MedImmune RSV Surveillance

Mark T. Esser, Ph.D. Sr. Director, Translational Medicine Infectious Disease IMED Email: esserm@medimmune.com Phone: 301-398-6849

WHO Meeting of Mid-term Review of the RSV Surveillance Pilot Based on the Global Influenza Surveillance & Response System

18 – 20 December 2017 PAHO, Washington DC, USA

Overview

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1) MedImmune 2) Purpose of RSV surveillance programs 3) United States

• RSV Alert™ • OUTSMART RSV

4) International • INFORM RSV

5) Q & A

MedImmune History in Antibody and Vaccine Development

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• Founded in 1988 • Acquired by AstraZeneca in 2007 • Headquarters located in Gaithersburg, MD • Sites in Mountain View, CA, Cambridge, UK, Frederick, MD,

Speke, UK, Nijmegen, Netherlands • Antibody/vaccine development and protein engineering • Manufacturing and CMC • Regulatory, legal, and business development support • Significant focus of AZ investment

• ~3,500 employees. R&D centers: Maryland, California, UK • Over 50 products in clinical development

MEDI8897: Passive Immunization for All Infants Technology

• Derived from human B-cells • Potent IgG1 neutralizing mAb • Targets a conserved epitope on F • Half-life extension technology

Highlights • Immediate protection • Once per season dosing • Fixed IM 50 mg dose (not weight based)

Clinical endpoint • Prevention of RSV lower respiratory tract infection

Proposed Indication • All infants entering first RSV season • Children with CLD/CHD entering first and second RSV seasons

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1. Q Zhu etl al. A highly potent extended half-life Ab as a potential RSV vaccine surrogate for all infants. Sci Transl Med. 2017 May 3;9(388) 2. P Griffin et al. Safety, Tolerability, and Pharmacokinetics of MEDI8897, the Respiratory Syncytial Virus Prefusion F-Targeting mAb with an Extended Half-Life, in Healthy Adults. Antimicrob Agents Chemother. 2017 Feb 23;61(3).

• Four pillars of the RSV Surveillance and resistance monitoring plan • Surveillance network leverages labs in the U.S via RSVAlert™ and in Europe, S. Africa, Japan, S.

America and Australia via the ReSViNET INFORM study • FDA Requirement to monitor for resistance based on 2006 guidance1

RSV Surveillance Programs Are Designed to Support Development of MEDI8897

Worldwide Network of

Laboratories

Sequencing and

Bioinformatics

Virus Rescue and

Engineering Susceptibility

Testing

Surveillance Studies and Clinical Trials

1Guidance for Industry: Antiviral Product Development — Conducting and Submitting Virology Studies to the Agency. Food and Drug Administration (CDER) June 2006. 5

MEDI8897 Binding Region

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MEDI8897 binds a conserved conformational region on the prefusion RSV F protein defined by co-crystal structure determination

RSV A 62SNIKENKC69 RSV B 62SNIKETKC69

196KNYIDKQLLPIVNKQSC212 196KNYINNQLLPIVNQQSC212

F1 F2 TM FP HR1 HR2

C C

MEDI8897 Binding Region is Conserved

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The majority of amino acids in the MEDI8897 binding site of RSV F in isolates from 1965 to 2017: • were conserved (> 99%) at 24 /25 positions in RSV A and 21 of 25 positions in RSV B • changes did not impact virus susceptibility to MEDI8897 neutralization

associated with significant reduction in susceptibility (>1000 fold) associated with moderate reduction in susceptibility (<10-100 fold)

Fre

qu

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of

po

lym

orp

his

ms

(%

)

RSV Surveillance – U.S. Sentinel Labs

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2017-18 Program • 27 regional labs • 50 samples each • 10 per month • F and G Sequencing • MEDI8897 and Palivizumab

susceptibility testing • RSV Alert covers core based statistical areas in U.S. • ~480 laboratories report weekly, de-identified data • ~500,000 RSV tests performed each year

□ Outside surveillance area ■ RSV-positives <10% ■ RSV positives ≥10% ■ RSV positives previously

