1. Astra Zeneca
Oncology Por1olio
(A Preliminary Assessment)
Prepared by Mark Ma;hews
April, 2016

2. Contents
• ExecuGve Summary
• Current AZ Oncology Por1olio
• ScienGfic pla1orms and disease focus
• Development Por1olio
– LCM and Phase 3 Clinical Programs
– MOA
• Treatment algorithms
• CompeGGve Landscape
• Key Issues/CriGcal Success factors
2

3. ExecuGve Summary (US focus)
• AZ has a robust oncology pipeline, with a total of 13 LCM, 17 Phase 3/reg,
10 Phase 2 and 26 Phase 1 clinical programs.
• LCM is focused primarily on the expansion of Lynparza (PARP inhibitor) and
Tagrisso (EGFR TKI), with emphasis on new NSCLC, ovarian and breast
cancer indicaGons.
• Phase 3/reg programs seek to generate approvals for 2 checkpoint
inhibitors (durvalumab/anG-PDL1, tremelimumab/anG-CTLA4), alone and
in combinaGon. Disease focus is NSCLC and SCCHN, as well as pancreaGc
and bladder cancer.
• Several TKI’s are in Phase 3 development, supporGng two of AZ’s core
areas, ovarian and hematologic cancers.
• Of 30 LCM/Phase 3 clinical programs, 14 (~50%) are expected to be filed in
the US in H2’16/2017, creaGng significant revenue potenGal, but also
significant commercializaGon resource requirements. Investment should
begin now, in order to adequately prepare for/opGmize launches and
brand potenGal.
3

4. ExecuGve Summary (cont.)
• The oncology market is extremely compeGGve in AZ’s core cancers
(breast, ovarian, lung, hematologic), and is projected to increase, a
result of extensive clinical development acGvity across all treatment
classes, but especially immuno-oncology (checkpoint inhibitors),
targeted kinase inhibitors and PARP inhibitors.
• Longer term, AZ is seeking to expand its oncology por1olio, via
exisGng technology pla1orms (Kinase Inhibitors and checkpoint
inhibitors), while adding mulGple new treatments/classes, including
MEK Inhibitors, OX40 agonists, STAT3 Inhibitors, GITR agonist fusion
protein, SERD, ADCs, WEE-1 Inhibitors, and TLR 7/8 agonist.
• Some por1olio gaps exist. These include addiGonal combinaGon
trials, as well as lack of CAR T and/or cellular immunotherapies. To
create a more balanced and a;racGve por1olio offering AZ should
consider expanding its partnerships and/or in-licensing acGviGes.
4

5. AZ Oncology Por1olio
Current Brands, Focus, Markets and
Standards of Care

6. AZ Current Oncology Por1olio
Product Primary Indica/on(s) MOA
Arimidex (anastrazole) Adjuvant/1st line treatment of post-
menopausal women with HR+ breast
cancer
Hormone therapy
(aromatase
inhibitor)
Caprelsa (vandetanib) SymptomaGc or progressive medullary
thyroid cancer
VEGFR Kinase
Inhibitor
Casodex (bicalutamide) In combinaGon with LHRH for Stage D2
metastaGc carcinoma of the prostate
Androgen receptor
inhibitor
Faslodex (fulvestrant) HR+ metastaGc breast cancer in post
menopausal women
Estrogen receptor
HR+ antagonist
Iressa (gefiGnib) 1st line metastaGc NSCLC EGFR Tyrosine
Kinase Inhibitor
Lynparza (olaparib) Monotherapy in BRCA mutated
advanced ovarian cancer
PARP = Poly (ADP-
ribose) polymerase
inhibitor
Nolvadex (tamoxifen) Early/advanced ER+ breast cancer
Tagrisso (osimerGnib) MetastaGc EGFR T790M mutaGon-
posiGve NSCLC
EGFR Tyrosine
Kinase Inhibitor 6

