ladenburg thalmann healthcare...

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)



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


Intratumoral

Intratumoral

Intravenous

Intravenous

Intravenous

Monotherapy


Monotherapy




CTCL, Solid tumors

CTCL

CTCL, PTCL, ALL

DLBCL, HL

Lymphoma, myeloma

Candidate




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)

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*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

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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

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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

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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

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Intratumoral

Intratumoral

Intravenous

Intravenous

Intravenous

Monotherapy


Monotherapy




CTCL, Solid tumors

CTCL

CTCL, PTCL, ALL

DLBCL, HL

Lymphoma, myeloma

Candidate




Phase 1/2a(POC)

Phase 2b/3(Pivotal)

Intravenous Administration Study (TTI-621-01)

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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

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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

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• 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

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• 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

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• 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

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• 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)


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)


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

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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


Intratumoral

Intratumoral

Intravenous

Intravenous

Intravenous

Monotherapy


Monotherapy




CTCL, Solid tumors

CTCL

CTCL, PTCL, ALL

DLBCL, HL

Lymphoma, myeloma

Candidate




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

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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

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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

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