Fractional Head of Chemistry (Bioinorganic Therapeutics)

Fractional Head of Chemistry (Bioinorganic Therapeutics)

Location: San Francisco Bay Area (Hybrid / Remote\-Flexible)
Role Type: Scientific Advisory (Phase 1\) → Fractional Head of Chemistry (Phase 2\)
Domain: Targeted Therapeutics \| Heterobifunctional Conjugates \| Bioinorganic Chemistry

About the Venture

We are a biotechnology startup based in the San Francisco Bay Area developing bioinorganic conjugates engineered to selectively inactivate our targets for treating aging\-related diseases.

Our founding team brings deep expertise in molecular biology, translational medicine, and early\-stage company building. We are seeking a Fractional Head of Chemistry to serve as our founding team member. This individual will bridge novel conjugate design, bioinorganic coordination chemistry, and hands\-on synthetic execution across global contract research organizations (CROs).

Progression Structure

Our lean pre\-seed strategy relies heavily on CROs for our operations. Because we expect a part time appointment will be sufficient for managing these external programs, we are structuring this partnership in two phases:

• Phase 1 (Pre\-Funding \- Strategic Advisor): Upon a successful mutual fit, we will onboard you immediately under an Advisor Agreement. In this phase, your commitment will be minimal (3\-5 hours/month), focused on strategy reviews and high\-level workflow alignment as we prepare for investor pitches. You will receive competitive equity for this role.
• Phase 2 (Post\-Funding \- Fractional Head of Chemistry): Immediately upon the closing of our pre\-seed round, the Advisor Agreement will terminate, and you will transition to the Fractional Head of Chemistry role (averaging 20 hours/week) for approximately one year. This phase will focus on active CRO management, IP generation, and establishing a strong working relationship, with the long\-term goal of exploring a full\-time transition as we scale.

Key Responsibilities

1\. Conjugate Architecture and Medicinal Chemistry Strategy

• Direct the Design\-Make\-Test\-Analyze (DMTA) cycle for novel heterobifunctional conjugates integrating homing moieties, linkers, and specialized coordination ligands.
• Establish Structure\-Activity Relationships (SAR) and Structure\-Property Relationships (SPR) balancing target binding affinity, linker integrity, and complex stability.
• Drive multi\-parameter optimization (MPO) for parenteral (IV/SC) administration, mitigating liabilities such as non\-specific systemic reactivity, transchelation/metal stripping by serum proteins, metabolic cleavage, and self\-aggregation.

2\. CRO Operations

• Architect and oversee an outsourced synthetic chemistry footprint across premier global CROs.
• Direct multi\-step organic synthesis of complex ligands, bioconjugation steps, metallation protocols, and the handling/purification of polar, charged, or zwitterionic molecular entities.
• Review raw analytical data (NMR, HRMS, LC\-MS, ICP\-MS) and troubleshoot synthetic bottlenecks, protecting\-group compatibilities, and challenging purification profiles (preparative RP\-HPLC, ion exchange).
• Establish rigorous quality control standards for conjugate purity, identity, counter\-ion control, and speciation stability.

3\. IP and Commercial Leadership

• Partner with the CEO and premier patent counsel to evaluate and expand our Invention Disclosure Forms (IDFs), ensuring robust synthetic enablement, defensible Markush structures, and long\-term Freedom to Operate (FTO).
• Act as the chemical design authority in investor meetings, partnering discussions, and Scientific Advisory Board (SAB) presentations.

Required Qualifications (Must\-Have)

• Education: Ph.D. in Synthetic Organic Chemistry, Bioinorganic Chemistry, Medicinal Chemistry, or a closely related discipline.
• Domain Track Record: 4\+ years of biotech or pharmaceutical industry experience working with metal\-chelating small molecules or conjugates (e.g., heterobifunctional molecules, radiopharmaceuticals/theranostics, bifunctional chelators \[BFCs], or metallodrugs).
• Bioinorganic Fluency: Strong practical understanding of metal chelation and coordination chemistry, including ligand field dynamics, metal complexation kinetics, thermodynamic stability vs. kinetic inertness, and serum stability challenges.
• CRO Management: Proven track record of architecting, contracting, and driving synthetic chemistry CROs through challenging multi\-step organic syntheses, route scouting, and compound delivery.
• IP Cleanliness: Fully unencumbered by restrictive IP assignments, non\-competes, or institutional conflicts of interest at the start of Phase 2 (paid executive role).

Preferred Qualifications

• Hands\-on familiarity with biophysical and analytical methods used to study metal\-ligand speciation and coordination stability in biological matrices (e.g., ICP\-MS, LC\-MS, spectroscopic assays).
• Practical experience formulating and optimizing conjugate solubility and stability for parenteral (IV/SC) delivery.
• Startup agility: Prior experience as a founder, consultant, or early scientific employee in a seed\- or Series A–stage virtual biotech.
• IP cleanliness unencumbered starting in Phase 1 (Advisory).

What We Offer

• Founding Equity: Substantial early\-stage equity grant reflecting founding\-tier contribution, transitioning to competitive cash \+ equity upon closing financing.
• Scientific Ownership: Complete technical leadership over a brand\-new therapeutic modality targeting critical unmet medical needs.
• Leadership Opportunity: The potential to help shape our long\-term chemistry strategy and explore a permanent executive role as company operations and pipeline programs expand.

How to Apply

Please submit your CV along with a brief cover letter (under 300 words) summarizing:

• Your experience managing multi\-step organic synthesis and conjugate assembly at external CROs.
• Your background with metal\-coordinating ligands, heterobifunctional conjugates, radiopharmaceuticals, or bioinorganic chemistry.
• Confirmation of your IP cleanliness / freedom to advise.

Pay: $6,000\.00 per month

Application Question(s):

• What is the maximum coordination denticity of an unmodified, fully deprotonated DOTA ligand toward a trivalent metal ion?
• Do you or will you in the future require sponsorship for US work authorization?

Education:

• Doctorate (Required)

Experience:

• metal chelation, industry: 4 years (Required)

Work Location: Remote