Corporate Presentation

Transcription

1 Corporate Presentation October 2018 NASDAQ/TSX: TRIL

2 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

3 Investment Highlights Immuno-oncology company taking cancer care to the next level, bridging innate and adaptive immunity Only company with two clinical product candidates targeting CD47, a 2 nd generation IO target that tumors use to evade the immune system Most differentiated & comprehensive 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

4 Clinical Pipeline Focused on CD47 Candidate TTI-621 (SIRPα-IgG1 Fc) Route Intratumoral Intratumoral Monotherapy/ Monotherapy (IFNα, PD-1/PD-L1) Indication CTCL, Solid tumors CTCL Preclinical Phase 1/2a (POC) Phase 2b/3 (Pivotal) TTI-621 (SIRPα-IgG1 Fc) Intravenous Intravenous Monotherapy (Rituximab, Nivolumab) CTCL, PTCL, ALL DLBCL, HL TTI-622 (SIRPα-IgG4 Fc) Intravenous Monotherapy, Lymphoma, myeloma 4

5 Targeting CD47 5

6 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 Many hematologic and solid tumors express high levels of CD47 High CD47 expression often correlates with aggressive disease and poor clinical outcomes 6

7 TTI-621: A Dual Function SIRPαFc Decoy Receptor that Blocks CD47 and Delivers an Activating Signal Blocks the CD47 DO NOT EAT signal Delivers an EAT signal through FcγRs 7

8 TTI-621 Activates Both the Innate and Adaptive Immune Systems 8

9 Differentiating TTI-621 From Other CD47 Blocking Agents 1. TTI-621 IgG1 Fc delivers a potent eat signal CD47 Blocker* (Company) TTI-621 (Trillium) TTI-622 (Trillium) Hu5F9 (Forty Seven) CC (Celgene) SRF231 (Surface Oncology) ALX148 (ALX Oncology) Isotype IgG1 IgG4 IgG4 IgG4 IgG4 Inert IgG1 *Clinical stage compounds Petrova et al. Clin. Cancer Res 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 9

10 Differentiating TTI-621 From Other CD47 Blocking Agents 2. TTI-621 Does Not Bind Human RBCs TTI-621 does not bind human RBCs TTI-621 does not agglutinate human RBCs CD47 is associated with the Rh Ag complex and anchored to the cytoskeleton in RBCs Petrova et al. Clin. Cancer Res Salomao et al. PNAS 2008 Advantages of non-rbc binding: Minimizes likelihood of anemia Avoids drug removal by the antigen sink Avoids interference with transfusion medicine testing 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 10

11 Clinical Development 11

12 Intratumoral Administration of TTI-621 Candidate TTI-621 (SIRPα-IgG1 Fc) Route Intratumoral Intratumoral Monotherapy/ Monotherapy (IFNα, PD-1/PD-L1) Indication CTCL, Solid tumors CTCL Preclinical Phase 1/2a (POC) Phase 2b/3 (Pivotal) TTI-621 (SIRPα-IgG1 Fc) Intravenous Intravenous Monotherapy (Rituximab, Nivolumab) DLBCL, CTCL, PTCL DLBCL, HL TTI-622 (SIRPα-IgG4 Fc) Intravenous Monotherapy, Lymphoma, myeloma 12

13 Intratumoral Administration Study (TTI ) 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 (NCT ) Advantages of direct injection: Obtain very high local drug concentrations Avoid systemic antigen sink Rapid responses Single injection (1, 3 or 10 mg) *10 mg 3x/wk for 2 wks then 10 mg weekly ^s: IFN-α, anti-pd-1/pd-l1, T-vec (melanoma only), radiation (plasmacytoma only) Multiple Injection (10 mg 3x/wk for 1 or 2 wks) ASH 2017 Induction* + continuation (monotherapy or combinations^) Ongoing Update recently reported at EORTC

14 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 Querfeld et al. EORTC CLTF 2018 Data Cut-off: August 3,

15 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 *Composite Assessment of Index Lesion Severity, a measure of local lesion responses Querfeld et al. EORTC CLTF 2018 Data Cut-off: August 3,

16 Examples of Rapid Tumor Regression in MF Patients A) B) C) Baseline Baseline Baseline 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 Day 3 Day 3 Day 3 B) 72M with stage IIB MF with large cell transformation received a single 1 mg injection of TTI-621 into the lesion on the dorsal surface of the left foot Week 4 Week 18 Week 12 C) CD4 staining of skin biopsies from patient in B). Querfeld et al. ASH

