AVROBIO, Inc. is seeking a full time Principal Research Scientist/Associate Director of Toxicology to join the Research & Development team, accountable for timely and effective drug safety support for selected programs in preclinical or clinical development.

The incumbent is expected to demonstrate competency in interpreting preclinical and toxicology data, development and implementation of strategic plans for pre/nonclinical development, as well as providing expertise and guidance in Regulatory Toxicology to project/program teams.

This individual will be highly analytical, decisive, goal-oriented, and timeline sensitive while maintaining the highest of scientific and ethical standards. The Principal Res Scientist Assoc/Director of Toxicology will actively participate on project/program/product teams, as well as collaborating with Early Development/POC initiatives and may assist in the identification and review of new business initiatives and in-licensing opportunities.

The incumbent will adhere to established processes, policies, and quality systems for outsourcing, managing and reporting regulatory toxicology programs, studies, and other activities in support of AVROBIO portfolio programs and to provide appropriate content and submission-ready documentation for the nonclinical development sections of regulatory submissions.

Reporting To: Director, Preclinical Development (PCD)
Work Location: Cambridge, MA
Function (Corp, SP, HGT, RM); Research & Development
Department: PCD
Job Level: Principal Res Scientist/Assoc Director

Responsibilities

• Timely and resource-efficient execution of selected pre/nonclinical projects supporting ex vivo gene therapy for rare diseases to generate IND filing efficacy and safety data, including collaboration with internal R&D and third parties (academic PIs, regulatory consultants). Generate, review, and approve Toxicology/Biodistribution study protocols, reports, associated nonclinical summaries, Regulatory submission sections and associated documentation, as well as abstracts/manuscripts for publication.
• Provide guidance and support to project/program/product teams and PCD management, including evaluation of conclusions and potential impact of study results on program and clinical/regulatory strategy.
• Design, manage, analyze, review, summarize, interpret and report results of pre/nonclinical studies, including Toxicology and Biodistribution studies.
• Maintain up-to-date Toxicology plans (linked to overall R&D plans) for selected projects/programs/products, including listings of studies, timelines, status and costs; update and refine as necessary.
• Provide scientific/technical due diligence support for Business Development activities as required.
• Prepare for and participate in regulatory agency interactions.

Qualifications:

• Established track record in gene therapy, ideally ex vivo gene therapy
• PhD in Toxicology, or in a related subject, with DABT certification preferred.
• 7+ (PhD) years industry-related experience in regulatory Toxicology working within the pharmaceutical or biotechnology industry.
• Hands-on experience in all aspects of Toxicology study conduct including general, genetic, developmental and reproductive toxicology, carcinogenicity, toxicokinetics, safety pharmacology, and environmental risk assessment experience.
• Experience representing function to global regulatory agencies in support of submissions at all stages of development, i.e., IND/CTA, CTD, IMPD, MAA/NDA/BLA/JNDA.
• Demonstrated knowledge of global regulatory requirements and expectations for nonclinical safety assessment packages to support first in human, clinical development, and product registration, including thorough knowledge of GLP, ICH and other applicable global guidelines.
• Extensive experience in the outsourcing and external oversight of nonclinical Toxicology studies conducted by qualified contract research organizations (CROs).
• Extensive experience with mice models, ideally NOD-SCID mice
• Experience in providing formal scientific/technical due diligence support for Business Development activities is desirable.
• Fluency in written and spoken English is required.

Key Skills, Abilities, and Competencies

• A broad understanding of the drug development process (in particular, large molecule, but ideally gene therapy) and the ability to provide expert guidance in designing and implementing nonclinical Toxicology/Biodistribution studies and development programs for ex vivo lentiviral-based human hematopoietic (HSC)-based gene therapies
• Demonstrated knowledge of global regulatory requirements and expectations for Toxicology/nonclinical safety packages to support FIH, clinical development, and product registration, including thorough knowledge of GLP, ICH and other applicable global guidelines.
• Capable of Toxicology report preparation, presentation of data, and serving as internal representative for nonclinical development/safety issues on Development Teams and to US and global regulatory agencies.
• Proficient in analysis and interpretation of nonclinical Toxicology and nonclinical data (pharmacology, PK/ADME) with overall responsibility to ensure that sufficient preclinical safety data and knowledge exist to underwrite safe and effective human administration.
• Understanding of nonclinical comparability studies to support formulation and/or manufacturing changes of drug substance/product as well as bioanalytical and/or method (assay) development and/or qualification/validation.
• Ability to manage scientific issues, provide strategic direction to development activities, and ensure that schedules are maintained for conduct of pre/nonclinical studies to meet regulatory requirements.
• Must be motivated, creative, energetic, resourceful and adaptable, responding constructively to challenging new ideas, information, situations, or criticism.
• Comfortable and effective within a team environment as a member and/or leader with strong organizational and interpersonal skills, including exceptional oral and written communication skills with a demonstrated ability to write protocols, nonclinical/clinical study reports and scientific peer-reviewed publications.
• Ability to influence through effective communication, respectful challenge, and persuasion across the R&D organization is essential.
• Ability to effectively represent the Company to key external stakeholders, in particular, the ability to effectively engage and present to staff at all levels, including senior management, clearly and at the appropriate level of detail in representing nonclinical strategy and findings.
• Ability to effectively engage with a wide variety of internal/external technical and business experts

Complexity and Problem Solving

• Sharp and objective intellect with facility in balancing big picture thinking with fine detail level analysis.
• Utilize collaborative work style, real-time communication, demonstrate accountability and trust within and across departments.
• Independently develop strategies for nonclinical plans for drug development, and obtain line alignment and approval. Notify line management of significant deviations from plan (costs, timelines, strategic direction).
• Ability to rapidly assimilate/synthesize data and information from diverse sources, assess complex/abstract problems and develop innovative solutions as necessary.
• Demonstrated ability in problem solving as applied to drug development.
• Demonstrate and cultivate comprehensive cross-functional and industry perspective, judgement and ability to apply understanding to individual projects and programs.

About AVROBIO, Inc.

AVROBIO, Inc., a leader in lentiviral-based gene therapies, is a clinical stage company developing disruptive therapies that have the potential to transform patients’ lives in a single dose. The Company is focused on the development of its Phase I programs in Fabry disease and pre-Phase 1/2 program in Gaucher disease, while actively building a pipeline of gene therapies to treat Pompe disease and other rare and non-rare genetic diseases. AVROBIO is headquartered in Cambridge, MA and has offices in Toronto, ON.