Cocrystal Pharma, Inc. · NASDAQ:COCP
Cocrystal Pharma — reImagine HEALTH Intervention and Prevention Symposium (January 2021)
28 slides from Cocrystal Pharma's conference presentation, Jan 21, 2021
Slide 1: reImagine HEALTH Intervention and Prevention Symposium
reImagine HEALTH Intervention and Prevention Symposium Application of Structure-Based Drug Design Platform Technology For Developing Broad Spectrum COVID-19, Influenza, and HCV Antivirals Sam Lee, Ph.D. January 21, 2021 NASDAQ: COCP
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including statements regarding expected results of our collaboration with Merck Sharp & Dohme Corp. (“Merck”), including the anticipated charac
Slide 3: Cocrystal Drug Discovery Platform Technology for Broad Spectrum Antivirals
Cocrystal Drug Discovery Platform Technology For Developing Broad Spectrum Antiviral Therapeutics Drug target X-ray crystals Drug pocket selection Hit-to-lead process Lead optimization Drug candidates 3 cocrystalpharma.com
Slide 4: Traditional Drug Discovery and Development Process: Slow Process and High Attrition Rate
Traditional Drug Discovery and Development Process: Slow Process and High Attrition Rate ▪ Target identification and target validation process required ▪ Compound screening and hit identification yield high attrition rate Target Target Lead Lead Preclinical HTS screening Hit to Lead Clinical trials
Slide 5: Advantages of Cocrystal's Structure-based Drug Discovery Platform Technology
Advantages of Cocrystal’s Structure-based Drug Discovery Platform Technology ▪ Provide 3D structures of inhibitor protein complexes at near-atomic Inhibitor C resolution with immediate insight Inhibitor B to guide SAR Inhibitor A ▪ Identify novel drug binding pockets ▪ Design and develop broad spect
Slide 6: Case Studies: Broad Spectrum Antiviral Development
Case Studies: Broad Spectrum Antiviral Development ▪ Broad spectrum NNI HCV NS5B polymerase ▪ Phase 2a completed ▪ Broad spectrum helicase inhibitors HCV NS3 helicase ▪ Preclinical stage Influenza A PB2 ▪ Broad spectrum influenza PB2 inhibitor ▪ Phase 1 in 2021 SARS-CoV 3CL (Main) ▪ Broad spectrum c
Slide 7: Large Scale X-ray Quality Crystal Production for High Throughput Protein Crystallography
Large Scale X-ray Quality Crystal Production For High Throughput Protein Crystallography HCV polymerase crystals (1.6-2.1 Å) GT1a GT1b GT2a GT4a GT5a GT6a GT1b* GT1b* HCV helicase crystals (1.7-2.6 Å) S282T N316Y GT1b GT1a GT1b FL GT2a GT3a GT4a GT5a GT6a Influenza PB2 crystals (1.0 – 2.5 Å) 7 cocry
Slide 8: Technology Platform Focuses on Well Validated Antiviral Drug Targets
Technology Platform Focuses on Well Validated Antiviral Drug Targets ▪ Viral enzymes are essential for viral replication and transcription >2,200 cocrystal structures Avg resolution 1.0-2.5 Å 8 cocrystalpharma.com 8
Slide 9: Case Study 1: HCV NNI Pan-genotypic Inhibitor CC-31244
Case Study 1: HCV NNI Pan-genotypic Inhibitor CC-31244 ▪ CC-31244 extends from the NNI-4 site to the active site ~90° CC-31244 CC-31244 NNI-4 NNI-4 Active site Active site 9 cocrystalpharma.com Cocrystal Pharma, Inc Confidential and Protected 9
