Our Approach

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.

NExMod Cycle.jpg

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).


NExMod™ demonstrate all the advantages of small-molecule therapeutics, while targeting classically ‘undruggable’ targets as well. The decreased molecular size of a NExMods™ versus a PROTAC manifests as decreased synthetic step count and increased probability of oral bioavailability.


NExMods™ degradation approach has distinct advantages over other therapeutic modalities

PROTAC versus NExMod.jpg

PROTACs have much higher MW, log P and PSA versus NExMods™

Comparison of the size difference between a NExMods™ (purple) which has a polar surface area of 398 Å2, while the known dBET23 PROTAC (blue) has a polar surface area of 765 Å2. Most of the increased surface area of the PROTAC is from the linker and added ligand for target protein recruiting.


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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