Trillium Therapeutics Corporate Presentation · 2020. 12. 7. · This presentation contains...

December 7, 2020

Corporate Overview

Forward-looking statements

2

This presentation contains forward-looking statements within the meaning of applicable securities laws. All statements contained herein that are not clearly historical in nature are forward-looking, and the words “anticipate”, “believe”, “expect”, “estimate”, “may”, “will”, “could”, “leading”, “intend”, “contemplate”, “shall”, “propose”, “plan” and similar expressions are generally intended to identify forward-looking statements. Forward-looking statements in this presentation include statements about, without limitation, the clinical plans and objectives for our TTI-621 and TTI-622 programs, the timing and ability to achieve certain milestones relating to our programs, including the announcement of updates at R&D day and the formation of indication specific KOL panels, and our expectations regarding our product candidates, including with respect to monotherapy activity, safety profile, solid tumor advantage and best-in-class status.

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, that preliminary data from a clinical trial may not be indicative of final trial results, that clinical trial results may not be favorable; uncertainties inherent in the product development process (including with respect to the timing of results and whether such results will be predictive of future results); 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 severity, duration and spread of the COVID-19 outbreak, as well as the direct and indirect impacts that the pandemic may have on our operations; 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.

A discussion of risks and uncertainties facing Trillium appears in Trillium's Form 40-F for the year ended December 31, 2019 filed with the U.S. Securities Exchange Commission and available at www.sec.gov and www.sedar.com, each as updated by Trillium's continuous disclosure filings, which are available at www.sedar.com and at www.sec.gov. Forward-looking statements are not guarantees of future performance and accordingly undue reliance should not be put on such statements due to the inherent uncertainty therein. Any forward-looking statements speaks only as of the date on which it is made and, except as may be required by applicable securities laws, the Company disclaims any intent or obligation, whether as a result of new information, future events or results or otherwise. All forward-looking statements herein are qualified in their entirety by this cautionary statement.

Company highlights

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• Leading next generation immuno-oncology player, with focus on CD47 target, an innate immune system checkpoint

• Two highly differentiated CD47 assets, with best-in-class monotherapy activity demonstrated across multiple heme malignancy indications and lack of RBC* binding

• Broad transformation program under new leadership, including strategy reset with focus on larger heme indications and solid tumors

• Strong healthcare focused investor base, including strategic investment from Pfizer; $292M in cash and investments as of 9/30/20

*RBC – Red blood cellNote: For a list of abbreviations please refer to the last page of this presentation

ASH update: New data, as of cutoff date Nov 3, 2020(prior data update on Sep 8, 2020)

4

TTI-622SIRPα-IgG4 Fc

TTI-621SIRPα-IgG1 Fc

• Completed safety evaluation of 12 mg/kg cohort; no DLTs or any major safety concerns observed; escalating to 18 mg/kg dose level

• 6/17 (35%) ORR in response evaluable patients at doses ≥0.8 mg/kgo 1 SD (DLBCL) at 12 mg/kg; 3 more patients at 12 mg/kg were pending response assessmento Updated ORR at 8 mg/kg at 3/7 (43%) patients (previously reported 3/6 or 50%), after one additional PD

(77% target lesion reduction, though new concurrent lesion triggering PD)

• Substantial increases in RO durability and serum TTI-622 concentration observed, with dose-dependent effects

• Continuing dosing at 2.0 mg/kg (10x of previously declared MTD under initial DLT criteria)

• One Gr4 thrombocytopenia DLT event observed at 2.0 mg/kg; expanding cohort to 6 patients

• 1 SD (+2 pending) in CTCL at 1.4 mg/kg; overall ORRs in lymphoma indications at 17-29% across dose levels

Other developments over past 3 months (since Pfizer investment and follow-on public offering on Sep 8-10)

5

Advisory infrastructure

• Announced Scientific Advisory Board, consisting of leading oncology experts from academia and industry, covering both clinical and pre-clinical activities

• In process of forming indication specific KOL panels, covering target heme malignancies and solid tumors

