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Director of Medicinal Chemistry & Induced Proximity

A-Alpha Bio

A-Alpha Bio

Seattle, WA, USA
Posted on Friday, July 28, 2023

A-Alpha Bio is an early-stage and rapidly-growing drug discovery company headquartered in Seattle, WA. We are enabling the next generation of high-impact therapeutics by combining high-throughput synthetic biology with state-of-the-art machine learning. We partner with leading pharma and biotech companies to enable the discovery of antibodies, molecular glues, and other protein interaction-related drugs. In parallel, we use our AlphaSeq technology internally to build a Biologics Pipeline for clinical development and/or asset licensing opportunities.

Candidates local to Seattle are preferred, but remote applicants are welcome to apply. Candidates must reside in the US.

Starting Salary Range: $194,000 - $221,000

Exemption Status: Exempt

Location Expectations: Remote-Eligible

Role Description

We are seeking an experienced Director of Medicinal Chemistry & Induced Proximity to spearhead the discovery and validation of monovalent compounds that agonize E3 ligases and neo-substrates, which A-Alpha Bio has identified as potentially gluable. This role will involve extracting insights from binding and structural data to prioritize discovery strategies and managing contract research organizations (CROs) for hit identification, optimization, and validation. This is an exceptional opportunity for the right candidate to join a fast-paced, pioneering venture, potentially forming the bedrock of a significant future initiative.

Responsibilities

  • Generate and execute a strategic blueprint for identifying small molecule agonists leveraging E3 ligase / neo-substrate pairs identified by A-Alpha Bio.
  • Guide the prioritization process of E3 ligase / neo-substrate pairs for small molecule discovery, leveraging both internal and external datasets pertaining to each pair.
  • Evaluate diverse approaches for molecular glue discovery, including experimental and computational HTS, fragment-based screening, DEL screening approaches, etc.
  • Manage CROs for the generation of recombinant protein, hit identification, lead optimization, and in vitro binding or functional validation.
  • Identify and propose changes to the strategic plan based on progress.

Qualifications

Required

  • PhD in chemistry, preferably with 8+ years of experience in the pharmaceutical/biotech industry alongside a strong track record of scientific innovation in the medicinal chemistry discipline.
  • Demonstrable track record of identifying development candidates, with a deep understanding of hit generation, structure-based drug design, and lead optimization.
  • Experience with induced proximity or targeted protein degradation.
  • Experience managing CROs for small molecule screening and validation.
  • Experience analyzing and interpreting outputs from small molecule screening campaigns.
  • Ability to collaborate with and manage internal experts and external consultants.
  • Drug discovery experience in multiple therapeutic areas and target classes.
  • High level of ownership and comfort in a fast-moving research environment with high tolerance for ambiguity and risk.

Preferred

  • Experience with DNA-encoded libraries.
  • Familiarity with startup environments.
  • Expertise in structure-based small molecule drug design or computational approaches that leverage structural data.

Candidates of all backgrounds and experience levels are encouraged to apply. Each application will be evaluated on a case-by-case basis.

We offer competitive compensation, including benefits and equity in a fast-growing start-up. Applicants must have legal authorization to work in the United States.

About A-Alpha Bio

A-Alpha Bio is an early-stage biotechnology company combining synthetic biology and machine learning to dramatically improve the discovery of high-impact therapeutics. We believe that abundant high-quality data is critical for understanding biology and curing disease – and synthetic biology is our catalyst. Our proprietary AlphaSeq platform uses genetically engineered cells to quantitatively measure millions of protein interactions – from which we generate high-resolution models of biology.

In 2018, we spun out of the University of Washington’s Institute for Protein Design and Center for Synthetic Biology – both fantastic communities of brilliant and highly entrepreneurial scientists. Since the company’s inception, we have focused on partnering with pharmaceutical companies to discover and optimize drugs for therapeutic areas ranging from infectious disease to cancer. We are growing rapidly, and new members of the team should expect a fast-paced and highly dynamic work environment. We are building a diverse, meritocratic, and supportive team that shares our values of speaking the truth, shooting for the moon, taking the reins, playing for the team, and improving the world.

A-Alpha Bio is headquartered in a brand-new combined office/lab space in downtown Seattle's Belltown neighborhood. While the startup lifestyle occasionally requires grueling hours, we strongly value the need for a work-life balance and time out of the lab/office. We are fortunate to be situated in a region that is renowned for its premier outdoor activities, including hiking, biking, climbing, skiing, kayaking, and sailing. At A-Alpha, you’ll find many who love the outdoors, but also gamers, amateur chefs, explorers, sports fans, bakers, crafters, photographers, brewers, jetsetters, animal lovers, and artists. Whatever your passions, you belong at A-Alpha Bio.