Cerevel Therapeutics Holdings Inc
Cerevel Therapeutics — SPAC Merger (July 2020)
68 slides from Cerevel Therapeutics's SPAC merger presentation, Jul 30, 2020
Slide 1: Transforming the Possible in Neuroscience
CONFIDENTIAL ©)cerevel Transforming the Possible in Neuroscience A Different Kind of Biopharma Company July 2020
Slide 2: Disclaimer
Disclaimer tation (*Presentation”) is for informational purposes only to assist interested parties in making their own evaluation nc. (*Cerevel” or the “Company”). The information contained herein does not purport to be all-inclusiv eries LLC and Goldman Sachs & Co. LLC nor any of their respective a
Slide 3: Investment Highlights
D Investment Highlights ieee Utilizing our differentiated understanding of disease-related biology and neurocircuitry of the brain with advanced chemistry to develop novel therapies for CNS diseases Broad portfolio of 11 assets targeting large markets with significant unmet need, including schizophr
Slide 4: Majority ownership; data-driven premier neuroscience company
Majority ownership ©cerevel = BainCapital — Pfizer) $350 million capital A data-driven premier Portfolio built on: commitment neuroscience company 10+ years of research $1 billion+ R&D investment 11 Neuroscience Novel targets; Experienced Development assets small molecules managementteam driven by d
Slide 5: Strong Track Record of Approvals
Strong Track Record of Approvals Tony Coles, M.D. Chief Executive Officer & Chairperson Kathy Yi Chief Financial Officer AbilifyMycite: Abilify Maintena Upton cre Raymond Sanchez, M.D. John Renger, Ph.D. Chief Medical Officer ®) Chief Scientific Officer eae Led by a Seasoned Life Sciences JYNARQUE*
Slide 6: Cerevel's Differentiated Approach to CNS Disease
‘ eres D Cerevel’s Differentiated Approach to CNS Disease ies me Pipeline Uniquely Based on Highly Selective Small Molecules — Created using Pfizer world-class chemistry Targeted Receptor Subtype Selectivity Receptor Binding/Modulation Optimized Receptor Pharmacology Differentiated Understanding of
Slide 7: Deep Pipeline: Multiple Value Inflections Near & Long-Term
D Deep Pipeline: Multiple Value Inflections Near & Long-Term Behs Sar 11 Assets ° x= Clinical Assets LRRK2* : =a 7 Programs Early Parkinson’s Late Parkinson’s Epilepsy Anxiety Schizophrenia Alzheimer’s Disease Apathy Substance Use Disorder Bec r Sobor sieren ose Skene) ay thet 8 Trials ta Phase 3 Tr
Slide 8: Cerevel Clinical Pipeline: Broad, Deep and Diverse
D Cerevel Clinical Pipeline: Broad, Deep and Diverse Compound Disease Area Eaten Tavapadon saan (adjunct with L-Dopa) eee Epilepsy CVL-865 Anxiety Substance Use Disorder Discov Pre-clini Phases Ph: Pt Mipopaupe Mechanism Milestone Ph. 3 Data Ds/D5 StrongPartial WW Agonist Ph. 3 Data Ph.2Data GABA, a
Slide 9: M4 PAM (CVL-231) in Schizophrenia
D M4 PAM (CVL-231) in Schizophrenia Selectively targeting the M4 muscarinic receptor with the goal of treating psychosis-related symptoms with improved side effect profile Gcerevel
Slide 10: M4 PAM (CVL-231) Opportunity for Innovation in Schizophrenia
M4 PAM (CVL-231) Opportunity for Innovation in Schizophrenia Potential New Standard of Care Current Standard of Care Uses Same Mechanism of Action (MOA) as Therapies from the 1950s 9 Te ~21M | >$oB | ~3.5% First-in-ClassTherapy [~ Market > Patients Revenues Growth with Novel MOA Worldwide in 2018 pe
Slide 11: M4 Receptor Activation Reduces Dopamine in the Striatum
D M4 Receptor Activation Reduces Dopamine in the Striatum Dopaminergic tone is CVL-231 enhances M4 : : auto-receptor activation Beano acethicrt direct in Hho nescence antagonistic activity on post- Neuron synaptic dopamine receptors Mg auto-receptor activation prevents additional Ach release cetylch
