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Ladenburg Thalmann Healthcare Conference
October 2, 2018
NASDAQ/TSX: TRIL
This presentation may contain forward-looking statements, which reflect Trillium's current expectationregarding future events. These forward-looking statements involve risks and uncertainties that may causeactual results, events or developments to be materially different from any future results, events ordevelopments expressed or implied by such forward-looking statements. Such factors include, but are notlimited to, Trillium's ability to obtain financing to advance the products in its development portfolio; changingmarket conditions; the successful and timely completion of pre-clinical and clinical studies; the establishmentof 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 sufficientquantity or at standards acceptable to health regulatory authorities to complete clinical trials or to meetcommercial demand; and other risks detailed from time to time in Trillium's ongoing quarterly and annualreporting. Forward-looking statements are made only as of the date of this presentation and except as requiredby applicable securities laws, Trillium undertakes no obligation to publicly update or revise any forward-lookingstatements, whether as a result of new information, future events or otherwise.
CONFIDENTIAL 2
Investment Highlights
• Immuno-oncology company taking cancer care to the next level, bridging innate and adaptive immunity
• Only company with two product candidates targeting CD47, a 2nd generation IO target that tumors use to evade the immune system
• Most differentiated & diversified approach:• IgG1 and IgG4 Fc decoy receptors• Mono- and combo-therapy• Intravenous and intratumoral administration
• Lead program has shown excellent tolerability and single agent activity in patients with blood cancers
• Five clinical programs targeting B- and T-cell lymphomas in 2019/20; multiple near-term catalysts
3
Clinical Pipeline Focused on CD47
4
PreclinicalIndication
Intratumoral
Intratumoral
Intravenous
Intravenous
Intravenous
Monotherapy
Combination(IFNα, PD-1/PD-L1)
Monotherapy
Combination(Rituximab, Nivolumab)
Monotherapy,Combination
Monotherapy/CombinationRoute
CTCL, Solid tumors
CTCL
CTCL, PTCL, ALL
DLBCL, HL
Lymphoma, myeloma
Candidate
TTI-622(SIRPα-IgG4 Fc)
TTI-621(SIRPα-IgG1 Fc)
TTI-621(SIRPα-IgG1 Fc)
Phase 1/2a(POC)
Phase 2b/3(Pivotal)
Targeting CD47
5
Many Tumor Cells Use the CD47 “Do Not Eat” Signal to Inhibit Macrophage Phagocytosis
CD47 delivers an inhibitory “do not eat” signal to macrophages through SIRPα
6
Many hematologic and solid tumors express high levels of CD47
High CD47 expression often correlates with aggressive disease and poor clinical outcomes
TTI-621: A Dual Function SIRPαFc Decoy Receptor that Blocks CD47 and Delivers an Activating Signal
7
Blocks the CD47 DO NOT EAT signal
Delivers an EAT signal through FcγRs
TTI-621 Activates Both the Innate and Adaptive Immune Systems
8
Differentiating TTI-621 From Other CD47 Blocking Agents1. TTI-621 IgG1 Fc delivers a potent “eat” signal
9
CD47 Blocker* (Company) Isotype
TTI-621 (Trillium) IgG1
TTI-622 (Trillium) IgG4
Hu5F9 (Forty Seven) IgG4
CC-90002 (Celgene) IgG4
SRF231 (Surface Oncology) IgG4
ALX148 (ALX Oncology) Inert IgG1
Petrova et al. Clin. Cancer Res. 2017
*Clinical stage compounds
