Assistant Director, DMPK

Ionis Pharmaceuticals, Inc.•Carlsbad, CA

159d•$153,848 - $200,000•Onsite

About The Position

The Assistant Director, DMPK, will contribute scientific expertise for the development and execution of fit-for-purpose DMPK strategies supporting Ionis therapeutic programs from discovery through clinical development, as a DMPK project representative under the supervision of Head of DMPK. This role will combine hands-on scientific expertise with technical oversight of internal laboratory activities and outsourced studies. They will bring exceptional expertise in metabolite identification and profiling, LC-MS/MS and high-resolution mass spectrometry, quantitative bioanalysis, and the interpretation of complex modalities MS data. The successful candidate will serve as a trusted DMPK partner and expert to multidisciplinary project teams, translate complex data into clear development recommendations, and help ensure that DMPK data are scientifically rigorous, timely, and decision-ready for candidate selection, IND/FIH, and later-stage development. This is an individual-contributor role with no direct reports; influence will be exercised through scientific leadership, collaboration, and technical mentorship.

Requirements

Ph.D. in pharmaceutical sciences, analytical chemistry, biochemistry, pharmacology, or a related discipline with at least 5 years of relevant industry experience
Extensive hands-on experience developing, qualifying, and applying bioanalytical and DMPK methods, with demonstrated expertise in high resolution mass spectrometry operation and troubleshooting.
Hand-on experience with diverse bioanalytical sample preparation methodologies such as protein precipitation, liquid-liquid extraction, solid phase extraction, immunocapture, hybridization, etc.
Hands-on experience with LC-MS/MS, HRMS, metabolite identification and profiling, quantitative bioanalysis, sample preparation, and interpretation of data from complex biological matrices.
Strong understanding of ADME principles across multiple delivery routes, dosing regimens, modalities, and conjugates.
Working knowledge of GLP requirements and regulatory guidance relevant to bioanalysis, DMPK, metabolite safety, and clinical development.
Excellent written and oral communication skills, including the ability to present complex technical findings to multidisciplinary audiences and provide constructive technical direction to CROs and laboratory personnel.
Strong organizational skills, attention to detail, commitment to data integrity, and ability to work collaboratively in a fast-paced, cross-functional environment.

Nice To Haves

Experience with bioanalysis/biotransformation of oligonucleotide therapeutics, including ASOs, siRNAs, ligand-conjugated oligonucleotides, peptide conjugates, or related novel modalities.
Experience with Thermo Exploris, Q-Exactive or comparable high-resolution mass spectrometry platforms and metabolite identification software such as BioPharmaFinder, Promass HR or MassMetasite.
Experience with CYP inhibition/induction, drug transporters and other DDI assays.
Experience supporting IND, IB, CTD, NDA, or other regulatory submissions.
A record of scientific leadership demonstrated through presentations, publications, cross-functional program contributions, or external collaborations.

Responsibilities

Support the development and execution of DMPK strategies for discovery, IND-enabling, and clinical-stage programs, under the guidance of the Head of DMPK
Review data and study reports addressing plasma protein binding, CYP and transporter interactions, hepatocyte stability, mass balance and excretion, QWBA, blood partitioning, and metabolite identification.
Recommend fit for purpose approaches for characterizing the active component, ligand, linker, and relevant metabolites.
Provide technical input on DMPK risks, assay limitations, study priorities and follow-on work.
Execute hands-on development, optimization, qualification, and application of methods using LC-MS/MS, UHPLC-HRMS, ligand-binding, and hybrid assay formats.
Establish fit-for-purpose workflows for metabolite identification, metabolite profiling, semi-quantitation, and ultra-sensitive quantitation in relevant biological matrices.
Help build laboratory capabilities for analyzing peptide-conjugated ASOs and siRNAs, VHH-Fc or albumin-binding half-life extenders, TfR-targeted conjugates, and other systemic or CNS-directed constructs.
Contribute to continuous improvement of in-house DMPK capabilities, workflows, training, and scientific standards.
Provide technical leadership for CRO activities, including provider selection, scope of work, timelines, method development and transfer, qualification, critical-reagent planning, data review, and report completion.
Review CRO protocols, methods, data, reports, and deviations for scientific quality, completeness, consistency, and alignment with program objectives.
Identify risks early, resolve technical issues, and ensure that outsourced studies generate reliable and interpretable data.
Review, and contribute to method-development and validation plans, qualification and validation reports, sample-analysis plans, bioanalytical and DMPK study reports, investigator-brochure summaries, and relevant IND, IB, CTD, and NDA sections.
Support responses to technical questions from regulatory agencies and maintain documentation suitable for inspection and regulatory review.
Present data, conclusions, and recommendations to internal project teams, senior leadership, external collaborators, partners, and potential partners.