• New CMO: Ingmar Bruns, MD, PhD – previously with Pieris Pharmaceuticals, Bayer, and hematologist at Albert Einstein College of Medicine

• New SVP Corporate Dev. & Strategy: Rose Harrison, PhD – previously with RA Capital, Novartis and Bain & Company

Intellectual Property

• US: Allowance received for use of SIRPαFc to treat hematologic & solid tumors (method of use)• US: Allowance received for a TTI-622 composition of matter patent• EU: Notice of claims allowable received for a TTI-622 composition of matter patent

Board additions

• Mike Kamarck, PhD – CTO at Vir Biotechnology; previously executive at Merck, Wyeth and Bayer, responsible for biologics/vaccine manufacturing

• Paolo Pucci – former CEO of Arqule; previously with Bayer and Eli Lilly; brings in executive, commercial and oncology experience

Team changes

Pipeline overview

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Target

CD47 – INNATE IMMUNE CHECKPOINT

Candidate

TTI-622Indication

Heme malignancies

Candidate

TTI-622Indication

Solid Tumors

Candidate

TTI-621Indication

Heme malignancies

Candidate

TTI-621Indication

Solid Tumors DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PIVOTAL

DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PIVOTAL

DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PIVOTAL

DISCOVERY PRECLINICAL PHASE 1 PHASE 2 PIVOTALPHASE 1

PHASE 1

Upcoming milestones for 2021

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• Around the end of 1Q21, hold R&D Day to:1. Provide data update on TTI-622 and 6212. Declare TTI-622 and 621 priorities3. Announce disease indication/patient settings & drug combination priorities4. Outline high-level clinical development plan

• Anticipate initiating 2-3 PoC studies in heme malignancies in combinations with other agents

• Anticipate initiating signal-seeking solid tumor study in a variety of indications and drug combinations

Contents

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• CD47 landscape and Trillium differentiation

• TTI-622 (SIRPα-IgG4 Fc) CD47 program


• Corporate

Tumors use CD47 “don’t eat me” signal to evade destruction by innate immune system

9

• Many hematologic and solid tumors express high levels of CD47

• High CD47 expression correlated with aggressive disease & poor outcomes

• CD47 delivers an inhibitory “don’t eat me” signal to macrophages through SIRPα

CD47 blockade emerging as a next-generation checkpoint inhibitor strategy in immuno-oncology

CD47 Pathway in Cancer

Don’t eat mesignal

DON’T EAT ME

Macrophage activation requires CD47 blockade anddelivery of an eat signal

10

• CD47 blockade alone is not sufficient to trigger macrophage anti-tumor activity

• Macrophages must also receive an “eat” (pro-phagocytic) signal

• IgG1 Fc delivers a strong “eat” signal, IgG4 Fc a moderate signal

TTI-621 and TTI-622: Two novel CD47 blocking agents that deliver different “eat” signals

Shared Properties• Do not bind RBCs• Monotherapy activity demonstrated in lymphoma patients• Half the size of an antibody

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TTI-621 TTI-622

SIRPα domain:Blocks CD47 DON’T EAT ME signal

(SIRPα-IgG1 Fc) (SIRPα-IgG4 Fc)

IgG1 Fc: Delivers strong EAT signal

IgG4 Fc: Delivers moderate EAT signal

Trillium molecules are differentiated by 1) monotherapy activity; 2) lack of RBC binding; 3) lower molecular weight

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Candidate TTI-621 TTI-622 Magrolimab ALX148 Lemzoparlimab AO-176 TG-1801

Molecule WT SIRPαFc fusion protein

WT SIRPαFc fusion protein CD47 mAb High aff. SIRPαFc

fusion protein CD47 mAb CD47 mAb Bi-spec. Ab CD47/CD19

Fc isotype IgG1 IgG4 IgG4 Inert IgG1 IgG4 IgG2 IgG1

Mol. weight (approx.) 75 kD 75 kD 150 kD 75 kD 150 kD 150 kD 150 kD

RBC binding No No Yes Yes Minimal Minimal No

Monotherapy / incl. CR Yes / Yes Yes / Yes Yes / No No / No No / No No data No data

