17th Annual BIO CEO & Investor Conference
February 9-10, 2015
This presentation may contain forward-looking statements, which reflect Trillium's current expectation regarding
future events. These forward-looking statements involve risks and uncertainties that may cause actual results,
events or developments to be materially different from any future results, events or developments expressed or
implied by such forward-looking statements. Such factors include, but are not limited to, Trillium's ability to
obtain financing to advance the products in its development portfolio; changing market conditions; the
successful and timely completion of pre-clinical and clinical studies; the establishment of corporate alliances;
the impact of competitive products and pricing; new product development risks; uncertainties related to the
regulatory approval process or the ability to obtain drug product in sufficient quantity or at standards
acceptable to health regulatory authorities to complete clinical trials or to meet commercial demand; and other
risks detailed from time to time in Trillium's ongoing quarterly and annual reporting. Except as required by
applicable securities laws, Trillium undertakes no obligation to publicly update or revise any forward-looking
statements, whether as a result of new information, future events or otherwise.
2
Investment Highlights

Immuno-oncology company developing a next
generation immune checkpoint inhibitor

Over a decade of immunotherapy research;
validated by several revenue-generating
partnerships – Genentech, Biogen, Medarex etc.

Lead program targets CD47, a “do not eat” signal
tumor cells exploit to escape destruction by the
innate immune system

Raised $30M (12/2013) from premier US healthcare
funds to support clinical development

IND in Q3/15; $90 million valuation
3
2014 Highlight
Capitalization
Listed on NASDAQ (TRIL) and TSX (TR)
6.7M Common & Pref. shares (as converted)
~70% institutional ownership
12M shares fully diluted
~$90M market cap (including Pref. shares)
Raised $30M in Dec 2013
$22M cash at December 31, 2014
5
Experienced Leadership
Management
Dr. Niclas Stiernholm – President & Chief Executive Officer (2002)
Dr. Robert Uger – Chief Scientific Officer (2003)
Dr. Penka Petrova – Vice President, Drug Development (2003)
Mr. James Parsons – Chief Financial Officer (2003)
Mr. Scott Duncan – Director, Patents and Licensing (2003)
Board of Directors
Affiliation
Dr. Calvin Stiller, Chair (2011)
Dr. Henry Friesen (2011)
Dr. Niclas Stiernholm (2011)
Dr. Michael Moore (2013)
Dr. Robert Kirkman (2013)
Dr. Thomas Reynolds (2014)
Mr. Luke Beshar (2014)
Chair, Ontario Institute for Cancer Research
President, Medical Research Council of Canada (former)
CEO, Trillium
CEO, Piramed (former)
CEO, Oncothyreon
CMO, SeattleGenetics (former)
CFO, NPS Pharmaceuticals
6
SIRPaFc Checkpoint Inhibitor Program
A pre-IND immunotherapy
program targeting CD47
SIRPaFc inhibits the ‘DO NOT
EAT’ signal of CD47 allowing
macrophages to engulf and
destroy tumor cells
7
Key Attributes of the SIRPaFc Program

SIRPαFc is a biologic cancer immunotherapy targeting the CD47 “do not eat” signal

Follows in the footsteps of CTLA-4 and PD-1 checkpoint inhibitors

Operates through macrophages (innate immune system) but can exert
downstream effects on the adaptive immune system (T cells)

Holds great promise as both monotherapy and combination therapy with other
immunological agents

Has broad clinical potential in both hematological and solid tumors

Mobilizes the immune system to attack bulk cancer cells and cancer stem cells
8
SIRPaFc: A Novel Biologic that Blocks the CD47
“Do Not Eat” Signal
9
SIRPaFc Enables Macrophages to Kill Human
Tumor Cells
CD47 Exp 377
Phagocytosis Index
500
100
Human AML cells labeled green
Human macrophages labeled red
Phagocytosis assessed by confocal microscopy after 2 hr co-culture
SIRPaFc (nM)
10
00
10
00
0
10
0
ro
l
10
0
Co
nt



