CD47 is an innate immune checkpoint that binds signalregulatory protein alpha (SIRPα) and delivers a "don’t eat me"signal to suppress macrophage phagocytosis (Figure 1).Overexpression of CD47 serves as a mechanism of immunesurveillance evasion and has been found to be associated withpoor prognosis in both hematologic and solid malignancies.TTI‐622 is a fusion protein consisting of the CD47‐bindingdomain of human SIRPα linked to the Fc region of human IgG4.It is designed to enhance phagocytosis and antitumor activityby preventing CD47 from delivering its inhibitory signal as wellas generating a moderate pro‐phagocytic signal via IgG4 Fc.Importantly, unlike many CD47‐blocking agents, TTI‐622 doesnot bind to human red blood cells (RBCs; Figure 2).

Krish Patel1, Radhakrishnan Ramchandren2, Michael Maris3,4, Alexander Lesokhin5, Gottfried R. von Keudell5, Bruce D. Cheson6, Jeffrey Zonder7, Erlene K. Seymour7,Tina Catalano8, Gloria H. Y. Lin8, Bob Uger8, Penka S. Petrova8, Kathleen Roberge8, Yaping Shou8, Swaminathan Iyer9

1 Swedish Cancer Institute, Seattle, WA, USA; 2 University of Tennessee, Knoxville, TN, USA; 3 Colorado Blood Institute, Denver, CO, USA;  4 Sarah Cannon Research Institute, Denver, CO, USA; 5 Memorial Sloan Kettering, New York City, NY, USA; 6 Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC, USA; 7 Karmanos Cancer Institute/Wayne State University, Detroit, MI, USA; 8 Trillium Therapeutics Inc., Mississauga, Ontario, CA; 9 University of Texas MD Anderson Cancer Center, Houston, TX, USA.

Investigational CD47‐Blocker TTI‐622 Shows Single‐Agent Activity in Patients with Advanced Relapsed or Refractory Lymphoma: Update from the Ongoing First‐in‐human Dose Escalation Study.

BACKGROUND• Presented in this poster are data (data cut‐off: November 3,2020) from 31 R/R lymphoma patients enrolled to Cohorts 1‐7, including patients with the following lymphomas: DLBCL(n=16), HL (n=5), FL, PTCL and CTCL w LCT (n=3, each), andMCL (n=1).

• Median age was 66 (range, 24–86); 13 males and 18 females.• Majority of patients had advanced stage disease: IV (n=20),III (n=8), I‐II (n=2), or not specified (n=1).

• Patients were heavily pre‐treated with a median of 3 priorlines of systemic therapy (range 1‐9); 10 patients receivedprior cellular therapy including 8 with HSCT and 6 with CAR‐T(Table 1).

• Additionally, 2 patients had been enrolled and treated with18 mg/kg in the ongoing Cohort 8.

Table 1. Demographic and Baseline Disease Characteristics

CONCLUSIONS• TTI‐622 administered weekly IV was well tolerated atdoses up to 12 mg/kg. Related thrombocytopeniaGrade 3‐4 intensity had occurred in only 3% ofpatients.

• Dose‐dependent increases in TTI‐622 serum exposuresupport continued dose escalation beyond 12 mg/kg.

• Dose‐dependent increases in peak RO and ROdurability were observed.

• Objective responses in 6/22 (27%) response evaluablepatients [6/17 (35%) at dose levels ≥0.8 mg/kg]occurred within the first 8 weeks across multiplelymphoma indications and included 5 PRs and a CR;the CR patient was ongoing through Day 534.

• Further dose escalation is ongoing at 18 mg/kg.

Acknowledgments: This study was funded by Trillium Therapeutics Inc.; the authors would like to thank all patients and their families, and all investigators for their valuable contributions to this study. 

ASH 2020 Abstract #1191

Table 2. Adverse Events in 3 or More Patients 

• The majority of all and related AEs in Cohorts 1‐7 had beenGrade (Gr) 1‐2 intensity (Table 2).

• The most frequent related AEs included thrombocytopeniain 5 (16%) patients, neutropenia in 4 (13%) patients, andnausea, anemia and fatigue in 3 patients (10%), each.

