Nurix Therapeutics is a biopharmaceutical company focused on the discovery, development and commercialization of small molecule therapies designed to modulate cellular protein levels as a novel treatment approach for cancer and immune disorders. Leveraging Nurix’s extensive expertise in E3 ligases together with its proprietary DNA-encoded libraries, Nurix has built DELigase, an integrated discovery platform to identify and advance novel drug candidates targeting E3 ligases, a broad class of enzymes that can modulate proteins within the cell. Nurix’s drug discovery approach is to either harness or inhibit the natural function of E3 ligases within the ubiquitin proteasome system to selectively decrease or increase cellular protein levels.
Nurix’s wholly owned pipeline comprises targeted protein degraders of Bruton’s tyrosine kinase, a B-cell signaling protein, and inhibitors of Casitas B-lineage lymphoma proto-oncogene-B, an E3 ligase that regulates T cell activation. Nurix is headquartered in San Francisco, California.
Nurix is currently seeking a Scientist/Senior Scientist, DMPK with expertise in drug discovery and early development. You will use your expertise to design and execute in vivo/in vitro studies to elucidate the absorption, distribution, metabolism, excretion (ADME) properties of our small molecule targeted protein degrader drug candidates. Working closely with Medicinal Chemistry, the successful candidate will integrate physicochemical properties, in vitro, and in vivo data, to inform structure activity relationships to enable compound design in early project research and translate data to predictions of clinical PK. You will be a key DMPK contributor, guiding and implementing strategies throughout the life cycle of CTM research optimization and development. You will be a key team member for identifying and advancing small molecule lead drug candidates in collaboration with colleagues in Medicinal Chemistry, Bioanalytical, Safety Assessment, Biology, Translational and Development Sciences. As part of this multi-disciplinary team, you will also be responsible for providing DDI support for Clinical Development.
- Guide project teams to characterize, select, and advance small molecule protein degraders with optimal ADME properties through the design and integration of in vitro and preclinical PK data.
- Designing and performing mechanistic studies to understand major clearance mechanisms in preclinical species and humans.
- Hands on experience in performing in vitro ADME metabolic stability assays in various subcellular and cellular fractions. This includes, microsomal and S9 preparations from various tissues, hepatocytes and co-culture systems to support medicinal chemistry in drug design and SAR.
- Provide metabolism and drug-drug interaction subject matter expertise for discovery teams.
- Identify and employ new technologies and strategies that address current and future ADME challenges.
- Manage the execution and quality of experiments and studies at external laboratories; review and evaluate protocols, results, and reports prior to reporting internally.
- Manage high quality routine inhouse in vitro ADME studies as well as establish new assays to support drug candidate selection in a fast-paced environment, while managing multiple projects and various timelines.
- Developing methodologies to profile and detect metabolites in biological matrices, including plasma, urine, feces, and bile from in vivo studies (preclinical and clinical).
- Deliver high quality preclinical and clinical biotransformation data and reports to support regulatory submissions.
- Address questions related to metabolism and DDI by designing experiments that help in understanding the mechanisms of biotransformation and formation of metabolites.
- Perform enzymology studies, including CYP and non-CYP phenotyping and assessing their contribution in the catalysis for metabolite formation, determination of kinetic parameters including KM, Vmax, Ki and possible implications to drug-drug interactions.
- Partner with the clinical pharmacology team to design clinical drug-interaction and other Phase 1 studies, as required, and serve as a subject matter expert in composing responses to regulatory queries.
- Familiar with regulatory guidance related to metabolism and DDI and ability to address MIST issues that arise during a development of a candidate.
- Write nonclinical sections of regulatory (IND/CTA) filings and IB updates.
Preferred Qualifications & Experience
- Minimum of 4 years related experience (PhD), or a minimum of 10 years related experience (MS), or a minimum of 12 years related experience (BA/BS) in an industry setting
- Prior experience in designing and executing hypothesis driven assays to address specific mechanistic ADME-related questions.
- Experience performing and interpreting high quality ADME in vitro studies and designing novel, hypothesis-driven ADME experiments for small molecules, including but not limited to metabolic stability, permeability, protein binding, enzyme induction/inhibition, transporter assays and drug interaction assessments.
- Experience investigating the fate of molecules in the beyond rule-of-5 (bro5) property space is highly desirable.
- Experience working within a discovery-driven pharmaceutical company, excellent critical thinking, with proven scientific expertise in small molecule metabolism and pharmacokinetics
- Strong technical understanding of DMPK principles and in vitro ADME assay design and translation to in vivo findings.
- Experience designing and executing in vitro ADME assays using cells, subcellular fractions and other biological matrices (e.g. plasma, blood)
- Strong interpersonal, communication, problem solving and collaborative qualities to deliver high quality results in a fast-paced environment.
- Be self-driven and enthusiastic with the ability to thrive in a dynamic environment.
- Prior experience in drug discovery and development functions (e.g., Nonclinical or Clinical) is desired
- Prior experience managing third parties and external service providers (worldwide) and consultants is preferred.
- Excellent writing skills as they relate to preparation of regulatory documents and reports are required.
- Knowledge of biotransformation, biochemistry of drug metabolizing enzymes and transporters and basic concepts of pharmacokinetics as they apply to discovery setting is essential.
- Ability to identify the need for clinical drug-interaction studies based on fundamental understanding of metabolic and transporter-based drug interactions.
Fit with Nurix Culture and Values
- Strong team orientation; highly collaborative
- Solutions and results-oriented focus
- Hands-on approach; resourceful and open to diverse points of view
Nurix is an Equal Opportunity Employer offering a competitive salary and benefits package. Applicants should be legally entitled to work for any employer in the US.
Note to Employment Agencies: Please do not forward any agency resumes. Nurix will not be responsible for fees related to unsolicited resumes.