Slide 12: Cerevel's Selective M4 Modulation
DB Cerevel’s Selective M4 Modulation: A Compelling and Differentiated Approach to Drive Antipsychosis Other M4 Muscarinic Potential Muscarinic Receptors Effect Receptor - Antipsychosis Vv Vv Cognition v vv GI Side Effects os v Cardiovascular v CVL-231: Highly Selective Once-daily (QD) M4 PAM Xanomel
Slide 13: Cardiovascular Effects may be Attenuated with Titration and Repeat Dosing
D Cardiovascular Effects may be Attenuated with Titration and Repeat Dosing Repeated dosing of M4 Agonist Tool in rodents showed attenuation of cardiovascular effects without impact on antipsychotic activity; in addition, CVL-231 showed attenuation of heart effects in a 3-month canine toxicology stu
Slide 14: M4 PAM Ongoing and Planned Studies - Data Expected 2H21
D M4 PAM Ongoing and Planned Studies - Data Expected 2H21 Multiple Ascending Dose Primary Objective Safety & tolerability Secondary Objective PK Exploratory PD Assessment Positive and Negative Syndrome Scale (PANSS)* Clinical Global Impression — Severity Scale (ccI-s)* Brief Assessment of Cognition
Slide 15: Dementia-Related Psychosis: Potential Opportunity for CVL-231 Beyond Schizophrenia
D Dementia-Related Psychosis (DRP): Potential Opportunity for CVL-231 Beyond Schizophrenia DRP Overview and Unmet Needs” + Psychosis incidence ranges from 10-75% of Alzheimer’s patients and varies by stage of disease + Upwards of 1M moderate to severe Alzheimer’s patients in the G7 experience sympto
Slide 16: Potential Indications for M4 PAM Beyond Schizophrenia
D Potential Indications for M4 PAM Beyond Schizophrenia Pipeline in a Pill Goal to be a novel MOA and next generation treatment in Schizophrenia Aiming for a Side Effect and Tolerability Profile Appropriate for Chronic Use in Elderly Populations Potential Large Indications Worldwide Schizophrenia ~2
Slide 17: GABA PAM (CVL-865) in Epilepsy
D GABA PAM (CVL-865) in Epilepsy Selectively targeting the a-2/3/5 subunits of the GABA receptor with the goal of enhancing anti-convulsive effects without dose-limiting sedation < Geerevel @cereelTheapaticsing 17
Slide 18: Cerevel's GABA PAM has Potential for Benzo-like Activity
D Cerevel’s GABA PAM has Potential for Benzo-like Activity, Improved Side Effects and Chronic Dosing GABA PAM (CVL-865) Potential to become first-line and adjunct therapy Opportunity for New Treatment Option in Epilepsy HCPs and patients are dissatisfied due to insufficient activity, side effects an
Slide 19: The Problem With Benzodiazepines
D The Problem With Benzodiazepines (abridged...) * BZDs are efficacious in a range of indications but . . eee) ets sal experience with BZDs is use and dose is limited by adverse events, even at low receptor occupancy * Sedation, somnolence, cognitive impairment, falls, overuse, misuse and addiction
Slide 20: Selective GABA Receptor PAM: Potential for Lower Seizure Rates
D Selective GABA, Receptor PAM: Potential for Lower Seizure Rates, Reduced Side Effects GABA a-2/3/5 Can Differentially Address Symptoms CVL-865 GABA subtype predicted effects: Anti-convulsant Anxiolysis Analgesia Muscle Relaxation Sedation Cognitive Impairment Addiction GC) To our knowledge, CVL-86
Slide 21: GABA PAM Data Showed a Favorable Side Effect Profile
BD GABA PAM Data Showed a Favorable Side Effect Profile Relative to Benzodiazepines Multiple doses of CVL-865 Phase 1 MAD Study — only mild AEs and limited somnolence up to 42.5 mg BID Able to achieve >80% receptor occupancy without significant somnolence observed whereas Benzodiazepines achieve 10%
Slide 22: GABA PAM Phase 2 Data Showed Benzo-like Anticonvulsant Activity
