Slide 1: First-in-Class Highly Selective, Potent Dual JAK/ROCK Inhibitor for Debilitating Autoimmune Diseases
First-in-Class Highly Selective, Potent Dual JAK/ROCK Inhibitor for Debilitating Autoimmune Diseases in Clinical Development, with Proven Clinical Safety and Efficacy Selective JAK kinase inhibitor in the treatment of immune-related diseases" co-financed under contract no. POIR.01.01.01-00- 0382/16.
Slide 2: CPL'116
CPL'116 First-in-Class Highly Selective, Potent Dual JAK/ROCK Inhibitor for Debilitating Autoimmune Diseases in Clinical Development, with Proven Clinical Safety and Efficacy
Slide 3: CPL'116: First-in-Class Therapy with Anti-inflammatory and Anti-fibrotic Activity
▪ Product CPL’116 CPL’116: First-in-Class Therapy with Anti-inflammatory ▪ Mechanism of Dual mechanism of action: Janus and Anti-fibrotic Activity Significant Market Opportunity: Action kinases and Rho-kinases inhibitor (JAK/ROCK) Celon's CPL’116 is a novel, orally administered, small molecule, kina
Slide 4: CPL'116: Unique Model of Dual JAK/ROCK Inhibitor
CPL’116: Unique Model of Dual JAK/ROCK Inhibitor KinomeScanTM for CPL’116 activity towards 403 kinases Potent inhibitor of JAKs (JAK1=JAK3>JAK2) Very high selectivity for JAKs and ROCKs families and ROCKs kinases with good selectivity: IC50 [nM] CPL’116 Tofacitinib JAK1 0,95 2,46 JAKs JAK2 5,36 2,23
Slide 5: Primary Pharmacodynamics – In vitro Cell Assays
Primary Pharmacodynamics – In vitro Cell Assays Evaluation of CPL’116 inhibition on cytokine production and STAT pphosphorylation in human PBMC IL - 2 1 c o n c e n t r a t io n [ p g /m l] #### IL - 1 c o n c e n t r a t io n [ p g /m l] 1500 IL - 4 c o n c e n t r a t io n [ p g /m l] 200 60 ###
Slide 6: CPL'116 – Potent Inhibitor of Rho-associated Kinases
CPL’116 – Potent Inhibitor of Rho-associated Kinases CPL’116, through ROCK inhibition, reduces phosphorylation of MYPT1 CPL’116 Fasudil ROCK P MYPT-1 Cell Contraction 6
Slide 7: Primary Pharmacodynamics – In vitro Cell Assays
Primary Pharmacodynamics – In vitro Cell Assays CPL’116, through ROCK inhibition, reduces actin stress fibers formation Ctrl (veh) Fasudil [3.0 µM] CPL’116 Fasudil ROCK Actin DAPI Tofacitinib [3.0 µM] CPL’116 [0.1 µM] Stress fibres Cell Migration Cell Morphology CPL’116 blocks stress fibres formatio
Slide 8: Primary Pharmacodynamics – Whole Blood Assay
Primary Pharmacodynamics – Whole Blood Assay CPL’116 has similar inhibitory activity against JAK and ROCK kinases in Human Whole Blood pSTAT5 (IL-15) pMLC pSTAT1 (IL-6) 120 100 120 100 100 80 % inhibition % inhibition % inhibition 80 80 CPL409116 CPL409116 60 60 60 CLP409116 Tofacitinib Tofacitinib
Slide 9: Primary Pharmacodynamics – In vivo Efficacy
Primary Pharmacodynamics – In vivo Efficacy Collagen induced arthritis 2 .6 4 T o t a l A r t h r it is S c o r e ( 0 - 1 6 ) A v e r a g e P a w T h ic k n e s s (m m ) 2 .4 3 ns N a iv e M e a n + /- S E M M e a n + /- S E M 2 .2 ns D is e a s e O n ly N a iv e 2 V e h ic le C o n tr o l D is e a
Slide 10: Anti-fibrotic Activity in Bleomycin-induced Pulmonary Fibrosis Mouse Model
CPL’116: Activation of Broad Anti-fibrotic Activity in Bleomycin-induced Pulmonary Fibrosis Mouse Model The performed studies showed that CPL’116 blocks immune cells migration to the lungs. There was also decrease in lung fibrosis development observed: Total CD45+ cells in BALF. Leukocytes (CD45+ H&
Slide 11: CPL'116: Clinical Development Overview
CPL’116: Clinical Development Overview Q4 2020 – Q3 2021 7 100% 3 65 healthy volunteers Phase 1 Safety, PK, PD SD and MD (2 weeks) Q2 2022 – Q2 2024 106 patients with Rheumatoid Enrollment: completed NCT04670757 Phase 2 Arthritis Study readouts: available Rheumatoid 3 doses vs placebo Arthritis Effi
