It s time. for a new approach to treat chronic neurological diseases Adamas Pharmaceuticals, Inc. All Rights Reserved.

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1 It s time for a new approach to treat chronic neurological diseases

2 Forward-looking statements Statements contained in this presentation regarding expected future events are forward-looking statements within the meaning of the Private Securities Litigation Reform Act of These statements are subject to significant risks and uncertainties, actual results could differ materially from those projected and Adamas cautions investors not to place undue reliance on the forwardlooking statements contained in this presentation. These risks and uncertainties include, without limitation, risks and uncertainties related to market conditions and satisfaction of customary closing conditions related to the public offering. There can be no assurance that Adamas will be able to complete the public offering on the anticipated terms, or at all. Risks and uncertainties relating to Adamas and its business can be found in the Risk Factors section of Adamas Form 10-Q filed with the SEC on May 3, Adamas undertakes no duty or obligation to update any forward-looking statements contained in this presentation as a result of new information, future events or changes in Adamas expectations. 2

3 Investment thesis Building a multi-product neuroscience company based upon time-dependent biology approach Products designed to maximize efficacy without compromising tolerability Yields differentiated, durable and protectable products/product candidates Launching GOCOVRI for dyskinesia in people with Parkinson s disease receiving levodopa-based therapy First and only medicine approved by the FDA for this indication First medicine clinically demonstrated to reduce both dyskinesia and OFF Non-dopaminergic/glutamate pathway treatment Advancing a robust portfolio of clinically differentiated assets ADS-5102 (GOCOVRI): initiated Phase 3 study in multiple sclerosis walking ADS-5102 (GOCOVRI): evaluating additional indications ADS-4101: positive feedback form FDA on planned Phase 3 program Additional research programs Financially sound $286.7M cash, cash equivalents and investments as of March 31,

4 Adamas is rooted in an understanding of time-dependent biology Address neurologic disorders with significant patient, care partner and societal burden understand + map timing patterns create medicines to match disease / drug timing develop for efficacy, maintain tolerability significant impact 4

5 Adamas portfolio Disease Program Phase 1 Phase 2 Phase 3 Approved/ Commercial Commercial Lead Dyskinesia in Parkinson s Disease Multiple Sclerosis Walking Additional Indications GOCOVRI (amantadine) ADS-5102 (amantadine) (GOCOVRI) ADS-5102 (amantadine) (GOCOVRI) Epilepsy Partial Onset Seizures ADS-4101 (lacosamide) Alzheimer s Dementia NAMZARIC (memantine HCl & donepezil HCl) (US) Additional product candidates in research based on potential new discoveries in Parkinson s disease, multiple sclerosis, epilepsy, and psychiatry. NAMZARIC is a trademark of Merz Pharma GmbH & Co. KGaA. 5

6 Dyskinesia in people with Parkinson s disease Physicians and patients struggle to balance dyskinesia and OFF Levodopa and disease progression drive changes that cause dyskinesia and OFF Levodopa is the gold standard treatment for Parkinson s disease to replace dopamine 1 As Parkinson s disease progresses, levodopa dysregulates the glutamate system leading to dyskinesia and OFF 2, 3 Limits the use of levodopa Dyskinesia and OFF affect 400k in the U.S., with k impacted by dyskinesia 4-6 Economic impact of Parkinson s disease is growing as population ages: >$20B by ,8 Significant impact on activities of daily living 9 Adamas focused on designing a novel time dependent solution Dyskinesia and OFF follow a diurnal pattern, more dyskinesia during the day 10, sleep disturbed at night Hornykiewicz, J Neurol (2010) 257 (Suppl 2):S249 S252; 2. Sgambato-Faure, Progress in Neurobiology 96 (2012) 69 86; 3. Shen, Science (2008), Vol 321; 4. Data on file, Adamas Pharmaceuticals, Inc, Emeryville, CA; 5. Paralysis Agitans IMS NDTI 2012; 6. Schrag, Brain (2000), 123, ; 7. Data on file; 8. Kowal, Mov Disord (2013), Vol. 28, No. 3, ; 9. Pahwa, Poster presented at 4th World Parkinson Congress, September 20 23, 2016, Portland, OR; 10. Pahwa, JAMA Neurol (2017), 74 (8), ; 11. Bruguerolle, Clin Neuropharmacology (2002), Vol. 25, No. 4, pp

