Cocrystal Pharma, Inc. · NASDAQ:COCP
Cocrystal Pharma — 2022 World Antiviral Congress
23 slides from Cocrystal Pharma's conference presentation, Dec 1, 2022
Slide 1: Influenza A Oral PB2 Inhibitor CC-42344
Potent antivirals to combat some of the most serious diseases facing humanity Influenza A Oral PB2 Inhibitor CC-42344 2022 World Antiviral Congress December 1, 2022
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 the market opportunities for the treatment of acute and chronic viral diseases which are the focus of our progra
Slide 3: The Influenza Pandemic: 100 Years, From 1918 Spanish Flu To 2009 Swine Flu
The Influenza Pandemic: 100 Years, From 1918 Spanish Flu To 2009 Swine Flu Influenza A is responsible for influenza pandemic and seasonal infections Taubenberger JK et al. Sci. Transl. Med. 2019; 11, eaau5485 3 3
Slide 4: Influenza Antivirals: Emerging Pandemic Influenza and Drug Resistance Threats
Influenza Antivirals: Emerging Pandemic Influenza and Drug Resistance Threats 1999 2014 2018 Tamiflu® (oseltamivir) Rapivab® (peramivir) Xofluza® (baloxavir) Neuraminidase inhibitor Neuraminidase inhibitor Influenza A/B PA inhibitor (Oral) (Intravenous) (Oral) Pimodivir (VX-787) CC-42344 Relenza (za
Slide 5: CC-42344 Inhibitor Targets PB2 of Influenza Polymerase Complex
CC-42344 Inhibitor Targets PB2 of Influenza Polymerase Complex Cap Binding (PB2), Endonuclease (PA), and Polymerase (PB1) are Essential for Influenza Viral Replication PB2 inhibitor CC-42344 Boivin S et al. J. Biol. Chem. 2010;285:28411-28417 5 5 5
Slide 6: Influenza Virus Polymerase Complex (PA:PB1:PB2)
Influenza Virus Polymerase Complex (PA:PB1:PB2) Cap binding domain Endonuclease domain PB2 PA Pimodivir Baloxavir marboxil CC-42344 RNA polymerase PB1 Viral RNA promoter Reich et al. (2014) Nature – PDB id 4WSB 6 6
Slide 7: Equipped With A Proprietary Drug Discovery Platform
Equipped With A Proprietary Drug Discovery Platform Leveraging X-ray crystallographic insights of target-inhibitor complexes to generate unique insights: • Novel chemistry to overcome drug resistance • Interrogate multiple binding pockets • Rapid iterative structure-based drug discover platform Drug
Slide 8: Essential Role of PB2 Protein In Viral Transcription and Replication
Essential Role of PB2 Protein In Viral Transcription and Replication (A) Crystal structures of PB2:ssRNA complex (B) Crystal structures of PB2:m7GTP complex m7GTP 3’ Y404 m7GTP binding pocket 5’ K376 Y363 E361 HO O O O O P O P O P O HO O O O O H 2N N N HN N O CH3 8 8
Slide 9: PB2 m7GTP Binding Site is Highly Conserved
PB2 m7GTP Binding Site is Highly Conserved H1N1 H2N2 H3N2 H5N1 H7N9 PB2 crystals (A) Pandemic and seasonal influenza A PB2 H1N1, H2N2, H3N2, H5N1, and H7N9 (B) Overlayed m7GTP binding pockets H432 N429 F325 M431 R355 F323 F404 Q406 H357 K376 F363 E361 S337 9 9
Slide 10: Structural Insight Into Broad-spectrum PB2 Inhibitor Design
Structural Insight Into Broad-spectrum PB2 Inhibitor Design ▪ Multiple hits bound to the highly conserved m7GTP binding pocket Fragment hits K353 F323 F363 E361 S337 m7GTP binding pocket 10 10
Slide 11: CC-42344: Oral Pandemic and Seasonal Influenza A Therapeutic
CC-42344: Oral Pandemic and Seasonal Influenza A Therapeutic Pandemic and seasonal influenza A PB2 crystals ▪ Potent anti-influenza structure-based inhibitor (H1N1, H2N2, H3N2, H5N1, and H7N9) ▪ Binds a highly conserved region of influenza A PB2 of polymerase complex (PA:PB1:PB2) ▪ Broad-spectrum ac
Slide 12: CC-42344 Shows Broad-spectrum Antiviral Activity Against Influenza A Strains