7. AZ Core ScienGfic Pla1orms
Pla@orm Descrip/on Example(s)
Immuno-oncology Therapies that use the bodies immune
system to help fight cancer
AnG-PDL1
(checkpoint
inhibitor)
Tumor drivers &
resistance
Therapies that target specific mutaGons
to a;ack cancer cells
EGFR TKI
DNA Damage
Repair
Therapies that target the DNA repair
process to block tumor cells’ ability to
replicate
PARP
inhibitor
AnGbody Drug
Conjugate (ADC’s)
Arming anGbodies with cancer-killing
agents for more specific tumor targeGng
AnG-PDL1
and AZD9150
7

8. AZ Core Cancer Focus
• Breast cancer
• Ovarian cancer
• Lung Cancer
• Blood cancers
– B cell related
– Hairy cell leukemia
Source: AZ Oncology Website
8

9. Core Cancer Markets (US)
Cancer Incidence Deaths Annually Comments
Breast ~230,000 ~42,000 ~70% ER+
~20% HER2+
Ovarian ~21,000 ~14,000
Lung ~221,000 ~158,000
Leukemia
(incl. AML, CML,
ALL, CLL)
~54,000 ~25,000
5yr survival 25-92%
~328,000 living with/in
remission
Lymphoma
(HL + NHL)
~81,000
(72,000 NHL,
9,000 HL)
21,000
(20,000 NHL, 1,000
HL)
5 yr. survival
88-94%
~762,000 living with/in
remission (584,000 NHL,
178,000 HL). B-cell
lymphomas ~85% NHL.
Diffuse large B-cell most
common (~35%)
Myeloma ~27,000 ~11,000
5 yr. survival ~47%
~96,000 living with/in
remission
Head and Neck ~62,000 ~13,000
Source: Lymphoma and Leukemia SocieGes (NCI SEER Program 2014-2015); Cancer Facts and Figures 2015; ACS 2015;NCI 2015 9

10. Commonly Used Cancer Therapies
• Cytotoxic Agents*
– AnG-tumor anGbioGcs ( e.g Anthracyclines doxorubicin, epirubicin)
– MitoGc inhibitors (e.g. Taxanes paclitaxel, docetaxel and Vinca Alkaloids vinblasGne,
vincrisGne)
– AnG-metabolites (e.g. gemcitabine, capecitabine, 5-FU, methotrexate)
– PlaGnum-based (e.g. cisplaGn, carboplaGn, oxalaplaGn)
– AlkylaGng agents (e.g. Nitrogen Mustards cyclophosphamide, chlorambucil,
melphalan)
– Topoisomerase Inhibitors (e.g etoposide, topetecan, teniposide)
– Protease Inhibitors (e.g. bortezomib/Velcade)
• Targeted Therapies
– EGFR TKI, VEGFR KI: small molecules (e.g. suniGnib/Sutent, sorafenib/Nexavar,
erloGnib/Tarceva, gefiGnib/Iressa, afiGnib/Gilotrif) and mAbs (e.g. bevacizumab/
AvasGn, cetuximab/Erbitux)
– mTOR inhibitors e.g.
– PARP inhibitors (e.g. oliparnib/Lynparza, )
• Immunotherapies
– Checkpoint inhibitors, CAR T’s, cellular based (“vaccines”)
*Source: ACS website
10

11. Astra Zeneca Oncology Por1olio
LCM and Clinical Development
(Phases 1, 2 and 3)

12. AZ Oncology Clinical Program - Overview
Type of Cancer Phase 1 Phase 2 Phase 3/Reg LCM Total
Bladder 0 0 1 0 1
Breast 1 2 0 3 6
Gastric 0 0 0 1 1
Hematologic 2 0 2 0 4
Melanoma 1 0 0 0 1
Mesothelioma 0 0 1 0 1
NSCLC 2 2 6 4 14
Ovarian 0 1 1 3 5
PancreaGc 0 0 1 1 2
Prostate 0 0 0 1 1
Renal 0 1 0 0 1
SCCHN 0 1 4 0 5
Solid Tumors 20 3 0 0 23
Thyroid 0 0 1 0 1
Total 26 10 17 13 66
Source: AZ Oncology Website 12