7 Dyskinesia and OFF result in a narrowing therapeutic window and difficult choices Aberrant NMDA receptor / glutamate signaling is involved in the progression of Parkinson s disease and the occurrence of dyskinesia and OFF Disease progression NMDA receptor dysregulation 1 Dyskinesia High levodopa levels result in dyskinesia Dopamine release Narrowing Therapeutic window 3 NMDA receptor dysregulation Normal buffering capacity 2 OFF Low levodopa levels result in OFF Levodopa doses: 1. Sgambato-Faure, Progress in Neurobiology 96 (2012) 69 86; 2. Carta, Brain (2007), 130, ; 3. Jankovic, Mov Disord (2005), Vol. 20, Suppl. 11 7

8 First and Only FDA-Approved Medicine for Treatment of Dyskinesia in Patients with Parkinson s Disease 1 FDA-approved medicine for treatment of dyskinesia in patients with Parkinson s disease receiving levodopa-based therapy, with or without concomitant dopaminergic medicines. The most common adverse reactions with GOCVORI were hallucinations, dizziness, dry mouth, peripheral edema, constipation, falls and orthostatic hypotension 1 1. GOCOVRI Package Insert 8

9 GOCOVRI unlocks the potential of amantadine Designed to match the timing pattern of disease and drug response Bedtime dosing with GOCOVRI provides amantadine plasma concentrations that are: Rises slowly during the night High upon waking and throughout the day Lower in the evening and nighttime Data from 2 pivotal, placebo-controlled studies demonstrated: Significant reduction in dyskinesia Secondary benefit in reduced OFF time Open-label study supports durability out to 2 years Most common AEs were hallucinations, dizziness, dry mouth, peripheral edema, constipation, falls and orthostatic hypotension Steady state profile of GOCOVRI 274 mg QHS is scaled from steady-state data from GOCOVRI 137 mg QHS based on demonstrated dose-proportionality and reduced renal clearance seen in PD patients (70 ml/min/1.73m 2 ). Amantadine IR steady state profile was simulated based on a model generated from steady-state data of amantadine IR bid (8 pm and 8 am) and scaled based on reduced renal clearance seen in PD patients (70 ml/min/1.73m 2 ). 1. Hauser, Clinical Pharmacokinetics, 2018; 2. Pahwa, Mov Disord, 2015; QHS = once daily at bedtime, BID = twice daily, IR = immediate release 9

10 GOCOVRI delivered significant reductions in dyskinesia from week 2 through 12 Effect was maintained out to Week 24 in EASE LID (Study 1) Baseline UDysRS total score: 40.1 Pooled data from Study 1 and Study 2; LS: Least squares, SE: standard error 1. Pahwa, Presentation at 69th AAN Annual Meeting, April 23-28, 2017, Boston, MA; 2. Pahwa, Poster presented at 2017 Annual Meeting of the American Neurological Association, October 15-17, 2017, San Diego, CA; 3. Pahwa, JAMA Neurol (2017), 74 (8), ; IMPORTANT SAFETY INFORMATION: Warning and Precautions with GOCOVRI, include falling asleep during activities of daily living, suicidality and depression, hallucinations/psychotic behavior. For complete safety information, please see the full GOCOVRI prescribing information. 10

11 GOCOVRI also achieved key secondary benefit of reducing OFF by ~36% First medicine clinically demonstrated to reduce both dyskinesia and OFF Baseline OFF time: 2.8 hours Pooled data from Study 1 and Study 2; LS: Least squares, SE: standard error 1. Tanner, 69th AAN Annual Meeting, April 23-28, 2017, Boston, MA; 2. Data on file, Adamas Pharmaceuticals, Inc., Emeryville, CA 11

12 GOCOVRI increased functional time by ~4 hours daily Key secondary benefit achieved Baseline ON time without troublesome dyskinesia: 8.4 hours Pooled data from Study 1 and Study 2; LS: Least squares, SE: standard error 1. Tanner, 69th AAN Annual Meeting, April 23-28, 2017, Boston, MA; 2. Data on file, Adamas Pharmaceuticals, Inc., Emeryville, CA 12

