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Jointly provided by Live Webcast This activity is supported by an independent educational Wednesday, July 1, 2020 grant from Sanofi Genzyme and Bristol-Myers Squibb. 12:00pm – 1:30pm ET

Welcome Michael Zeglinski, RPh SVP & CEO Optum Specialty & Infusion Pharmacies

Agenda 12:00-12:05 PM Opening Comments/Overview Michael Zeglinski, RPh 12:05-12:35 PM Assessing the Clinical Benefits of Current and Emerging MS Therapies in a Specialty Pharmacy Setting Mitzi Joi Williams, MD 12:35-1:00 PM Special Pharmacy Management Services for Optimal Outcomes in MS Michael Zeglinski, RPh 1:00-1:15 PM Shared Decision-Making: Aligning MS Specialty Pharmacy Care with Patient Needs Alexis Crispino 1:15-1:25 PM Audience Question & Answer Session Faculty Panel 1:25-1:30 PM Key Takeaways and Closing Comments

Learning Objectives • Discuss where current and emerging therapies fit into the MS management algorithm • Review the potential impact of and value of real-world evidence to inform clinical decision making in MS • Explore how to integrate electronic health technology into MS care management • Employ treatment optimization approaches to balance costs with improved outcomes in MS management

Asse sessi ssing the C Clinical B Benefi fits o ts of Current a and Emer erging M MS T Ther erapies es in a a Sp Specialty P Pharmacy cy Se Setting Mitzi Joi Williams, MD Founding Director, Joi Life Wellness Group Assistant Professor of Neurology, Emory University

Learning Objectives • Discuss where current and emerging therapies fit into the multiple sclerosis (MS) management algorithm • Review the potential impact of and value of real-world evidence to inform clinical decision making in MS

What is Multiple Sclerosis? • Chronic progressive immune- Genetic and environmental factors contribute to activation mediated disease of the CNS and proliferation of autoreactive lymphocytes 1 • Associated with demyelination, Migration of autoreactive lymphocytes between the axonal damage, and subsequent periphery and CNS 2 Blood- Brain scar or plaque formation Barrier • Associated with significant disability CNS inflammation 1 Neurodegeneration 3 • Primary etiology unknown, but likely multifactorial Demyelination 1 1. Sospedra M, Martin R. Annu Rev Immunol . 2005;23:683-747; 2. Larochelle C, Alvarez JI, Prat A. FEBS Lett . 2011;585(23):3770-80; 3. Wu GF, Alvarez E. Neurol Clin . 2011;29(2):257-78.

MS Epidemiology • MS is the most common cause of neurologic disability in the 18- to 60- year-old population MS affects an • More prevalent in females estimated • Peak incidence occurs between 20 1,000,000 people and 40 years old in the US • Annual cost in the US estimated to be $6.8 to $11.9 billion Calabresi PA, Newsome SD. Multiple sclerosis. In: Weiner WJ et al. Neurology for the Non-Neurologist . 6th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2010:192-221; Ascherio A. Expert Rev Neurother . 2013;13(12 Suppl):3-9; Whetten-goldstein K, Sloan FA, Goldstein LB, Kulas ED. Mult Scler . 1998;4(5):419-25; Wallin MT, Culpepper WJ, Campbell JD, et al. Neurology . 2019;92(10):e1029-e1040 .

Patients with MS Can Exhibit a Variety of Symptoms and Experience Significant Disability Physical Symptoms 1-5 Nonphysical Symptoms • Cognitive impairment 1 Visual disturbances Vertigo Headache • Depression and mood/emotional Heat sensitivity Lhermitte’s sign changes 2 (electrical shocks down the Bowel & bladder spine) • Pseudobulbar affect 6 dysfunction Weakness Pain Spasticity Numbness & tingling Poor balance & Impaired gait coordination 1. Compston A, Coles A. Lancet . 2008;372(9648):1502-17; 2. Calabresi PA. Am Fam Physician . 2004;70(10):1935-44; 3. Gelfand JM. Handb Clin Neurol . 2014;122:269- 90; 4. Olek MJ. Current Clinical Neurology: Multiple Sclerosis . Totowa, NJ: Humana Press Inc; 2005:15-53; 5. Milo R, Miller A. Autoimmun Rev . 2014;13(4-5):518-24; 6. Work SS, Colamonico JA, Bradley WG, Kaye RE. Adv Ther . 2011;28(7):586-601.

What is the lowest Extended Disability Status Scale (EDSS) score that indicates severe disability? a) 1.0 b) 2.0 c) 3.0 d) 4.0 e) 5.0 f) 6.0 g) 7.0 h) 8.0 i) 9.0

Disability Progression Based on the Extended Disability Status Scale (EDSS) Disability Progression Based on the EDSS 1,2 EDSS 4.0 EDSS 0.0 – 3.0 EDSS 5.0 – 9.0 Fully Ambulatory Minimal-to-Moderate Disability Loss of Ambulation; Daily Activities Fully Impaired despite severe disability 1. Renoux C. Neurol Clin. 2011;29(2):293-308. 2. Kurtzke JF. Neurology . 1983;33(11):1444-52 .