Standardized Photosensitive Range ORI IG) . . te @) ere GABA PAM Phase 2 Data Showed Benzo-like Anticonvulsant cherie Activity in Photosensitive Epilepsy yet OK “ae CVL-865 in Single-Dose “Ces Photosensitive Epilepsy Study Treatment CVL-865 10 4 © Placebo s Qt eyes Anticonvulsant activity comparable
Slide 23: GABA PAM Phase 2 Design in Focal Onset Epilepsy
D GABA PAM Phase 2 Design in Focal Onset Epilepsy Data Expected 2H22 Targeting ~60 sites in 4 countries Inclusion criteria Adults (18-75) with drug-resistant focal onset epilepsy History of 4+ seizures per month for at least 3 months 1-3 stable background AEDs allowed Primary endpoint Reduction in f
Slide 24: Potential Indications for GABA PAM Beyond Epilepsy
D Potential Indications for GABA PAM Beyond Epilepsy Pipeline in a Pill Potential Large Indications Worldwide > Epilepsy ‘ieee 65M Patients Potential for benzo-like activity with targeted GABA a 2/3/5 receptor selectivity > Anxiety Disorders oy 13M Patients (G7) Benzos (Non-selective GABA Modulators
Slide 25: Tavapadon in Parkinson's Disease
D Tavapadon in Parkinson’s Disease Partial agonist selectively targeting the dopamine D1 receptor with the goal of enhancing motor control while minimizing side effects erevel
Slide 26: Tavapadon has Potential to be a Differentiated Treatment for Parkinson's
OILED EF n . . 7 x GR OK®)) BD Tavapadon has Potential to be a Differentiated Treatment for Parkinson Su er Designed to be a novel backbone therapy for patients from diagnosis to the end of treatment: ) Bice Only* D1/D5 selective Avoid D2/D3 Side Effects: Sudden daytime somnolence, ta molecule hallu
Slide 27: Tavapadon Designed to Address Unmet Needs Across All Stages of Parkinson's
CXS OKOMDRCX GO) . ox: phen p Tavapadon Designed to Address Unmet Needs Across All Stages ters j rae @) of Parkinson’s: Early and Late “tH S Ds Early-Stage Parkinson’s Mid-Stage Parkinson’s Late-Stage Parkinson’s oes < MAO-B On D2/D3 MAO-B oe D2/D3 Escalating Doses Inhibitors Agonists Inhibitors“! A
Slide 28: Selective Direct Motor Pathway Activation in Early Parkinson's
Selective Direct Motor Pathway Activation Designed to Provide ef se Differentiated Treatment Option in Early Parkinson’s eosctere) es Potential for motor control as good or better than D2/D3s with once-daily dosing gee and improved side effect profile ai! S Phase 2 Data: Tavapadon in Early PD* Addit
Slide 29: Ongoing Registration-Enabling Global Phase 3 Program (Early PD)
D Ongoing Registration-Enabling Global Phase 3 Program CG) Three Phase 3 trials optimally designed to maximize treatment effect Early PD: Data Expected 2H23 Key inclusion criteria - Adults 40-80 years old - Baseline MDS-UPDRS® Part III Score >10 and Part II Score >2 + Modified Hoehn & Yahr®) stage 1
Slide 30: Predictable 24-hour Activity: Once Daily, Oral Dosing
D Predictable 24-hour Activity > Sustained Effect: Once Daily, Oral Dosing eiere ee Oy Ec Phase 1B: Sustained Motor Control on par with L-Dopa Sx € L-Dopa vs. Tavapadon in Late-Stage PD* Study 1005: Tavapadon in Late-Stage PD? mos: L-Dopa is a FULL agonist with SHORT half-life aa H . fl eae &2 paiva
Slide 31: Tavapadon Phase 2 Results: Clinically Meaningful ON-Time
> Tavapadon Phase 2 Results: Clinically Meaningful ON-Time without Troublesome Dyskinesias Tavapadon generally demonstratedat least 1 hour of improvement in ON-time without troublesome dyskinesias in late-stage PD N= 6 8 6 37 5 6 7 32 3 Fy 5 25 a: a 5 14 = r en z of i2.03 ‘75mm g 1 . 10 129) | fg205
Slide 32: Ongoing Registration-Enabling Global Phase 3 Program (Late PD)