≥10% now <10%

www.rsvalert.com

RSVAlert® Surveillance Program 5-Year Historical National Report with Current Season Overlay

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Season Date Range Number of Labs Total RSV Tests

2012 – 2013 Aug 11, 2012 – Aug 3, 2013 482 680,168

2013 – 2014 Aug 10, 2013 – Aug 2, 2014 504 521,820

2014 – 2015 Aug 9, 2014 – Aug 1, 2015 482 648,874

2015 – 2016 Aug 8, 2015 – July 30, 2016 460 646,912

*2016 - 2017 Jan 7, 2017 – May 27, 2017 477 411,345 *The RSVAlert® Program was not active during Aug-Dec 2016 and June –July 2017

Perc

ent R

SV P

ositi

ve

10% threshold

Core-Based Statistical Area Report Washington DC-Arlington-Alexandria (DC-VA-MD-WV)

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0%

5%

10%

15%

20%

25%

30%

0

50

100

150

200

% P

ositi

ve P

ast 7

Day

s

Num

ber o

f Tes

ts

Date (month/day/year)

# RSV Tests % RSV-Positive

Observational US Targeted Surveillance of Monoclonal Antibody Resistance and Testing of RSV (OUTSMART RSV)

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31522 25

31520 24

31337 23

31337 23

31298 22

24701 21

24353 20

22745 19

21565 18

21525 17

20866 16

20594 15

20469 14

20394 13

20002 12

9629 11

8319 10

7015 9

7005 8

6043 7

5071 6

5013 5

2218 4

2123 3

2117 2

2028 1

North East

South

West

Mid-West

Design •27 Laboratories •4 census regions •10/samples per month •5 months

Information Collected Location Age Sex Type of RSV test In-patient vs. out-patient Length of stay <24 hr or

>24 hr

RSV A and B Co-Circulated in 2015-16

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Number, % RSV A RSV B RSV A and B co-infection

Number 242 146 4

Percent 62% 37% 1%

MEDI8897 Binding Region Was Conserved in 2015/2016

MEDI8897 Binding Region

Freq

uenc

y

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International Network For Optimal Resistance Monitoring RSV (INFORM-RSV)

Surveillance laboratories in Brazil, UK, Spain, Netherlands, Finland, S. Africa, Australia and Japan Investigators: Annefleur C. Langedijk, Frank Coenjaerts, Anne Geenough, Terho Heikkinen, Peter D. Sly, Carmen Rodríguez-Tenreiro Sanchez, Marta Nunes, Mitsuaki Hosoya, Renato Stein, Joanne Wildenbeest and Louis J. Bont 14

Summary MedImmune is developing an RSV neutralizing, monoclonal antibody

(MEDI8897) directed against site φ of the pre-fusion F molecule

MEDI8897 is more potent than Palivizumab (Synagis®) and has a YTE modification that extends it’s half-life in vivo to 62-73 days

MEDI8897 is currently being evaluated in a phase 2b trial in approximately 1,500 pre-term infants

MedImmune has initiated a US centric RSV surveillance program (OUTSMART RSV) to collect approximately 1,000 RSV isolates each RSV season

MedImmune, in collaboration with ReSViNET, is piloting an international surveillance program (INFORM RSV) to collect approximately 500 RSV isolates each year 15

Acknowledgements

Marla Chiu Fiona Fernandes Hong Jin Bin Lu Steve Projan Alexey Ruzin JoAnn Suzich Dave Tabor Tonya Villafana Ebony Williams Dee Wilkins Qing Zhu

Sue Pastula John Fryzek Xiaohui Jian Liz Levin-Sparenberg Carole Ambrose

Roxanne Turner

Bart Hendriks Leyla Kragten-Tabatabaie

Louis J. Bont Annefleur C. Langedijk Frank Coenjaerts, Joanne Wildenbeest

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Annefleur C. Langedijk Frank Coenjaerts Anne Geenough Terho Heikkinen Peter D. Sly Marta Nunes Mitsuaki Hosoya Renato Stein Joanne Wildenbeest Carmen Rodríguez-Tenreiro Sanchez Louis J. Bont

Questions

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