As delivered to the Endpoints News breakfast at JPM18 on January 9, 2018

1. IO LANDSCAPE ANALYSIS
JPM18
JANUARY 9, 2018
AIMAN SHALABI PHARMD, MBA
CHIEF MEDICAL OFFICER
CLINICAL ACCELERATOR
PHILANTHROPIC VENTURE FUND
CANCER RESEARCH INSTITUTE

2. Page 2

3. 26 IMMUNO-ONCOLOGY AGENTS APPROVED GLOBALLY
Therapy type Therapy name Company Target
T-cell targeted
immunomodulator
(6 in total)
Ipilimumab Bristol-Myers Squibb Co CTLA-4
Nivolumab Bristol-Myers Squibb Co PD-1
Pembrolizumab Merck & Co Inc PD-1
Atezolizumab Roche/Genentech Ltd PD-L1
Avelumab Merck KGaA PD-L1
Durvalumab AstraZeneca/MedImmune LLC PD-L1
Other
immunomodulator
(8 in total)
Aldesleukin Novartis AG IL2R
Imiquimod Valeant Pharmaceuticals Intl Inc TLR7
Interferon alfa
Sumitomo Dainippon Pharma Co
Ltd
IFNAR1; IFNAR2
Interferon alfa-1b Shenzhen Kexing Biotech Co Ltd IFNAR1
Interferon alfa-2a Cadila Healthcare Ltd IFNAR1; IFNAR2
Interferon alfa-2b Merck & Co Inc IFNAR1; IFNAR2
Interferon beta Toray Industries Inc IFNAR1
Interferon gamma-1a Otsuka Pharmaceutical Co Ltd IFNAR1
Therapy type Name of Therapy Company Target
Cancer vaccine
(7 in total)
BCG Live Shire Plc TLR
ImmuCyst Sanofi TLR
Immuno BCG
Ataulpho Paiva
Foundation
TLR
Mycidac-C
Cadila
Pharmaceuticals Ltd
TLR2
Sipuleucel-T Dendreon Unspecified TAA
TICE BCG Merck & Co Inc TLR
Uro-BCG Medac Inc TLR
Cell therapy
(2 in total)
Tisagenlecleucel Novartis AG CD19
Axicabtagene ciloleucel Gilead CD19
Oncolytic virus
(2 in total)
Oncorine
Shanghai Sunway
Biotech Co Ltd
CD40L
Talimogene
laherparepvec
Amgen Inc GMCSFR
CD3-targeted
bispecific ab
Blinatumomab Amgen Inc CD19 X CD3
Page 3
Annals of Oncology Dec 2017
Tang, Shalabi, Hubbard-Lucey

4. Therapy type_JT_..
0 50 100 150 200 250 300 350
Number of Records
T-cell targeted
immunomodulator
Other
immunomodulator
cancer vaccine
Cell therapy
oncolytic virus
BiTE
144130
112
34
72
54
12
24
30
12
33
22
42
29
96
16
24
12
4
5
2
5
1
2
2
7
8
6
A REVOLUTION IS UNDERWAY: 2,004 IO AGENTS IN DEVELOPMENT
940 AGENTS ARE IN CLINICAL STAGES, AND 1,064 IN PRECLINICAL
Therapy type_JT_AS ..
050100150200250300
Number of Records
Checkpoint-activator
Immunomodulator
Cancer vaccine
Cell Therapy
Oncolytic virus
BiTE
0 5050100150200250300350 100 150 200 250 300 350
Number of Agents
199
284
261
179
95
46
Other immunomodulator
T-cell targeted immunomodulator
Cancer vaccine
Cell therapy
Oncolytic virus
CD3-targeted bispecific antibody
Clinical
agent count
99
170
344
224
69
34
Clinical stage
Approved
Phase III
Phase II
Phase I/II
Phase I
Preclinical & Discovery
Page 4
Annals of Oncology, Dec 2017
Tang, Shalabi, Hubbard-Lucey

5. Target
0 10 20 30 40 50 60 70 80 90 100 110 120
Number of Clinical Agents
Unspecified TAA
CD19
PD-1
HER2
NY-ESO-1
PD-L1
CD20
CD40
EGFR
CSF1R
GD2
WT1
IFNAR1
MUC1
PSMA
TERT
Survivin
HPV E6
Personalization
BCMA
CEA
LAG-3
OX40
TLR
TLR7
CD123
GITR
GPC3
HPV E7
IDO1
IL2
mesothelin
PSA
TLR9
CD22
CD30
CD47
MAGE-A3
ADORA2A
CD25
34
12
10
10
57
13
11
14
13
11
11
11
12
13
19
98
5
6
7
7
1
1
2
4
5
5
9
5
8
9
3
1
6
6
2
7
3
2
8
1
4
8
9
7
6
3
6
9
9
2
4
5
8
1
5
5
1
6
7
7
2
1
3
3
2
1
1
1
4
4
7
1
3
2
1
3
1
271 IO TARGETS IN CLINICAL TESTING, BY 462 DIFFERENT ENTITIES
TOP 40 LISTED BELOW
Therapy type
T-cell targeted immunomodulator
Other immunomodulator
Cancer vaccine
Cell therapy
Oncolytic virus
CD3-targeted bispecific mAb
Page 5
Annals of Oncology, Dec 2017
Tang, Shalabi, Hubbard-Lucey