First-in-human Feb 2016 Jun 2018 Aug 2014 Feb 2017 June 2019 Feb 2019 Mar 2019

Development stage P1 P1 P3 P1 P1 P1 P1

Sources: Company web sites, publications, presentations and filings; www.clinicaltrials.gov • Other companies with clinical stage CD47-targeting agents: Akeso, ImmuneOncia, ImmuneOnco, Innovent, Jiangsu Hengrui, Kahr Medical, Shattuck Labs, Zai Lab

• Companies with discontinued CD47 programs: Celgene, Seattle Genetics, Surface Onc.

Unlike most other CD47 agents, TTI-621 & 622 do not bind to red blood cells (RBCs)

Benefits of RBC avoidance

• Reduces risk of anemia in patients

• Lowers amount of drug required by avoiding massive antigen sink

• Does not interfere with transfusion medicine testing

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TTI-621 and TTI-622 do not bind human RBCs1

1Results confirmed by independent group (Piccione et al. Clin. Cancer Res. 2016)Petrova et al. Clin. Cancer Res. 2017

Even at low doses, TTI-621 & 622 are showing Best-in-Class single agent response rates in the CD47 field

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1NCT02216409; Sikic, JCO 2019 3NCT03013218; Lakhani, ASCO 20184NCT02641002; Zeidan, ASH 2019

5NCT03512340; Surface Oncology strategic reset (Dec 2018)2NCT03248479; ASCO 2019

TTI-621(Trillium)

TTI-622 (Trillium)

Magrolimab(Gilead)

ALX148 (ALX Oncology)

CC-90002(Celgene)

SRF231 (Surface Onc.)

N=82 N=17 N=10 & 44 N=15

17-29% ORR in lymphomas at

up to 1.4 mg/kg*

*Dose escalation ongoing (now dosing at 2.0 mg/kg)

35% ORR in lymphomas at≥0.8 mg/kg*

*Dose escalation ongoing (now dosing at 18 mg/kg)

10% ORR in AML/ MDS at

30 mg/kg2

5% ORR in solidtumors &

lymphomas at ≥20 mg/kg1

0% ORR insolid tumors at

≥10 mg/kg3

MonoTx study in AML/MDS

terminated due to lack of efficacy,

doses up to 4 mg/kg4

MonoTxexpansion phase

discontinued5

ORR with Monotherapy by Agent & Indication(s)

*As of 3 Nov 2020

Contents

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• Corporate

TTI-622-01 study overview(NCT03530683)

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Phase 1a: Dose escalation (monotherapy) Phase 1b/2: Combination treatment

Indications: • Relapsed & refractory (all-comer) lymphomas

• Open-label; multi-center• 3+3 dose escalation schema• TTI-622 single agent intervention

• Characterize safety profile and DLTs• Identify MTD and/or starting P1b doses

• Characterize PK and immunogenicity• Characterize preliminary evidence of

monotherapy activity

• Relapsed & refractory lymphomas and multiple myeloma

• Open-label; multi-center• TTI-622 administered in combination with other

agents in select patient settings

• Characterize safety & determine recommended dose of TTI-622 when combined with other agents

• Evaluate preliminary activity of TTI-622 combination treatments

• Characterize PK and immunogenicity of TTI-622 combination treatments

Design:

Primary objectives:

Secondary objectives:

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.05-.05-.1 mg/kg

0.2-0.2-0.3 mg/kg

0.4-0.4-0.8 mg/kg

1.0-1.0-2.0 mg/kg

2.0-2.0-4.0 mg/kg

8.0 mg/kg flat

12 mg/kg flat

18 mg/kg flat

Completed

OngoingTTI-622-01 Phase 1a: Now dosing at 18 mg/kg

Cohort #

1

2

3

4

5

6

7

8

DosingWk 1 - Wk 2 - Wk 3+

4 (3)

