Medimmune Delivering the Next Wave of Scientific Innovation

MedImmune Delivering the next wave of scientific innovation

Bahija Jallal, Executive Vice President, MedImmune Building on the fundamentals

Next wave of science

1 – MedImmune MedImmune has a 25+ year history in biologics; pioneering scientists are still driving discoveries today

RespiGam 1996

2002

Gail Wasserman, PhD Mike McCarthy, MD, MPH, MS Tris Vaughan, PhD 1998 Biopharmaceutical Dev. Infectious Diseases / Vaccines Antibody Discovery & Pennsylvania State Uni. U. Maryland University College Protein Engineering Montclair State Uni. Georgetown U. School of Med. 2011 University of Toronto University of Leeds

1998

2003 2006

JoAnn Suzich, PhD Mark Schenerman, PhD Hong Jin, PhD Infectious Disease / Biopharmaceutical Dev. Infectious Diseases / Vaccines Cornell University Vaccines Purdue University University of Florida Northwestern Uni. 2009 2012 Glasgow Uni.

2 – MedImmune MedImmune continues to attract world class scientists with strong expertise in areas of interest

Yong-Jun Liu, MD, PhD Jack Ratchford, MD Head of Research Neuro-Immunology Baylor Research Institute Chief Scientific Johns Hopkins U. School of Medicine Officer and Director of Immunology Columbia U. College of Physicians and Research Surgeons

David Howe, MD Jacob Wesley, PharmD, MS Autoimmunity Oncology Cornell University Johns Hopkins University University of Toronto University of Maryland Edinburgh U. Medical School

Brett Hall, PhD Eliezer Katz, MD Translational Science - Oncology Neuro-Inflammation West Virginia University U. of Massachusetts Medical Center Ohio State University Hebrew U. - Hadassah Medical School

Jiping Zha, MD, PhD John Kurland, PhD Translational Medicine - Oncology Translational Medicine – Oncology U. Texas Southwestern Med Ctr Dallas Cold Spring Harbor Laboratory Harvard Medical School U. Texas M. D. Anderson Cancer Center University of Tennessee Shanghai Medical University

3 – MedImmune MedImmune has a collaborative work environment where staff are encouraged to publish & innovate

4 – MedImmune Our sustainable pipeline is built on excellence in science

Expertise in Strength Excellence in technology & in translational protein immunology research engineering

5 – MedImmune MedImmune’s strong heritage in immunology is leveraged across therapeutic areas

Respiratory, inflammatory, Oncology: Immuno- autoimmune diseases oncology therapies

Tempering overactive or Harnessing / activating the inappropriate immunity immune system

Immune system

Chronic inflammation Chronic inflammation Essential for combat of (unfolded protein response) pathogens

Neurological Cardiovascular & Infectious diseases / diseases metabolic diseases vaccines

6 – MedImmune Disease biology drives our tech focus: Novel (non mAb) drug formats represent >50% of our research portfolio

Deep “toolkit” of non-mAb …and growing as a proportion of the approaches… preclinical pipeline

60% Ab-drug Ab Bispecific conjugate mimetic Ab 50% Dual peptide 40%

30%

mAb 20% (+YTE) Peptide mAb- fusion 10%

0% Jan Jan Jan Jan Jan Sep -10% 2010 2011 2012 2013 2014 2014

Preclinical (MsB-CD)

7 – MedImmune Personalised healthcare is a core principle: More than 80% of our biologics portfolio employs a PHC approach

Example: PD-L1

PD-L1 protein expression may not be an absolute determinant of response…we leverage multiple tools to identify responders

Antibody and TCR diversity

Circulating Genomics Flow cytometry Tumour cell Tumour cells and proteomics Target expression

8 – MedImmune Building on the fundamentals

Next wave of science

9 – MedImmune MedImmune’s Research & Early Development portfolio is robust with emphasis on core TAs Lead Optimisation Pre-clinical Phase I Phase IIa Phase IIb MEDI3617 MEDI-551 MEDI2070/AMG-139 anifrolumab Onc RIA Onc Ang2; GBM CD19; MS IL-23p19; Crohn’s IFNaR; SLE MEDI-565 MEDI5872/AMG-557 tralokinumab sifalimumab Onc RIA Onc CEA BiTE; GI tumors B7RP1; SLE IL-13; IPF IFNa; SLE MEDI6469 MEDI4920 MEDI-551 mavrilimumab Onc RIA Onc mOx40; Solid tumors CD40L;Sjögren’s CD19; CLL, DLBCL GM-CSFR; RA MEDI6383 MEDI6012 MEDI-573 MEDI7183/AMG-181 Onc RIA Onc OX40 FP; Solid Tumors LCAT; ACS IGF; MBC A4b7; UC, Crohn’s MEDI4736+BRAF/MEK MEDI8111 MEDI4736 PD-L1 brodalumab Onc RIA Onc PD-L1; melanoma FII; trauma bleeding solid tumours IL-17R; severe asthma MEDI4736 + Treme MEDI4893 MEDI4736+Iressa MEDI9929/AMG-157 Onc RIA Onc PDL1/CTLA4 solid tumor staph alpha toxin PD-L1/EGFR; NSCLC TSLP; asthma MEDI0680 MEDI-550 moxetumomab Onc RIA Onc PD-1; solid tumors pandemic flu library CD22; pALL MEDI-551+CD20 MEDI8897 Onc RIA Onc DLBCL RSV anti-F NG