17 CAILS Responses Occurred Rapidly Within the 2-Week Induction Period * Patients received maximally 2 weeks of study treatment (induction phase) Response assessments beyond day 14 are provided if patients have not progressed or continued onto another therapy # The first patient treated obtained a CR of the injected lesion that is ongoing after 52+ weeks Querfeld et al. EORTC CLTF 2018 Data Cut-off: August 5,

18 Local-Regional Responses Were Observed in Non- Injected, Adjacent Control Lesions 7 patients with reduced CAILS had a paired CAILS assessments in an adjacent noninjected 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 cm) All CAILS scores: Injected vs Non-Injected Control Lesions Injected Control Querfeld et al. EORTC CLTF 2018 Data Cut-off: August 3,

19 Abscopal (Systemic) Effects Were Observed in One of Two Patients Receiving Continuation Monotherapy Injected Lesion T01 (Left Calf) 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 Week 2 Week 7 Week 11 Distal Non-Injected Lesion Abdomen Screening Week 2 Week 2 Week 9 Querfeld et al. EORTC CLTF 2018 Data Cut-off: August 3,

20 V 9 + o f C D 4 + (% ) C D 4 :C D 8 C D 4 :C D 8 Peripheral Responses Were Observed Following Local Injections Single 1 mg Injection Single 1 mg Injection Single 3 mg Injection Screening Day 8 S e z a r y C e ll C o u n t Screening Day 8 C D 4 :C D 8 Screening Day 8 C D 4 :C D P r e - T r e a t m e n t D a y 3 D a y 8 0 P r e - T r e a t m e n t D a y 8 0 P r e - T r e a t m e n t D a y 8 Querfeld et al. EORTC CLTF

21 Intralesional TTI PEG-IFN-α2a Resulted in More Rapid Systemic Effects than Expected for PEG-IFN-α2a Alone TTI-621: Single 3 mg Injection (Week 1) PEG-IFN-α2a: Two 90 mg Injections (Week 2-3) Screening Week 2 Week 4 Screening TTI-621: Multiple 10 mg Injections MWF x 2 (Week 1-2) PEG-IFN-α2a: Two 90 mg Injections (Week 3-4) Week 5 Querfeld et al. EORTC CLTF

22 Development Plan for Intratumoral TTI-621 in CTCL Early Stage CTCL Local disease control CTCL Stage IA-IIA Continuous Monotherapy CAILS-based response Data Disclosure Q Q Phase III randomized study vs topical therapy Advanced CTCL Global disease control CTCL Stage IIB-IVB IFNα combination mswat-based response Data Disclosure Phase III randomized study vs IFNα alone Q Q

23 Intravenous Administration of TTI-621 Candidate TTI-621 (SIRPα-IgG1 Fc) Route Intratumoral Intratumoral Monotherapy/ Monotherapy (IFNα, PD-1/PD-L1) Indication CTCL, Solid tumors CTCL Preclinical Phase 1/2a (POC) Phase 2b/3 (Pivotal) TTI-621 (SIRPα-IgG1 Fc) Intravenous Intravenous Monotherapy (Rituximab, Nivolumab) DLBCL, CTCL, PTCL DLBCL, HL TTI-622 (SIRPα-IgG4 Fc) Intravenous Monotherapy, Lymphoma, myeloma 23

24 Intravenous Administration Study (TTI ) Multicenter, open-label phase 1 study in patients with relapsed/refractory hematologic malignancies (NCT ) Dosing Dose Escalation (0.05, 0.1, 0.2, 0.3 mg/kg) 0.2 mg/kg (mono) 0.1 mg/kg (combo) 0.2 mg/kg + higher (Dose Intensification) Monotherapy Indications Lymphoma Heme Malignancies CTCL, PTCL, ALL Indications None CD20+ (Rituximab) CD20+ (Rituximab) chl (Nivolumab) ASH 2016 Identified starting dose of (0.2 mg/kg) ASH 2017 Expanded Safety Data Preliminary DLBCL Efficacy Data Ongoing Update recently reported at Discovery on Target

25 Intravenous TTI-621 is Well Tolerated Most frequent AEs were lowgrade infusion reactions, clinically managed by premedication 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 Related Adverse Events n(%) Adverse Event Grades Cohort(s): All Grade 1-2 Grade 3 Total n=153* 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 Grade (3) 11 (7) 16 (10) Pyrexia Grade 3 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) AE Reports (%) * Patients with at least one reported AE were included in the analysis The following data summaries are based on interim data and thus should be regarded as preliminary Based on Data Snapshot of Aug 10,

26 Transient Thrombocytopenia Not Associated with Increased Risk of Bleeding Median Platelet Levels in All Subjects During Week 1 (N=163) Bleeding Adverse Events in All Subjects (N=163) Pre-dose Platelet Levels in All Subjects Over Study Course (N=163) 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 Based on Data Snapshot of Apr 10,

