Cocrystal Pharma, Inc. · NASDAQ:COCP

Cocrystal Pharma — ISIRV AVG Conference (November 2018)

24 slides from Cocrystal Pharma's conference presentation, Nov 13, 2018

  1. Slide 1: Preclinical characterization of CC-42344, a broad spectrum influenza A PB2 inhibitor

    674 ISRV AVG CONFERENCE Preclinical characterization of CC-42344, a broad spectrum, potent influenza A PB2 inhibitor for potential triple route (oral, inhalation, IV) treatment Sam Lee November 13, 2018 C#CRYSTAL PHARMA,INC.

  2. 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. Forward-looking statements are prefaced by words such as “expect,” "plan," "intend," "anticipate," and similar words. Forward-looking statement

  3. Slide 3: Cap Binding (PB2), Endonuclease (PA), and Polymerase (PB1) Are Essential For Influenza Viral Replication

    Cap Binding (PB2), Endonulcease (PA), and Polymerase (PB1) Are Essential For Influenza Viral Replication Onrrnnrw MA chimeric viral mRNA Polymerase ‘complex (és t i 1 i \ 1 ‘ ao. s Boivin $ et al. J. Biol. Chern. 2010;285:28411-28417

  4. Slide 4: Baloxavir marboxil, VX-787 (Pimodivir) and Cocrystal's PB2 inhibitors

    Baloxavir marboxil 4 9 @ VX-787 (Pimodivir) 3 Cocrystal’s PB2 inhibitors Viral RNA ee Promoter PB2 a

  5. Slide 5: Cocrystal Drug Discovery Platform Technology

    Cocrystal Drug Discovery Platform Technology For Developing Broad Spectrum Antiviral Therapeutics Influenza PB2 crystals e Drug target X-ray crystals @ Drug pocket selection @ Hit-to-lead process @ Lead optimization Drug candidates =

  6. Slide 6: Cocrystal Technology Platform Focuses on Well Validated Drug Targets

    Cocrystal Technology Platform Focuses on Well Validated Drug Targets: Viral Replication Enzymes CC-31244 CC-31647 Phase 2a ®& ® Preclinical os Lead Discovery % cc-42344 Preclinical

  7. Slide 7: Slide 7

  8. Slide 8: PB2 sequence comparison and m7GTP binding pocket

    (A) PB2 sequence comparison (B) m7GTP binding pocket La dat MEaNeAs capo miwten oH Hive cept (HUNRAN OREM i mnMaAs HY TTT RUE BONNCHESI HE Bont KOAKEE BONN HE BONN CI RQAREL BONWCHEN EME BONN CEN HE BON CI ME BON! ME Ranch

  9. Slide 9: Slide 9

  10. Slide 10: Crystal Structure of PB2-ssRNA Complex Determined

    Crystal Structure of PB2-ssRNA Complex Determined (1) ssRNA binding activity of PB2 (2) ssRNA binding activity of PB2 100 80 ssRNA 60 40 20 0 20 40 60 80 100 120 140 % of Bound 32P-labeled Oligo nucleotide Purified PB-2, pmol 2.7 A

  11. Slide 11: Highly Conserved Binding Modes of PB2 Inhibitors

    Highly Conserved Binding Modes of PB2 Inhibitors H1N1 Spanish 1918 NN H3N2 Victoria 1975 ain \ a @ i 9 H5N1 Guangdong 1996 H7N9 Zhejiang 2013 ay a, C#CRYSTAL

  12. Slide 12: Cocrystal's PB2 Leads

    Cocrystal’s PB2 Leads Cocrystal Preclinical Lead Cocrystal’s backup PB2 inhibitors Influenza strain VX-787 42344 42343 42487 42500 42530 ECSO ECSO ECSO ECSO ECSO ECSO nM nM nM nM nM Pandemic H1N1 => Influenza 2.4 =» 0.12 5 0.9 2.7 ND A/CA/07/2009 H1N1 Influenza 1 1 1.2 1.2 2 0.5 PR/8/34 Pandemic H5N

  13. Slide 13: Influenza A Lead CC-42344 Properties

    Influenza A Lead CC-42344 Properties CC-42344 cocrystals ac = Binds to the highly conserved m7GTP binding pocket of PB2 = Exhibits broad spectrum activity against seasonal and pandemic influenza strains,EC,, 0.12-9 nM = Favorable preclinical safety profile and pharmacokinetic properties