Advantages of an IgG1 Fc:• Maximizes potency by delivering an activating signal to
macrophages through Fc receptors• Higher likelihood of monotherapy activity - not dependent
upon a combination with another IgG1 antibody• Could be used to treat tumors where no anti-cancer
antibody is available
Differentiating TTI-621 From Other CD47 Blocking Agents2. TTI-621 Does Not Bind Human RBCs
10
Petrova et al. Clin. Cancer Res. 2017
CD47 is associated with the Rh Ag complexand anchored to the cytoskeleton in RBCs TTI-621 does not bind human RBCs TTI-621 does not agglutinate human RBCs
Salomao et al. PNAS 2008
Why does TTI-621 not bind RBCs?• Moderate binding affinity – need bivalent interaction• Lack of CD47 mobility in the RBC membrane prevents
clustering and limits bivalent binding
Advantages of non-RBC binding:• Minimizes likelihood of anemia• Avoids drug removal by the “antigen sink”• Avoids interference with transfusion medicine testing
Clinical Development
11
Intratumoral Administration of TTI-621
12
PreclinicalIndication
Intratumoral
Intratumoral
Intravenous
Intravenous
Intravenous
Monotherapy
Combination(IFNα, PD-1/PD-L1)
Monotherapy
Combination(Rituximab, Nivolumab)
Monotherapy,Combination
Monotherapy/CombinationRoute
CTCL, Solid tumors
CTCL
CTCL, PTCL, ALL
DLBCL, HL
Lymphoma, myeloma
Candidate
TTI-622(SIRPα-IgG4 Fc)
TTI-621(SIRPα-IgG1 Fc)
TTI-621(SIRPα-IgG1 Fc)
Phase 1/2a(POC)
Phase 2b/3(Pivotal)
Intratumoral Administration Study (TTI-621-02)
Multicenter, open-label phase 1 study of direct intratumoral injection of TTI-621 in patients with relapsed/refractory mycosis fungoides (MF) or percutaneously accessible solid tumors (NCT02890368)
13
*10 mg 3x/wk for 2 wks then 10 mg weekly
^Combinations: IFN-α, anti-PD-1/PD-L1, T-vec (melanoma only), radiation (plasmacytoma only)
Single injection(1, 3 or 10 mg)
Multiple Injection(10 mg 3x/wkfor 1 or 2 wks)
Induction*+ continuation
(monotherapy or combinations^)
ASH 2017
Ongoing
• Advantages of direct injection:• Obtain very high local drug
concentrations
• Avoid systemic antigen sink
• Rapid responses
Update recently reported at EORTC 2018
Intralesional TTI-621 Injections Were Well Tolerated in CTCL Patients
• Related adverse events (AEs) all Grade 1 or 2; no Grade ≥3 AEs
• Common related AEs include chills, injection site pain, and fatigue
• No related serious adverse events or dose-limiting toxicity
14Querfeld et al. EORTC CLTF 2018 Data Cut-off: August 3, 2018
CAILS Reductions in Injected Lesions Were Observed in the Majority of Patients
18 patients have available CAILS scores*
• 16 (89%) with decreased CAILS
• 8 (44%) with ≥50% reduction in CAILS
• CAILS decreases:
• Occurred at all dose levels
• Following single and multiple injections
• In all stages IA to IVB
15Querfeld et al. EORTC CLTF 2018 Data Cut-off: August 3, 2018
*Composite Assessment of Index Lesion Severity, a measure of local lesion responses
Examples of Rapid Tumor Regression in MF Patients
A) 85M with stage IIB MF with large cell transformation received a single 10 mg injection of TTI-621 into the proximal lesion on the left foot
16
Baseline Baseline
Day 3
Week 4
Day 3
Week 18
Day 3
Week 12
Baseline
A) B) C)
B) 72M with stage IIB MF with large celltransformation received a single 1 mginjection of TTI-621 into the lesion on thedorsal surface of the left foot
C) CD4 staining of skin biopsies frompatient in B).