13. AZ Oncology – Drug Focus, By Phase
Phase Drugs/types
LCM Lynparza (PARP inhibitor)
Tagrisso (EGFR TKI)
Phase 3 Durvalumab (anG-PDL1 mAb), tremelimumab (anG-CTLA4 mAb)
Tagrisso (EGFR TKI), acalabruGnib (Brutons TKI), cediranib (VEGFR TKI),
selumeGnib (MEK inhibitor), moxetumomab pasudotox (anG-CD22
recombinant immunotoxin)
Phase 2 Durvalumab (anG-PDL1 mAb), Tagrisso (EGFR TKI), AZD1775 (WEE-1
inhibitor), AZD2014 (mTOR KI), AZD4547 (FGFR TKI), AZD5365 (AKT KI),
MEDI-551 (CD19 mAb), MEDI-573 (IGF mAb), selumeGnib (MEK inhibitor),
savoliGnib/voliGnib (MET TKI)
Phase 1 Durvalumab (anG-PDL1 mAb), tremelimumab (anG-CTLA4 mAb), other
compounds including: OX40 agonists, ATM KI, Aurora BKI, androgen
receptor inhibitor, P13 KI’s, STAT3 inhibitor, SERD, CD19 mAb, CEA BiTE
mAb, Dll-4 mAb, GITR agonist fusion protein, ANG-2 mAb, HER2 bispecific
ADC mAb, TLR 7/8 agonist
13

14. AZ Pipeline - MOA
Type/example Mechanism
Checkpoint
Inhibitors/
durvalumab,
tremilimumab
Targeted blockade of PD1, PD-L1 or CTLA-4 with antagonist mAbs “releases
the brakes” on T cells, to boost anG-tumor acGvity. PD1 is over-expressed
on the surface of tumor cells, while CTLA4 is up-regulated on the surface of
T cells. Both mechanisms dampen T cell response to tumor cells.
EGFR TKIs /
Tagrisso, Iressa
AcGvaGon of EGFR (epidermal growth factor receptor) is linked to tumor
proliferaGon, invasion, metastases and angiogenesis. EGFR TKIs inhibit at
the TK ATP binding site.
PARP
Inhibitors/
Lynparza
(olaparib)
PARP1 (poly ADP ribose polymerase) helps repair single strand breaks in
DNA. PARP inhibitors cause mulGple double-strand breaks to form, and in
tumors with BRCA mutaGons these double strands cannot be efficiently
repaired, leading to cell death.
OX40 agonists/
(MEDI0562)
GeneraGng opGmal killer CD8+ T cell response requires T cell receptor
acGvaGon and co-sGmulaGon. This can be provided by ligaGon TNF receptor
family members, incl. OX40 (Cd134) and 4-1BB (CD137). OX40 agonist
augments T cell differenGaGon and cytolyGc funcGon, leading to enhanced
anG-tumor immunity. 14

15. AZ Pipeline MOA (cont.)
Type/example Mechanism
WEE-1 Inhibitors/
AZD1775
WEE-1 is a key regulator of cell cycle progression in healthy cells. It
influences cell size by inhibiGng the entry into mitosis, via inhibiGon of
CdK1. WEE-1 is a kinase which is a component of the cellular cell size
checkpoint. It determines the Gme point of entry into mitosis, influencing
the size of daughter cells. Irregular acGvity has been linked to cancers,
incl. ovarian and lung cancers. InhibiGng WEE-1 interferes with DNA
damage response in tumor cells and can lead to cell death.
MEK Inhibitors/
selumeGnib
Inhibit the mitogen-acGvated protein kinase enzymes MEK1 and/or
MEK2. They affect the MAPK/ERK pathway which is overacGve in some
cancers.
AKT Kinase
Inhibitors/
AZD5363
Many cellular processes are regulated by a signaling network of 3 key
enzymes which are disrupted in cancers. Gene acGvaGon of AKT (protein
kinase B) is a tumor driver. InhibiGng AKT offers potenGal to treat
advanced solid tumors and metastaGc malignancies.
15

