th annual rodman & renshaw global investment conference ......competition by the presence of an...

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20 th Annual Rodman & Renshaw Global Investment Conference September 5, 2018

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Page 1: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

20th Annual Rodman & Renshaw Global Investment ConferenceSeptember 5, 2018

Page 2: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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. Forward-looking statements are made only as of the date of this presentation and 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.

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Page 3: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

Investment Highlights

3

Immuno-oncology company developing therapies to bridge the innate and adaptive immune systems

Two clinical programs focused on CD47, a molecule that tumors frequently use to evade the immune system

Lead program, TTI-621, has shown single agent activity in patients with blood cancers

CD47 programs are differentiated from competitors

Page 4: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

Our Pipeline: A Strong Focus on CD47

4

PreclinicalClinical

Proof-of-Concept PivotalIndication

T-cell lymphoma,Blood cancers

TTI-621(Systemic)

T-cell lymphoma,Solid cancers

TTI-621(Intratumoral)

Blood cancersTTI-622

TTI-2341 Brain cancers

Undisclosed Cancer

Undisclosed Cancer

CD47Innate Immune

Checkpoint

EGFRTyrosine Kinase

Undisclosed IO Targets

CandidateTarget

Page 5: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Targeting CD47

Page 6: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

Many Tumor Cells Use the CD47 “Do Not Eat” Signal to Inhibit Macrophage Phagocytosis

6

High CD47 expression often correlates with aggressive disease and poor clinical outcomes

Many hematologic and solid tumors express high levels of CD47

CD47 delivers an inhibitory “do not eat” signal to macrophages through SIRPα

Page 7: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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

Page 8: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

TTI-621 Activates Both the Innate and Adaptive Immune Systems

8

Page 9: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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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 Agents1. TTI-621 IgG1 Fc delivers a potent “eat” signal

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

*Clinical stage compounds

Petrova et al. Clin. Cancer Res. 2017

*Clinical stage compounds

Page 10: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Advantages of non-RBC binding:

Minimizes likelihood of anemia

Avoids drug removal by the “antigen sink”

Avoids interference with transfusion medicine testing

Differentiating TTI-621 From Other CD47 Blocking Agents2. TTI-621 Does Not Bind Human RBCs

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

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

Salomao et al. PNAS 2008

Page 11: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Clinical Development

Page 12: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Multicenter, open-label phase 1 study of direct intratumoral injection of TTI-621 in patients with relapsed/refractory mycosis fungoides or percutaneously accessible solid tumors (NCT02890368)

Advantages of direct injection:

Obtain very high local drug concentrations

Avoid systemic antigen sink

Rapid responses

Intratumoral Administration Study (TTI-621-02)

Single injection(1, 3 or 10 mg)

Multiple Injection(10 mg 3x/wkfor 1 or 2 wks)

Induction*+ continuation

(monotherapy or combinations^)

ASH 2017

*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)

Ongoing

Page 13: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Intratumoral TTI-621 is Very Well Tolerated

Querfeld et al. ASH 2017

No dose-limiting toxicity

No ≥ G3 drug-related toxicity

Page 14: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Intratumoral TTI-621 Has Single Agent Activity in CTCLReduction in circulating Sézary cells suggests a systemic effect

Patient #1 Patient #70

102030405060

200

400

600

800

CD

4:C

D8

Pre-Treatment

Day 7

Querfeld et al. ASH 2017

Reduction in CAILS scores observed in 9/10 of patients

Reduction in circulating Sézary cells observed in 3/3 patients

Page 15: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Examples of Rapid Tumor Regression in MF Patients

BaselineWeek 4

Day 3Baseline

Day 3A) 85M with Stage IIB MF withlarge cell transformation (patient#10) received a single 10 mginjection of TTI-621 into theproximal lesion on the left foot

B) 72M with stage IIB MF withlarge cell transformation (patient#1) received a single 1 mginjection of TTI-621 into the lesionon the dorsal surface of the leftfoot.

C) CD4 staining of skinbiopsies (patient #1)

Day 3

Week 4

Day 3

Week 18

Querfeld et al. ASH 2017

Day 3

Week 12

Baseline

A) B) C)

Page 16: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

The TTI-621 Intratumoral Trial – Building on the Promising Signal of Clinical Activity in MF Patients

Intratumoral Trial Expanding:

Further characterize the efficacy of repeat weekly intratumoral TTI-621 monotherapy in patients with CTCL to assess durability and potential for systemic responses

Assess efficacy in combination with other immunomodulatory therapies (anti-PD-1, IFN-alpha, etc.)

Probe the biological effects of TTI-621 on the tumor microenvironment following intratumoral administration (cellular infiltration, cytokine profile, etc.)