Querfeld et al. ASH 2017
Local-Regional Responses Were Observed in Non-Injected, Adjacent Control Lesions
17
All CAILS scores: Injected vs Non-Injected Control Lesions
Injected
Control
Data Cut-off: August 3, 2018Querfeld et al. EORTC CLTF 2018
• 7 patients with reduced CAILS had a paired CAILS assessments in an adjacent non-injected lesion
• Injected lesion CAILS decreased -14% to -67% in all patients
• Non-injected lesions CAILS decreased -12% to -67% in 6/7 patients
• Median distance between paired injected and non-injected lesions is estimated to be 5.3 cm (range 0.2 - 15 cm)
Abscopal (Systemic) Effects Were Observed in One of Two Patients Receiving Continuation Monotherapy
18Data Cut-off: August 3, 2018Querfeld et al. EORTC CLTF 2018
Rapid resolution of lesions on abdomen (lower panel), left flank/back and arms (not shown) following TTI-621 injections of target lesions on left calf (upper panel), left ankle and right foot
Screening
Injected Lesion – T01 (Left Calf)
Distal Non-Injected Lesion – Abdomen
Screening Week 2 Week 9
Week 2 Week 11Week 7
Week 2
Development Plan for Intratumoral TTI-621 in CTCL
19
CTCL Stage IA-IIAContinuous
Monotherapy
Phase III randomized study vs topical
therapy
DataDisclosure
CTCL Stage IIB-IVBIFNα combination
Phase III randomized study vs IFNα alone
DataDisclosure
CAILS-based response
Early Stage CTCL – Local disease control
mSWAT-based response
Q1 2019 Q1 2020
Q3 2019 Q2 2020
Advanced CTCL – Global disease control
Intravenous Administration of TTI-621
20
PreclinicalIndication
Intratumoral
Intratumoral
Intravenous
Intravenous
Intravenous
Monotherapy
Combination(IFNα, PD-1/PD-L1)
Monotherapy
Combination(Rituximab, Nivolumab)
Monotherapy,Combination
Monotherapy/CombinationRoute
CTCL, Solid tumors
CTCL
CTCL, PTCL, ALL
DLBCL, HL
Lymphoma, myeloma
Candidate
TTI-622(SIRPα-IgG4 Fc)
TTI-621(SIRPα-IgG1 Fc)
TTI-621(SIRPα-IgG1 Fc)
Phase 1/2a(POC)
Phase 2b/3(Pivotal)
Intravenous Administration Study (TTI-621-01)
21
Multicenter, open-label phase 1 study in patients with relapsed/refractory hematologic malignancies (NCT02663518)
Dose Escalation(0.05, 0.1, 0.2, 0.3 mg/kg)
MonotherapyIndications
Identified first dose MTD(0.2 mg/kg)
ASH 2016
Lymphoma
None
0.2 mg/kg (mono)0.1 mg/kg (combo)
Heme Malignancies
CD20+ (Rituximab)
0.2 mg/kg + higher(Dose Intensification)
CTCL, PTCL, ALL
CD20+ (Rituximab)cHL (Nivolumab)
Dosing
CombinationIndications
ASH 2017 Ongoing
Expanded Safety DataPreliminary DLBCL Efficacy Data
Update recently reported at Discovery on Target 2018
Intravenous TTI-621 is Well Tolerated
22
Cohort(s): All
Grade 1-2 Grade ≥3
Infusion Related Reaction 64 (42) 3 (2) 67 (44)
≥ 15% Thrombocytopenia 8 (5) 29 (19) 37 (24)
Chills 30 (20) 30 (20)
Fatigue 24 (16) 24 (16)
Nausea 20 (13) 20 (13)
Diarrhoea 16 (10) 1 (1) 17 (11)
Anaemia 5 (3) 11 (7) 16 (10)
Pyrexia 16 (10) 16 (10)
Vomiting 14 (9) 1 (1) 15 (10)
≥ 5% Headache 13 (8) 13 (8)
Neutropenia 11 (7) 11 (7)
Hypotension 6 (4) 2 (1) 8 (5)
Decreased Appetite 7 (5) 7 (5)
Epistaxis 5 (3) 2 (1) 7 (5)
Related Adverse Events
n(%)Adverse Event Grades
Total
n=153
0 25 50 75 100
AE Reports (%)
Grade 1-2
Grade ≥3
* Patients with at least one reported AE were included in the analysis
*
Based on Data Snapshot of Aug 10, 2018