16. AZ Life Cycle Management Programs
Focus Product Indica/on MOA Est. US Filing
Breast Faslodex 1st line HR+ advanced BC Oest. Rec. antagonist H2’16
Breast Lynparza gBRCA adjuvant BC PARP inhibitor 2020
Breast Lynparza gBRCA metastaGc BC PARP inhibitor H2’16
Lung Tagrisso Adjuvant EGFRm NSCLC EGFR TKI 2022
Lung Tagrisso ≥2nd line ad. EGFRm NSCLC EGFR TKI 2017
Lung Tagrisso 1st line adv. EGFRm NSCLC EGFR TKI 2017
Lung Tagrisso +
durvalumab
≥2nd line adv. EGFRm
NSCLC
EGFR TKI + anG-PDL1
mAb
N/a
Ovarian Lynparza 1st line BRCAm ovarian PARP inhibitor 2017
Ovarian Lynparza 2nd line or greater BRCAm
PSR ovarian cancer
PARP inhibitor H2’2016
Ovarian Lynparza gBRCA PSR ovarian PARP inhibitor 2018
PancreaGc Lynparza PancreaGc cancer PARP inhibitor 2018
Gastric Lynparza 2nd line gastric cancer PARP inhibitor N/a
Prostate Lynparza Prostate cancer PARP inhibitor Breakthrough
16

17. AZ Phase 3/Reg Programs
Focus Product Indica/on MOA Est. US Filing
Lung Tagrisso ≥2nd line adv. EGFRm NSCLC EGFR KI Launched
Lung Durvalumab Stage 3 NSCLC AnG-PDL1 2017
Lung Durvalumab +
tremilimumab
3rd line NSCLC AnG-PDL1
AnG-CTLA4
2017
Lung Durvalumab +
tremilimumab
1st line NSCLC AnG-PDL1
AnG-CTLA4
2017
Lung Durvalumab +
tremilimumab
1st line NSCLC AnG-PDL1
AnG-CTLA4
2019
Lung SelumeGnib 2nd line KRASm NSCLC MEK inhibitor 2017
Head/Neck Durvalumab 2nd line (PDL1 +) SCCHN AnG-PDL1 2017
Head/Neck Durvalumab +
tremilimumab
2nd line (PDL1-) SCCHN AnG-PDL1
AnG-CTLA4
2017
Head/Neck Durvalumab +
tremilimumab
2nd line SCCHN AnG-PDL1
AnG-CTLA4
2019
Head/Neck Durvalumab +
tremilimumab
1st line SCCHN AnG-PDL1
AnG-CTLA4
2018
17

18. AZ Phase 3/Reg Programs (cont.)
Focus Product Indica/on MOA Est. US Filing
Hematologic AcalabruGnib B-cell blood cancers Brutons TKI H2’16
Hematologic Moxetumomab
pasudotox
Hairy cell leukemia AnG-CD22
recominant
immunotoxin
2017 (orphan
status)
Ovarian Cediranib PSR Ovarian Cancer VEGFR TKI N/a
PancreaGc Durvalumumab +
tremelimumab
MetastaGc pancreaGc
ductal carcinoma
AnG-PDL1
AnG-CTLA4
2017
Bladder Durvalumumab +
tremelimumab
1st line bladder cancer AnG-PDL1
AnG-CTLA4
2018
Thyroid SelumeGnib DifferenGated thyroid
cancer
MEK inhibitor 2018
Meso-
thelioma
Tremelimumab Mesothelioma AnG-CTLA4 H2’16
(orphan, fast
track)
18

19. Astra Zeneca Disease Focus
Treatment Algorithms
and
CompeGGve Landscape

20. Breast Cancer - Adjuvant Endocrine Therapy
NCCN Guidelines (BINV-J) Version 1. 2016
NCCN Treatment Guidelines Version 3. 2013 (AI = Aromatase Inhibitor)
Pre-
menopausal
Tamoxifen
5 yrs or AI
5yrs
Pre-
menopausal
Post-
menopausal
Consider tam for an
additional 5 yrs. or
no further treatment
AI 5 yrs or consider
Tam 5+ yrs
AI to complete 5 yrs or
up to 5 yrs AI
Post-
menopausal
AI contra-
indicated,
decline,
intolerant
Tamoxifen
4.5-6 yrs
AI 5 yrs or
Tamoxifen
2-3 yrs or
AI 2-3 yrs
Tamoxifen 5 yrs or
consider tamoxifen up
to 10 yrs
AI 5 yrs or consider
tam for +5 yrs
Tamoxifen to complete
5 yrs
20