D Ongoing Registration-Enabling Global Phase 3 Program CG) Three Phase 3 trials optimally designed to maximize treatment effect Late PD: Data Expected 1H23 Adjunct to levodopa 27 Weeks Treatment Key inclusion criteria + Adults 40-80 years old FLEXIBLE - At least 2.5 hours OFF-time on 2 DOSE consecut
Slide 33: Tavapadon Commercial Potential in Parkinson's
DB Tavapadon Commercial Potential in Parkinson’s Tavapadon Novel Di/D5 Potential similar or Potential favorable Once-daily Target Profile mechanism better motor control side effect profile dosing Pricing & Launch Branded US price Payor research supports Strong side effect profile and Patients and ph
Slide 34: Slide 34
Slide 35: Expected Portfolio Timeline
D Expected Portfolio Timeline Phase 1b / : —_+ Schizophrenia CVL-865 GABA Phase 1 / Anxiety a CVL-865 GABA Phase 2/ Epilepsy *> o Fixed Dose (CVL-751-PD-001) ri Tavapadon Phase 3 / Early PD Flex Dose (CVL-751-PD-002) *> « aa Phase 3 /Late PD > dopa) Phase 2a / Alzheimer’s > o _ Disease Apathy Phase
Slide 36: Cerevel is Transforming Possibilities for Tomorrow
Cerevel is Transforming Possibilities for Tomorrow Multiple Programs Aimed at Providing New Options for Millions of Patients Schizophrenia Epilepsy Parkinson's Alzheimer’s Psychosis Anxiety Apathy Substance Abuse Disorder Disease-modifying therapies based on human genetics and novel targets addressi
Slide 37: Summary
Summary Three Lead NCEs Across Five Clinical Programs M4 PAM (CVL-231) in Schizophrenia: Selectively targetingthe M4 muscarinic receptor GABA PAM (CVL-865) in Epilepsyand Anxiety: Selectively targeting GABA receptor a-2/3/5 subunits Tavapadon in Early-and Late-Stage Parkinson’s Disease: Potential fi
Slide 38: Cerevel and ARYA II to Combine
D Cerevel and ARYA II to Combine
Slide 39: Combination with ARYA II - Transaction Summary
DB Combination with ARYA II — Transaction Summary Cerevel Therapeutics, Inc. (“Cereval”) and ARYA Sciences Acquisition Corp IT (“AVRA IT”, Nasdaq: ARYB) tomergepursuantto abusiness combination agreementto be entered intobetween ARVAII and Cereval Cerevelisa cinical-stagebiopharmacentical company tha
Slide 40: Terms of Transaction
D Terms of Transaction Shares and $ in thousands (other than shareprice) Pro Forma Valuation Sources of Funds “3) Uses of Funds Pro Forma Shares Outstanding 129,187 Implied Share Price $ 10.00 itty Tessa tS Cetera ; Cash Held in Trust $ 149,500 | | Shareholders PF Equity Value $1291865 | | Cee Share
Slide 41: Use of Proceeds
axcnenes D Use of Proceeds eee 2 Approximately $445 million of post-transaction cash projected on the combined company balance sheet to ie) pursue Cerevel's research and development programs € Expected to provide cash runway into 2023 Projected proceeds will be primarily used to fund Cerevel's resea
Slide 42: Appendix
D Appendix
Slide 43: Combination with ARYA II - Key Highlights
D Combination with ARYA II - Key Highlights = Provides a faster path to becoming a public company Addresses one of the leading questions from potential crossover investors by enabling Cerevel to go public “te in one step vs. a typical two step process including crossover and IPO Provides an investme
Slide 44: M4 PAM (CVL-231) in Schizophrenia: Additional Slides
D M4 PAM (CVL-231) in Schizophrenia Additional Slides
Slide 45: Xanomeline Clinical Data: Compelling Activity, Limited by Side Effect Profile
DB Xanomeline Clinical Data: Compelling Activity, Limited by Side Effect Profile 2008 Phase 2 in Schizophrenia Mien . fn im a — hy oy nm Pi I O = tn kay) ag wean yoy <a 3° 7 ao i | os, ‘as Re Sane “mm Si Statistically significant 2% 4 ] | | = o 2 Ro ie impactontotalBPRS £§ : & S- i 2 i ig i ¢ and PA
Slide 46: Preclinical Evidence: M4 Modulation Drives Antipsychosis