• Most frequent AEs were low-grade infusion reactions, clinically managed by pre-medication and close monitoring
• ≥ Grade 3 thrombocytopenia occurred in 19% patients
• Diverse patient population from the following expansion cohorts: AML, MDS, MPN, B-NHL, T-NHL, HL, MM, CLL, SCLC
The following data summaries are based on interim data and thus should be regarded as preliminary
Transient Thrombocytopenia Not Associated with Increased Risk of Bleeding
23
• Thrombocytopenia is likely an on-target effect resulting from CD47 blockade and the TTI-621 IgG1 Fc
• Thrombocytopenia is reversible within a week
• Pre-dose platelet levels remain relatively stable over the course of the study
• Transient platelet decreases did not lead to an increased risk of bleeding
• Platelet decreases did not impact drug delivery – 1/163 patients had dosing discontinued due to thrombocytopenia
Median Platelet Levels in All Subjects During Week 1 (N=163)
Pre-dose Platelet Levels in All Subjects Over Study Course (N=163)
Bleeding Adverse Events in All Subjects (N=163)
Based on Data Snapshot of Apr 10, 2018
Doses Higher than the MTD Are Tolerated in Dose Intensified Patients
24
• Dose intensification at Investigator’s discretion allowed per protocol; later standardized in Amendment 8
• 16 patients dose intensified to 0.5 mg/kg and maintained at 0.5 mg/kg for 1-27 weeks (range)
• No patients escalated to 0.5 mg/kg have been discontinued due AEs
Based on Data Snapshot of Aug 10, 2018
IV TTI-621 Has Single Agent Activity in T-Cell Lymphoma Patients
25
• Monotherapy ORR: 19% in MF, 25% in PTCL
• 5/7 responses observed in patients receiving weekly doses of 0.2 mg/kg
Based on Data Snapshot of Jul 24, 2018
Response
n (%)
Objective Response
median days (range)
CR PR SD ORR Time to Resp Tmt Duration
Mycosis Fungoides 21 --- 4 (19) 6 (29) 4 (19) 37 (16-51) 103 (41-281)
Sezary Syndrome 5 --- --- 3 (60) --- --- ---
Peripheral TCL 12 --- 3 (25) 2 (17) 3 (25) 79 (20-81) 143 (85-288)
Total / Overall 38 --- 7 (18) 11 (29) 7 (18) 50 (16-81) 135 (41-288)
TTI-621-01: T-Cell
LymphomaN
IV TTI-621 Has Activity as Monotherapy and in Combination with Rituximab in DLBCL Patients
26
• DLBCL efficacy:• 25% ORR monotherapy• 25% ORR rituximab
combo
• Majority of responses were observed in patients receiving weekly doses of 0.2 mg/kg (monotherapy, 2/2 pts) or 0.1 mg/kg (combination, 8/9 pts)
TTI-621 Monotherapy TTI-621 + Rituximab Combination Therapy
Based on Data Snapshot of Jul 24, 2018
Response
n (%)
Objective Response
median days (range)
CR PR SD ORR Time to Resp Tmt Duration
DLBCL 24 1 (4) 5 (21) 10 (42) 6 (25) 62 (21-78) 165 (127-247)
iNHL 4 --- 2 (50) 2 (50) 2 (50) 21 (18-23) 145 (127-162)
MCL 3 --- 1 (33) --- 1 (33) 31 (31-31) 172 (172-172)
Total / Overall 31 1 (3) 8 (26) 12 (39) 9 (29) 31 (18-78) 162 (127-247)
*excludes 3 subjects: ABCL (n=1, SD); PTCL and Other (both NA)
TTI-621-01: B-Cell
NHL Rituximab
Combination*
N
Response
n (%)
Objective Response
median days (range)
CR PR SD ORR Time to Resp Tmt Duration
DLBCL 8 1 (13) 1 (13) 3 (38) 2 (25) 106 (78-133) 139 (134-143)
iNHL 9 --- --- 7 (78) --- --- ---
MCL 1 --- --- --- --- --- ---
Total / Overall 18 1 (6) 1 (6) 10 (56) 2 (11) 106 (78-133) 139 (134-143)