21. Breast Cancer Pre-Op/Adjuvant Therapy
Common Regimens
HER2
Sub-type
Preferred Regimens (examples) mAbs
HER2- AC: Anthracycline (e.g.doxorubicin) and an
alkylaGng agent (e.g. cyclophosphamide),
followed by a taxane (e.g. paclitaxel)
TC: Taxane (e.g. docetaxel) and alkylaGng
agent (e.g. cyclophosphamide)
CMF: Cyclophosphamide, methotrexate
(anG-metabolite), 5-FU
No
HER2+ As above Yes
HercepGn (trastuzumab)
Perjeta (pertuzumab)
Tykerb (lapaGnib)
Kadcyla (trast. + chemo)
Source: NCCN Breast Cancer Guidelines Version 1. 2016 PreoperaGve/Adjuvant Therapy Regimens Invasive BC (BINV-K) 21

22. Clinical Studies in Breast Cancer*
Search Term # Trials Listed # Phase 3**
PARP Inhibitors in Breast Cancer 54 29
AnG-PD1 Breast Cancer 8 5
AnG-PDL1 Breast Cancer 10 3
AnG-CTLA4 Breast Cancer 5 4
mAb Breast Cancer 285 175
mTOR inhibitor Breast Cancer 146 89
Advanced or MetastaGc Breast
Cancer
877 474
*Based upon described search terms uGlizing ClinicalTrials.gov March 3, 2016
**Includes completed, suspended, terminated, recruiGng, acGve/not yet recruiGng, unknown, withdrawn, mis-idenGfied
22

23. Advanced or MetastaGc Breast Cancer (gBRCA1/2)
Near Term CompeGGve Landscape (examples)
Company Therapy Class Phase
AZ Lynparza (olaparib) PARP Inhibitor 3
BioMarin Talazoparib PARP Inhibitor 3
Abbvie Veliparib PARP Inhibitor 3
Tesaro Niraparib PARP Inhibitor 3
Clovis Oncology Rucaparib PARP Inhibitor 2
23

24. Ovarian Cancer Primary Chemo/Primary Adjuvant
NCCN Guidelines Version 2. 2015
• Stages 1A or 1B – Observe or IV taxane/carboplaGn
• Stage 1C – IV taxane/carboplaGn
• Stages II, III,IV – Intraperitoneal chemotherapy or IV taxane/
carboplaGn
– Recurrence Therapies include: bevacizumab (Avas/n) and
olaparib (Lynparza)
Common Treatment Regimens:
- Paclitaxel, carboplaGn
- Docetaxel, carboplaGn
- Paclitaxel, carboplaGn, bevacizumab (mAb)
24

25. Clinical Studies in Ovarian Cancer*
Search Term # Trials Listed # Trials in Phase 3**
PARP Inhibitor Ovarian Cancer 54 31
AnG-PD1, AnG-PDL1, AnG-CTLA4
Ovarian Cancer
10 7
Tyrosine Kinase Inhibitor Ovarian
Cancer
28 11
EGFR Inhibitor Ovarian Cancer 13 7
VEGFR Inhibitor Ovarian Cancer 13 4
mTOR Inhibitor Ovarian Cancer 32 16
Immunotherapy Ovarian Cancer 67 34
*Based upon described search terms uGlizing ClinicalTrials.gov March 3, 2016
**Includes completed, suspended, terminated, recruiGng, acGve/not yet recruiGng, unknown, withdrawn, mis-idenGfied
25

26. Ovarian Cancer
Near Term CompeGGve Landscape (examples)
Company Therapy Class/Indica/on Phase
AZ Lynparza (olaparib) PARP Inhibitor/(BRCAm) 3
AZ Cediranib VEGFR TKI/(PSR) 3
AbbVie Veliparib PARP Inhibitor 3
BMS Yervoy (ipilimumab) AnG-CTLA4 2
Clovis
Oncology
Rucaparib PARP Inhibitor 3
MulGple Immunotherapy mAbs, vaccines 1/2
26