4 (3)

4 (3)

4 (3)

8 (7)

4 (1+3

3 (2)

Highlights*

• 31 patients dosed weekly with TTI-622 IV, including 22 response evaluable**

• No significant safety signals observed at doses up to 12 mg/kgo One DLT of Gr 4 thrombocytopenia at 8 mg/kg; no clinical sequelae

• 6/17 (35%) ORR in response evaluable pts at doses ≥0.8 mg/kg (cohorts 3-7)o 1 CR + 5 PRs (+ 1 active SD at 12 mg/kg)o In R/R patients with median of 3 (range 1-9) prior systemic therapieso Across multiple dose levels (0.8, 2.0, 4.0 and 8.0 mg/kg) o Across multiple indications: DLBCL, CTCL (with LCT) and PTCLo All responses observed at first response assessment at 8 weekso Three patients at 12 mg/kg (cohort 7) were pending response assessment

• Dose-dependent increases in RO durability & serum concentration* As of 3 Nov 2020 (ASH poster data cut-off date); data are subject to change prior to final database lock** Sep 8 update included 3 pts (Cohorts 3-5, one pt each) who were considered response evaluable based on clinical progression, without supporting scan measurements; as no scans were available as of cutoff date, the pts are classified as response non-evaluable here

N*All (response eval.)

2 (pending)

pending)

TTI-622 shown to be well tolerated

18

• Overall low incidence of AEs; related Gr≥3 AEs limited to hematologic AEs

• 1 DLT reported to dateo Gr4 TC at 8 mg/kg, requiring

prophylactic platelet transfusion per PI discretion; event quickly resolved without sequelae (patient resumed study at 4 mg/kg)

• Brief drug interruptions (≤ 1 week) due to related AEs were required in 3 patients; neutropenia (n=2) and TC (n=1)

• One neutropenia Gr 3 event at 12 mg/kg

All Related Gr 1-2 Gr 3-4 Gr 1-2 Gr 3-4Nausea 8 (26) 3 (10) 8 (26) 3 (10)

Thrombocytopenia 8 (26) 5 (16) 5 (16) 3 (10) 4 (13) 1 (3)

Constipation 6 (19) 6 (19)

Pyrexia 6 (19) 2 (6) 6 (19) 2 (6)

Diarrhoea 4 (13) 3 (10) 1 (3)

Fatigue 4 (13) 3 (10) 4 (13) 3 (10)

Neutropenia 4 (13) 4 (13) 4 (13) 4 (13)

Anaemia 3 (10) 3 (10) 2 (6) 1 (3) 2 (6) 1 (3)

Insomnia 3 (10) 3 (10)

Leukocytosis 3 (10) 1 (3) 3 (10) 1 (3)

Decreased appetite 3 (10) 1 (3) 3 (10) 1 (3)

Back pain 3 (10) 1 (3) 3 (10) 1 (3)

Fall 3 (10) 3 (10)

Dyspnoea 3 (10) 1 (3) 2 (6) 1 (3) 1 (3)

Abdominal pain 3 (10) 2 (6) 3 (10) 2 (6)*A = All AEs, R = Related AEs

Adverse Eventsn (%)

Total n=31 All AEs Related AEs

0 10 20 30

*ARARARARARARARARARARARARARARAR

Patients (%)

All Gr 1-2 All Gr 3-4Rel Gr 1-2 Rel Gr 3-4

As of 3 Nov 2020 *TC - thrombocytopenia

TTI-622 showing single agent activity across multiple lymphoma indications and broad therapeutic window

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• 6/17 (35%) ORR in response evalu-able pts at dose levels ≥0.8 mg/kg

o 6/22 (27%) at all dose levels

• Activity across multiple lymphoma indications (DLBCL, CTCL, PTCL, HL)

• Responses incl. CR and ‘near-CR’

• Broad therapeutic window (0.8-8.0 mg/kg)

• Heavily pre-treated patients (3-9 prior systemic Tx in responders)