MEDI4736/0680 MEDI7510 Onc RIA Neuro PD-L1/PD-1; NSCLC older adult RSV vaccine

MEDI6469/4736 MEDI3902 Onc CVMD RIA solid tumors PcrV/Psl bispecific

MEDI4736+AZD9291 PRVV Onc CVMD RIA PD-L1/EGFR; NSCLC RSV prevention MEDI0639 Onc CVMD RIA DLL-4; SCLC MEDI1814 Onc CVMD RIA A-Beta NG; AD Onc CVMD RIA

Onc CVMD RIA

Onc CVMD RIA Oncology Neuro CVMD CVMD RIA Neuro CVMD ID/Vax CVMD Neuro CVMD ID/Vax ID / Vaccine Neuro ID/Vax ID/Vax Neuroscience ID/Vax

ID/Vax

10 – MedImmune MedImmune’s programme for Sjögren's employs the novel Tn3 scaffold to avoid mAb-related complications

MEDI4920: Target

• Blocks co-stimulatory path for CD40L on T cells to bind to CD40 on B cells

Rationale

• mAbs efficacious in animal models Platelet Aggregation • mAbs tested in the clinic with some 400nM 200nM 100nM Biogen 5c8 positive data, but terminated due to blood clots MEDI4920 Differentiation • Tn3 scaffold is a novel non-mAb Biogen 5c8 technology; avoids blood clotting

characteristic of anti-CD40L mAbs aggregation Percent • First small protein technology at MEDI to enter clinic

11 – MedImmune MedImmune’s novel ADC candidate employs the PBD payload and demonstrates early efficacy against cancer

ADC: Target H1975 NSCLC xenograft: Tumor regression with single dose ADC • Cancer stem cell target • Limited expression in normal tissues

Indication

• Overexpressed in several tumor types – Lung – Breast

Candidate

• Novel ADC conjugated with PBD payload Best Scientific • Tumor regression after single dose Innovation:

12 – MedImmune We are building our early ADC pipeline; vigorously pursuing a broad range of oncology targets

ADC research portfolio 2015 2016 2017

ADC1 IND

ADC2 IND

ADC3 IND

ADC4 IND

ADC5 IND

ADC6 IND

ADC7 IND

ADC8 IND ADC9 IND

• Forecast is subject to project attrition • Target discovery activities have launched additional projects for IND delivery beyond 2017

13 – MedImmune MedImmune is progressing a next generation, extended half-life mAb for RSV

MEDI8897 : Target • Novel, neutralizing epitope on the RSV F protein, located on the surface of the virion Serum PK in NHP Model

Indication • Passive immunization of all infants entering their 1st RSV season • Children with chronic lung or chronic heart disease entering their 1st and 2nd RSV seasons for the prevention of lower respiratory tract illnesses

Candidate • Binds to novel epitope, neutralizing RSV • Extended half-life based on proprietary, clinically validated YTE technology

14 – MedImmune MedImmune is pursuing an innovative multi-functional, bi-specific approach for the treatment of P. aeruginosa

MEDI3902 : Target #1: PcrV – Virulence

• Prevents toxin injection anti-PcrV into host cells anti-Psl • High affinity mAb to low density target

Target #2: Psl – Colonisation Persistence • Dual mechanism of action: Clearance and blocks cell adherence

• Lower affinity mAb to high density target

15 – MedImmune Protein X presents an opportunity to deliver a step change in diabetes therapy

Protein X: Target 18

• Novel protein with novel mechanism of Veh action 14

** Low 12

Glucose (mM) Indication 10 High *** *** 8 * ** • Type 2 Diabetes * ***

6 • Goal 0 10 20 30 – Dose-dependent reductions in blood sugar Days of treatment – Significantly improved islet health Data are presented as mean±SEM n=28 (veh), n=22 (Prot-X groups) – Improved insulin sensitivity Vehicle Control 3 mg/kg/d Prot-X

Candidate • May regulate pancreatic β-cell function

16 – MedImmune Summary

We have created a vibrant environment, promoting innovation and scientific excellence

We have a robust, balanced, sustainable portfolio

We are moving beyond mAbs, pioneering the next wave of biologics innovation

17 – MedImmune We push the boundaries of science to deliver life-changing medicines

18 – MedImmune Q&A

Briggs Morrison, moderator Mene Pangalos Bahija Jallal