Cerevel Therapeutics Holdings Inc
Cerevel Therapeutics — Corporate Update (June 2021)
22 slides from Cerevel Therapeutics's corporate update, Jun 29, 2021
Slide 1: Topline Data for Phase 1b Trial of CVL-231 in Schizophrenia
Transforming the Possible in Neuroscience Topline Data for Phase 1b Trial of CVL-231 in Schizophrenia June 2021 Exhibit 99.2
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements that are based on management’s beliefs and assumptions and on information currently available to management. In some cases, you can identify forward-looking statements by the following words: “may,” “will,” “could,” “wo
Slide 3: Agenda
Agenda Introduction Overview CVL-231 Background and MOA Trial Design & Results Q&A All Matthew Calistri Vice President, Investor Relations Tony Coles, M.D. Chairperson & Chief Executive Officer John Renger, Ph.D. Chief Scientific Officer Raymond Sanchez, M.D. Chief Medical Officer
Slide 4: Summary of Topline Results
Summary of Topline Results Both doses of CVL-231 demonstrated clinically meaningful improvements in PANSS Total Score: 30 mg QD: -19.5 pts at week 6 20 mg BID: -17.9 pts at week 6 Statistically significant difference in PANSS Total Score versus placebo*: 30 mg QD: -12.7 pts (p=0.023) at week 6 20 mg
Slide 5: Cerevel's M4 PAM is a Potential Next Generation Antipsychotic
60% Cerevel’s M4 PAM is a Potential Next Generation Antipsychotic Side Effect and Tolerability Issues Potential First-in-Class Therapy with Novel MOA M4 Selective Targeted Muscarinic Activity Improved Tolerability Opportunity for Innovation in Schizophrenia Current Standard of Care Uses Same Mechani
Slide 6: Overview & Summary of CVL-231
Overview & Summary of CVL-231 CVL-231 is designed to be a novel once-daily treatment that selectively targets the M4 muscarinic receptor with the potential to provide antipsychotic activity while minimizing side effects
Slide 7: M4 Receptor Activation Reduces Dopamine in the Striatum
M4 Receptor Activation Reduces Dopamine in the Striatum Potential for Decreased Psychosis In the absence of Ach, dopamine output decreases, which dampens hyperdopaminergic activity in striatum Dopamine Nicotinic Receptors Originates from Ventral Tegmental Area (VTA) Dopamine Neuron Schizophrenia sym
Slide 8: M4 Selectively Impacts Brain Functions
Other Muscarinic Receptors Potential Effect M4 Muscarinic Receptor - Antipsychosis üü üü Cognition ü üü GI Side Effects - ü Cardiovascular ü M4 Selectively Impacts Brain Functions Receptor Subtype Selectivity Offers Potential Improvement Xanomeline (M1/M4) data from Schizophrenia and Alzheimer’s pat
Slide 9: Trial Design & Results
D Trial Design & Results i Care
Slide 10: CVL-231 Phase 1b Trial Design
CVL-231 Phase 1b Trial Design * Trial not designed to demonstrate statistical significance Exploratory PD Assessment Positive and Negative Syndrome Scale (PANSS)* PANSS Positive Score PANSS Negative Score Clinical Global Impression – Severity Scale (CGI-S)* Brief Assessment of Cognition in Schizophr
Slide 11: Phase 1b Part B: Demographics & Baseline Characteristics
Phase 1b Part B: Demographics & Baseline Characteristics PBO N= 27 PBO N= 27 CVL-231 30 mg QD N= 27 CVL-231 20 mg BID N= 27 All CVL-231 N= 54 Total N= 81 Demographics Age (years) at Screening: Mean (SD) 41 (9.7) 41 (9.7) 41 (8.1) 38(9.8) 40(9.0) 40(9.2) % Male: N (%) 19 (70%) 19 (70%) 23 (85%) 21 (7
