Slide 1: CPL'36 Unlocking New Possibilities in LiD Treatment – Phase 2 Top-Line Results
CPL’36 Unlocking New Possibilities in LiD Treatment – Phase 2 Top-Line Results
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) Mechanizm of PDE10A inhibitor – potentially best- Action in-class 2nd generation molecule Schizophrenia Market Potential Route of Oral, QD administration 24M $8,1B +3,9% Patients Population Global M
Slide 3: Mode of Action
Mode of Action PDE10A modulates corticolstriatal circuits by a balanced activation of in- and direct pathways Schizophrenia Parkinson’s disease and L-DOPA induced dyskinesia (LiD) PDE10A is highly enriched in striatal Pathophysiology state of Parkinson’s medium spiny neurons expressing D1 diseas
Slide 4: CPL'36 Exerts Antidyskinetic and Antiparkinsonian Action in Animal Model of LID
CPL’36 Exerts Antidyskinetic and Antiparkinsonian Action in Animal Model of LID Domain Test MED [mg/kg] Stepping test 0,1 Antiparkinsonian action Cylinder test 0,3 (6-OHDA lesion) Deacreasing action of L-DOPA ND Antidyskinetic action Antidyskinetic action for developed diskinesia 0,03 (6-OHDA lesion
Slide 5: 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 readouts are available 56 healthy volunteers NCT05278156 Phase 1 Safety, PK SD and MD (2 weeks
Slide 6: Long-Term Levodopa Treatment: Fluctuations in Response and Motor Complications
Long-Term Levodopa Treatment: Fluctuations in Response and Motor Complications (dyskinesias) More than 50% of patients develop fluctuations of response to levodopa after 5 to 10 years of treatment. Significantly bothersome and often have a pronounced negative effect on patient motor function. Ap
Slide 7: CPL'36: Competitive landscape
CPL’36: Competitive landscape Intestinal Treating motor fluctuations and dyskinesia levodopa infusion Oral Levodopa On-Demand Adjunctive Deep brain stimulation Dose Adjustments Therapies Therapies Advanced Stimulation of the globus Dopamine SC (Surgical) pallidus interna or Increase subthalamic nucl
Slide 8: Competitive Landscape Analysis for LiD
Competitive Landscape Analysis for LiD Approved therapies GOCOVRI (Supernus Pharmaceuticals) Amantadine ER has undergone pivotal Phase 3 clinical trials to evaluate its efficacy and safety in managing levodopa-induced dyskinesia (LID) in patients with Parkinson’s disease. The clinical Mechanism: Ext
Slide 9: Parkinson's Disease Levodopa-induced Dyskinesia Emerging Drugs
Parkinson's Disease Levodopa-induced Dyskinesia Emerging Drugs Late-Stage Pipeline Candidates Mesdopetam (IRLAB Therapeutics) JM-010 (Bukwang Pharmaceutical/Contera Pharma) Mechanism: D3 antagonist with agonist-like binding properties. Mechanism: Combination of buspirone (5-HT1A agonist) and zolmitr
Slide 10: CPL'36: Market Potential
In prospective controlled trials, Reported incidence 40% to 50% of those with of dyskinesia after CPL’36: Market Potential Treatment 10-15+ years of levodopa PD develop dyskinesia after 5 initiation with treatment as high as levodopa years of treatment 90% to 95% Levodopa-induced dyskinesia I N C R
Slide 11: Clinical Development Plan - Phase 2 in LiD - Completed
Clinical Development Plan - Phase 2 in LiD - Completed Phase 2 Proof-of-concept design Screening Period Baseline Period Double-Blind Treatment Period Follow-up Period Days 35 (± 1 day) Up to 24 days Up to 4 days Day 1 to 28 and 42 (± 1 day) R E R Randomization Placebo (N=34) End of treatment E &prim
Slide 12: Phase 2 in Levodopa Induced Dyskinesia (LiD)
Phase 2 in Levodopa Induced Dyskinesia (LiD) Participant disposition, demographics and characteristics at baseline Patient Disposition Placebo, N=34 CPL’36 20 mg, N=36 CPL’36 40 mg, N=35 Randomized 34 (100.0%) 36 (100.0%) 35 (100.0%) Completed treatment, n (%) 30 (88.2%) 29 (80.6%) 29 (82.9%) Comple
Slide 13: CPL'36 Significantly Reduces Dyskinesia Symptoms in UDysRS – Primary Endpoint
CPL'36 Significantly Reduces Dyskinesia Symptoms in UDysRS – Primary Endpoint 39% improvement in dyskinesia with CPL’36 (in UDysRS from baseline) Change from baseline in total UDysRS score at Week 4 by randomized treatment of CPL’36 or placebo (FAS) CPL’36 Placebo, N=34 20 mg, N=36 40 mg, N=35 mean
Slide 14: CPL'36 Significantly Reduces Dyskinesia Symptoms in UDysRS – Primary Endpoint
CPL'36 Significantly Reduces Dyskinesia Symptoms in UDysRS – Primary Endpoint 39% improvement in dyskinesia with CPL’36 (in UDysRS from baseline) 0 -5 LS Mean (SE) Change in UDysRS CPL’36 demonstrates significant -10 reduction improvement in UDysRS scores over placebo at Week 4, comparable to -15 **
Slide 15: CPL'36 Shows Promising Impact on Dyskinesia: Significant Functional Improvement at Week 4
CPL'36 Shows Promising Impact on Dyskinesia: Significant Functional Improvement at Week 4 Secondary outcome measures Indirect comparison. Efficacy of CPL'36 and Amantadine ER in reducing dyskinesia: comparative changes in MDS-UPDRS part 4/A scores, LS Mean (SE): CPL’36 change from baseline in MDS-UP
Slide 16: CPL'36: Safety and Tolerability in Phase 2
CPL’36: Safety and Tolerability in Phase 2 CPL’36 data showed a favorable safety and tolerability profile* Safety profile of CPL'36 in Phase 2 study in LiD Category Placebo, CPL’36 20 mg, CPL’36 40 mg, CPL'36 demonstrated an acceptable safety N=34 N=36 N=35 profile with no major safety signals in
Slide 17: CPL'36: Free from Typical Amantadine ER-Related Adverse Events in Phase 2 LiD Study
CPL'36: Free from Typical Amantadine ER-Related Adverse Events in Phase 2 LiD Study No reported hallucinations, peripheral edema, or constipation—key side effects commonly associated with Amantadine ER Indirect comparison. Amantadine ER Pooled results from CPL’36 - Phase 2 in LiD EASE LID 3 and EASE
Slide 18: What Makes CPL'36 Unique?
What Makes CPL’36 Unique? 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 during clinical deve
Slide 19: Thank You!