Associate Director, Medicinal Chemistry - Helicon Degrader Design

Why join us?

Parabilis Medicines is a highly distinctive young biopharmaceutical company whose intention is to grow over time into the ranks of major therapeutics companies. Our foundational platform of Helicon™ therapeutics are peptides capable of efficient cell entry and modulation of both protein-protein and protein-DNA interactions. Through Helicon therapeutics, Parabilis is poised to revolutionize the medical possibilities for patients by precisely drugging intracellular targets long understood to be significant drivers of disease but never before drugged due to the limitations of existing drug modalities to act within the cell.

An important distinctive element of Parabilis is our lead program FOG-001, the company's first-in-class TCF-blocking β-catenin inhibitor. This compound is approximately 18 months and ~50 patients into our early development program for patients with advanced solid tumors, most importantly colorectal cancer. There are few products in the ecosystem with the medical and economic potential of FOG-001. Parabilis is fully leveraging the unprecedented potential Helicons present by deploying proprietary, custom-built machine learning and computational methods as part of its discovery and development process. Parabilis Medicines has raised more than $500 million to date from leading life sciences investors. Parabilis Medicines is headquartered in Cambridge, Mass.

What's the opportunity?

This is an exciting opportunity to bring a transformational new modality, our Helicon degraders, to clinical development with first-in-class and best-in-class programs. We are seeking a creative drug designer, ideally with experience in targeted protein degradation or other induced proximity modalities. Helicons have the ability to bind tightly to a broad range of targets that traditionally are thought to be undruggable and this provides a unique opportunity to expand the accessible drug space by incorporating degrader and molecular glue functionalities. The successful candidate will be responsible for leading the molecular design on Helicon degrader programs from hit to development candidates. In addition, the candidate may have opportunities to lead program teams to deliver development candidates. Specifically:

• Lead drug design teams applying our AI design platform to facilitate rapid SAR decision-making using state-of-the art methods in medicinal chemistry and targeted protein degradation
• Optimize drug design team engagement and efficiency to drive hypothesis-based drug design, addressing key optimization issues
• Develop, implement and communicate an integrated medicinal chemistry strategy, working in concert with partners in Synthesis, Data Science, De Novo Discovery, Molecular and Cellular Biology, DMPK and Pharmacology to reach hit-to-lead and lead optimization goals
• Drive progression of lead molecules to pharmacological proof-of-concept studies and development candidate nomination
• Collaborate closely with data scientists to evolve machine learning models for acceleration of Helicon degraders platform
• Expand our ligands for validated and new E3 ligases
• Set ambitious goals and aggressive timelines for reaching key discovery milestones and rapid delivery of first-in-class Helicon™ peptide drugs to patients
• Participate in company portfolio and stage-gate reviews
• Collaborate with Lead IP Counsel to formulate intellectual property strategies
• Mentor colleagues across functions in medicinal chemistry principles
  
  

What you will need to be successful in this role:

• PhD. in Chemistry with 8 years of Industry experience in pharmaceutical/Biotech setting
• Demonstrated expertise and a track record of success in advancing discovery programs involving PROTAC, molecular glues or other induced proximity modality from target validation through lead optimization and into clinical development
• Fluency in applying modern computational methods to medicinal chemistry design problems
• Innovative thinker with growth mindset – open to challenging dogma and testing new methods
• Solid understanding of cellular/molecular biology, biochemistry, biophysics, mechanisms of drug metabolism, pharmacokinetic and pharmacodynamic science
• Passionate about drug discovery and ability to motivate team and find creative solutions to problems. Demonstrated influence, negotiation, and conflict resolution skills
• Capacity to execute tasks independently to achieve company goals on an established timeline
• Excellent communication, organization, multi-tasking, flexibility, and team skills
• Enthusiasm to work in a dynamic research environment
• Able to work on-site and attend in-person meetings
  
  

Core Values

Parabilis Medicines is a team of passionate pioneers who are trailblazing the future of precision medicine with the aim of making a meaningful difference in the lives of patients. The company is committed to promoting an inspiring and flourishing working environment for all employees across the business, in all departments, and driving innovation for patient benefit.

• Growth-Minded. We're inventing a new class of medicines—one applicable to therapeutic targets that have been dreamt about, but always considered impossible to drug. Our work requires us to be curious, humble and adaptable.
• In(ter)dependent. We are fiercely independent as a leader in defying the limitations of current therapeutic modalities, and interdependent as a team as we work collaboratively to shift drug discovery paradigms and provide patients with better treatment options.
• Patient-focused. We are deeply focused on patient outcomes, and all energy in the company is focused on science as it translates to patient impact.
• All-In. We're All-In on solving some of the hardest scientific challenges and delivering one of the most effective new classes of drugs in history.
  
  

As an equal opportunity employer, Parabilis Medicines values diversity and welcomes applicants of all backgrounds and experiences. All qualified applicants will receive consideration for employment without discrimination on the basis of race, color, religion, sex, sexual orientation, gender identity, national origin, protected veteran status, disability, or any other factors prohibited by law.

30 Acorn Park Drive | Cambridge, MA 02140 | www.parabilismed.com