Slide 12: Key Pharmacodynamic Assessments
Key Pharmacodynamic Assessments
Slide 13: Pharmacodynamic Results Summary
Pharmacodynamic Results Summary* Week 6 (Day 42) Placebo N=27 CVL-231 30 mg QD N= 27 CVL-231 20 mg BID N= 27 Combined CVL-231 N=54 PANSS Total Score LS Mean Change from Baseline -6.8 -19.5 -17.9 -18.7 Difference vs Placebo (p-value)† -12.7† p = 0.023 -11.1† p = 0.047 -11.9† p = 0.014 PANSS Positive
Slide 14: Key Pharmacodynamic Endpoint – PANSS Total Score
Key Pharmacodynamic Endpoint – PANSS Total Score 30 mg QD: 12.7 Point improvement versus placebo at Week 6 (19.5 of 30 mg QD vs 6.8 placebo) with P=0.023 20 mg BID: 11.1 Point improvement versus placebo at Week 6 (17.9 of 20 mg BID vs 6.8 placebo) with P=0.047 Combined CVL 231: 11.9 Point improvemen
Slide 15: PANSS Positive Symptoms Score
PANSS Positive Symptoms Score * P<0.05 vs Placebo ** P<0.01 vs Placebo 30 mg QD: 4.3 Point improvement versus placebo at Week 6 (6.8 of 30 mg QD vs 2.5 placebo) with P=0.016 20 mg BID: 2.4 Point improvement versus placebo at Week 6 (4.9 of 20 mg BID vs 2.5 placebo) with P=0.166 Combined CVL 231: 3.3
Slide 16: PANSS Negative Symptoms Score
PANSS Negative Symptoms Score * P<0.05 vs Placebo ** P<0.01 vs Placebo 30 mg QD: 3.1 Point improvement versus placebo at Week 6 (3.0 of 30 mg QD vs -0.1 placebo) with P=0.009 20 mg BID: 3.7 Point improvement versus placebo at Week 6 (3.6 of 20 mg BID vs -0.1 placebo) with P=0.002 Combined CVL 231: 3
Slide 17: Safety & Tolerability
D Safety & Tolerability
Slide 18: Safety & Tolerability – Adverse Events
Safety & Tolerability – Adverse Events PBO N= 27 CVL-231 30 mg QD N= 27 CVL-231 20 mg BID N= 27 All CVL-231 N= 54 Days on IMP Mean (SD) 37 (9.6) 36 (12.8) 35 (13.6) 36 (13.1) Range 8, 42 4, 42 2, 42 2, 42 Number (%) Subjects with TEAE 14 ( 52%) 14 ( 52%) 15 ( 56%) 29 ( 54%) Number (%) Subjects with
Slide 19: Safety & Tolerability – Adverse Events
Safety & Tolerability - Adverse Events PBO N= 27 CVL-231 30 mg QD N= 27 CVL-231 20 mg BID N= 27 All CVL-231 N= 54 Number (%) Subjects Headache 7 ( 26%) 8 ( 30%) 7 ( 26%) 15 ( 28%) Nausea 1 ( 4%) 2 ( 7%) 2 ( 7%) 4 ( 7%) Back pain 1 ( 4%) 2 ( 7%) 1 ( 4%) 3 ( 6%) Blood creatine phosphokinase increased
Slide 20: Serious Adverse Events and AESIs
* AESIs specified in the protocol include 1. AEs that result in the discontinuation of treatment with IMP, 2. events that satisfy the criteria for suspected Hy’s Law (ALT or AST >3 × ULN, AND serum bilirubin ≥2 × ULN, AND alkaline phosphatase <2 × ULN), 3. events of heart rate >120 bpm, and confirme
Slide 21: Summary of Topline Results
Summary of Topline Results Both doses of CVL-231 demonstrated clinically meaningful improvements in PANSS Total Score: 30 mg QD: -19.5 pts at week 6 20 mg BID: -17.9 pts at week 6 Statistically significant difference in PANSS Total Score versus placebo*: 30 mg QD: -12.7 pts (p=0.023) at week 6 20 mg
Slide 22: Multiple Milestones Expected Over Next Three Years
Multiple Milestones Expected Over Next Three Years Compound Mechanism Phase / Disease Area 2023 Estimated Trial Initiation Estimated Topline Data Darigabat Phase 1 / Anxiety GABA Darigabat Phase 21 / Epilepsy GABA CVL-231 M4 CVL-936 Phase 12 / Substance Use Disorder D3 Phase 1b / Schizophrenia CVL-8
Cerevel Therapeutics Holdings — Corporate Update (June 2021) on 6ix