  14. Slide 14: CC-42344 Shows Broad Spectrum Antiviral Activity

    CC-42344 Shows Broad Spectrum Antiviral Activity Against Seasonal and Pandemic Strains nfluenza serotype Strain CC-42344, EC,, nM HIN1 A/PR/8/34 1 H1N1 A1/Denver/1/57 3 H1N1 A/Fort Monmouth/1/47 2 HIN1 A/NY/18/09 5 H3N2 A/AICHI/2/68 0.2 HSN1 Duck/MN/1524/81. <3.2 HSN1 Hong Kong/213/2003 4.5 HSN1 Tha

  15. Slide 15: CC-42344: Pharmacological, Safety, Toxicity, and PK Evaluations Completed To Date

    CC-42344: Pharmacological, Safety, Toxicity, and PK Evaluations Completed To Date GGOBEBBEEEBEGEE SBBBE In vitro antiviral profiling against seasonal and pandemic influenzaA strains Cytotoxicity including larger screen: HepG2/high content analysis and 13 cell lines Caco-2 bidirectional permeability

  16. Slide 16: In Vitro and In Vivo Assessment of CC-42344

    In Vitro and In Vivo Assessment of CC-42344 ae 4 CC-42344 H1N1EC50,nM 1 H1N1EC90, nm. 2 Cytotoxicity (HepG2) at 10 1M No Cytotoxicity (13 cell lines) at 10 14M No Mitochondria toxicity at 10 1M No Off-target inhibition at 10 »M No Solubility in PBS, 1M 90.8 Caco2 A-B, 10 cm/s 20 Caco2 B-A, 10° cm/s

  17. Slide 17: Multiple Routes of Administration (Oral, Inhalation, IV) Explored

    Multiple Routes of Administration (Oral, Inhalation, IV) Explored Vehicle 1: 40% Miglyol 812 40% VE TPGS 20% PEG400 Vehicle 2: 8% DMA, 37% PEG300, 5% poloxamer188, 50% pH 8 USP buffer Dry powder 56 BEG360 Vehicle 3: 2% PVP/0.5% Tween80 -2 um 10% Solutol H515 10% 50% Phosphate buffer pH 7.45

  18. Slide 18: In Vivo Assessment of CC-42344

    In Vivo Assessment of CC-42344 Comparative maximum formulation single PO dose exposure: Test formulation PO Dose Fedor kp Plasma (mg/kg) fasted (hours) AUC ast (ng.h/mt) 40% miglyol/40% VE i 2,333 7,857 TPGS/20% PEG400 (5.3 pM) 2% PVP/0.5% Tween80 500 Fed 2.15 30,633 1.17 95,913 (70 um) 800 1.96 65,

  19. Slide 19: In Vivo Assessment of CC-42344

    In Vivo Assessment of CC-42344 = Single dose inhalation pharmacokinetics in the female Balb/c mouse Q) Dry power formulation developed C QO) Dose 0.8-1.2 mg of dry power (~200 ug of CC-42344) a sia Time course CC-42344 concentration CC-42344 concentration lhr os4um 5.6 uM ¢am 24 br 218 uM 0.081 pM 4

  20. Slide 20: PB2 Cap binding domain

    PB2 Cap binding domain C®CRYSTAL

  21. Slide 21: CC-42344 Inhibits The Endonuclease Activity of Influenza A Trimeric Complex

    CC-42344 Inhibits The Endonuclease Activity of Influenza A Trimeric Complex (PA:PB1:PB2) (A) PA:PB1:PB2 trimeric complex (B) PA endonuclease x 190% ono vx-787 4 4 VX-787 e | ze | CC-42344 mm 2 80 4 z 805 2 oJ 2 aw 2°) ¢C-42344 mp gf 3 40+ s 40-4 z 20 | 2 2054 of on 0.001 0.01 01 1 10 100 0.001 0.01

  22. Slide 22: Drug Resistant Profile of Cocrystal PB2 Lead, CC-42344

    Drug Resistant Profile of Cocrystal PB2 Lead, CC-42344 Cocrystal PB2 lead 3 mutations identified after 1 mutation identified after treatment with VX-787 treatment with CC-42344

  23. Slide 23: CC-42344 Shows Strong Synergistic Effects With Approved Influenza Antivirals

    CC-42344 Shows Strong Synergistic Effects With Approved Influenza Antivirals Polymerase inhibitor t ° a 42344 PA inhibitor Neuraminidase inhibitor

  24. Slide 24: Summary

    Summary Property Antiviral activity against seasonal and pandemic influenza Cocrystal CC-42344 Single digit nanomolar, Broad spectrum Single digit nanomolar, Broad spectrum Drug resistance profile One mutation F363L Three mutations D256N, $324N, M4321 Route of Administration Inhalation, IV, and oral

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