DISCLOSURES: SMA has received research funding from Bristol-Meyers Squibb, Affimed, Merck, Celldex, and Seattle Genetics; IF has received research funding from Seattle Genetics, Genentech, Forty Seven Inc., Pfizer, Janssen,Beigene, Curis, Takeda, Acerta, Novartis, Merck, Pharmacyclics LLC, Verastem, AbbVie Company, Celgene, TG Therapeutics, Trillium Therapeutics Inc. (TTI), Incyte, Gilead, Calithera, Agios, KITE, Constellation, Portolo; OAO’C has received honoraria and research funding from Celgene and research funding from TTI; AA has been a consultant for Pfizer and has received research funding from Takeda/Millenium; M-EP has received research funding from FLXbio; DV has received honoraria and acted as an advisor for Roche, Lundbeck, Seattle Genetics, Celgene and received honoraria from Janssen. LDSJ is an employee of TTI; TC is an employee of TTI, and was previously an employee of Apotex Inc; MI is an employee of and has equity ownership in TTI, and was previously an employee of/has equity ownership in Hoffmann La Roche; PSP is an employee of and has equity ownership in TTI, RAU is an employee of, has equity ownership in, and holds patents/royalties in TTI, ELS is an employee of and has equity ownership in TTI, RC has participated in a Speaker’s Bureau for Genentech, acted as a consultant for and participated in a Speaker’s Bureau for Merck, acted as a consultant, participated in a Speaker’s Bureau, and received research funding from Seattle Genetics, acted as a consultant for and received research funding from Bristol-Meyers Squibb, acted as a consultant for Pfizer, acted as a consultant for and received research funding from Pharmacyclics, and received research funding from Affimed.

TTI-621 (SIRPαFc), an Immune Checkpoint Inhibitor Blocking the CD47 “Do Not Eat” Signal, Induces Objective Responsesin Patients with Advanced, Relapsed/Refractory Diffuse Large B-cell Lymphoma (DLBCL)

Stephen M Ansell1, Ian Flinn2, Michael B Maris3, Owen A O’Connor4, Alexander M Lesokhin5, Anjali Advani6, Mark Minden7, Mary-Elizabeth Percival8, Diego Villa9, Lisa DS Johnson10, Tina Catalano10, Meghan Irwin10, Penka S Petrova10, Robert A Uger10, Eric L Sievers10, Robert Chen11

1Mayo Clinic, Rochester, Minnesota, USA; 2Sarah Cannon Research Institute/Tennessee Oncology, Nashville, TN, USA; 3Colorado Blood Cancer Institute, Denver, CO, USA; 4Columbia University Medical Center, New York Presbyterian Hospital, New York City, NY, USA; 5Memorial Sloan-Kettering Cancer Center, New York City, NY, USA; 6Cleveland Clinic, Cleveland, OH, USA; 7Princess Margaret Cancer Center, Toronto, ON, Canada; 8University of Washington/Fred Hutchinson Cancer Research Center, Seattle, WA, USA; 9BC Cancer Agency, Vancouver, BC, Canada; 10Trillium Therapeutics Inc., Mississauga, Ontario, Canada; 11City of Hope, Duarte, CA, USA

ASH 2017Abstract 4116

CharacteristicDLBCL

n=22 (%)All Expansion

n=89 (%)

Age, median (range) 61 (42-84) 62 (21-84)

Sex, male 12 (55) 52 (58)

Baseline ECOG 012

8 (36)13 (59)

1 (5)

26 (29)57 (64)

6 (7)

Prior therapies, median (range) 3.5 (1-10) 5 (1-18)

Prior transplant 8 (36) 39 (44)

Prior radiation 7 (32) 31 (35)

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

Figure 1. Percentage change (pre- to 4 hours post dose) in platelets and hemoglobin at weeks 1, 2 and 3

*All 11 subjects with ≥ Grade 3 anemia had Grade 2 anemia at screening and/or prior to Week 1 TTI-621 infusion (CTCAE v.4.03)

Background Tumor cells frequently evade macrophage-mediated destruction by overexpressing CD47,

an immune checkpoint that binds SIRPα and delivers an anti-phagocytic (“do not eat”) signal.