MS Disease Course Relapsing-Remitting Secondary Progressive Preclinical CIS Age ~10–40 years Primary Progressive Age? Age ~>40 years Clinical Course Disability Opportunity to Brain Volume minimize progression? Lesion Load Contrast enhancing/ CIS: clinically isolated syndrome new MS lesions Hersh CM, Fox RJ. Multiple Sclerosis. Cleveland Clinic Medical School. Time TeachMeMedicine.org. https://teachmemedicine.org/cleveland-clinic- multiple-sclerosis. Published: June 2014. Accessed March 2020.

MS Disease Subtypes Radiologically or Relapsing-Remitting Secondary Progressive Primary Progressive Clinically Isolated (RRMS) (SPMS) (PPMS) Syndrome (RIS/CIS) First episode of Disability Disability Disability neurologic symptoms; must last for ≥24 hours; may not evolve into MS Time Time Relapse RRMS Active (relapse or new MRI Active (relapse or new MRI activity) Active without worsening activity) with progression with progression Worsening (incomplete recovery Not active without Active (relapse or MRI activity) from relapse) progression (stable) without progression Stable without activity Not active with progression Not active with progression New MRI activity Active without progression Not active without progression (stable) New MRI activity New MRI activity Types of MS. National Multiple Sclerosis Society. www.nationalmssociety.org/What-is-MS/Types-of-MS. Accessed March 2020; Lublin FD, Reingold SC, Cohen JA, et al. Neurology . 2014;83(3):278-86

Frequency of MS Clinical Subtypes 15% 15% are diagnosed with PPMS at disease onset Left untreated, 85% ~50% diagnosed with RRMS of RRMS cases 50% at disease onset transition to SPMS within 10 years of the initial diagnosis Types of MS. National Multiple Sclerosis Society. www.nationalmssociety.org/What-is-MS/Types-of-MS. Accessed March 2020; Lublin FD, Reingold SC, Cohen JA, et al. Neurology . 2014;83(3):278-86.

Components of the MS Diagnosis • Clinical: symptoms and exam findings suggestive of MS • MRI: objective evidence of CNS white matter lesions disseminated in time and space • Lab tests: blood work to rule out mimics (e.g., antinuclear antibody and neuromyelitis optica) • CSF studies: findings supportive of MS such as cell count, IgG index, and oligoclonal bands • Neurophysiology: evoked potential supportive of MS (e.g., Lhermitte’s phenomenon) Polman CH, Reingold SC, Banwell B, et al. Ann Neurol . 2011;69(2):292-302; Polman CH, Reingold SC, Edan G, et al. Ann Neurol . 2005;58(6):840-6.

Predictors of MS Disability Clinical 1 Imaging 2,3 Patient 4,5 • Longer disease duration • Spinal cord lesions • Age • Younger age of disease onset • Higher relapse rate • Diffuse abnormalities in the spinal cord • Gender • More frequent early relapses • Males have increased risk for • Cortical lesions and atrophy • Poor recovery from relapses disability • Ethnicity • Higher Patient-derived MS Severity Score (P-MSSS) in African-American and Hispanics vs. Caucasians 1.Jokubaitis VG, Spelman T, Kalincik T, et al. Ann Neurol . 2016;80(1):89-100; 2. Kearney H, Miszkiel KA, Yiannakas MC, Altmann DR, Ciccarelli O, Miller DH. Mult Scler . 2016;22(7):910-20; 3. Scalfari A, Romualdi C, Nicholas RS, et al. Neurology . 2018;90(24):e2107-e2118; 4. Ventura RE, Antezana AO, Bacon T, Kister I. Mult Scler . 2017;23(11):1554-1557; 5. Jokubaitis VG, Spelman T, Kalincik T, et al. Ann Neurol . 2016;80(1):89-100.

Treatment Goals in MS Traditional Measures Evolving Measures Reduce relapses End relapses Clinical disease progression and Slow disease relapse Stop progression progression Halt disease activity, reduce Reduce disease Stop MRI MRI disability, burden progression improve QoL Cognitive function Improve function and quality of life and quality of life Smith AL, et al. Neurotherapeutics . 2017;14:952-960; Rotstein DL, Healy BC, Malik MT, Chitnis T, Weiner HL. JAMA Neurol . 2015;72(2):152-8; Lazibat I, Šamija RK, Rotim K. Acta Clin Croat . 2016;55(1):125-33.

Evolving Clinical Outcome Measures in MS No Evidence of Expanded No No Evidence of Conventional Composite Disease Disability Measurement Disease Activity Disability Disability Progression & Progression & (NEDA) 3 Disease Activity Disease Activity      EDSS    Assessment of T25-FW Disability    9-HPT Progression  SDMT/cognitive measure    Relapses Assessment of    MRI activity Disease Activity  Atrophy measure EDSS=extended disability status scale; T25-FW=timed 25-foot walk test; 9-HPT=9-hole peg test; SDMT=symbol digit modalities test; MRI=magnetic resonance imaging Van munster CE, Uitdehaag BM. CNS Drugs . 2017;31(3):217-236.