Scientific Director, Neuro-therapeutics

Job Description

Job Description

About Violet Research Institute

Violet Research Institute (VRI) is building the future of personalized medicine for patients with genetic diseases. We're at the frontier of a new era in medicine — one where treatments can be designed for individual patients based on their unique biology. Recent breakthroughs in science, engineering, and regulatory pathways have made this possible, but much of this work remains nascent and distributed across disparate efforts globally. We're unifying, refining, and scaling these efforts into a cohesive platform. For each patient we serve, we deeply understand their biology, then design and manufacture a targeted treatment that can be delivered in months instead of years.

We combine the urgency and execution mindset of a startup with the mission-driven openness of a nonprofit, allowing us to collaborate broadly and move quickly on behalf of the patients we serve. We've brought together leading researchers, engineers, and organizations across omics, therapeutic design, manufacturing, clinical care, and AI to move from insight to action as quickly as possible.

VRI is founded by the family of our first patient, Violet, and is led by Michael Buckley, Siranush Babakhanova and Steve Turner. Our team is deeply cross-disciplinary and first-principles driven. We value builders, experts, and generalists who are excited to work across domains, challenge conventional approaches, and increase access to personalized medicine.

Location: Remote (travel required — SF Bay Area, San Diego, East Coast)

Compensation: $175k to $250k, depending on experience

Employment Type: Full-Time, Exempt

Reports to: Chief Scientific Officer

VRI built its first therapeutic program for Violet, our founding patient, a child with SYT1 Neurodevelopmental Disorder. We went from a family genetic diagnosis to human-dose manufacturing launch in three months. That program now has a pre-IND under FDA review, parallel regulatory paths in the UAE and Europe, a 300+ candidate ASO screening campaign with lead candidates in rat toxicology, and human-dose manufacturing underway.

Our second patient needs treatment for a rare neurological disease. This role exists to build that program from the ground up and to own it completely.

There is no existing pipeline for this program at VRI. There is, however, a proven organizational model for doing this kind of work at extraordinary speed, a scientific leadership team with deep oligonucleotide and CNS expertise, and a patient who cannot wait for a conventional drug development timeline.

The organizational model that built our first program — founder-driven, network-heavy, parallel-everything — now has a second program to run. What it needs is a single person who owns the scientific and therapeutic strategy: from the earliest bioinformatics work to identify disease-relevant sequences and targets, through lead optimization, IND-enabling studies, and first patient dosing.

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.

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

The non-negotiable core of this role is oligonucleotide fluency. Everything else can be grown into or supplemented by VRI's scientific team and advisor network. What cannot be taught on the job is a genuine working understanding of ASO and siRNA biology, chemistry, and development. That is the foundation everything else is built on.

Must Have

• 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. You understand the chemistry (backbone modifications, 2'-MOE, LNA, PS), the biology (RNase H, RISC, off-target risks), and the practical realities of moving these molecules through a development pipeline. You do not need to have been the only person on a program, but you need to have been close enough to the work to have an informed opinion on it
• 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

Should Have Most Of

• Direct involvement in IND-enabling programs: you know what a CMC section requires, what rat tox study reports contain, and what FDA expects at the pre-IND stage
• 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

Preferred

• Background from organizations with strong oligonucleotide platforms, particularly those with CNS program experience
• Prior experience serving as a scientific lead or Compound Development Team Leader (CDTL) in an integrative program role
• Experience working on or managing rare disease programs
• Experience working with patient foundations or advocacy organizations where family urgency creates non-negotiable deadlines

Behavioral Essentials

• Execute independently from loosely specified tasks — you are self-directing, not waiting for a detailed brief
• Ask for help only when truly blocked, communicating clearly what is needed and what you have already tried
• Thrive in early-stage, ambiguous, high-pace environments where the path is built as you walk it
• Mission-driven with genuine, active care for patient impact (a daily operating principle at VRI)

At VRI we genuinely embrace AI at every step of the process. Claude and other AI tools are used throughout the day, across every function. Computational fluency and comfort with AI-assisted analysis and literature synthesis are expected. If you treat AI as a novelty or an occasional aid, this is not the right environment.

If you have spent your career at large pharma managing one workstream within a 200-person program team, this will overwhelm you.

If you have been the person at a lean biotech or nonprofit who built the screening cascade, picked the lead series, and stood in front of the FDA at a pre-IND meeting and defended the nonclinical package, then you already know what this job is.

The difference here is that you won't have a team of functional experts handing you analysis. You will be generating the scientific strategy, stress-testing it yourself, and rebuilding it when the data says you're wrong. The target biology work, the vendor network, the screening campaign, the regulatory strategy.

That is either energizing or terrifying, and your honest reaction to that sentence is probably the best signal of whether this is the right role.

We are looking to hire immediately and are moving quickly. Our anticipated process can take as little as 5 days: Apply → Initial Recruiter Call → Hiring Manager Interview → Technical Stakeholder Interview → Executive Director Interview → Offer.

VRI provides competitive compensation based upon experience, qualifications, and role scope. We also offer a full suite of benefits.