• Related AEs of Gr≥3 intensity included neutropenia in 4patients (13%), and thrombocytopenia and anemia in 1patient (3%), each.

• DLTs to date included Gr4 thrombocytopenia in 1 patient inCohort 6 (8 mg/kg), based on Gr4 thrombocytopeniarequiring prophylactic platelet transfusion per investigatordiscretion; the event quickly resolved without bleeding.

• Treatment interruptions for 1‐2 weeks had been required in3 patients due to neutropenia in 2 patients andthrombocytopenia in 1 patient.

Efficacy: Objective Responses in  Subjects  

Adverse Events

Translational Assessments

Disclosures: KP has consultancy relationships with AstraZeneca, Pharmacyclics, Janssen, Genentech, BeiGene, Kite, Bristol‐Myers Squibb, Morphosys; speakers’ bureau relationship with Genentech, Bristol‐Myers Squibb, Pharmacyclics/Janssen; and research funding from AstraZeneca; RR has consultancy relationships with Seattle Genetics, Sandoz‐Novartis, Pharmacyclics/Janssen, Bristol‐Myers Squibb; and research funding from Merck, Seattle Genetics, Janssen and Genentech; AL has consultancy and Honoraria relationships with BMS, GenMab, Juno, Takeada; and research funding from BMS, Genentech, Janssen; and patents and royalties with Serametrix Inc.; GvK has research funding from Pharmacyclics, Genentech, and Bayer; BC has consultancy relationships with Abbvie, Janssen and Pharmacyclics; JZ has a consultancy relationships with Caelum, Intellia, Amgen, Takeada, Janssen, Regeneron, Alnylam, Oncopeptides; research funding from Celgene and BMS; ES has membership on a Board of Directors or advisory committees for Janssen/Pharmacyclics, Karyopharm; and has research funding from Karyopharm, Bristol‐Myers Squibb, Genentech, Incyte, Merck, and Seattle Genetics; TC, GL, BU, PP, KR, and YS are employees of Trillium Therapeutics Inc.; SI has research funding from Arog, Bristol‐Myers Squibb, Genentech/Roche, Incyte and Seattle Genetics; MM has no disclosures.

Patients

Figure 1. CD47 Pathway in Cancer and TTI‐622 Structure

Figure 2. Binding of TTI‐622 or CD47 mAb to RBCs

Dose Escalation

Study Design 

• Generally moderate platelet decreases occurred on dosingdays, counts typically recovered over the initial andsubsequent weeks to generally support continued weeklydosing without interruption (Figure 4).

Platelet Counts 

Dose ExposureTreatment exposure through Cohort 7 to date:• Median cumulative dose received: 1251 mg (range, 6‐11,135).

• Median number of doses received: 7 (range, 2‐47).

• The median (min‐max) time to response was 49 days (45‐51);the median duration of treatment for responders was 113days (92‐534) with ongoing CR in 1 patient (CR for 289D).

• Figure 7 below shows images of a partial response achievedin subject 006‐006 with DLBCL.

Figure 7. Subject 006‐006 Partial Response  

Pharmacokinetics

Lin et al. AACR 2018

Figure 9. TTI‐622 Mean Trough Concentrations Following IV Infusion

• Dose‐dependent increase in TTI‐622 serum exposurefollowing single and repeat infusions. No plateau relationshipup to 12 mg/kg, supporting dose escalation beyond 12 mg/kg(Figure 8).

• Dose‐dependent increase in serum trough levels (Figure 9).• Steady state TTI‐622 serum exposures likely not reached untilweek 5+.

• As of the time of data cut‐off, 7 dose levels had been testedand determined safe and tolerable per 3+3 dose escalation;summary data from these first 7 cohorts are included in thispresentation.

• Of the 31 patients enrolled to date in Cohorts 1‐7, 5 continueto receive treatment in Cohorts 3, 6, and 7 (Figure 3).

• Cohort 8 (18 mg/kg) is currently ongoing; 2 patients wereenrolled and treated by November 3rd, and 1 had completedthe DLT evaluation; no DLTs and other significant AEs hadbeen observed.