* *
200
1
SIRPαFc (10 mM)
*
300
0
0.
00
1
Control Fc (10 mM)
400
Fc
No Treatment
*
*p<0.01
10
SIRPaFc is Active Against a Diverse Panel of AML Samples
Phagocytosis Assay
SIRPaFc
Control Fc
300
*
**
200
**
*
** **
**
*
100
***
NS
*p<0.05
**p<0.01
***p<0.001
0
80
55
80 9
56
90 7
17
90 4
54
90 3
59
90 6
65
90 0
7
10 65
01
10 16
06
10 22
08
57
Phagocytosis Index
400
AML Patient Characteristics
AML Patient
Patient
Age
Sex
FAB Subtype
Blast %
80559
68
M
M5a
20
80567
69
F
M5a
90
90174
41
M
M4
NA
90543
33
M
M2
82
90596
69
M
M0
97
90650
67
M
M1
90
90765
94
F
M2
90
100116
66
F
M4
NA
100622
65
F
M4Eo
40
100857
73
M
M2
10
11
SIRPaFc Induces Tumor Cell-Specific Phagocytosis
CD47 Exp 381
Phagocytosis Index
300
250
*
SIRPaFc
Control Fc
200
150
100
50
0
AML + SIRPαFc
Normal cells + SIRPαFc
AML cells
Normal monocytes
Results consistent with a model in which CD47 blockade enables macrophages to
kill only target cells that express pro-phagocytic signals (i.e, tumor cells)
12
Evaluating SIRPaFc Efficacy In Vivo
Xenografts in NOD.SCID mice: the “gold standard” model in AML
Intrafemoral
injection
AML cells from
cancer patient
SIRPαFc
Measure leukemia
by flow cytometry
treatment
NOD.SCID mouse
Isolate bone marrow
& spleen
13
SIRPaFc Has Potent Anti-leukemic Activity In Vivo
Injected Bone Marrow
% AML Engraftment
50
25
p=3x10-8
75
50
25
p=0.003
0
0
SIRPaFc
SIRPaFc
Control Fc
Injected Bone Marrow
% AML Engraftment
% AML Engraftment
50
25
SIRPaFc
Control Fc
p=0.008
0
SIRPaFc
Control Fc
Control Fc
Spleen
8
100
75
p=0.02
Non-Injected Bone Marrow
100
Patient
#90191
1.1
1.0
0.9
0.8
0.7
0.6
0.5
0.4
0.3
0.2
0.1
0.0
% AML Engraftment
% AML Engraftment
75
% AML Engraftment
100
100
Patient
#90543
Spleen
Non-Injected Bone Marrow
75
50
25
p=0.003
7
6
5
4
3
2
1
p=0.0004
0
0
SIRPaFc
Control Fc
SIRPaFc
Control Fc
Human SIRPaFc treatment: 8 mg/kg IP 3x/wk for 4 wks, starting 21d after engraftment
14
SIRPaFc Has Strong Anti-leukemic Activity Even At
Low Doses
100
6
75
50
p<0.001
25
p<0.001
0
50
40
30
20
10
p<0.001
p<0.001
p<0.001
1 mg/kg
SIRPaFc
5 mg/kg Control Fc
5
4
3
2
1
p<0.001
p<0.001
p<0.001
0.2 mg/kg
1 mg/kg
5 mg/kg Control Fc
0
0
0.2 mg/kg
% AML Engraftment
60
% AML Engraftment
% AML Engraftment
Spleen
Non-Injected Bone Marrow
Injected Bone Marrow
0.2 mg/kg
1 mg/kg
5 mg/kg Control Fc
SIRPaFc
SIRPaFc
Mouse SIRPaFc treatment: 0.2, 1 or 5 mg/kg IP 3x/wk for 4 wks, starting 21d after engraftment
Mouse (NOD) SIRPαFc binds both human and mouse CD47 (antigen sink effect)
15
SIRPaFc Pre-Clinical Development Plan
2013
Q3
Q4
2014
Q1
NHP Study
Q2
Q3
Q4
2015
Q1
Q2
Q3
Q4
NHP Study
AML Xenograft Studies
In Vitro Pharmacology Studies
Manufacturing (CMC)
Pre-IND
GLP Toxicology
IND
Phase I
Solid and Other Hematological Tumor Xenograft Studies
16
SIRPaFc Has Broad Clinical Potential
Many different tumors express
high levels of the CD47 “do not
eat” signal
High CD47 levels are often
associated with disease
progression
Blood cancers
AML
ALL
CLL
CML
DLBCL
Follicular lymphoma
Mantle cell lymphoma
Multiple myeloma
Solid cancers
Bladder
Brain
Breast
Colon
Leiomyosarcoma
Liver
Melanoma
Ovarian
Prostate
Pre-clinical program has been
expanded to other liquid and
solid oncology indications
17
SIRPaFc Triggers Macrophage-mediated Phagocytosis of
Many Different Human Blood Cancer Cell Lines
100
120
100
80
60
*
40
20
***
150
100
***
50
NS
*
E N L -1
C1R
J u rk a t
***
60
40
*
P h a g o c y to s is In d e x
P h a g o c y to s is In d e x
Ly1
N a m a lw a
R a ji
***
60
**
40
NS
***
20
A M L -2
H L -6 0
K G -1
T H P -1
T F -1
SIRPaFc
Control Fc
70
80
***
60
50
40
**
30
***
20
NS
10
0
0
K562
80
M u lt ip le M y e lo m a
CML
20
***
0
0
0
P h a g o c y to s is In d e x
200
***
P h a g o c y to s is In d e x
P h a g o c y to s is In d e x
140
AML
B Lym phom a
ALL
K U812
M M 1 .s
8226
H929
***p<0.0001
**p<0.01
*p<0.05
U266
18
A Second Clinical Pathway: SIRPaFc Combination Therapy