Slide 12: CPL'116: Phase 1 Study Design
CPL’116: Phase 1 Study Design Safety and Pharmacokinetics of JAK/ROCK Inhibitor in Healthy Volunteers Open label Double-blind, placebo-controlled, randomized Single ascending dose Dose administered with food Multiple ascending dose, 2 weeks twice daily administration Part A Food effect cohort Part B
Slide 13: Phase 1: Safety Results
Phase 1: Safety Results CPL'116 is safe and well tolerated after single and repeated administration in healthy volunteers Part A: Safety conclusion: In total 11 AE's were reported: elevaled bilirubin level, increased leukocyte number, elevated creatine kinase serum level) with no ▪ Generally safe an
Slide 14: Pharmacodynamic - Phase 1
Pharmacodynamic - Phase 1 CPL'116 inhibits JAK and ROCK kinases in healthy volunteers JAK’s inhibition ROCK’s inhibition CPL’116 decreased JAKs and ROCKs downstream proteins (STATs and MLC respectively) in human blood of healthy volounteers. Blood samples were collected before (t0) and 2 h after IMP
Slide 15: Phase 2 Study Design
Phase 2 Study Design A 12-week, Phase 2, multicentre, randomised, double blind, efficacy and safety study comparing CPL’116 to placebo, in combination with methotrexate in participants with active rheumatoid arthritis who have an inadequate response to methotrexate Screening Period Double-Blind Trea
Slide 16: Clinical Development – Phase 2 Rheumatoid Arthritis
Clinical Development – Phase 2 Rheumatoid Arthritis Phase 2 double-blind, randomized, placebo controlled, parallel group efficacy and safety study comparing CPL’116 to placebo in patients with active Rheumatoid Arthritis Study overview Status Completed Objectives To determine the efficacy of CPL’116
Slide 17: CPL'116 Phase 2: Primary Endpoint
CPL’116 Phase 2: Primary Endpoint Efficacy based on change in DAS28-CRP scale at week 12 Change from baseline in DAS28-CRP at week 12 by randomized treatment of CPL’116 (Intent to treat set); Overall, N=106: -0,887* (p=0,010) DAS28- -0,564 (p=0,103) CPL’116 CRP -0,145 (p=0,668) difference Placebo, b
Slide 18: CPL'116 Key Secondary Endpoints – Comparison of Efficacy
CPL’116 Key Secondary Endpoints – Comparison of Efficacy Superior Effect of CPL'116 in DAS28-Defined Remission vs. Other RA Therapies 70,0% 61,5% 60,0% 50,0% 48,7% 46,2% 44,0% 42,3% 40,8% 38,5% 40,0% % Patients 40,0% 34,3% 28,8% 30,0% 30,0% 26,9% 26,9% 26,0% 27,0% 27,0% 21,6% 23,9% 22,0% 21,5% 21,6%
Slide 19: CPL'116: Safety and Tolerability in Phase 2
CPL’116: Safety and Tolerability in Phase 2 Safety profile consistent with drug class Summary of adverse events by randomized treatment of CPL’116 CPL’116 Category Overall, N=106 Placebo, N=28 60 mg, N=27 120 mg, N=25 240 mg, N=26 Adverse event (AE) 170 (100.0%) 35 (100.0%) 36 (100.0%) 47 (100.0%) 5
Slide 20: What makes this asset unique?
What makes this asset unique? Mechanism of Action Dual Mechanism of Anti-inflammatory Selective Action with Limited Kinase and Anti-fibrotic Action in One Capsule Binding Activity CPL'116’s mechanism of In addition to RA, CPL'116’s Preclinical Efficacy Demonstrated action is mainly based on mechanis
Slide 21: Strategic Opportunity
Strategic Opportunity First-in-class dual JAK/ROCK inhibitor with broad potential in autoimmune diseases featuring inflammatory and fibrotic components Reference market dynamics vs. market value CPL’116 (bubble size: CPL’116 Target Market Population (7MM) estimated peak sales in MLN USD, 7MM): for O
Slide 22: THANK YOU!
THANK YOU!