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Principal Scientist, Pharmacology

4D Molecular Therapeutics

4D Molecular Therapeutics

Emeryville, CA, USA
Posted on Saturday, February 10, 2024

At 4D Molecular Therapeutics, Inc. (“4DMT”), we boldly innovate to unlock the full potential of genetic medicines for countless patients. We are committed to breaking boundaries and daring to cure as we develop new and foundational products and product components through our growing technology platforms.

4DMT is a clinical-stage biotherapeutics company harnessing the power of directed evolution for targeted genetic medicines. We seek to unlock the full potential of gene therapy using our platform, Therapeutic Vector Evolution (TVE), which combines the power of directed evolution with our approximately one billion synthetic AAV capsid-derived sequences to invent evolved vectors for use in our products. We believe key features of our targeted and evolved vectors will help us create targeted product candidates with improved therapeutic profiles. These profiles will allow us to treat a broad range of large market diseases, unlike most current genetic medicines that generally focus on rare or small market diseases.

We have built a deep portfolio of AVV-based gene therapy product candidates, with five product candidates in clinical trials: 4D-150 for the treatment of wet age-related macular degeneration (wet AMD) and diabetic macular edema (DME), 4D-710 for the treatment of cystic fibrosis lung disease, 4D-310 for the treatment of Fabry disease cardiomyopathy, 4D-125 for the treatment of X-linked retinitis pigmentosa (XLRP), and 4D-110 for the treatment of choroideremia. In addition, we have two product candidates in preclinical studies: 4D-175 for geographic atrophy (GA) and 4D-725 for alpha-1 antitrypsin deficiency.

To-date, we have demonstrated clinical proof-of-concept for three evolved vectors in three therapeutic areas and routes of administration with five products and patient populations. We believe this validates the power of our directed evolution platform for discovering superior vectors compared to wildtype viral vectors. We have built a robust and efficient product engine with 6 open Investigational New Drug Applications (INDs) in the U.S., 1 IND in Taiwan, and 1 Clinical Trial Approval (CTA) in Australia. We believe we are positioned to create, develop, manufacture and, if approved, effectively commercialize targeted genetic medicines that could transform the lives of patients suffering from debilitating diseases.

In addition to TVE, our technology includes a robust AAV manufacturing platform and onsite manufacturing facility that allows us to rapidly produce and test research grade material and scale up to GMP clinical material. This internal capability and close collaboration between our R&D and Manufacturing teams has greatly accelerated the pace of discovery at 4DMT.

Company Differentiators:

• Fully integrated clinical-phase company with internal manufacturing
• Demonstrated ability to move rapidly from idea to IND
• Five candidate products in the clinic and two declared pre-clinical programs
• Robust technology and IP foundation, including our TVE and manufacturing platforms
• Initial product safety and efficacy data substantiates the value of our platforms
• Opportunities to expand to other indications and modalities within genetic medicine


The Senior Scientist Pharmacology role will be in the Biomarkers & Immunology group. The group performs pharmacokinetic (PK) evaluations, pharmacodynamic (PD) biomarker measurements, immunogenicity risk assessments, and exploratory clinical research during AAV product development. Our responsibilities include both in-depth data analysis and bioanalytical method development. Methods are rigorously validated at CROs to characterize their performance and ensure that high-quality data are generated. Working closely with multiple cross-functional stakeholders, such as Clinical Sciences, Pharmtox, Clinical Operations, Technology Innovation, and Project Management, our data deliverables and analyses have significant impact on key program decisions.

This role will report to the Senior Director of Biomarkers & Immunology and be part of a talented, motivated, and creative team of scientists who are critical for the success of 4DMT’s mission and development of our deep portfolio of targeted genetic medicines. A flexible hybrid work schedule can be accommodated when analyzing data, working on cross-functional teams, and remotely managing partner organizations.


