application for employment.