Target Lesion Response

Based on the data in clinical database as of 3 Nov 2020; data are subject to change prior to final database lockAbbreviations: DLBCL – Diffuse Large B Cell Lymphoma; PTCL – Peripheral T Cell Lymphoma; CTCL – Cutaneous T Cell Lymphoma; FL – Follicular Lymphoma

; 3) Overall response declared PR due to positive residual signal on PET

3

4) Patient reclassified from FL to DLBCL (final diagnosis still pending)

4

Responders showing consistently fast onset of action

20

• Fast onset of action – all responses observed first at 8 wks (first response assessment)

• Responder statuso CR pt ongoing at 534 days

o 2 PR pts discontinued treatment for reasons other than PD

o 3 PR pts progressed

• 4 patients pending assessment as of Nov 3 (3 pts at 12 mg/kg and 1 pt at 8 mg/kg)

Response Onset and Duration

Based on the data in clinical database as of 3 Nov 2020; data are subject to change prior to final database lock

PD

Subject withdrawal

Dose-dependent increases in peak RO & RO durability

21

0

2 0

4 0

6 0

8 0

1 0 0C o h o r t 1

% R

O

0 D 7 0 D 7 0 D 7W e e k 1 W e e k 6 W e e k 1 2

0

2 0

4 0

6 0

8 0

1 0 0C o h o r t 3

% R

O


0

2 0

4 0

6 0

8 0

1 0 0C o h o r t 6

% R

O


0

2 0

4 0

6 0

8 0

1 0 0C o h o r t 2

% R

O


0

2 0

4 0

6 0

8 0

1 0 0C o h o r t 4

% R

O


0

2 0

4 0

6 0

8 0

1 0 0C o h o r t 5

% R

O


0

2 0

4 0

6 0

8 0

1 0 0C o h o r t 7

% R

O


• RO on peripheral blood T cells was determined using a flow cytometry-based competitive binding assay• Measurements were taken pre-dose, at end of infusion, and 24 hours and 7 days post-infusion in weeks 1, 6 and 12• Dotted line represents the upper limit of quantitation• Mean (≥2 data points) ± SD are shown; negative RO values due to changing CD47 levels are reported as 0

Dose-dependent TTI-622 serum concentration profiles

22

Figure 1: TTI-622 Mean Concentration Profiles

Figure 2: TTI-622 Mean Trough Concentrations

n = subjects at Week 3; some time points may have fewer subjects

Week 1 – Single Infusion Week 6 – Repeat Infusions• Dose-dependent increase in TTI-622

serum exposure following single and repeat infusions (Figure 1)

• No plateau relationship up to 12 mg/kg, supporting dose escalation beyond 12 mg/kg

• Dose-dependent increase in serum trough levels (Figure 2)

• Steady state TTI-622 serum exposures likely not reached until week 5+

Emerging TTI-622 profile

23

• Monotherapy activity => (i) de-risk program; (ii) stronger foundation for combination therapies, including with PD-1

• Strong safety profile … no RBC binding => no anemia

• Potential solid tumor advantage … half molecular weight of mAbs

Contents

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• Corporate

Intratumoral TTI-621 injections in CTCL induced rapid lesion reductions and provide initial PoC of bioactivity

25

Querfeld et al. ASH 2018

*CAILS - Composite Assessment of Index Lesion Severity, a measure of local lesion responses

6* 6 6* 7* 1 4 6 9* 5* 1 6 1 5* 3 1 6 10* 6* 1 6 1 14* 12*

IB IIB IIB IA IIB IIB IIB IIB IB IVB IB IIB IIB IIA IVA IIB IIB IA IIB IIB IA IA IIB

†

-100

-50

0

50

CAI

LS C

hang

e (%

) fro

m B

asel

ine

CTCL: Overall CAILs Score Decrease

1 mg 3 mg10 mg

Injections

Stage

* Injections across 2 or 3 lesions; all other patients received injection(s) in a single lesion† received TTI-621 + IFNα2a maintenance

• Phase 1 dose escalation & expansion studyo R/R CTCL; N=22 response-evaluable patientso NCT02890368