SIRPαFc-mediated enhancement of innate immunity could be synergistic with
other immune therapies, such as:
 Approved cancer antibodies (e.g., Rituxan®)
 T cell checkpoint inhibitors (e.g., anti-PD-1)
 Cancer vaccines
 Oncolytic viruses
 CAR T cells

Preliminary evidence suggests that CD47 blockade can enhance the potency of
anti-cancer antibodies and promote T cell responses

We will be evaluating SIRPαFc in preclinical combination studies
19
Competition

Trillium is the only group developing a SIRPαFc fusion protein and has developed IP
around this approach

Three others are pursuing anti-CD47 antibodies:
 Stanford, through a non-commercial entity (CIRM grant)
 Celgene (licensed from Inhibrx)
 Novimmune (bispecific anti-CD47/anti-CD19 antibody)

Trillium’s SIRPαFc has much lower binding to human RBCs compared to anti-CD47
mAbs – potential best in class through:
 Lower hemotoxicity
 More favorable PK (no RBC “antigen sink”)
20
SIRPaFc Binds Very Poorly to Human RBCs Compared to
CD47 Antibodies
RBCs
CD47 mAbs
2000
1500
1000
500
CD47 mAbs
350
Geometric Mean
Geometric Mean
2500
AML-2
300
250
200
150
100
50
R
IC
12
6
C
C
2C
6
SI
R
Pa
Fc
12
0
B
6H
B
c
6
c
6
aF
12
lF
2C
P
o
C
C
I
R
tr
C
R
SI
B
on
C
6H
12
B
3
2D
2D
3
0
Binding of commercially available anti-CD47 mAbs and SIRPαFc to human RBCs
(n=14 donors) and AML-2 cells
21
Upcoming Milestones
 AACR presentation – Q2’14
 GMP master cell bank generation – Q3’14
 CMC engineering run – Q3’14
 NASDAQ listing Q4’14
 Pre-IND meeting with the FDA – Q4’14 (scheduled Jan 2015)
 Initiate GLP toxicology studies – Q1’15
 Production of GMP lot – Q2’15
 IND filing – Q3’15
 Preclinical data supporting additional clinical indications – Q4’15
22
Trillium Therapeutics Inc. (NASDAQ:TRIL/TSX:TR) is an
immuno-oncology company dedicated to the discovery and
development of novel and innovative cancer therapies.