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Molecular Glues

Small-molecule, targeted protein degraders (TPD) are an emerging class of drugs which capitalizes on the body’s natural system for clearing damaged or unwanted proteins. TPD eliminate versus inhibit proteins. In addition, TPD do not require a binding site for activity. As such, targeted protein degradation expands the proteome of potential therapeutic opportunities previously considered undruggable. f5 Therapeutics understands that not all undruggable targets provide drugs.

We assess targeted degradation in therapeutically relevant screening conditions (phenotypic screening). Combining protein degradation and phenotypic screening truly differentiates f5 Therapeutics in our ability to identify and prosecute on undruggable, clinical viable targets.

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Our Differentiated Approach

f5 Therapeutics' platform is expanding the scope of degradable targets in the Targeted Protein Degradation space. Our methods allow access to the abundance of undiscovered neosubstrates available for degradation with potential in multiple indications. We identify these new targets in context with cellular assays allowing us to fully realize the wide class of neosubstrates afforded by cereblon. Multiple new targets we have discovered are currently not being pursued by other degrader companies. NExMods™ have demonstrated in vitro POC across five therapeutic areas (immuno-oncology, Wnt-driven cancers, auto-immune disease, NASH, liver fibrosis) and demonstrated 100X cereblon binding potency versus known clinical IMiDs. 

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NExMods™ re-direct nature’s machinery to degrade disease-causing proteins. In this model, penetration of the NExMods™ into a diseased tissue samples the proteome (2). Only proteins capable of generating a productive ternary complex (3) lead to tagging the target (ubiquitylation, 4) for degradation (7).

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The NExMods™ Platform leverages in silico design and cheminformatic assessment placing a premium of preparing analogs with optimal predicted properties (Lipinski compliant). In vitro pharmacology relies on phenotypically relevant assays, such as 3D cultures for cancer models. Once we have identified NExMods™ with the desired phenotypic activity, proteomic assessment uncovers the target(s) driving activity (Target Identification). The proteomic profile will be collected, curated, and mined (AI, machine learning) to yield additional therapeutic hypotheses for the team to explore.

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