Role Description The Scientific Director, Neuro-therapeutics will serve essentially as the early Compound Development Team Leader (eCDTL) for VRI’s second therapeutic program. In this capacity, you will convene and lead a cross-functional team of internal and external experts — spanning bioinformatics, therapeutic design, in vitro biology, in vivo pharmacology, manufacturing, and regulatory affairs — and be accountable for driving the program forward across all of those disciplines simultaneously. This role reports to the Chief Scientific Officer and works in close coordination with VRI’s Executive Director and program leads. What You'll Own - Scientific Strategy & Target Selection - Lead target identification and sequence prioritization for VRI’s therapeutic program, including known causative genes and emerging targets relevant to the disease biology. - Determine therapeutic modality — ASO vs. siRNA, backbone chemistry, modification strategy — with scientific rationale grounded in both biology and practical development considerations. - Evaluate sequence candidates, apply scoring frameworks, and converge on lead molecules most likely to succeed in CNS delivery. - Define Plan B and Plan C candidate strategies to ensure program progress is never contingent on a single compound. - Translate target biology insights into actionable design criteria for the synthesis and screening pipeline. - Oligonucleotide Design & Candidate Advancement - Provide scientific direction for ASO and siRNA design, guiding vendor partners and internal scientists on backbone chemistry, modification strategy, and design tradeoffs. - Lead design reviews, evaluate screening data, and make candidate advancement and termination decisions in coordination with the CSO. - Assess in vitro and in vivo datasets against advancement criteria, identifying signal from noise and recommending next steps. - Stay current on the relevant oligonucleotide literature and competitive landscape, flagging findings that should influence VRI’s strategy. - In Vitro & In Vivo Oversight - Define the scientific questions that in vitro campaigns must answer, including cell-based assays, disease-relevant neuronal models, and functional readouts appropriate to the target biology. - Evaluate in vivo study designs for scientific rigor and IND-relevance; interpret results in context of regulatory requirements. - Provide scientific oversight to external labs and CROs on study design and endpoint validity. - Manufacturing Oversight - Oversee manufacturing of ASO and siRNA candidates, ensuring designs meet research-scale synthesis requirements and can be scaled appropriately toward GMP production. - Bring CMC awareness to program planning, anticipating manufacturing constraints that could affect IND timelines. - Regulatory & IND Scientific Input - Own the scientific content of the IND package: nonclinical study rationale, pharmacology and toxicology summaries, and the scientific narrative that ties target biology to clinical hypothesis. - Make or delegate all scientific judgment calls required for IND sections; what data is sufficient, what gaps require additional studies, and what the FDA will scrutinize on the nonclinical side. - Ensure all nonclinical studies are designed and executed in alignment with IND-enabling standards and FDA expectations for rare disease therapeutics. - Engage with expedited regulatory pathways (Fast Track, Orphan Drug, Expanded Access) as appropriate, and maintain contingency pathway awareness across alternative jurisdictions. Qualifications - Advanced degree (PhD or equivalent) in medicinal chemistry, biochemistry, molecular biology, or a related field. - Direct involvement in oligonucleotide drug development like ASOs, siRNAs, or closely related modalities. - Expertise with oligonucleotide modalities including gapmers, SSOs, siRNA, and saRNA. - Demonstrated experience leading or coordinating cross-functional drug development work, including managing external partners toward shared milestones. Requirements - Direct involvement in IND-enabling programs. - CNS delivery expertise: intrathecal delivery, CNS tissue distribution, and the design implications of targeting the central nervous system with oligonucleotides. - Experience with disease-relevant in vivo models and familiarity with what meaningful efficacy readouts look like in the context of CNS neurodegeneration. - Computational fluency: comfort using bioinformatics tools and sequence design platforms as a normal part of scientific work. - Experience with expedited regulatory pathways (Fast Track, Orphan Drug, Expanded Access) in a rare disease context. Benefits - Competitive compensation based upon experience, qualifications, and role scope. - Full suite of benefits.

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