13 Open-label GOCOVRI study supports durability out to 2 years 1 Treatment effect maintained for 100 weeks Subjects on prior placebo, DBS and amantadine IR all showed significant reduction in dyskinesia and OFF when switched to GOCOVRI 2,3 Prior GOCOVRI treatment Prior placebo treatment Prior DBS Prior AMT IR SE = Standard Error. 1. Hauser, J Park Disease (2017) 7: ; 2. Isaacson, Movement Disorders Clinical Practice (2017), 3. Isaacson, Poster Presented at the XXIII World Congress of Neurology (WCN), Sept 16-21, 2017, Kyoto Japan. 13

14 Open-label GOCOVRI study supports durability out to 2 years 1 During the 2-year study, 9% of patients discontinued due to adverse drug reactions Discontinuations due to ADRs typically occurred early in GOCOVRI treatment Safety data are consistent with the previously reported safety profile of GOCOVRI and most adverse drug reactions were of mild to moderate intensity SE = Standard Error. 1. Hauser, J Park Disease (2017) 7: ; 2. Isaacson, Movement Disorders Clinical Practice (2017), 3. Isaacson, Poster Presented at the XXIII World Congress of Neurology (WCN), Sept 16-21, 2017, Kyoto Japan. 14

15 GOCOVRI launch update 1 Sales force deployed Jan 8, Neurology Account Specialists deployed targeting ~6,500 physicians Campaigns launched Pivotal manuscripts in hand Pleased with response of payers, physicians and patients Off to a solid start: ~550 unique prescribers from Oct 2017 March 31, or 1/12 of target HCPs 1,608 GOCOVRI prescriptions filled in the 1 st quarter $2.6 million in revenue in 1 st quarter 1. As of March 31,

16 Helping patients get access to GOCOVRI Partnered with a prominent US pharmacy Facilitate access and distribution of GOCOVRI to patients Quick Start program provide patients access during insurance coverage adjudication period Co-pay assistance program for commercially insured Patient assistance program for under insured or uninsured Provision of information for government insured patients about available assistance programs Working through government and commercial payer review processes to gain formulary coverage Anticipate broad coverage for GOCOVRI, given GOCOVRI s novel indication and established clinical benefit for patients 16

17 GOCOVRI related publications and presentations 7 peer reviewed publications and 30 presentations at conferences GOCOVRI Scientific Congress Activity ( ) * *Estimate 17

18 Advancing the pipeline ADS-5102 (GOCOVRI) in multiple sclerosis walking ADS-5102 (GOCOVRI) in other indications ADS-4101 in epilepsy (partial onset seizures) New product discovery

19 Walking impairment in multiple sclerosis Among the most common symptoms reported by MS patients Progressively disabling, leading to poor quality of life and decreased independence 1 Only one approved product, which is effective for a subset of patients 2 400K MS patients in the U.S. 3, majority experience walking impairment 4 Adamas is taking ADS-5102 (GOCOVRI) forward Dysregulation of the NMDA receptor / glutamate signaling has been associated with the symptoms and progression of MS 5 Validated effects in preclinical, Phase 2 studies 6,7 Multiple Sclerosis 1. Coleman, PLoS ONE (2013) 8(1): e54756; 2. Ampyra [Package insert], Acorda Therapeutics Inc., Ardsley, NY; 3. Multiple Sclerosis Association of America website. Accessed on Jan 18, 2018; 4. Sutliff, Curr Med Res Opin (2010); 26:109 19; 5. Rossi, Plos ONE (2013) 8(6): e67357; 6. Nguyen, ECTRIMS Online Library, 2015; 7. Cohen, Multiple Sclerosis, 2018 (in press) 19

20 ADS-5102 (GOCOVRI) demonstrated statistically significant improvement in walking speed Phase 2 study results in MS Walking Clinical Trial Findings Timed 25 Foot Walk (T25FW), Speed 17% change in walking speed (p < 0.05) ~90% of ADS-5102 subjects improved, compared to ~60% of placebo Effect on walking speed did not plateau by Week 4 Trend for positive effect on TUG and 2 Minute Walk Test (2MWT) Timed Up and Go (TUG) 1. Cohen, Multiple Sclerosis Journal (2018) 20