Slide 10: CC-31244: Potent, Broad Spectrum Non-nucleoside Inhibitor
CC-31244: Potent, Broad Spectrum Non-nucleoside Inhibitor ▪ CC-31244: HCV EC50 fold change, <6-fold Genotype CDI-31244 EC50 Sofosbuvir EC50 EC50, nM Fold change EC50, nM fold change 1b 5 1.0 42 1.0 1a 9 1.8 34 0.8 2b 26 5.2 28 0.66 3a 11 2.2 14 3.2 4a 21 4.2 47 1.1 5a 2 0.4 75 1.7 10 cocrystalpharma
Slide 11: CC-31244 Shows Superior Activity Against All Known HCV Drug Resistant Polymerases
CC-31244 Shows Superior Activity Against All Known HCV Drug Resistant Polymerases ▪ CC-31244: IC50 fold-change against NNI drug resistant polymerases, <5-fold; Reference compound, HCV-796:IC50 fold-change, >1,600-fold ▪ Liver targeting of CC-31244 (>1,000 above EC50) observed 1800 HCV-796 (NNI-4 ref
Slide 12: CC-31244 Exhibits High Barrier to Drug Resistance
CC-31244 Exhibits High Barrier to Drug Resistance ▪ C445F: only drug resistant variant isolated from in vitro screening ▪ Fold shift: IC50 <2-fold and EC50 <7-fold (A) GT1b wild type (B) GT1b C445F 1.6 Å 1.7 Å 12 cocrystalpharma.com
Slide 13: Novel Mechanism of Inhibition by CC-31244
Novel Mechanism of Inhibition by CC-31244 RNA substrate CC-31244 blocks RNA entry into the active site Rotate CC-31244 HCV polymerase Back view CC-31244 (NNI) HCV polymerase Front view 13 cocrystalpharma.com
Slide 14: Case Study 2: HCV NS3 Helicase Inhibitors
Case Study 2: HCV NS3 Helicase Inhibitors Novel Drug Binding Pocket (CBP-1) Identified (A) HCV NS3 helicase structure (B) Fragment screening Proprietary ARTIST ATPase fragment libraries 4-8 fragments/cocktail Soaked with protein crystals Cocrystals 14 cocrystalpharma.com
Slide 15: Novel Mechanism of Inhibition by HCV NS3 3'-5' Unwinding Inhibitors
Novel Mechanism of Inhibition by HCV NS3 3’-5’ Unwinding Inhibitors (A) HCV NS3 helicase fragment hits (B) HCV NS3 helicase:dT15 structure dT15 W501 15 cocrystalpharma.com
Slide 16: Pan-Genotypic Binding Mode of HCV Helicase Inhibitor
Pan-Genotypic Binding Mode of HCV Helicase Inhibitor HCV helicase crystals GT1b GT1a GT1b FL GT2a GT3a GT4a GT5a GT6a Overlay structure of HCV helicases (GT1-6) complexed with CDI-30103 W501 16 cocrystalpharma.com
Slide 17: Case Study 3: Influenza A PB2 Inhibitor, CC-42344
Case Study 3: Influenza A PB2 Inhibitor, CC-42344 Broad Spectrum Pandemic and Seasonal Influenza Antiviral ▪ Binds to the highly conserved CC-42344 m7GTP binding pocket of PB2 ▪ Exhibits broad spectrum activity against seasonal and pandemic influenza strains,EC50 0.12-9 nM ▪ Favorable preclinical sa
Slide 18: Cap Binding (PB2), Endonuclease (PA), and Polymerase (PB1) Are Essential For Influenza Viral Replication
Cap Binding (PB2), Endonuclease (PA), and Polymerase (PB1) Are Essential For Influenza Viral Replication Trimeric RNA polymerase complex Boivin S et al. J. Biol. Chem. 2010;285:28411-28417 18 cocrystalpharma.com
Slide 19: PB2 Fragment Screening Reveals Highly Conserved Pocket