D Preclinical Evidence: M4 Modulation Drives Antipsychosis No Effect of Xanomeline in M4 Knock-out Mouse Model Reduction in Hyperactivity in M1 Knock-out Mice i q 2 i | xan 0.5/Sal (Xan 1.0/Sal @asalAmph (Z2Xan 0.5/Amph 29 Xan 1.0/Amph Box crossing (counts) 8 8 8 8 Box crossing (counts) 8 8 8 8 Xano
Slide 47: Important Insights on Side Effects of M4 PAM
D Important Insights on Side Effects of M4 PAM Results of a Phase 1 SAD trial indicated CVL-231 was generally well-tolerated with asymptomatic transient effects on heart rate and blood pressure Phase 1 SAD Trial (N=17) Insights Tested doses up to 30 mg Preclinical studies show CV effects attenuated
Slide 48: + Randomized double-blind proof g_,°
+ Randomized double-blind proof g_,° of-concept trial as adjunctive $7) AEs (>5%) (m=119) therapy in mild-to-moderate as] — pine aes) a a 7(6.8%) Alzheimer's disease st ane a-- MK-7622(n-64) * Conducted by Merck; data 2 05 Headache 11 (9.296) 6 (5.0%) published 2018 & 0 - + Trial stopped early for f
Slide 49: M4 PAM Preclinical Data in Psychosis
D M4 PAM Preclinical Data in Psychosis 96PPL Total Distance (em) Dose (mg/kg) In multiple rodent models of psychosis, CVL-231 demonstrated antipsychotic activity consistent with xanomeline and atypical antipsychotics
Slide 50: CVL-231 Commercial Potential in Schizophrenia
D CVL-231 Commercial Potential in Schizophrenia Potential for CVL-231 to be a New Standard of Care + Potential for improved SE profile could position CVL-231 as first-line treatment of newly diagnosed and ongoing schizophrenia patients, including DRP + Ifan improved tolerability and metabolic profil
Slide 51: Schizophrenia Therapies: Rapid Historic Uptake Despite Limited Differentiation
D Schizophrenia Therapies: Rapid Historic Uptake Despite Limited Differentiation Da US 2018 2018 Schizophrenia US Sales Ramp — Actuals eee) 8 Schizophrenia Sales US Share (through 2018 or untilfirst non-schizophrenia indication launch) > Latuda Salezwntepprocl (urasidone) $973M 13.5% 100% diner 90%
Slide 52: GABA PAM (CVL-865) in Epilepsy: Additional Slides
D GABA PAM (CVL-865) in Epilepsy Additional Slides @cerevel @cereethenpaaisine 52
Slide 53: OOO rs65
OOO rs65 is designed to selectively enhance GABA, GABA is the major inhibitory neurotransmitter that dampens down neuronal hyperexcitation e@ Anticonvulsant Cortex — BGPOD SBWOO mons @ senzodiazepines non-selectively Basal enhance GABA, receptor activity, which can cause side effects primarily drive
Slide 54: CVL-865: Favorable Pharmacology in NeuroCart
D CVL-865: Favorable Pharmacology in NeuroCart, Differentiated From a BZD » NeuroCart is a comprehensive battery of tests to evaluate CNS functional domains + CVL-865 first-in-human study tested the following brain functions based on known GABA, receptor pharmacology: + Saceadic peak velocity (SPV)
Slide 55: CVL-865 was Anticonvulsant in a Range of Preclinical Models
D CVL-865 was Anticonvulsant in a Range of Preclinical Models Site ies Se + Strong correlation of animal models of seizures translating to clinical activity across mechanism “ee as * CVL-865 demonstrated broad spectrum of activity : + Amygdala kindling is a validated model for predicting activity in
Slide 56: CVL-865 TPP: Benzo-like Activity for Chronic Treatment
D CVL-865 TPP: Benzo-like Activity for Chronic Treatment ie oe CVL-865 Summary Pricing & Launch Se © Large markets (Focal & Generalized) High branded sales despite many generics e Novel mechanism Branded US price analogs >$10K/year Potential for better activity than chronic treatment alternatives Co
Slide 57: History of CVL-865 Development
