th annual rodman & renshaw global investment conference ......competition by the presence of an...
TRANSCRIPT
20th Annual Rodman & Renshaw Global Investment ConferenceSeptember 5, 2018
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.
2
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
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
5
Targeting CD47
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
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
9
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
10
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
11
Clinical Development
12
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
13
Intratumoral TTI-621 is Very Well Tolerated
Querfeld et al. ASH 2017
No dose-limiting toxicity
No ≥ G3 drug-related toxicity
14
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
15
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)
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)
16
17
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
18
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
19
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
20
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
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
22
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
23
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
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
25
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
Trillium Therapeutics Inc. (NASDAQ/TSX:TRIL) is an immuno-oncology company dedicated to the discovery and
development of novel and innovative cancer therapies