27. NSCLC Chemotherapy for Neoadjuvant & Adjuvant Therapy
NCCN Treatment Guidelines Version 4.2016
• CisplaGn, vinorelbine
• CisplaGn, etoposide
• CisplaGn, gemcitabine
• CisplaGn, docetaxel
• CisplaGn, pemetrexed
Regimens may vary based upon concurrent or sequenGal use of RT
27

28. 1st Line Systemic Therapy for Advanced or MetastaGc NSCLC
NCCN Treatment Guidelines Version 4.2016 NSCL-F (1-4)
• Adenocarcinoma Large Cell NSCLC NOS (PS 0-1)
– Targeted Therapy (mAb) , PlaGnum, Taxane (e.g. bevacizumab/carboplaGn/paclitaxel)
– PlaGnum, Taxane
– PlaGnum, AnG-metabolite
• Adenocarcinoma Large Cell NSCLC NOS (PS 2)
– Taxane
– PlaGnum, Taxane
– PlaGnum, Topoisomerase Inhibitor
– AnG-metabolite or AnG-metabolite,Taxane
• Squamous Cell Carcinoma (PS 0-1)
– PlaGnum, Taxane
– PlaGnum, AnG-metabolite or PlaGnum, AnGmetabolite, mAb
– PlaGnum, Topoisomerase Inhibitor
• Squamous Cell (PS 2)
– Taxane
– PlaGnum, Taxane
– PlaGnum, Topoisomerase Inhibitor
– AnG-metabolite or AnG-metabolite, Other Microtubule Inhibitor
In pa/ents with disease progression AFTER 1st line, consider checkpoint inhibitor
(nivolumab/Opdivo or pembrolizumab/Keytruda in PDL1 tumors), or other systemic
therapies (docetaxel, pemetrexel, gemcitabine), erlo/nib, afa/nib, gefi/nib, crizo/nib)
28

29. Clinical Studies in NSCLC Cancer*
Search Term # Trials Listed # Trials in Phase 3**
NSCLC 3,523 1,795
AnG-PD1, AnG-PDL1, AnG-CTLA4 NSCLC 32 20
MEK Inhibitor NSCLC 32 23
EGFR TKI NSCLC 157 67
VEGFR Inhibitor NSCLC 38 24
PARP Inhibitor NSCLC 9 8
mTOR Inhibitor NSCLC 45 23
Immunotherapy NSCLC 99 60
*Based upon described search terms uGlizing ClinicalTrials.gov March 3, 2016
**Includes completed, suspended, terminated, recruiGng, acGve/not yet recruiGng, unknown, withdrawn, mis-idenGfied
29

30. NSCLC
Near Term CompeGGve Landscape (examples)
Company Therapy Class Phase
AZ Durvalumab AnG-PDL1 3
AZ Tagrisso + durvalumab EGFR TKI, anG-PDL1 3
AZ Tagrisso EGFR TKI 3
AZ SelumeGnib MEK inhibitor 3
Boehringer AfaGnib EGFR TKI 3
Merck Keytruda (pembrolizumab) AnG-PD1 Approved Q4’15
Merck KGaA Alezolizumab (MPDL3280A) AnG-PDL1 3
BMS Opdivo (nivolumab) +
Yervoy (ipilimumab)
AnG-PD1, AnG-CTLA4 3
Peregrine
Pharma
Bavituximab mAb 3
Daiichi
Sankyo
Patritumab mAb 3
Various TherapeuGc vaccines Cellular Immunotherapies 2/3
30

31. Blood Cancers - Leukemia
HematopoieGc
Stem Cell (bone marrow)
RBCs
Mega-
Karyocytes
B cells T cells
Mono-
cytes
Granulo-
cytes
Pre-cursor
blasts
Myeloid
Blast
Lymphoid
Blast
In acute leukemia blast cells are
unable to differenGate, and “build
up” in the bone marrow
prevenGng normal cell producGon.
Loss of RBCs Loss of platelets Loss of neutrophils
Anemia Thrombo-
cytopenia
Neutropenia
ACUTE LEUKEMIA SYMPTOMS
FaGgue Bleeding InfecGons
Source: Wikipedia (leukemia) 31