6. 0 2020406080 40 60 80 100
Number of Agents
98
51
13
Country (gr..
020406080
Number of Clinical Agents
China
USA
Other
Country (gr..
0 20 40 60 80 100
Number of Clinical Agents
China
USA
Other 8
37
32
1
2
1
4
10
64 1
2
23
76
30
Clinical stage
Approved
Phase III
Phase II
Phase I/II
Phase I
Preclinical & Discovery
Clinical agent count
China
US
Other
CAR-T CELL THERAPY LANDSCAPE
CRI FOLLOWING 291 AGENTS, WITH 162 ALREADY IN CLINICAL TESTING
Page 6
Annals of Oncology, Dec 2017
Tang, Shalabi, Hubbard-Lucey

7. PD-1/L1 AGENTS WILL CONTINUE TO BE
TRANSFORMATIONAL
…. BUT AN URGENT NEED FOR EFFICIENCIES
Page 7

8. CRI FOLLOWING 164 PD-1/L1-TARGETING AGENTS
50 CLINICAL STAGE AGENTS (34 MONOCLONAL ANTIBODIES)
Page 8
Preclinical &
Discovery
Phase I Phase I/II Phase II Phase III Approved
0
20
40
60
80
100
120
Number of Records
59
15
27
20
3 5
8
4
6
1
1
2
1 3
9
114
30
3
9
3 5
Molecule type
Monoclonal antibody
Bispecific antibody
Small molecule
Other biologic
Therapy type - Split 2 (group)
Monoclonal antibody
Bispecific antibody
small molecule
Other biologic
Annals of Oncology, Dec 2017
Tang, Shalabi, Hubbard-Lucey

9. INCREASE OF NEW PD-1/L1 COMBO TRIALS
2009 2010 2011 2012 2013 2014 2015 2016 2017
Number
of new
trials
Planned
new
enrollment
Trial
Start
Year
1
136
5
2,473
2
582
13
4,867
20
5,031
58
11,276
190
39,821
329
46,153
469
52,539
Clinical phase
Phase 4
Phase 3
Phase 2
Phase 1/2
Phase 1
Page 9
Annals of Oncology, Dec 2017
Tang, Shalabi, Hubbard-Lucey

10. PD-1/L1 COMBO PARTNER ANALYSIS
165 DIFFERENT TARGETS ARE BEING COMBINED
Page 10
CTLA-4
251
Chemotherapy
170
Radiotherapy
64
VEGFA
43
Chemoradio
therapy
42
Numbers of Trials Using Common Combo Strategies:
1. Anti-CTLA-4 agents: 251
2. Chemotherapies: 170
3. Radiotherapies: 64
4. Anti-VEGFA agents: 43
5. Chemoradiotherapy combos: 42
Annals of Oncology, Dec 2017
Tang, Shalabi, Hubbard-Lucey

11. PD(L)-1 STUDIES ARE MOSTLY SMALL, SINGLE CENTER TRIALS
655
450
Number of Trials
(1,105 in total)
Sponsorship
Non-industry-sponsored trials
Industry-sponsored trials
Page 11
Annals of Oncology, Dec 2017
Tang, Shalabi, Hubbard-Lucey

12. INNOVATION LIVES IN ACADEMIC CENTERS…
Page 12
First approved
CAR-T therapy
First approved tissue-agnostic
cancer therapy
Multiple PDL-1 + CTLA-4 Ph3 Trials

13. MASTER PROTOCOLS
ENABLING FASTER AND MORE COST EFFICIENT CLINICAL INFRASTRUCTURE
Page 13
Build Multi-Lanes (in one trial)
Drive Multiple (combos)
Get Multiple Results
Keep Highway OPEN
Build 1 Highway (Trial)
Drive 1 Car (Recruit)
Get to 1 Result
Dismantle the Highway
50% of study costs to build trial
9-12 mos to start
OLD
1 Question = 1
Study = 1 Result
NEW
1 Platform =
Multiple
Questions

14. CRI: FUNDING THE FULL SPECTRUM OF IO INNOVATION
CLINICAL ACCELERATOR CULTIVATES INNOVATION, COLLABORATION, INTEGRATION
Page 14
CRI Irvington
Postdoctoral
Fellowship
Basic laboratory
research and
early training for
young scientists
Clinic and
Laboratory
and Integration
Program (CLIP)
Translational
research grants to
top investigators
Clinical Accelerator
Clinical trials of
promising cancer
immunotherapies
Cancer
Immunotherapy
Consortium (CIC)
Biopharma think tank
addressing late-stage
development issues
The Answer to Cancer
Patient and caregiver
resources and clinical
trial finder
Impact Grants
Directed funding
to advance solutions
to scientific and
technological
challenges

15. GLOBAL IMMUNO-ONCOLOGY COLLABORATION
PARTNERING CRI IO EXPERTISE WITH CCTG GLOBAL CLINICAL AND OPERATIONAL EXCELLENCE
Page 15
Press Release Jan 8, 2018
65 year legacy in
tumor immunology
$357m funding
Proven speed and
cost effectiveness
Near 40 year legacy
leading practice
changing trials
Global footprint:
over 500 trials in
over 40 countries
Global IO expert network
Efficiently evaluate the most
promising immunotherapies
on a global scale