CC-42344 Shows Broad-spectrum Antiviral Activity Against Pandemic and Seasonal Influenza A Strains Influenza serotype Strain CC-42344, EC50 nM H1N1 A/PR/8/34 1 H1N1 A1/Denver/1/57 3 H1N1 A/Fort Monmouth/1/47 2 H1N1 A/NY/18/09 5 H3N2 A/AICHI/2/68 0.2 H5N1 Duck/MN/1524/81 <3.2 H5N1 Hong Kong/213/2003
Slide 13: CC-42344 Shows Strong Synergistic Effects With Approved Influenza Antivirals
CC-42344 Shows Strong Synergistic Effects With Approved Influenza Antivirals Polymerase inhibitor Synergy/antagonism compared to 95% CI 30 20-30 20 10-20 10 0-10 0 -10-0 Favipiravir -10 0 -20--10 -20 7 -30--20 14 -30 28 56 0 2 113 4 8 225 16 450 32 64 128 Cocrystal Synergy/antagonism compared to 95%
Slide 14: CC-42344 vs Pimodivir (VX-787): Key Differentiators
CC-42344 vs Pimodivir (VX-787): Key Differentiators Property Pimodivir (VX-787) Cocrystal CC-42344 Hit identification Anti-influenza hits PB2 structural hits From influenza cell-based screening From Cocrystal drug discovery platform Drug binding pocket PB2 m7GTP PB2 m7GTP Broad-spectrum activity Sin
Slide 15: CC-42344 Showed No Lung Toxicity in Human Nasal and Bronchial Airway Epithelia
CC-42344 Showed No Lung Toxicity in Human Nasal and Bronchial Airway Epithelia (HAE) 3 D ALI ai r w a y e p i t h e l i a p r o d u c t s | M u c i l Ai r ™ & Sm a l l Ai r ™ Features: ✓Ready to use ✓Long shelf-life ✓Several pathologies / donor available CRO: Epithelix, Switzerland 15
Slide 16: Human Nasal Epithelia Destruction Upon Influenza Infection
Human Nasal Epithelia Destruction Upon Influenza Infection Uninfected human respiratory epithelia Infected human respiratory epithelia H1N1 • Layer of intact cells with numerous • Cells are killed by H1N1 virus, and cilia visible most cilia are destroyed 16
Slide 17: Excellent Antiviral Activity of CC-42344 in H1N1-Infected Human Bronchial Epithelia
Excellent Antiviral Activity of CC-42344 in H1N1-Infected Human Bronchial Epithelia No treatment Normal human respiratory epithelia No CC-42344 With CC-42344 + CC-42344 17
Slide 18: A Phase 1 Study in Healthy Participants to Evaluate Safety, Tolerability, and PK
A Phase 1 Study in Healthy Participants to Evaluate the Safety, Tolerability, and PK of the Oral Influenza A PB2 Inhibitor CC-42344 18 18
Slide 19: Phase 1 CC-42344 Study Completed: Database Lock Pending
Phase 1 CC-42344 Study Completed: Database Lock Pending Phase 1 trial site: Linear Clinical Research-Harry Perkins Research Institute , Perth, Australia Participants: ▪ Single-center, randomized, double-blind, placebo-controlled ▪ Single dose, multiple dose; 7-day nontreatment follow-up period ▪ Hea
Slide 20: Key Entry Criteria
Key Entry Criteria ▪ Healthy males and females ≥ 18 and ≤ 55 years ▪ Body weight ≥ 50 kg ▪ Body mass index ≥ 18 and ≤ 32 kg/m2 ▪ Non-pregnant, non-lactating ▪ Must abstain from alcohol or caffeine from 48 hours before study confinement through study ▪ Must not have taken prescribed medication in 14
Slide 21: Phase 1 SAD Study Summary and Next Steps
CC-42344 Oral PB2 Inhibitor Phase 1 SAD Study Summary and Next Steps ▪ Phase 1 study healthy volunteer study completed: Database lock pending ➢ No serious AEs reported ▪ Phase 2a human challenge study planned in 2H of 2023 ➢ CRO: hVIVO, Queen Mary’s Bioenterprise Centre, London, UK ➢ Study design: r
Slide 22: Best-in-Class Influenza A PB2 Inhibitor CC-42344
Best-in-Class Influenza A PB2 Inhibitor CC-42344 🗸 Activity against pandemic and seasonal Broad-spectrum activity influenza A strains and drug resistant strains 🗸 Single digit nanomolar potency with high Potency and resistance barrier to resistance 🗸 Mechanism of Action Novel inhibition…
Slide 23: Influenza A Oral Inhibitor CC-42344
Influenza A Oral Inhibitor CC-42344 Nasdaq: COCP www.cocrystalpharma.com