Slide 1: CPL'36 Phase 2 Success in Acute Schizophrenia
CPL’36 Potentially the Best-in-Class Treatment of Neuropsychiatric Diseases CPL’36 Phase 2 Success in Acute Schizophrenia
Slide 2: CPL'36 Potential for Innovation in Schizophrenia and Levodopa-induced Dyskinesia
▪ Product CPL’36 Potential for Innovation in Schizophrenia and Levodopa- induced Dyskinesia (LiD) ▪ Mechanism of PDE10A inhibitor – potentially best- Action in-class 2nd generation molecule Schizophrenia Market Potential ▪ Route of Oral, QD administration 24M $8,1B +3,9% Patient Population Global Ma
Slide 3: CPL'36: Potential Best-in-Class Therapy
CPL’36: Potential Best-in-Class Therapy CPL'36 differs structurally Binding affinity of PDE10A inhibitors: from other PDE10A inhibitors: KD (PDE10A1) IC50 (PDE10A1) kon x105(1/Ms) nM CPL’36 CPL’36 57± 2.2 CPL’36 71 ± 8.6 TAK-063 43 ± 5.0 TAK-063 25 ± 0.0 MP-10 22 ± 0.5 MP-10 94 ± 0.0 MP-10 (Pfizer)
Slide 4: CPL'36: Robust Preclinical Efficacy Profile in Both Psychotic and PD/Dyskinesia Models
CPL’36: Robust Preclinical Efficacy Profile in Both Psychotic and PD/Dyskinesia Models Antipsychotic effects Antidyskinetic and antiparkinsonian effects Test MED (mg/kg) Model and effect MED (mg/kg) Conditioned avoidance response 0,2 6-OHDA PD rat model: antiparkinsonian 0,1 Inhibition of PCP-induce
Slide 5: Possible Positive Impact of CPL'36 on Body Weight Reduction
Possible Positive Impact of CPL’36 on Body Weight Reduction Preclinical study shows that CPL’36 treatment may lead to lower weight gain on Day 28 450 Body weight 400 body weight [g] * 350 300 Vehicle CPL'36 (0.6 mg/kg) 250 0 10 20 30 Day of treatment *The study was carried out on male Sprague-Dawley
Slide 6: CPL'36: Clinical Development Overview
CPL’36: Clinical Development Overview Q2 2021 – Q2 2024 100% 3 7 189 patients with acute 3 Phase 2 exacerbation Schizophrenia 2 doses vs placebo Q4 2018 – Q3 2019 Efficacy, Safety, PK MD (4 weeks) Top-line data are available 56 healthy volunteers NCT05278156 Phase 1 Safety, PK SD and MD (2 weeks) Q3
Slide 7: Clinical Development – Phase 1
Clinical Development – Phase 1 Phase 1 Readouts Compare Favorably to Other Compounds ng/ml*h ng/ml*h ng/ml*h ng/ml*h 7
Slide 8: Clinical Development – Phase 2 in Schizophrenia - Completed
Clinical Development – Phase 2 in Schizophrenia - Completed Phase 2 proof-of-concept design Screening Period and Washout Period Double-Blind Treatment Period Follow-up Period Up to 10 days Day 1 to 28 7 days (± 1 day) and 14 days (± 1 day) post last dose of IMP R E R Randomization Placebo (N=65) End
Slide 9: Phase 2 in Schizophrenia: Participant Disposition and Demographics
Phase 2 in Schizophrenia Participant disposition, demographics and baseline characteristics Patient Disposition Placebo, N=65 CPL’36 20 mg, N=58 CPL’36 40 mg, N=66 Randomized 65 (100.0%) 58 (100.0%) 66 (100.0%) Completed treatment, n (%) 53 (81.5%) 52 (89.7%) 52 (78.8%) Completed Follow-up period, n
Slide 10: CPL'36 Demonstrated Statistically Superior Improvement vs Placebo in Key Symptoms of Schizophrenia
CPL’36 Demonstrated Statistically Superior Improvement vs Placebo in Key Symptoms of Schizophrenia Change from baseline in PANSS total score Change from baseline in PANSS total score at Day 28 by randomized treatment 5 Placebo of CPL’36 or placebo CPL'36 20 mg CPL’36 Placebo, N=65 LSM CHANGE FROM BA
Slide 11: CPL'36 Efficacy Compares Favorably to SoC, KarXT and MK-8189
CPL’36 Efficacy Compares Favorably to SoC, KarTX and MK-8189 Today standard of Care (SoC) KarXT Phase II study MK-8189 Phase II study (atypical antipsychotics (emerging invastigational therapy) (emerging investigational therapy, risperidone, ariprazole) PDE10 potential competitor) 4,7ns 8,9-11,2 9,6
Slide 12: CPL'36: Summary of Safety and Tolerability in Phase 2
CPL’36: Summary of Safety and Tolerability in Phase 2 CPL’36 data showed a favorable tolerability profile* Safety profile of CPL'36 in Phase 2 study in Schizophrenia Placebo, CPL’36 20 mg, CPL5’36 40 mg, ▪ CPL’36 was generally well tolerated. Category N=65 N=57 N=65 ▪ There were only few TESAEs (1,5
Slide 13: Placebo Improvement in Randomized Studies in Schizophrenia is Recently Rising but the Range is Still Wide
Placebo Improvement in Randomized Studies in Schizophrenia is Recently Rising but the Range is Still Wide CPL’36 Phase 2 placebo improvement was approx 2 units in PANSS total score at week 4. It is within the range of placebo counts in Schizophrenia in the recent 2 decades Leucht et al., Am J Psychi
Slide 14: What Makes CPL'36 Unique?
What Makes CPL’36 Unique? Robust efficacy Potential best-in-class 2nd generation molecule Unique pharmacodynamic profile, distinct from other PDE10A inhibitors. Safe and free from metabolic adverse effects with procognitive effect. The safety and tolerability of CPL'36 were generally consistent duri
Slide 15: Thank You!