32. Blood Cancers
• 4 main sub-types of leukemia (pre-cursor myeloblasts or lymphoblasts cant
differenGate and build up in the bone marrow):
– ALL (acute lymphoblasGc leukemia >20% lymphoid blasts in bone marrow)
– CLL (chronic lymphocyGc leukemia B or T lymphoblasts overflow into blood,
CNS)
– AML (acute myeloid leukemia - >20% myelooid blasts in bone mrrow) )
– CML (chronic myelogenous leukemia – blasts overflow into blood, CNS)
• 5 main sub-types of lymphoma (blood cell tumors that develop from
lymphaGc cells – previously Hodgkin’s and Non-Hodgkin’s Lymphoma)
– Mature B-cell neoplasms
– Mature T cell and NK neoplasms
– Precursor lymphoid neoplasms
– Hodgkins Lymphoma
– Immuno-deficiency associated lymphoproliferaGve disorders
• MulGple Myeloma (a cancer of plasma cells, a type of WBC normally
responsible for producing anG-bodies)
– Many organs affected (“CRAB” = Calcium, Renal Failure, Anemia, Bone Lesions/pain)
– Develops in B lymphocytes 32

33. Non-Hodgkin’s Lymphoma
NCCN Guidelines Version 2.2016
• Chronic lymphocyGc leukemia/small lymphocyGc lymphoma
• Follicular lymphoma
• Marginal zone lymphomas (4)
• Mantle cell lymphoma
• Diffuse large B cell lymphoma
• Burki; lymphoma
• LymphoblasGc lymphoma
• AIDs related B cell lymphoma
• Hairy cell leukemia
• Primary cutaneous B cell lymphomas
• Peripheral T cell lymphomas
• Mycosis Fungoides/Sezary Syndrome
• Primary cutaneous CD30+ T cell lymphoproliferaGve disorders
• T cell large granular lymphocyGc leukemia
• Adult T cell leukemia/lymphoma
• T cell prolymphocyGc leukemia
• Extranodal NK/T cell lymphoma, nasal type
• Post-transplant lymphoproliferaGve disorders
• Castlemanae Disease 33

34. Blood Cancers: ALL and AML
NCCN Guidelines Version 2.2015/1.2016
• ALL (Acute LymphoblasGc Leukemia)
– Treat. goal directed to control of bone marrow and systemic disease, and
treatment for spread, especially into CNS. Age of paGent impacts treatment
regimen:
• InducGon chemo (anthracycline/microtubule inhibiGon/prednisone) +/- TKI
• ConsolidaGon therapy to eliminate remaining leukemia cells. Typically high-
dose mulG-agent chemo regimen +/- TKI)
• CNS prophylaxis (consider RT and/or intrathecal chemotherapy)
• Maintenance (low dose chemo up to 3 years)
• Evaluate for allogeneic HCT (hematopoieGc cell transplantaGon) for high
risk/relapsed pts.
• AML (Acute Myeloid Leukemia)
– Same treatment goal
• InducGon (usually cytarabine with idarubicin or daunorubicin).
• ConsolidaGon (cytarabine with anthracycline (idarubicin or daunorubicin)
• CNS prophylaxis (consider RT and/or intrathecal chemotherapy)
• Evaluate for allogeneic HCT 34

35. Blood Cancers – CLL and CML
NCCN Guidelines Version 2.2016/1.2016
• CLL/SLL (Chronic LymphocyGc Leukemia/Small LymphocyGc
Lymphoma) – Non-Hodgkin’s Disease
– Treatment is age and gene dependent
– Low-grade disease o{en not treated
– More advanced pts. receive an alkylaGng agent (chlorambucil,
cyclophosphamide) +/- mAb (obinutuzumab, rituximab; anG-CD20 on
surface of B cells) +/- a corGcosteroid as 1st line therapy.
– Refractory pts. may get ibruGnib, alemtuzumab +/- rituximab, FCR, PCR,
RCHOP, CFAR
– Allogeneic HCT
• CML (Chronic Myelogenous Leukemia)
– Primary treatment TKI/mAb (imaGnib/Gleevec, dasaGnib, niloGnib)
– Relapse may require allogeniec HCT
35