21 ADS-5102 (GOCOVRI) multiple sclerosis walking Phase 3 study design Study initiated, first patient enrolled in Q1 18 Complete enrollment expected in H2 19 Enrolling ~570 subjects, randomized 1:1:1 Key Inclusion years old EDSS 6.5 T25FW 8 45 seconds, inclusive Endpoint measures Primary: Efficacy of 274 mg dose of ADS-5102 measured by T25W at Week 12, (20% responder analysis) Key secondary: Efficacy of a 274 mg dose of ADS-5102 measured by TUG & 2MWT; Efficacy of a 137 mg dose of ADS-5102 measured by the T25FW, TUG & 2MWT at Week 12 (LS Mean change from baseline) Randomization 7 Weeks 2 Wk 10 Weeks Screening and Run In R Up- Titration Phase 274 mg QHS ADS mg QHS ADS-5102 Placebo Maintenance Phase 21

22 Potential additional indications for GOCOVRI ADS-5102 in research and development Motor disorders Parkinson s: Delay Motor Complications Parkinson s: Wearing OFF Tardive dyskinesia Huntington s chorea Tourette syndrome Non-motor disorders Depression Anti-psychotic induced weight gain 22

23 Treatments for partial onset seizures Epilepsy results in profound physical, psychological, and social consequences 1 Reduced education Reduced independence Increased isolation 3.0 M adults with epilepsy in U.S. 2 Partial onset seizures (POS) occur in ~2/3 of patients with epilepsy 3 30% of patients with POS have poor seizure control with current anti-epileptic drugs (AEDs) 3 Adamas confirmed seizure frequency higher during daytime Suggests advantage to maintaining high plasma concentrations of anti-epileptic medication throughout the day 4 Epilepsy 1. ILAE, Epilepsia, (2003), 44(Suppl. 6); 2. Zack, MMWR, Vol. 66 / No. 31 August 11, 2017; 3. Margolis, JAMA Neurol. (2014);71(8): ; 4. Data on file, Adamas Pharmaceuticals, Inc., Emeryville, CA 23

24 ADS-4101 (lacosamide) designed to provide benefit when seizures occur EEG studies suggest seizures have a diurnal pattern Higher frequency of seizures during the day than at night 1 Phase 1b study showed 600 mg ADS-4101 provided 1.7-fold increase in lacosamide AUC throughout the day, compared to 400 mg daily dose of VIMPAT 2 AEs incidence similar between 600 mg ADS-4101 and 200 mg VIMPAT BID Positive interaction with FDA; expect to initiate pivotal Phase 3 study in Data on file, Adamas Pharmaceuticals, Inc. Emeryville, CA; 2. Patni, Poster presented at American Epilepsy Society (AES) Annual Meeting, December 1 5, 2017, Washington, DC 24

25 New product discovery Proven time-dependent biology approach Responsible for: GOCOVRI ADS-5102 MSW ADS-4101 Epilepsy Adamas will conduct 4-5 discovery projects per year Focus remains neurology and psychiatry Goal to nominate 1 additional clinical development program per year Psychiatry Epilepsy Parkinson s Disease Multiple Sclerosis 25

26 Adamas products protected by multiple, distinct discoveries GOCOVRI estimated exclusivity and patents* Regulatory Exclusivity New Clinical Investigation Exclusivity Aug. 24, 2020 Regulatory Exclusivity Orphan Drug Exclusivity Aug. 24, 2024 Slope Patent Family Amantadine compositions and methods of treatment with slower rate of rise, dissolution profiles Nov. 23, 2025 Jan. 22, 2028 Diurnal Patent Family Bedtime administration of ER amantadine Dec. 2, 2030 ON/OFF Patent Family Increasing ON time or reducing OFF time by administration of ER amantadine June 17, 2034 Gait Patent Family Method of improving gait (walking) by administering amantadine once-daily Nov. 3, * Reflects issued patents and patent applications 26

27 Achieved and upcoming milestones Program Date Milestone/Event GOCOVRI Commence full U.S. commercial launch Report final EASE LID 2 Phase 3 open-label safety and efficacy data Quarterly Provide updates on commercial progress with physician and patient adoption 2018 Present data at key annual scientific meetings, including AAN, MDS; publish additional preclinical, Phase 1, and Phase 3 results ADS-5102 (GOCOVRI) Initiate first Phase 3 study in multiple sclerosis walking Q4 18 H2 19 Q1 19 Initiate open-label safety and efficacy study Complete enrollment of first Phase 3 study in multiple sclerosis walking Select additional indications for ADS-5102 (GOCOVRI) for clinical development ADS-4101 Present Phase 1a & 1b data FDA feedback received for Phase 3 development plan Enroll Phase 3 study in patients with partial onset seizures Discovery By H2 20 Start clinical development of two (2) additional products 27

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