N-MOmentumA Clinical Research Study for Neuromyelitis Optica

MedImmune NMO Clinical Trial Webinar

9:00 a.m. PST, 12 p.m. EST

Wednesday, 12/17/14

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Webinar Format

Session is 45 minutes in length (Welcome, Intro, Presentation, Q&A)

Attendees may submit questions in the Q&A window online - please be as succinct as possible if you choose to submit a question

After the presentation is complete, the presenters & panelists will address as many questions as time allows

Thank you for understanding that not all questions will be addressed

Webinar slides and audio will be posted on the foundation website for later viewing / audio

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Presenter

Armando Flor, M.D.Director of Clinical DevelopmentMedImmune

Michael Yeaman, Ph.D.Advisor, The Guthy-Jackson

Charitable Foundation

Brian Weinshenker, M.D.Expert NMO ClinicianMayo Clinic

Panelist Moderator3

Presentation Format Content is solely that of the respective industry or its representative

Presenters are afforded a maximum of 15-20 minutes total time

Questions / answers are then afforded up to 20 minutes of time

The webinar is being recorded for purposes of future distribution

All perspectives are offered only for stakeholder self-education

The Guthy-Jackson Charitable Foundation does not perform clinical trials nor does it endorse any particular clinical trial design or drug

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NMO Clinical Trial Webinar

9:00 a.m. PST, 12 p.m. EST

Wednesday December 17th, 2014

• B-cells have important roles in the pathogenesis of autoimmune diseases including

NMO

• CD-19 B cells are responsible for the production of the AQP4 autoantibodies

MEDI-551

Evidence suggests

CD-19 B lymphocyte

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MEDI-551

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• Humanized, monoclonal antibody that binds with high

affinity to CD19 B cells

• Depletes B cells using body’s own immune system

What is MEDI-551?

• Phase I in Scleroderma completed

• Phase I in Multiple Sclerosis completed

• Phase II/III in NMO/NMOSD initiated

• Phase II in B cell malignancies on-going

Phase of development of MEDI-551

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Rituximab

MEDI-551: Targets a Broader Spectrum of B Cells

MEDI 551

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MEDI-551; Mechanism of action and B cell depletion

MEDi-551 anti CD19

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CD-19 B lymphocyte

MEDI-551; Mechanism of action and B cell depletion in NMO

• Population: Sero-positive and sero-negative NMO/NMOSD

subjects.

• Primary endpoint: Time to first attack

• Drug: MEDI-551 300 mg Intravenously at Day 1 and Day 15

and then every 6 months

• Comparator: Placebo

• Randomization ratio: 3:1 (MEDI-551: Placebo) 75% on MEDI551 25% on

placebo

• Treatment period: 6.5 months (197 days) followed by open label period

• Study end: 67 adjudicated attacks

• Safety monitoring: Telephone calls every two weeks. Liberal escape

allows treating physician to treat attacks with

rescue medications

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Placebo Study Design

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Screening

28 days

Randomization

3:1

MEDI-511 (3)

Placebo (1)

Open Label

Period (min 1y max 3 y)

(MEDI-551 only)

Primary EndpointTime to NMO Attack

During Randomized

Controlled Period

Total of 67 relapses required

Randomized Controlled Period – 6.5 months

A Double-masked, Placebo-controlled Study with

Open-label Period in Adult Subjects with

NMO/NMOSD

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A Double-masked, Placebo-controlled Study with

Open-label Period in Adult Subjects with

NMO/NMOSD

Eligibility

(please visit https://clinicaltrials.gov/ct2/show/NCT02200770?term=NMO&rank=8 for the complete list

of the inclusion/exclusion criteria)

Key Inclusion Criteria

Men and women 18 years or older with diagnosis of NMO/NMOSD

Seropositive or seronegative NMO/NMOSD patients with at least one attack in one

year or two attacks in the last two years requiring rescue therapy prior randomization

Expanded Disability Status EDSS ≤ 7.5

Key Exclusion Criteria:

Lactating and pregnant females

Know history of a severe allergic reaction or anaphylaxis after any biologic therapy

Known active severe bacterial, fungal or viral infection or any major episode of

infection requiring hospitalization.

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A Double-masked, Placebo-controlled Study with

Open-label Period in Adult Subjects with

NMO/NMOSD

Eligibility

Exclusion Criteria: (cont’)

NMO patients diagnosed with a concurrent autoimmune disease requiring

immunosuppressive agents.

History of cancer, apart form squamous cell or basal cell carcinoma of the skin with

documented success of curative therapy.

Receipt of Rituximab, unless the subject’s B cells have returned to the normal limit

of normal prior randomization.

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A Double-masked, Placebo-controlled Study with

Open-label Period in Adult Subjects with

NMO/NMOSD

Concomitant Medications:

Prednisone

Two weeks of 20 mg/day of prednisone follow by one week of tapering during

randomized period.

MEDI-551 is not biologically active for first 2 weeks

Supports tapering for patients previously on steroids

Infusion Reaction prophylaxis:

IV methylprednisolone (Steroids)

Benadryl

Tylenol

Rescue Medications

Immunosuppressant therapy after randomization is not permited

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A Double-masked, Placebo-controlled Study with

Open-label Period in Adult Subjects with

NMO/NMOSD

Study Visit details:

Screening visit:

– AQP4-IgG sero-status

– Physical/neurological examination

– Vitals signs and ECG

– Blood and urine collection

– EDSS and ophthalmology examination

– MRI

9 Randomized controlled period visit at days: 1,8,15,29,57,85,113,155 and197

– Physical/neurological examination

– Vitals signs

– Blood and urine collection

– Assessment of adverse events

– EDSS and ophthalmology examination at visit day 1, day 85 and day197

– MRI at visit day 197

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Open Label

Period

(MEDI-551 only)Randomizatio

n

3:1

Screening

28 days

MEDI-511 (3)

Placebo (1)

Randomized Controlled Period – 6.5 months

Safety Follow-up

Period

Beyond the randomized controlled period

Open Label period:

Gather extended safety data

Opportunity for patient to receive a B cell depleting agent

Minimum for 1 year, maximum for 3 years, or until local approval

Safety Follow-up period:

All about B cell recovery

Follow-up for 12 months after last dose of MEDI-551

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A Double-masked, Placebo-controlled Study with

Open-label Period in Adult Subjects with

NMO/NMOSD

SUMMARY

– MEDI-551 depletes CD 19 B cells source of production of AQP4-IgG

autoantibodies that cause NMO

– N-Momentum is a pure placebo controlled study with a masked treatment

period of 6.5 months and a randomization of 3:1, where 75% of patients

will be on MEDI-551 and 25% will be on placebo only.

– After the randomized controlled period, trial participants will have the

option to enter the Open Label period where all participants will received

MEDI 551

– For more information, please visit

https://clinicaltrials.gov/ct2/show/NCT02200770?term=NMO&rank=8 or

contact the AstraZeneca Clinical Study Information Center at

1-877-240-9479 or email information.center@astrazeneca.com

Questions

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Learn More

This webinar will be hosted on the

foundation website at:

http://nmotion.guthyjacksonfoundation.org/series-one-nmo-

clinical-trial-update/

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Conclusion

Content is solely that of the respective industry or its representative

Webinar slides and audio will be posted on the foundation website for later viewing/audio

All perspectives are offered only for stakeholder self-education

The Guthy-Jackson Charitable Foundation does not perform clinical trials nor does it endorse any particular clinical trial design or drug

We hope this webinar has been informative to all stakeholders

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