bioPROTACNext Generation PROTAC with Biologics

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bioPROTAC's mechanism of action

EPDeg™: bioPROTAC Platform Technology

EPDeg™ bioPROTAC is composed of a target binder (nanobody) and a modified E3 protein as a form of direct fusion protein between the two, providing the following advantages.

1Capable of degrading the most undruggable targets which cannot be targeted by small molecules
2No need to use a linker of small molecule-based PROTAC which expedites the process of lead candidate selection
3No need to find a binder to E3 proteins which enables us to utilize all existing human E3 proteins & Capable of enhancing the target protein degradation efficacy by engineering E3 proteins

With the aim of overcoming small molecule-based PROTAC, EPDBio develops a next-generation of targeted protein degraders, bioPROTAC, termed as EPDeg™ (Engineered Protein Degraders).
bioPROTAC: A next-generation of targeted protein degraders utilizing biologics (ex. antibody fragment, peptide, etc.) as a selective binder to the protein of interest

EPDeg™ bioPROTAC
EPDeg™ vs.	Main advantage of EPDeg™ bioPROTAC(proved by data)
PROTAC	Possible to degrade novel targets that cannot be degraded by small-molecule based PROTAC at this moment & There is no need to have the linker used in PROTAC synthesis → We proved that EPDeg™ bioPROTAC can potently degrade currently intractable targets by PROTAC (ex. SOX2, ATXN1)
PROTAC	Possible to show higher potency by utilizing new E3 ligases that cannot be recruited by small molecule E3 ligands at this moment → We proved that EPDeg™ bioPROTAC can have much higher potency than PROTAC for the same target (ex. STAT3)
siRNA / ASO	Much higher level of down-regulation and much faster therapeutic effects were observed with the use of EPDeg™ bioPROTAC
Other bioPROTACs	Possible to improve TPD efficiency by using EPD’s own engineered E3 proteins We proved substantially enhanced STAT3 degradation when one of engineered E3s was used to generate EPDeg™

bioPROTAC has superiority over knock-down approach by siRNA or shRNA as following.

bioPROTAC and siRNA / shRNA
	siRNA / shRNA	bioPROTAC
Target selectivity	Off-target knock down often reported (2D sequence-based selectivity)	Potentially lower off-target effect (3D structure-based selectivity)
Subpopulation specific effect	Subpopulation specific knock down possible	Subpopulation specific degradation possible · Mutant selective degradation(vs. WT) · Post-translational modification selective degradation (ex. phosphorylation, acetylation, etc.) · Paralog selective degradation(ex. ERK1 vs. ERK2)
Kinetics	Impossible to degrade target protein that was already created before drug injection. If the protein has a long half-life and is stable, it may take a long time for the drug effect to be observed.	Able to degrade target proteins that have already been generated before drug injection. The drug effect can be expected in a faster time.
Applicability to aggregated proteins	Not applicable to insoluble protein aggregates observed in degenerative brain diseases	Applicable to insoluble protein aggregates

Nanobody and E3 Protein Engineering Technology

1Utilization of a yeast display system optimized for engineering: Compared to phage display, it increases the potential for bioPROTAC development through optimization of post-translational modifications (PTM) and protein folding.
2Simultaneous improvement of protein expression levels and thermal stability.
3Rapid and precise variant screening technology: Real-time variant screening is possible using a sorter with an optimized protocol.