Copyright © 2018 IQVIA. All rights reserved.

October 2018

Nikos Kostaras, General Manager, IQVIA Greece

The impact of innovation in Oncology:

New opportunities and challenges

1

• The analyses, their interpretation, and related information contained herein are made and provided subject to the assumptions, methodologies,

caveats, and variables described in this report and are based on third party sources and data reasonably believed to be reliable. No warranty is

made as to the completeness or accuracy of such third party sources or data.

• As with any attempt to estimate future events, the forecasts, projections, conclusions, and other information included herein are subject to certain

risks and uncertainties, and are not to be considered guarantees of any particular outcome.

• All reproduction rights, quotations, broadcasting, publications reserved. No part of this presentation may be reproduced or transmitted in any

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written consent of IQVIA.

• ©2018 IQVIA Incorporated and its affiliates. All rights reserved. Trademarks are registered in the United States and in various other countries.

Disclaimer

2

US, top five EU, and Japan = 75% of the global oncology market

10%

22%

46%

9%

14%

PharmergingEU5

RoWUS Japan

0%

2%

4%

6%

8%

10%

12%

14%

16%

18%

20%

2012 2013 2014 2015 2016 2017

US EU5 Pharmerging Japan RoW Global%

gro

wth

Oncology market share by region 2017

$109 Bn (list price, pre-rebates and discounts)

Oncology growth by region 2012-17 (list

price, pre-rebates and discounts)

Source: IQVIA MIDAS Restricted MAT Q4 2017; Growth in LCUS,

3

The cancer treatment landscape has been transformed since 2011New Active Substance Launches 2011–2017 by Indication

Source: IQVIA, ARK R&D Intelligence, Feb 2017; IQVIA Institute, Mar 2017; IQVIA MIDAS QTR restricted MAT Q3 2017

Lung

Pancreatic

Leukemia

Thyroid

Neuro-

blastoma

GIST

Sarcoma

Multiple

myelomaProstate

Gastric Polycythemia

vera

Basal

cell

carcinoma

Cervical

Ovarian

Castleman’s

Lymphoma

Colorectal

cancer

Melanoma

Breast

RenalBladder

Head andNeck

• cabozantinib

• lenvatinib

• nivolumab• abemaciclib

• ado-trastuzumab emtansine

• neratinib

• palbociclib

• ribociclib

• cobimetinib

• dabrafenib

• nivolumab

• pembrolizumab

• talimogene

laherparepvec

• trametinib

• nivolumab

• ramucirumab

• tipiracil/trifluridine

• acalabrutinib (MCL)• axicabtagene ciloleucel (DLBCL)

• belinostat (PTCL)• copanlisib (FL)• ibrutinib (MCL, WM)

• idelalisib (CLL, FL, SLL)• nivolumab (Hodgkin’s)• obinutuzumab (FL)

• pembrolizumab (HL)

• bevacizumab

• niraparib

• olaparib

• rucaparib

• sonidegib

• daratumumab

• elotuzumab

• ixazomib

• panobinostat

• pomalidomide• ra 223 dichloride

• eribulin

• olaratumab

• trabectedin

• afatinib

• alectinib

• atezolizumab

• brigatinib

• ceritinib

• gefitinib

• necitumumab

• nivolumab

• osimertinib

• pembrolizumab

• ramucirumab

• blinatumomab (ALL)

• daunorubicin + cytarabine (AML)

• enasidenib (AML)

• ibrutinib (CLL)

• inotuzumab ozogamicin (ALL)

• midostaurin (AML)

• obinutuzumab (CLL, FL)

• tisagenlecleucel (ALL)

• venetoclax (CLL)

• lenvatinib mesylate

• dinutuximab

• atezolizumab

• avelumab

• durvalumab

• nivolumab

• pembrolizumab

• nivolumab

• pembrolizumab

• pembrolizumab

• ramucirumab

• ruxolitinib

• bevacizumab

• irinotecan

liposome

• siltuximab

• regorafenibMerkel

cell

Liver

• nivolumab

• regorafenib

• avelumab

4

75% of all targeted treatments in Oncology are used in multiple indications especially checkpoint inhibitors

8

3

14

30

18

0

5

10

15

20

25

30

2-4 10+5-7 8-101

Targeted drugs by Number of Indications in EU5 + Japan

Number of Indications

Nu

mb

er

of D

rug

s

Checkpoint inhibitors make up the

upper crust with many used in an

array of 10+ Indications

The majority of targeted cancer

products are used in 2-4 indications

Source: IQVIA Thought Leadership, Oncology Dynamics, MAT Q4 2017, Patient Level Oncology Survey Data, Excludes patients participating in Clinical Trials

5

A wide array of immuno-oncology drugs, some with novelmechanisms, are in development across multiple tumor types

Select Mechanisms of Action for Multiple Tumor Types

Chart notes: Data query included immuno-oncology therapies sorted by highest status. Diagnostic molecules were not included. Sponsors include industry and

non-industry. For molecules with multiple mechanisms and disease, the first listed mechanism or disease was chosen. PD-1 = Programmed cell death protein 1;

PD-L1 = Programmed death-ligand 1; INDO = Indoleamine-pyrrole-2,3-dioxygenase inhibitor; CTLA4 = cytotoxic T-lymphocyte-associated protein 4; APRIL = A

proliferation-inducing ligand; TKIs = tyrosine kinase inhibitors; EGFR = Epidermal growth factor receptor; * includes metastatic

Source: Clarivate Analytics Cortellis, Apr 2018; IQVIA Institute, Apr 2018..