TTI-621 (SIRPαFc) is an immune checkpoint inhibitor consisting of SIRPα linked to an IgG1 Fc domain. It is designed to block the CD47 “do not eat” signal and deliver an activating signal through Fcγ receptors.

TTI-621-01 (NCT02663518) is a multi-center, open label, phase 1 clinical trial for relapsed or refractory heme malignancies and select solid tumors. Dose escalation results were previously presented (n=18; ASH 2016).

Here we report a comprehensive safety profile of all patients enrolled in the expansion phase of TTI-621-01 and preliminary anti-tumor activity in patients with diffuse large B-cell lymphoma (DLBCL).

Study Design and Patients Key Eligibility Criteria:

Histologically documented advanced malignancy Hemoglobin >8 g/dL and platelets ≥50,000/mm3 (transfusions permitted) ECOG ≤2 Measurable disease per IWG-2014 in NHL patients DLBCL: failed prior CD20-based therapy

Patients receive weekly IV infusions of TTI-621 starting at 0.2 mg/kg for monotherapy patients and 0.1 mg/kg for patients receiving TTI-621 and rituximab. At the investigator’s discretion, the protocol allows dose intensification in 0.1 mg/kg increments to a maximum of 0.5 mg/kg.

Data cut-off: November 6, 2017; n=89.

Table 1. Patient Demographics of DLBCL and Expansion Cohort(s)

Weekly Infusions of TTI-621 are Well Tolerated

Table 2. Adverse Events in Phase 1 Dose Expansion ≥10% of Subjects (n=89)

Manageable infusion-related reactions.

Attenuated thrombocytopenia after the first dose.

Stable hemoglobin levels, consistent with lack of RBC binding by TTI-621.

Preliminary experience indicates that patients can be safely dose intensified beyond 0.2 mg/kg.

Figure 2. Five of 18 evaluable patients (not including four currently on study) achieved a best response ofCR/PR. An additional three patients are not shown (1 dose limiting toxicity in escalation, 2 off study priorto week 8). Arrows indicate patients still on study. Six patients received TTI-621 monotherapy, 14 patientsreceived combination therapy with rituximab and two received monotherapy followed by combinationtherapy. Progressive disease (PD); stable disease (SD); partial/complete metabolic response (PMR/CMR).

Time on Study and Tumor Response in DLBCL Patients Receiving Weekly Intravenous TTI-621

Complete Metabolic Response in a DLBCL PatientTreated with TTI-621 and Rituximab

Figure 3. 62-year old male with DLBCL (previously positive for BCL2 and MYC) had received eightprior therapies including haploidentical NK cells, and five prior CD20-based regimens. Patientreceived 0.1 mg/kg TTI-621 and rituximab. Pseudoprogression was noted at Week 4 and acomplete metabolic response (CMR) was observed at Week 12. The patient remained on study toWeek 36.

Conclusions CD47 blockade employing weekly intravenous infusions of TTI-621 (SIRPα-IgG1 Fc) is well-

tolerated in over 100 patients to date.

Multiple patients with heavily pre-treated, relapsed/refractory DLBCL achieved objective responses and/or prolonged progression-free intervals.

Based upon preliminary and promising anti-tumor activity, expanded enrollment of B- and T-cell lymphoma patients is ongoing.

Baseline Week 4Pseudoprogression

Week 8 Week 12CMR

Pharmacokinetics

0.1 mg/kg 0.2 mg/kg

Week 1 Week 6 Week 1 Week 6

Cmax(ng/mL)

365 ± 109 (n=8)

491 ± 269(n=6)

1029 ± 495 (n=52)

1311 ± 522 (n=13)

AUC†

(ng*h/mL)8105 ± 3047

(n=6)22525 ± 5318

(n=4)21726 ± 8357

(n=49)40369 ± 14903

(n=13)

T1/2

(h)17 ± 5(n=6)

126 ± 30(n=4)

48 ± 33(n=46)

102 ± 40 (n=13)

Table 3. TTI-621 PK Parameters

Thrombocytopenia is Attenuated After the First Dose

TTI-621 exposure increases with dose and repeat administration.

After 6 infusions the half-life is approximately 4-5 days.

†AUC 0-168h for the dosing interval of the Week 1 infusion; AUCτ for the dosing interval of the Week 6 infusion. Mean ± standard deviation are shown.