  • Representing Biomarkers & Immunology function on cross-functional teams
  • Leading subteams responsible for analysis of PK, PD biomarkers, immunogenicity, and molecular endpoints in investigational AAV therapeutics programs
  • Utilizing appropriate scientific approaches to understand characteristics of AAV vector-mediated gene expression and transgenic protein function
  • Collaborating with bioanalytical teams to forecast analytical requirements for projects and assess suitable method performance
  • Leveraging a strong understanding of bioanalytical assays to analyze and interpret data to drive key decisions in AAV product development, e.g., FIH dose selection
  • Leading design, execution, and analysis of PK/PD, biodistribution, metabolism, germline transmission, and shedding studies in AAV therapeutics programs
  • Assessing potential impact from immunogenicity of therapeutic candidates on PK, PD biomarkers, and clinical efficacy or safety endpoints
  • Applying quantitative skills to support model-based drug development and address complex issues via modeling and simulation, e.g. candidate selection, dose optimization
  • Contributing to the design and implementation of non-clinical and clinical studies, including IND-enabling studies
  • Designing experiments, analyzing data using next-gen analytical techniques, and presenting data to line management, study teams, and regulatory agencies
  • Effectively mentoring junior level staff and acting as a resource for scientific expertise
  • Support the preparation of content for regulatory interactions and submissions (e.g. pre-IND Briefing Books, IND filings, Orphan Drug Designation, EMA submissions)
  • Maintaining current awareness of scientific literature and regulatory guidance
  • Writing and reviewing technical documents, study protocols and reports, manuscripts and presenting results at scientific meetings
  • Maintaining compliance with company Environmental Health and Safety policies, procedures, and practices
  • Contributing to building a culture that embraces continuous learning, improvement, and innovation and encourages team members to expand their skill base and deepen their gene therapy expertise.


Education & Experience:

  • Ph.D. in pharmacology, pharmaceutics, pharmacokinetics and metabolism, pharmacometrics, biomedical engineering, computational biology, or related field
  • 7+ years of industry experience with relevant pharmaceutical development experience
  • Independent scientist with strong background in ADME and/or clinical pharmacology
  • Strong scientific acumen as demonstrated by first or last author publications in peer-reviewed scientific journals and ability to work in a matrixed environment
  • Previous experience in cross-functional teams and work in a scientific or clinical setting supporting drug development.
  • Experience with AAV therapeutics development is preferred


  • Successfully demonstrated ability to conduct research with strong attention to detail and rigorously analyze and interpret PK/PD, biomarker, and immunogenicity data
  • Sound knowledge of DMPK and PK/PD analysis principles; experience in PK/PD modeling and simulation is highly desirable
  • Proficiency in common pharmacometrics software, such as Phoenix WinNonlin/NLME, NONMEM, Watson, MONOLIX, WinBUGS, STAN, Matalab, R or S+.
  • Working knowledge of FDA, EMA, and ICH guidances relevant for AAV therapeutics development, immunogenicity assessments, and bioanalytical methods
  • Ability to multi-task and support more than one project simultaneously
  • Highly organized and motivated; self-starter with strong analytical and problem-solving skills
  • Strong work ethic, flexibility, and cooperative can-do attitude
  • Ability to work in a team-based environment; supportive of multiple viewpoints and approaches
  • Strong communication skills (both written and oral) with demonstrated ability to present ideas, information and data effectively via one-on-one discussions, team meetings, and external partnership interactions
  • Understanding and knowledge of key scientific software programs (including Microsoft Office, JMP or Prism, Adobe Photoshop).

Base salary compensation range: $ 156,000/yr - $186,000/yr

4DMT provides equal employment opportunities to all employees and applicants for employment without regard to race, color, religion, gender, sexual orientation, national origin, age, disability, genetic information, marital status, status as a covered veteran, and any other category protected under applicable federal, state, provincial and local laws.
Equal Opportunity Employer/Protected Veterans/Individuals with Disabilities