Principal Scientist / Associate Director of Drug Discovery
Stealth Startup, Boston, MA, United States
We are a seed stage biotech company focused on discovering modulators of the RNA lifecycle to address disease drivers previously considered undruggable.
We are seeking a motivated Principal Scientist / Associate Director of Drug Discovery with a background in induced proximity to lead and execute our small-molecule discovery efforts from hit validation through lead optimization. As one of our earliest scientific hires, you will work closely with the founders to translate novel RNA biology into developable chemical matter and help build a scalable discovery engine.
This role requires both independent development and execution of rigorous biophysical and biochemical experiments and management of a small team within an early-stage biotech environment. The successful candidate will combine strong experimental skills with the ability to communicate clearly and manage a small team of scientists across multiple disciplines to validate hits, guide SAR, and progress compounds through lead optimization.
This is a highly cross‑functional role requiring strong scientific judgment, hands‑on problem solving, and the ability to drive multiple programs forward in a fast‑moving startup environment. We were founded by academic leaders in RNA biology and are financed by The Column Group, based in Cambridge, Massachusetts.
Responsibilities
Lead multiple small molecule drug discovery from hit validation through lead optimization, including defining strategy, goals, timelines, and progression criteria
Design, build and execute an assay cascade (biophysical, biochemical, and cell-based) to support SAR, mechanism of action, selectivity and cellular target engagement
Provide day‑to‑day scientific leadership to both internal team and CRO partners, ensuring experimental rigor and clear scientific communication
Manage and mentor internal team
Drive external CRO execution, scope work, select vendors, oversee timelines and quality, and track budget
Contribute hands‑on experimentally, especially during assay build/validation and critical inflection‑point experiments
Qualifications
PhD in Biochemistry, Chemical Biology, Chemistry, or related field
5+ years of industry experience in small‑molecule drug discovery (biotech or pharma) with direct ownership of hit‑to‑lead and/or lead optimization activities
Demonstrated hands‑on experience developing and running biophysical, biochemical, and cell‑based assays to assay small molecule properties
Experience designing assay funnels to confirm target engagement, selectivity and mechanism
Experience leading a small team, with the ability to coach and drive execution
Experience coordinating CRO partners
Strong project leadership skills: setting priorities, managing ambiguity, and delivering against ambitious timelines
Strong ability to prioritize across multiple programs under resource constraints
Excellent written and verbal communication skills; ability to synthesize data into clear decisions and recommendations
Authorized to work in US
On‑site role, 5 days per week in Cambridge, MA
Preferred
Experience in early‑stage biotech environment(s)
Track record of publications or patents in small‑molecule drug discovery
Background in induced proximity (e.g., PROTACs, molecular glues)
Familiarity with medicinal chemistry concepts, SBDD/ligand efficiency metrics, and compound progression criteria
What we offer
Ground floor opportunity to shape a pioneering RNA‑targeting platform and discovery strategy
Highly collaborative, science‑driven culture with direct founder interaction
Direct impact on project strategy and company direction
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We are seeking a motivated Principal Scientist / Associate Director of Drug Discovery with a background in induced proximity to lead and execute our small-molecule discovery efforts from hit validation through lead optimization. As one of our earliest scientific hires, you will work closely with the founders to translate novel RNA biology into developable chemical matter and help build a scalable discovery engine.
This role requires both independent development and execution of rigorous biophysical and biochemical experiments and management of a small team within an early-stage biotech environment. The successful candidate will combine strong experimental skills with the ability to communicate clearly and manage a small team of scientists across multiple disciplines to validate hits, guide SAR, and progress compounds through lead optimization.
This is a highly cross‑functional role requiring strong scientific judgment, hands‑on problem solving, and the ability to drive multiple programs forward in a fast‑moving startup environment. We were founded by academic leaders in RNA biology and are financed by The Column Group, based in Cambridge, Massachusetts.
Responsibilities
Lead multiple small molecule drug discovery from hit validation through lead optimization, including defining strategy, goals, timelines, and progression criteria
Design, build and execute an assay cascade (biophysical, biochemical, and cell-based) to support SAR, mechanism of action, selectivity and cellular target engagement
Provide day‑to‑day scientific leadership to both internal team and CRO partners, ensuring experimental rigor and clear scientific communication
Manage and mentor internal team
Drive external CRO execution, scope work, select vendors, oversee timelines and quality, and track budget
Contribute hands‑on experimentally, especially during assay build/validation and critical inflection‑point experiments
Qualifications
PhD in Biochemistry, Chemical Biology, Chemistry, or related field
5+ years of industry experience in small‑molecule drug discovery (biotech or pharma) with direct ownership of hit‑to‑lead and/or lead optimization activities
Demonstrated hands‑on experience developing and running biophysical, biochemical, and cell‑based assays to assay small molecule properties
Experience designing assay funnels to confirm target engagement, selectivity and mechanism
Experience leading a small team, with the ability to coach and drive execution
Experience coordinating CRO partners
Strong project leadership skills: setting priorities, managing ambiguity, and delivering against ambitious timelines
Strong ability to prioritize across multiple programs under resource constraints
Excellent written and verbal communication skills; ability to synthesize data into clear decisions and recommendations
Authorized to work in US
On‑site role, 5 days per week in Cambridge, MA
Preferred
Experience in early‑stage biotech environment(s)
Track record of publications or patents in small‑molecule drug discovery
Background in induced proximity (e.g., PROTACs, molecular glues)
Familiarity with medicinal chemistry concepts, SBDD/ligand efficiency metrics, and compound progression criteria
What we offer
Ground floor opportunity to shape a pioneering RNA‑targeting platform and discovery strategy
Highly collaborative, science‑driven culture with direct founder interaction
Direct impact on project strategy and company direction
#J-18808-Ljbffr