• Dosing regimens evaluatedo Single dose injections @ 1, 3 or 10 mgo Multiple injections @ 10 mg 3x/wk for 1-2 wkso Induction regimen (10 mg 3x/wk for 2 wks) +

continuation Tx of weekly 10 mg injections

• Patient example

Baseline Week 4

85M with stage IIB MF with large cell transformation who failed 4 prior systemictherapies, PUVA & radiation; received a single 10 mg injection of TTI-621

Querfeld et al. ASH 2017

Intravenous TTI-621 dose escalation study overview

26

0.05, 0.1, 0.2, 0.3 0.2 up to 0.5 (mono)0.1 up to 0.5 (combo) 0.2 ramp-up to 0.5 0.5, 0.7, 1.0, 1.4, 2.0

LymphomaHeme Malignancies(Lymphoma, Leukemia,

Multiple Myeloma)CTCL, PTCL CTCL

CD20+ NHL (+rituximab)cHL (+nivolumab)

Completed (N=18)Identified initial

MTD (0.2 mg/kg)

Completed (N=154)Signal seeking across a range of indications

Completed (N=42)Further efficacy evaluation

in TCLs

Ongoing (N=17)Re-assess MTD under

amended protocol

Dosing (mg/kg)

Monotherapy Indications

Combination Indications

Part 1:Dose Escalation

Part 2: Initial Expansion

Part 3: Focused Expansion

Part 4: Dose Optimization

Indication Expansion at Low doses(Most patients dosed at 0.2 mg/kg; some dose-intensified up to 0.5 mg/kg

per investigator discretion or by a fixed ramp-up schedule)

Status (N)

Completed

Under revised DLT criteria(Grade 4 Thrombocytopenia lasting 72+ hours or ≤10K)

Under initial DLT criteria(Grade 4 Thrombocytopenia of

any duration)

Ongoing

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0.5 mg/kg

0.7 mg/kg

1.0 mg/kg

1.4 mg/kg

2.0 mg/kg

Completed

OngoingTTI-621-01 Part 4: Now enrolling at 2.0 mg/kg

Dosing

3 (3)

6 (6)

3 (1+2 pending)

2 (pending)

3 (3)

Highlights*

• A total of 17 patients with R/R CTCL were dosed across 5 dose levels (0.5-2.0 mg/kg) and completed DLT evaluation by November 3, 2020o The 2.0 mg/kg cohort is ongoing

• TTI-621 was well tolerated at doses up to 1.4 mg/kg

• Activity observed at doses 0.7-1.4 mg/kg:o 1 PR (bridge to transplant)o 3 SDs with 1 blood CR, 1 skin CR and 1 bridge to transplant

*As of 3 Nov 2020 (ASH poster data cut-off date)

N*All (response eval.)

Intravenous TTI-621 well tolerated

28

• IRRs reached Gr≥3 intensity in 8 (3%) pts overall, and 2 (12%) in Part 4; o Majority IRRs occurred at first infusiono Managed by extending infusion time and pre-

medication with corticosteroids at initialinfusions only

• TC of Gr≥3 intensity occurred in 51 (22%) patients overall, and 4 (24%) in Part 4

• Two DLTs were observed• 1 Grade 3 infusion related reaction (IRR) at 1.0

mg/kg; occurred at the 1st infusion and managed by extending infusion time

• 1 Grade 4 thrombocytopenia with a platelet nadir of 10K/dL at 2.0 mg/kg

• No worsening or Gr4 thrombocytopenia up to 1.4 mg/kg

Related AdverseEvents n(%)

