* Fulcrum requires all employees to be fully vaccinated against COVID-19. This requirement is a condition of employment at Fulcrum, and it applies regardless of whether or not the position is located onsite at Fulcrum’s headquarters in Cambridge, MA. If you are unable to receive the vaccine due to a serious medical condition, or because it is prohibited as a result of your sincerely held religious beliefs, you will have an opportunity to request a reasonable accommodation.

Company Overview

Fulcrum Therapeutics is a clinical-stage biopharmaceutical company focused on improving the lives of patients with genetically defined rare diseases in areas of high unmet medical need. Fulcrum’s two lead programs in clinical development are losmapimod, a small molecule for the treatment of facioscapulohumeral muscular dystrophy (FSHD) and FTX-6058, a small molecule designed to increase expression of fetal hemoglobin for the treatment of sickle cell disease and other hemoglobinopathies, including beta-thalassemia. The company’s proprietary product engine, FulcrumSeek^TM, identifies drug targets that can modulate gene expression to treat the known root cause of gene mis-expression.

Description

Reporting to our Chief Scientific Officer, The Director and Head of Medicinal Chemistry will be a highly driven scientific leader who is dedicated to transforming novel target biology into innovative first-in-class medicines. They are a dedicated drug hunter and will be responsible for the design, synthesis, and optimization of small-molecule drug candidates, from hit identification through Development Candidate selection. In this strategic role, the successful candidate will engage with colleagues in FulcrumSeek™ and in exploratory biology, and will drive insights in novel target biology to transformative new medicines. Specifically, this individual will optimize small molecule “hits” by identifying structure-activity relationships and thereby design novel chemical entities optimized for potency, selectivity, pharmacokinetics, in vivo efficacy, and overall pharmaceutical properties. You will collaborate with a dynamic multi-disciplinary team of biologists and pharmacologists, and you will also manage and lead a large team of synthetic chemists at our external CROs. As our Head of Medicinal Chemistry, you will have collaborative engagement with the external scientific community, routinely present to our Executive Team, and make direct contributions to Fulcrum’s external reputation.

Responsibilities

”Own” the medicinal chemistry function at Fulcrum, bringing in new capabilities as required, identifying key collaborators and CROs, and inspiring best-in-class approaches to small molecule drug discovery
Further cultivate and lead our consortium of thought leaders and consultants in medicinal chemistry, structural biology and machine learning/AI to bring best-in-class innovation to our drug discovery workstreams
Develop strategies and tactics for ‘drugging’ the novel target biology identified from our FulcrumSeek platform and our exploratory biology efforts
Design new bioactive compounds by collaborating with your colleagues in the biological sciences to optimize potency, selectivity, DMPK, in vivo pharmacology, and pharmaceutical properties
Refine our outsourcing strategy with our external CROs, and lead the efforts of a large team of synthetic chemists in the focused and effective optimization of our drug leads
Identify novel composition-of-matter, and liaise with our patent attorneys to create intellectual property strategies that leverage our inventions

Qualifications

Ph.D. in synthetic organic chemistry or equivalent with 10+ years of industry experience
Proven track record in drug discovery; has served as a project team leader or co-leader or key innovator for a discovery program that successfully identified an IND candidate; routine inventor/co-inventor of composition-of-matter IP
Excellent knowledge of medicinal chemistry; conversant in project biology and pharmacology, and with treatment modalities beyond small molecules
Demonstrated excellence in organic synthesis; conversant with principles of structure-based drug design and in silico/AI/ML approaches to both structure- and ligand-based drug design
Exceptional knowledge of ADME, physicochemical, biochemical and pharmacological principles as applied to drug discovery
Proven leadership capability in cross-functional team settings, either as project team leader or co-lead
Exceptional interpersonal, verbal and written communication skills, and able to present the rationale, key data, issues and accomplishments of our drug discovery efforts to internal and external collaborators

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