36. Blood Cancers – Lymphoma, MM & HCL
NCCN Guidelines Versions 2.2016/3.2016
• NHL (e.g. Diffuse Large B-Cell Lymphoma)
– 1st line therapy RCHOP (rituxumab, cyclophosphamide, doxorubicin,
Oncovin (vincrisGne), prednisone) +/- RT
– HSCT
• MulGple Myeloma
– Primary therapy bortezomib/Velcade (proteasome inhibitor) +
steroid +/- cyclophosphamide, doxorubicin, thalidomide or
thalidomide-like drug.
– Relapse or progressive disease consider ASCT
• Hairy Cell Leukemia
– If symptom-free usually no treatment
– Treatment with cladribine (inhibits cancer cells ability to process
DNA) or 6 months pentostaGn. Other treatments may include
rituximab or IFN-alpha
36

37. Clinical Studies in Blood Cancers*
Search Term # Trials Listed # Trials in Phase 3**
Tyrosine Kinase Inhibitor B cell leukemia 49 31
Tyrosine Kinase Inhibitor B cell lymphoma 59 39
mTOR Inhibitor B cell leukemia 51 42
mTOR Inhibitor B cell lymphoma 66 49
mAb B cell leukemia 312 211
mAb B cell lymphoma 399 286
CAR T B cell leukemia 43*** 31***
CAR T B cell lymphoma 51*** 34***
*Based upon described search terms uGlizing ClinicalTrials.gov March 3, 2016
**Includes completed, suspended, terminated, recruiGng, acGve/not yet recruiGng, unknown, withdrawn, mis-idenGfied
***MulGple NCI/Teaching Hospital sponsored studies, primarily phase 1/2
37

38. Blood Cancer
Near Term CompeGGve Landscape - Examples
Company Therapy Class Phase Type
AZ acalabruGnib Brutons TKI 3 B cell
AZ Moxetumomab AnG-CD22 3 Hairy cell
Pharmacyclics PCI-32765 Brutons TKI 3 CLL/SLL
Janssen ibruGnib Brutons TKI 3 CLL/SLL, Diffuse
large B cell
lymphoma,
TG
TherapeuGcs
Ublituxumab
(TG-1101)
mAb (anG-CD20) 3 CLL
38

39. Key Issues
• MulGple therapeuGc opGons for treaGng cancer are being developed, with
greatest acGvity from large companies, including BMS, Merck, AZ and NovarGs.
This is increasing pressure to idenGfy clinical trial centers/subjects, bring
therapies to market quickly, and with opGmal launch strategies.
• Oncology treatments are become increasingly complex, requiring high experGse
and knowledge of the immune system by companies and prescribers.
• Immunotherapy is changing treatment expectaGons for cancer. Early data
suggests that uGlizing mulGple approaches (“combinaGons”) provides the
greatest potenGal for success. This requires a broad por1olio and/or increased
partnerships.
• Use of combinaGon therapies will have a significant effect on the cost of
treatment, both for payers and the paGent.
• As more treatment opGons reach the market they will need to offer clear
differenGaGon from the compeGGon. 39

40. CriGcal Success Factors
• More efficient product development and launches.
• AllocaGng sufficient resources to accelerate product development, pre-
launch planning and launch opGmizaGon.
• Educated companies/employees.
• Educated prescribers, paGents and other key stakeholders.
• Increased partnering and in-licensing.
• Developing algorithms to idenGfy which combinaGons of treatments offer
the greatest probability for success.
• Emphasis on early and comprehensive differenGaGon. Understand the
compeGGve landscape, defining the opGmal Target Product Profile (TPP)
and incorporaGon of “brand value measures” during clinical development.
• EffecGve intelligence systems, to enable the rapid assimilaGon of large
amounts of informaGon quickly.
• Extensive Thought Leader engagement/development.
40