Modulating oncogenic transcription factors by targeting PTM PTM¹-driven PPIs PPIs²: Addressing drug resistance in cancer

 

1PTM = Post Post-translational modification
2PPIs = Protein Protein-protein interactions

 

 

 

Overview of PPI Technology Platform

 

 

1. Chemical Biology platform to produce milligram quantities of custom custom-made PPI complexes for FRET FRET-based screening

• ▷ Rapidly generate any phosphorylation phosphorylation-dependent PPI complex to assess suitability for pharmacological intervention
• ▷ Exclusive license for US patent (from KAIST) for chemical biology technology

 

2. FRET HTS using 110,000 compound library or 7,000 covalent fragments to identify functionally active PPI inhibitors

• ▷ Detailed in vitro studies to validate mechanism of action
• ▷ Patent application (PCT) for screening technology filed

 

3. Drug Discovery : Lead optimization efforts benefiting from ~20 years of Big Pharma experience

• ▷ StateState-of -the art drug discovery engine
• ▷ In -house in vitro screening, cell biology, structural biology, and chemical biology enables rapid cycle cycle-time

 

 

 

Competitive Advantages of Technology Platform

 

 

1. Proprietary platform enables high high-throughput screening for PPI inhibitors using
phosphoproteins:

• ▷ Competitors are limited to using small phosphopeptides and typically only focus on identification of competitive inhibitors
• ▷ Many phosphoproteins are intrinsically disordered and only adopt a well well-defined shape upon phosphorylation and binding to the partner in the PPI complex; 1Such intrinsically disordered proteins may harbor binding sites suitable for small molecules; 2Our platform can exploit such binding sites

 

2. HTS platform delivers functional readout: Detects PPI breaking irrespective of which PPI protein partner that compounds bind to or whether inhibition is competitive or allosteric

 

3. Platform amenable to various modalities including cyclic peptides and covalent fragments; Hits from covalent fragment screening using our platform will be functionally active

 

 

 

 

State-Of-The-Art Medicinal Chemistry and Drug Discovery Engine

Rapid DMTA cycles: Initial in vitro data available five days after compound arrival from CRO

 

 

 

 

Team Organization – Expanding with Highly Experienced Consultants

 

 

 

 

Summary and Next Steps

• As a VC VC-backed, pre pre-Series A company, Promedigen has already made significant progress:

• ▶ Building a novel drug discovery platform targeting PTM PTM-driven protein protein-protein interactions to access accessfirst -in -class target space including modulation of transcription factors
• ▶ Demonstrated that our platform can deliver high high-quality chemical matter for PPI targets that have previously been considered undruggable
• ▶ Demonstrated activity in cell cell-based assays and achieved cellular mechanistic proof proof-of -concept
• ▶ Demonstrated in vivo and ex vivo proof proof-of -concept data

• Promedigen is benefiting from world world-class chemical biology expertise, ~20 years of Big Pharma drug discovery experience, a track record of bringing high quality molecules into clinical development, and a highly motivated team
• Next step: Seeking strategic partnerships to further refine platform technology, and advance additional programs to rapidly bring novel medicines to patients

 

 

 

Opportunities for Partnership / Collaboration

 

1. Feasibility study / collaboration leading to first-right-of-negotiation to license asset

• • Jointly select 1-3 targets for assay development, hit ID, hit-to-lead discovery
• • Promedigen to use proprietary platform to progress targets as indicated below (using covalent fragment and/or 100K non-covalent compound set)

 

 

2. Research collaboration to jointly advance FoxM1 program

• • Promedigen to continue advancement of lead series: lead optimization, mechanism-of-action studies, in vivo studies
• • Collaboration partner to have access lead compounds (first-in-class modulator of master regulator transcription factor) to evaluate combination treatments and effect on drug resistance