TotalN=231

Grade 1-2 3-4 1-2 3-4IRR 86 (40) 6 (3) 8 (47) 2 (12) 102 (44)Thrombocytopenia 17 (8) 47 (22) 1 (6) 4 (24) 69 (30)Chills 46 (21) 2 (12) 48 (21)Fatigue 31 (14) 2 (1) 1 (6) 34 (15)Anaemia 10 (5) 20 (9) 30 (13)Pyrexia 25 (12) 1 (6) 26 (11)Nausea 22 (10) 2 (12) 24 (10)Diarrhoea 19 (9) 1 (0.5) 2 (12) 22 (10)Neutropenia 4 (2) 15 (7) 1 (6) 20 (9)Headache 15 (7) 2 (12) 17 (7)Vomiting 14 (7) 1 (0.5) 1 (6) 16 (7)Hypotension 9 (4) 1 (0.5) 10 (4)

IRR = Infusion Related Reaction 8 (4) 8 (3)Myalgia 8 (4) 8 (3)Leukopenia 1 (0) 7 (3) 8 (3)

Parts 1-3n=214

Part 4n=17

10 20 30 40 50 60

P1-3P4

P1-3P4

P1-3P4

P1-3P4

P1-3P4

P1-3P4

P1-3P4

P1-3P4

P1-3P4

P1-3P4

P1-3P4

P1-3P4

Patients (%)

P1-3 Gr1-2 P1-3 Gr 3-4P4 Gr 1-2 P4 Gr 3-4

P1-3 - Parts 1-3; P4 - Part 4Based on the data in clinical database as of 3 Nov 2020; data are subject to change prior to final database lock

Post-dose platelet and HGB decreases transient; pre-dose levels consistent over time

29

Week 1 Median Plts and HGB Levels:

Parts 1-3 vs Part 4

Pre-dose Plts and HGB Levels Weeks 1-12 in

all patients

Plts - Platelets; HGB - HemoglobinBased on the data in clinical database as of 3 Nov 2020; data are subject to change prior to final database lock

TTI-621 monotherapy activity observed across Lymphoma indications

30

Indication TherapyResponse

evaluable N CR PR ORR

CTCL TTI-621 monoTx 53 1 (2%) 8 (15%) 9 (17%)

PTCL TTI-621 monoTx 22 2 (9%) 2 (9%) 4 (18%)

DLBCL TTI-621 monoTx 7 0 (0%) 2* (29%) 2 (29%)Based on the data in clinical database as of 3 Nov 2020; data are subject to change prior to final database lock*Includes one patient initially classified as CR, later reclassified to PR; query still ongoing and final PR/CR status TBD

CTCL response: mSWAT change and response duration

31

Tumor (n)

Response Evaluable n (%) Tmt Duration in Responders (days)

med (min-max)

Time to Response(days)

med (min-max)CR PR ORR

MF (34) 0 7 (21) 7 (21) 162 (41-1015) 57 (23-218)

SS (19) 1 (5) 1 (5) 2 (11) 617 (185-1049) 206 (108-303)

All (53) 1 (2) 8 (15) 9 (17) 183 (41-1049) 106 (23-303)


PTCL response: Lesion change and response duration

32

Tumor(n)

Response Evaluable n (%) Tmt Duration in

Responders (days)med (min-max)

Time to Response (days)med (min-max)CR PR ORR

PTCL (22) 2 (9) 2 (9) 4 (18) 379 (127-575) 50 (20-79)


Emerging TTI-621 profile

33

• Monotherapy activity => (i) de-risk program; (ii) stronger foundation for combination therapies, including with PD-1

• Well tolerated => no anemia (no RBC binding); transient thrombo-cytopenia, IRRs

• Potential solid tumor advantage … half molecular weight of mAbs

• Low dose … today 2 mg/kg vs. other CD47 blockers up to 30 mg/kg

Contents

34




• Corporate

Comprehensive IP, including granted composition of matter patents expiring in 2033 (excl. PTE)

35

Combinations

• Macrophage stimulation

Pending

• T cell checkpoint inhibitors

• HDAC inhibitors

• Proteasome inhibitors

• Radiation therapy

• anti-CD38 antibody

• anti-EGFR antibody

• Others (not disclosed)