D History of CVL-865 Development Results of early clinical trials were believed to be limited by Pfizer's self-imposed dosing cap Micronuclei March 2017: formation observed in 2014: FDA Response to Type C early preclinical rat. -—- Multiple Early Phase 1 meeting Request studies studies . rao: Permit
Slide 58: Prior Clinical Studies in Anxiety and Chronic Low Back Pain
D Prior Clinical Studies in Anxiety and Chronic Low Back Pain Use of subtherapeutic doses and small sample size believed to account for lack of activity in prior tri iat pe Phase 2: Generalized Anxiety Disorder Phase 2: Chronic Low Back Pain “ax + Included drug-resistant patients on continued backgr
Slide 59: CVL-865 Favorable Side Effect & Tolerability Profile Across Trials
CORIO) D CVL-865 Favorable Side Effect & Tolerability Profile Across Tr eee ter CVL-865 has been tested in 289 subjects and was generally well-tolerated. There have been no clinically significant side ‘~~ Oxo effect observations from physical examination, vital sign measurements, laboratory safety a
Slide 60: CVL-865: Phase 1 Program in Acute Anxiety
D CVL-865: Phase 1 Program in Acute Anxiety HYPERCAPNIA: PROOF-OF-PRINCIPLE MODEL FOR GABA (PAM) ANXIOLYTIC ACTIVITY KEY TRIAL DESIGN ASPECTS * CO, inhalation challenge (hypercapnia) Healthy volunteers well established in healthy volunteers and patients with panic disorder Primary endpoints: Panic s
Slide 61: Tavapadon in Parkinson's Disease: Additional Slides
D Tavapadon in Parkinson’s Disease Additional Slides @cerevel 61
Slide 62: Parkinson's Disease Overview
. 7 : D Parkinson’s Disease Overview ay Parkinson’s disease is a progressive neurodegenerative disorder affecting regions of the brain that control balance and movement gee ee Description Common Symptoms os: < + Parkinson’s disease is a degenerative neurological disorder + Symptoms of Parkinson’s di
Slide 63: Selectively Targeting Partial Agonism Designed to Improve Motor Control and Tolerability
“Os pce D Selectively Targeting Partial Agonism Designed to Improve Motor: er Control and Tolerability Di/D5 Receptor Selectivity D2/D3 Di/D5 Activation Potential Activation (ndirect Pathway) Effect (irect Pathway) Fs Motor Control ++ Cognition t+ Motivation / Drive na Dose-Limiting - Hypotension Im
Slide 64: First Partial Agonist for Parkinson's Avoids Dyskinesias
Dp First Partial Agonist for Parkinson’s > Avoids Dyskinesias Unique and attractive combination of activity and low dyskinesias in highly translatable model of Parkinson's Effect of Tavapadon vs. L-dopa Potential to Reduce L-dopa Dose to Achieve on Disability and Dyskinesia Motor Control with Reduce
Slide 65: Phase Program Designed to Show Superior Treatment Profile
Bec ro cbrereierens D Phase 3 Program Designed to Show Superior Treatment Profile cherie : Phase 2 Results Inform Phase 3 Design “eee OK as Phase 2 Results Phase 3 Design os: Baseline score of 2 or . MDS-UPDRS III MDS-UPDRS II+III greater on Placebo Attenuation MBS-UPDRSII at 6 Months Primary ron —
Slide 66: D2/D3 Side Effects
D2/D3 Side Effects: Somnolence (Monotherapy) 40% Requip Nausea (Monotherapy) 60% Requip Sudden daytime somnolence is safety concern, but rates are not reported in labels 22% 956 ‘Mirapex ‘Neupro (6mg) 48% 28% Mirapex ‘Neupro (6mg) Sudden daytime somnolence, hallucinations, nausea and acute orthostas
Slide 67: Overview of Tavapadon Clinical Trials To Date
D Overview of Tavapadon Clinical Trials To Date ate) eoclen Ox) Bete ae OX B7601001 Phases 7Feb2014 18/18 Single ascending dose (0.25-2.5mg)in healthy volunteers (HV) a B7601002 Phase 16Apr 2015 61/77 Multiple ascending dose study in HV (0.5-5mgQD) By601007 Phases o4Dec2014 9/9 Single ascending dose
Slide 68: Thank you
Thank you Contact: Matt Calistri Investor Relations [email protected]