Head of Chemistry (Medicinal and Computational) Job at Twicefold Bio, United States

  • Twicefold Bio
  • United States

Job Description

Head of Chemistry (Medicinal and Computational)

Location: San Francisco Bay Area (Hybrid / Remote-Flexible)

Role Type: Scientific Advisory (Phase 1) → Head of Chemistry (Phase 2)

About the Venture

We are a biotechnology startup based in the San Francisco Bay Area developing small molecules 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 Head of Chemistry to serve as our founding team member.

Progression Structure

We are structuring this engagement in two phases:

  • Phase 1 (Pre-Funding - Scientific 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 - Head of Chemistry): Upon closing of our funding round, transition into a full-time compensated role (Head of Chemistry) with competitive base salary and equity stake.

Key Responsibilities

1. In Silico Design

  • Lead the Design-Make-Test-Analyze (DMTA) cycle, designing novel chemical matter with optimal potency, selectivity, and drug-like properties (ADMET/PK).
  • Formulate clear Structure-Activity Relationships (SAR) and Structure-Property Relationships (SPR) using structure-based and ligand-based drug design (SBDD/LBDD).
  • Implement advanced computational workflows to accelerate hit identification and lead optimization.

2. CRO Operations

  • Architect and oversee an outsourced synthetic chemistry footprint across premier global CROs.
  • Direct multi-step organic synthesis.
  • Review raw analytical data (NMR, HRMS, LC-MS, ICP-MS) and troubleshoot synthetic bottlenecks.
  • Establish rigorous quality control standards.

3. Conjugate Architecture and Medicinal Chemistry Strategy

  • Direct the Design-Make-Test-Analyze (DMTA) cycle for novel heterobifunctional conjugates.
  • Establish Structure-Activity Relationships (SAR) and Structure-Property Relationships (SPR).

4. IP and Commercial Leadership

  • Partner with the CEO and 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, Medicinal Chemistry, or a closely related discipline.
  • Domain Track Record: 8+ years of biotech or pharmaceutical industry experience.
  • CRO Management: Proven track record of architecting, contracting, and driving synthetic chemistry CROs through challenging multi-step organic syntheses, route scouting, and compound delivery.
  • Python proficiency: Advanced Ability to build custom pipelines using Python.
  • Practical experience running Molecular Dynamics (MD) simulations (e.g., GROMACS, Desmond, AMBER, OpenMM) to evaluate target-ligand binding kinetics, cryptic pockets, conformational flexibility, or other relevant applications.
  • IP Cleanliness: Fully unencumbered by restrictive IP assignments, non-competes, or institutional conflicts of interest at the start of Phase 2 (paid role).

Preferred Qualifications

  • Prior experience as a founder, consultant, or early scientific employee in a Seed- or Series A-stage biotech.
  • IP cleanliness unencumbered starting in Phase 1 (Advisory).
  • Experience working with heterobifunctional molecules.
  • Experience with Density Functional Theory (DFT) or quantum mechanical calculations.

How to Apply

Please submit your CV along with a brief cover letter (under 300 words) summarizing, at a minimum, the items below. Since there is no field available on the application for the cover letter, please include it as the first page of your CV.

  • Your approach for sourcing and managing external CROs and their multi-step organic synthesis.
  • Affirmation of previous CRO management experience and Python proficiency.
  • Confirmation of your IP cleanliness / freedom to advise.

Job Tags

Full time, Immediate start, Remote work, Flexible hours

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