Composition of Matter

• TTI-621• Granted in US, EU, Japan, China, AUS, HK;

expiring Dec. 2033 plus ~4 yrs PTE• Pending in Canada

• TTI-622 • Allowed in US, granted in Japan• Pending in others

Method of Use

• Use of SIRPαFc fusion proteins to treat heme and solid tumors

• Granted in JAP, CAN, AUS• Allowed in US• On appeal in EU• Additional applications pending

in US, Europe and othersBiomarkers

• Biomarkers for CD47 blockade Pending

1

2

3

4

Management team and Board of Directors

36

Jan Skvarka, PhD

Chief Medical Officer

Ingmar Bruns, MD, PhD

Chief Scientific Officer

Bob Uger, PhD

Chief Financial Officer

James ParsonsChief Development

Officer

Penka Petrova, PhDSVP, Corp Dev &

Strategy

Rose Harrison, PhD

Management Team

Board of DirectorsRobert Kirkman, MD Board Chair; Former CEO, Oncothyreon Paolo Pucci Former CEO, Arqule

Jan Skvarka, PhD CEO, Trillium Thomas Reynolds, MD PhD Former CMO, Seattle Genetics

Luke Beshar Former CFO, NPS Pharma Helen Tayton-Martin, PhD CBO, Adaptimmune

Mike Kamarck, PhD CTO Vir; frm exec roles at Merck, Wyeth Paul Walker Partner, NEA

Chief Executive Officer

Karen Ferrante, MD• *Head of Onc TA, Takeda• *CMO, Millennium• *Head of Onc clin dev, Pfizer=> Velcade, Taxol, Tarceva

Gordon Freeman, PhD• Immunologist, Dana Farber• Prof, Harvard Med School=> PD-1/PD-L1

Tom Reynolds, MD, PhD• Trillium Board member• *CMO, Seattle Genetics=> Adcetris

Steve Rosen, MD• CSO & Provost, City of Hope

Cancer Center=> interferon, Lemtrada

Jeff Settleman, PhD• CSO Onc R&D, Pfizer• *Head of Onc Discovery, Genentech• *Mass General Hospital & Dana Farber• *Prof Harvard Med School=> Iressa, Xalkori

*Former positions

Scientific Advisory Board

Company highlights

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• Leading next generation immuno-oncology player, with focus on CD47 target, an innate immune system checkpoint

• Two highly differentiated CD47 assets, with best-in-class monotherapy activity demonstrated across multiple heme malignancy indications and lack of RBC* binding

• Broad transformation program under new leadership, including strategy reset with focus on larger heme indications and solid tumors

• Strong healthcare focused investor base, incl. strategic investment from Pfizer; $292M in cash and investments as of 9/30/20

*RBC – Red Blood CellNote: For a list of abbreviations please refer to the last page of this presentation

Contact information

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Jan Skvarka, PhDChief Executive Officer+1-857-412-7029 [email protected]

James ParsonsChief Financial Officer+1-416-595-0627 [email protected]

Appendix: Abbreviations

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• CR – Complete Response • CTCL – Cutaneous T Cell Lymphoma • DLBCL – Diffuse Large B Cell Lymphoma• DLT – Dose Limiting Toxicity• FL – Follicular Lymphoma• Gr – Grade• HGB – Hemoglobin• IRR – Infusion-Related Reaction• KOL – Key Opinion Leader• LCT – Large Cell Transformation• monoTx – Monotherapy• MF – Mycosis Fungoides• mSWAT – Modified Severity/Weighted

Assessment Tool• MTD – Maximum Tolerated Dose• ORR – Overall Response Rate

• PD – Progressive Disease• Plts – Platelets• PoC – Proof of Concept• PR – Partial Response• PTCL – Peripheral T Cell Lymphoma • PTE – Patent Term Extension• Pts – Patients • RBC – Red Blood Cell• RO – Receptor Occupancy• SAB – Scientific Advisory Board• SD – Stable Disease• SS – Sézary syndrome• TC – Thrombocytopenia• Tmt – Treatment• Tx – Therapy

Trillium Therapeutics Corporate Presentation · 2020. 12. 7. · This presentation contains...

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