27 Dose Intensification is Well Tolerated 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,

28 IV TTI-621 Has Single Agent Activity in T-Cell Lymphoma Patients TTI : T-Cell Lymphoma N Response n (%) Objective Response median days (range) CR PR SD ORR Time to Resp Tmt Duration Mycosis Fungoides (19) 6 (29) 4 (19) 37 (16-51) 103 (41-281) Sezary Syndrome (60) Peripheral TCL (25) 2 (17) 3 (25) 79 (20-81) 143 (85-288) Total / Overall (18) 11 (29) 7 (18) 50 (16-81) 135 (41-288) 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,

29 IV TTI-621 Has Activity as Monotherapy and in with Rituximab in DLBCL Patients 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 : B-Cell NHL (ABCL/IBCL)* TTI-621 Monotherapy 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 ( ) inhl (78) MCL Total / Overall 18 1 (6) 1 (6) 10 (56) 2 (11) 106 (78-133) 139 ( ) *Excludes ABCL (n=1, PD) and Other (n=2, SD, PD) TTI Rituximab Therapy TTI : B-Cell NHL Rituximab * N 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 ( ) inhl (50) 2 (50) 2 (50) 21 (18-23) 145 ( ) MCL (33) (33) 31 (31-31) 172 ( ) Total / Overall 31 1 (3) 8 (26) 12 (39) 9 (29) 31 (18-78) 162 ( ) *excludes 3 subjects: ABCL (n=1, SD); PTCL and Other (both NA) Based on Data Snapshot of Jul 24,

30 Development Plan for Intravenous TTI-621 CTCL Simon 2-stage First stage enrollment (N=18) Data Disclosure Simon 2-stage Second stage enrollment (N=17) Data Disclosure Ongoing Q Q PTCL Simon 2-stage First stage enrollment (N=18) Data Disclosure Simon 2-stage Second stage enrollment (N=17) Data Disclosure Ongoing Q Q DLBCL (Rituximab combo) Phase Ib dose optimization + rituximab (N=12-15) Phase II + rituximab (N=68) (Interim analysis N=20) Interim Analysis Data Disclosure Q Q3/Q Q

31 Intravenous Administration of TTI-622 Candidate TTI-621 (SIRPα-IgG1 Fc) Route Intratumoral Intratumoral Monotherapy/ Monotherapy (IFNα, PD-1/PD-L1) Indication CTCL, Solid tumors CTCL Preclinical Phase 1/2a (POC) Phase 2b/3 (Pivotal) TTI-621 (SIRPα-IgG1 Fc) Intravenous Intravenous Monotherapy (Rituximab, Nivolumab) DLBCL, CTCL, PTCL DLBCL, HL TTI-622 (SIRPα-IgG4 Fc) Intravenous Monotherapy, Lymphoma, myeloma 31

32 Expanding our CD47 Pipeline with TTI-622 TTI-622 does not bind human RBCs Both agents allow us to block CD47 and tune the amount of eat signal a macrophage receives Mean Fluorescence Intensity TTI-622 control Fc BRIC126 2D3 CC2C6 B6H12 5F9 CD47 mabs migg1 migg2b Control mabs 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 RBCs 32

33 TTI Clinical Study Multicenter, open-label phase 1 study in patients with relapsed/refractory lymphoma or myeloma (NCT ) Dosing Dose Escalation (Monotherapy, 3+3) Phase 1b Starting Dose + Patients Lymphoma Lymphoma Myeloma First patient dosed June 2018 Update expected Q None Rituximab Anti-PD-1 Proteasome Inhibitor Ongoing 33

34 Multiple Catalysts in the Next 24 Months Ph1 TTI Single Agent - CTCL Q4/18 Q1/19 Q2/19 Q3/19 Q4/19 Q1/20 Q2/20 Q3/ Q4/20 1. TTI ASH update 2. Early stage CTCL cohort data Ph 1 TTI IFN Combo - CTCL 3 Ph1 TTI Single Agent - CTCL 1 2 Ph1 TTI Single Agent - PTCL Ph 1b/2 TTI RTX Combo - DLBCL Ph 1 TTI Advanced CTCL IFN combination data 1. First Simon stage CTCL data 2. Second Simon stage CTCL data 3. First Simon stage PTCL data 4. Second Simon stage PTCL data 5. Optimized-dose selection 6. Interim data DLBCL + rituximab 1. Single agent dose selection 2. B-NHL rituximab combination data 34

35 Trillium Key Messages 1. Multiple Shots on Goal: The most systematic and comprehensive approach to CD47 as a novel IO target IgG1 Fc (TTI-621) and 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 35