PB2 Fragment Screening Reveals Highly Conserved Pocket ▪ The fragment binding pocket confirmed to be m7GTP binding pocket Fragment hits K353 F323 F363 E361 S337 m7GTP binding pocket m7GTP binding pocket 19 cocrystalpharma.com
Slide 20: PB2 m7GTP Binding Pocket is Highly Conserved
PB2 m7GTP Binding Pocket is Highly Conserved (A) Influenza A PB2 sequence comparison (B) m7GTP binding pocket of all influenza A strains H432 N429 F325 M431 R355 F323 F404 Q406 H357 K376 F363 E361 S337 20 cocrystalpharma.com
Slide 21: Crystal Structure of PB2:ssRNA Complex Further Revealed m7GTP Binding Pocket:ssRNA Interactions
Crystal Structure of PB2:ssRNA Complex Further Revealed m7GTP Binding Pocket:ssRNA Interactions PB2:ssRNA cocrystals ssRNA M431 K376 E361 m7GTP binding pocket 21 cocrystalpharma.com
Slide 22: CC-42344 Shows Broad Spectrum Antiviral Activity Against Pandemic and Seasonal Influenza Strains
CC-42344 Shows Broad Spectrum Antiviral Activity Against Pandemic and Seasonal Influenza Strains Influenza serotype Strain CC-42344, EC50 nM H1N1 A/CA/07/2009 0.12 H1N1 A/PR/8/34 1 H1N1 A/Fort Monmouth/1/47 2 H1N1 A/NY/18/09 5 H3N2 A/AICHI/2/68 0.2 H5N1 A/VN/1193/2004 <3.2 H5N1 Hong Kong/213/2003 4.
Slide 23: Case Study 4: COVID-19 Direct-Acting Antivirals
Case Study 4: COVID-19 Direct-Acting Antivirals No effective approved COVID-19 therapeutic or prophylactic treatment Source: World Health Organization 23 cocrystalpharma.com
Slide 24: Cocrystal Focuses On Multiple SARS-CoV-2 Drug Targets
Cocrystal Focuses On Multiple SARS-CoV-2 Drug Targets End Papain-like protease 3CL (Main) protease Endonuclease Helicase Replicase complex 24 cocrystalpharma.com
Slide 25: SARS-CoV-2, SARS-CoV-1, and MERS-CoV Protease Crystals
SARS-CoV-2, SARS-CoV-1, and MERS-CoV Protease Crystals SARS-CoV-2 (1.8 Å) SARS-CoV-1 (1.56 Å) MERS-CoV (1.9 Å) 25 cocrystalpharma.com
Slide 26: Cocrystal 3CL Protease Inhibitors Target a Highly Conserved Cysteine Residue of Coronavirus Proteases
Cocrystal 3CL Protease Inhibitors Target a Highly Conserved Cysteine Residue of Coronavirus Proteases (A) Overlay structures of coronavirus proteases Cys 144 (B) Highly conserved Cys144 residue SARS-CoV-2 SARS-CoV-1 MERS HKU1 229E NC63 26 Confidential cocrystalpharma.com
Slide 27: SARS-CoV-2 3CL Protease Inhibitors
SARS-CoV-2 3CL Protease Inhibitors ▪ Exhibits broad spectrum activity Protease inhibitor against viral cysteine proteases including coronaviruses, noroviruses, and picornaviruses ▪ Binds to a highly conserved, essential residue (Cys144) of SARS-CoV-2 3CL (Main) protease ▪ Shows favorable ADMET prope
Slide 28: Summary: Cocrystal's Drug Discovery Platform Technology
Summary: Cocrystal’s Drug Discovery Platform Technology For Developing Broad Spectrum Antivirals ▪ Potent, pan-genotypic NNI HCV NS5B polymerase ▪ Phase 2a completed ▪ Pan-genotypic helicase unwinding inhibitors HCV NS3 helicase ▪ Preclinical stage ▪ Broad spectrum pandemic and seasonal inhibitor In
Cocrystal Pharma — reImagine HEALTH Intervention and Prevention Symposium (January 2021) on 6ix