6

The number of oncologists has steadily been growing, but the noise generated by new drugs and companies is overwhelming

Number of specialist oncologists

2018

63’708

2012

54’903

USJPCN*ESITUKFRDE

2018

524 per Mn people

2012

457 per Mn people

Number of specialist oncologists per Mn people

Note: *13 main cities represented only; for JP: Oncology specialty does not exist and patients are treated by the respective specialists according to the type of cancer, i.e.: gastrologists, urologist, gynecologist or pneumologist; population data

from world bank open data 2016 numbers used for 2018

Source: IQVIA Channel Dynamics

7

Payers enacted several new provisions in 2017 to modify theirapproach to purchasing and reimbursement

Chart notes: ICER = Institute for Clinical and Economic Review; FDA = Food and Drug Administration: NICE = National Institute for Health and Care Excellence;

CDF = Cancer Drugs Fund; NRDL = National Reimbursement Drug List; DLO = Dopolnitel’noe Lekarstvennoe Obespechenie, or the Programme for Supplementary

Pharmaceutical Provision.

Source: IQVIA Institute, IQVIA PharmaQuery, Mar 2018

Selected Purchasing and Reimbursement Actions Globally

8

Higher focus on exploring multiple potential applications of products in the earlier stages of drug development

49% 53%

64% 67%

20%23%

25%25%

8%

10%

13%8%

7%

5%

1%1%

Phase 4

3%4%

2% 2% 3%3%

3%

4%

Phase 2

100%

Phase 3Phase 1

6+

2

3

1

5

4

More then 50%

of Phase I Trials

include multiple

indications

This number

drops down to

35% in Phase III

Number of

indications

included

simultaneously

in a single trial

Number of Indications included in Oncology Clinical Trial started 2014 to 2017

Source: IQVIA Thought Leadership, www.clinicaltrial.gov, Last access April 2018,

9

Trials using biomarkers to stratify patients susceptible toresponse made up 34% of oncology trials in 2017

Chart notes: Citeline’s Trialtrove’s dataset was used to create a year over year analysis for the number of biomarkers in oncology trials. Biomarker trials were identified

using the following trial tags: biomarker/efficacy, biomarker/toxicity, PGX-biomarker identification/evaluation, PGX-pathogen, PGX-patient preselection/stratification.

Trials were industry only and interventional. Terminated and planned trials were excluded. Trials with healthy volunteers were excluded.

Source: Trialtrove, Pharma Intelligence, Apr 2018; IQVIA Institute, Apr 2018

Number and Percent of Oncology Trials by Biomarker Type, Phase I-III, 2010—2017

10

Today’s Clinical Trials present familiar challenges and new complexities

1 Impact Report (2013) Tufts CSDD 15(1) 2 Impact Report (2016) Tufts CSDD 18(1). 3 Clinical Trial Delays: America’s Patient Recruitment Dilemma (2012). Drugdevelopment-technology.com 4 Getz KA & Campo RA (2017) Nature Reviews

Drug Discovery 16, 307

57%of trials have a

protocol amendment2

80%of trials are delayed, often

recruitment related3

48%of sites miss their

targets1

61%increase in

inclusion/exclusion criteria4

The shift towards targeted therapies in oncology creates the following challenges resulting in

significant costs and inefficiencies.

11

Consequences: 1) net price pressures, 2) more stringent evidence requirements and 3) increasing RWE expectations

Key market trends

Source: IQVIA Consulting Services PMA Solution and European Thought Leadership

Net price pressures Evidence Requirements1 2 RWE Expectations3

Growing net price

constraints due to

persisting budgetary

pressures

Increasingly stringent

evidence requirements,

with payers have an

increasing preference for

OS, with PFS only accepted

in specific situations or pro

tem

Greater pressure on

manufacturers to generate

RWE to prove value pre-

and post-launch especially

when seeking approval

based on a phase 2 or

single arm trial

12

Pharma facing new challenges to commercialization

Source: IQVIA Thought Leadership

Increased difficulty to define

launch sequence of indications

and price strategy across multiple

indications

Better scientific understanding

resulting in increased scrutiny

over product value and benefits

by payers and regulators

Tightly defined patient populations

resulting in increased number of

trials, missed enrolment targets,

elongation of trial duration and

inevitably protocol amendments

Misalignment between regulators

and payers regarding evidence

needs and comparator to use

13

The ‘noise’ generated by a large pipeline is going to intensify

Late Phase Oncology Pipeline Molecules, 2006–2016

Note: Late Phase includes phase II to registration

Source: IQVIA, ARK R&D Intelligence, Dec 2016; IQVIA Institute, Mar 2016

0

100

200

300

400

500

600

700

2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016

Targeted Small Molecules Targeted Biologics Cytotoxics Hormonals Radiotherapies

# o

f m

ole

cu

les

Year

14

Clinical trials incorporating digital health tools in oncology havebeen limited, but show a range of positive impacts

Chart notes: Withings Wi-Fi Scale used in one of the studies to send data to app was mapped to Nokia HealthMate as the likely receiving app

Source: IQVIA AppScript Evidence Database; Apr 2018; IQVIA Institute, May 2018

Clinical Efficacy Studies on Oncology Apps in 2017 &

Tools Used in These Trials

Mobile Cancer Apps by Cancer

Sub-Type Targeted

Thank you

Nikos Kostaras

General Manager, IQVIA, Greece