*Excludes ABCL (n=1, PD) and Other (n=2, SD, PD)
TTI-621-01: B-Cell
NHL (ABCL/IBCL)*N
Development Plan for Intravenous TTI-621
27
Simon 2-stageFirst stage enrollment
(N=18)
Simon 2-stageSecond stage enrollment
(N=17)
DataDisclosure
Q2 2019
CTCL DataDisclosure
Q2 2020
Simon 2-stageFirst stage enrollment
(N=18)
Simon 2-stageSecond stage enrollment
(N=17)
DataDisclosure
Q3 2019
DataDisclosure
Q3 2020
PTCL
Phase Ib dose optimization+ rituximab(N=12-15)
Interim Analysis
Data Disclosure
Q3 2020
DLBCL (Rituximab Combination)
Q2 2019
Phase II + rituximab(N=68)
(Interim analysis N=20)
Dose Selection
Ongoing
Ongoing
Q4 2019
Intravenous Administration of TTI-622
28
PreclinicalIndication
Intratumoral
Intratumoral
Intravenous
Intravenous
Intravenous
Monotherapy
Combination(IFNα, PD-1/PD-L1)
Monotherapy
Combination(Rituximab, Nivolumab)
Monotherapy,Combination
Monotherapy/CombinationRoute
CTCL, Solid tumors
CTCL
CTCL, PTCL, ALL
DLBCL, HL
Lymphoma, myeloma
Candidate
TTI-622(SIRPα-IgG4 Fc)
TTI-621(SIRPα-IgG1 Fc)
TTI-621(SIRPα-IgG1 Fc)
Phase 1/2a(POC)
Phase 2b/3(Pivotal)
Expanding our CD47 Pipeline with TTI-622
29
TTI-622
contr
ol Fc
BRIC
126
2D3
CC2C
6
B6H
12 5F9
mIg
G1
mIg
G2b
100
101
102
103
104
105
106
Mean
F
luo
rescen
ce In
ten
sit
y
CD47 mAbs ControlmAbs
TTI-622 does not bind human RBCs
Lin et al. AACR 2018
• Expect to achieve higher drug levels with TTI-622• Being developed as combination therapy• TTI-622, like TTI-621, is differentiated from
antibodies by a lack of binding to human RBCsBoth agents allow us to block CD47 and tune the amount of “eat” signal a macrophage receives
TTI-622-01 Clinical Study
30
Multicenter, open-label phase 1 study in patients with relapsed/refractory lymphoma or myeloma (NCT03530683)
Patients
Phase 1b Starting Dose +Combination
LymphomaMyeloma
RituximabAnti-PD-1
Proteasome Inhibitor
Dosing
Combination
Ongoing
Dose Escalation(Monotherapy, 3+3)
Lymphoma
None
• First patient dosed June 2018
• Update expected Q3 2019
Multiple Catalysts in the Next 24 Months
31
Q4/18 Q1/19 Q2/19 Q3/19 Q4/19 Q1/20 Q2/20 Q3/20
Ph1 TTI-621-02Single Agent - CTCL
21
Ph 1 TTI-621-02IFN Combo - CTCL 3
Ph1 TTI-621-01Single Agent - CTCL
1 2
Ph1 TTI-621-01Single Agent - PTCL
3 4
Ph 1b/2 TTI-621 +RTX Combo - DLBCL 5
Ph 1 TTI-622-01Combination
21
Q4/20
1. TTI-621-02 ASH update2. Early stage CTCL cohort data
3. Advanced CTCL IFN combination data
1. First Simon stage CTCL data2. Second Simon stage CTCL data
3. First Simon stage PTCL data4. Second Simon stage PTCL data
5. Interim data DLBCL + rituximab
1. Single agent dose selection2. B-NHL rituximab combination data
Trillium Key Messages
1. Multiple Shots on Goal: The most systematic and diversified approach to CD47 as a new IO target• IgG1 Fc (TTI-621) and an IgG4Fc (TTI-622) decoy receptors
• Mono- and combo-therapy
• Delivered either intravenously or intratumorally
2. Efficacy: TTI-621 has shown single agent activity by both local and/or systemic delivery in multiple B- and T-cell lymphoma indications
3. Tolerability: TTI-621 has been well-tolerated in over 180 patients to date
4. Clear Paths Forward:• Intratumoral mono- and combination-therapy in CTCL
• IV monotherapy in both CTCL and PTCL
• IV combination therapy in B-cell lymphoma
32