Explore other indications amenable to local administration in a commercial setting

Updated data to be presented at the EORTC Cutaneous Lymphoma Task Force Meeting (Sep 27-29, 2018)

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Page 17: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Multicenter, open-label phase 1 study in patients with relapsed/refractory hematologic malignancies (NCT02663518)

Intravenous Administration Study (TTI-621-01)

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

Page 18: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Weekly Infusions of TTI-621 are Well Tolerated

Preferred TermAll Events Related Events

All grades (%) ≥ Grade 3 (%) All grades (%) ≥ Grade 3 (%)

Fatigue 32 (36) 1 (1) 13 (15) 0

Infusion-related reaction 30 (34) 3 (3) 28 (32) 3 (3)

Thrombocytopenia/ decreased platelet count 24 (27) 19 (21) 21 (24) 17 (19)

Nausea 20 (23) 0 12 (14) 0

Pyrexia 17 (19) 0 6 (7) 0

Chills 16 (18) 0 13 (15) 0

Diarrhea 16 (18) 2 (2) 5 (6) 0

Anemia 15 (17) 11 (12)* 10 (11) 8 (9)

Headache 14 (16) 0 6 (7) 0

Vomiting 13 (15) 1 (1) 8 (9) 1 (1)

Decreased appetite 12 (14) 0 4 (5) 0

Cough 11 (12) 0 0 0

Adverse Events in Dose Expansion ≥10% of Subjects (N=89)

Manageable, low grade infusion reactions Stable hemoglobin levels, consistent with lack of TTI-621 binding to RBCs Preliminary experience indicates that patients can be safely dosed above 0.2 mg/kg

Ansell et al. ASH 2017*All 11 subjects with G3 anemia had G2 anemia at screening and/or prior to week 1 TTI-621 infusion

Page 19: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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1. Thrombocytopenia is an on-target, pharmacodynamic effect

Platelet removal likely due to macrophage phagocytosis triggered by CD47 blockade and IgG1 Fc of TTI-621

2. Platelet loss is transient

Platelet values typically rebound to baseline within one week

3. Platelet loss is attenuated

Drop in platelets is generally less after cycles 2 and 3

4. Pre-dose platelet counts remain stable over time

No evidence for chronic/progressive thrombocytopenia

5. Thrombocytopenia is generally not clinically significant

Low frequency of bleeding events or transfusions

No impact on study dose delivery

The Facts About TTI-621 and Thrombocytopenia

Safety data will be updated in Q4 2018

Page 20: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Objective Responses in Heavily Pre-treated DLBCL Patients(Monotherapy and in Combination with Rituximab)

Ansell et al. ASH 2017

Baseline Week 4Pseudoprogression

Week 8 Week 12CMR

62-year old male with DLBCL who had received 8 prior therapies,including 5 prior CD20-based regimens, received 0.1 mg/kg TTI-621and rituximab. Pseudoprogression was noted at Week 4 and acomplete metabolic response (CMR) was observed at Week 12.

Time on Study and Tumor Responses in DLBCL PatientsComplete Metabolic Response in a DLBCL Patient

Treated with TTI-621 and Rituximab

5/18 (28%) Evaluable DLBCL Patients Achieved CR/PR

Page 21: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

The TTI-621 Intravenous Trial – Broad Clinical Effort with a Focus on Emerging Signals of Clinical Activity

Standardized dose intensification regimen to increase drug exposure

Expand enrollment of T cell lymphoma patients (including CTCL and PTCL), building upon efficacy data observed in the intratumoral study

Added elements to optimally characterize clinical benefit, including independent response assessments

Next program update expected Q4 2018

21

We believe that dose intensification beyond 0.2 mg/kg is the key to achieving even greater clinical activity with TTI-621

Page 22: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Expanding our CD47 Pipeline with TTI-622

Differences in the Fc region affect potency and tolerability

Expect to achieve higher drug levels with TTI-622

TTI-622, like TTI-621, is differentiated from antibodies by a lack of binding to human RBCs

Both agents allow us to block CD47 and tune the amount of “eat” signal a macrophage receives

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

yCD47 mAbs Control

mAbs

TTI-622 does not bind human RBCs

Lin et al. AACR 2018

Page 23: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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Multicenter, open-label phase 1 study in patients with relapsed/refractory lymphoma or myeloma (NCT03530683)

TTI-622-01 Clinical Study

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

Page 24: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

Capitalization and Intellectual Property

24

SHARES OUTSTANDING

CASH AND MARKETABLE SECURITIES

INSTITUTIONALOWNERSHIP

INTELLECTUAL PROPERTY

19.6M Common & Preferred

$64.7M CAD as of June 30, 2018

~70%

Two SIRPaFc patent families covering method of use and composition of matter through 2030 and 2033, and combination therapies through 2037

Page 25: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

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1. TTI-621 is differentiated from the competition by the presence of an IgG1 Fc and lack of RBC binding

2. TTI-621 is safe and well tolerated, dosing above 0.2 mg/kg in progress

3. TTI-621 has demonstrated efficacy in multiple indications

4. TTI-621 exhibits single agent activity

5. Enhanced presence in the CD47 space with TTI-622

Trillium Take Home Messages

Page 26: th Annual Rodman & Renshaw Global Investment Conference ......competition by the presence of an IgG1 Fc and lack of RBC binding 2. TTI-621 is safe and well tolerated, dosing above

Trillium Therapeutics Inc. (NASDAQ/TSX:TRIL) is an immuno-oncology company dedicated to the discovery and

development of novel and innovative cancer therapies