Phase 1a of a multicenter, Phase 1 study of a CD47 blocker,TTI‐622 (NCT03530683) in patients with relapsed/refractory(R/R) lymphoma to characterize:• Safety and maximum tolerated dose or recommended phase2 dose

• Pharmacokinetics and pharmacodynamics• Preliminary antitumor activityEligible patients were adults with R/R lymphoma who hadpreviously progressed on at least 2 prior standard anticancertherapies or for whom no other approved therapy exists.Dose Escalation was based on a modified 3+3 schemeescalating weekly doses through dose levels of 0.05‐18 mg/kg.The dose limiting toxicity (DLT) period was 3 weeks. During thefirst 2 weeks, patients in Cohort 1‐5 (doses 0.05‐4 mg/kg)received a lower 'run in' dose followed by the higher planneddose at week 3. For example, a low dose of 0.05 mg/kg wasreceived in Weeks 1 and 2 followed by 0.1 mg/kg in Week 3and thereafter, continuing once per week. Starting with Cohort6, all doses are administered at a flat dose without the lowerinitial weekly doses.PK and PD assessments included serial PK sampling in Weeks1, 6, and 12 with pre‐infusion trough samples obtained beforeall other doses. Samples for PD assessments were obtained inWeeks 1, 2, 6, 7, 12, and 13.Response assessments were performed by the investigator perLugano criteria every 8 weeks within the first 6 months, every3 months up to two years, and every 6 months thereafter untilthe end of treatment.

Figure 3. Dose Escalation   

Figure 8. TTI‐622 Mean Concentration Profiles Following IV Infusion Week 1 – Single Infusion Week 6 – Repeat Infusions

RESULTS

Unlike anti‐CD47 antibodies, TTI‐622 binds minimally to human RBCs.

TTI-622

contro

l Fc

BRIC126

2D3

CC2C6

B6H12 5F

9

mIgG1mIgG2b

100

101

102

103

104

105

106

Mea

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Inte

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CD47 mAbs ControlmAbs

Binding of TTI‐622 or anti‐CD47 monoclonal antibodies (mAbs) to fresh human RBCs at saturating concentrations is shown. Data were analyzed by flow cytometry and the graph represents mean fluorescence intensity for 43 human donors.

ASH2020@trilliumtherapeutics.comPlease direct correspondence to  

Baseline  First Restaging  

• 68 y/o female• DLBCL

• Prior lines of therapy: 1. Bendamustine + Rituximab (CR)2. Lenalidomide + Obinutuzumab (CR)3. Plamotamab (PD)

• Dose 8 mg/kg 

• Achieved PR at Week 8

• Objective responses were achieved in 6/22 (27%) responseevaluable patients including 1 CR in DLBCL and 5 PRs in CTCL(n=2; per Lugano), DLBCL (n=2) and PTCL (n=1; Figures 5 and6).

Efficacy Continued  

Baseline Characteristics Totaln=31

Median Age, years (min‐max) 66 (24‐86)Male, n (%)  13 (42)ECOG PS 0‐1, n (%) 31 (100)Primary Diagnosis, n (%)

Diffuse Large B Cell Lymphoma 16 (52)Hodgkin Lymphoma 5 (16)Follicular Lymphoma 3 (10)Peripheral T Cell Lymphoma 3 (10)Cutaneous T Cell Lymphoma – Large Cell Transformation 3 (10)Mantle Cell Lymphoma 1 (3)

Overall Stage at Study Entry, n (%)I or II 2 (6)III 8 (26)IV 20 (65)Not Specified 1 (3)

Prior Therapy, n (%)Systemic 31 (100)HSCT 8 (26)CAR‐T 6 (19)

Median Lines of Prior Treatment, (min‐max)Systemic 3 (1‐9)

Figure 10. Receptor Occupancy 

• Dose‐dependent increases in peak receptor occupancy (RO)and RO durability were observed (Figure 10).

• 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.

• Increased peripheral T cell clonality and expansion of newand existing T cell clones observed in a patient achieving a CR(subject 006‐001; Figure 11).

Figure 11. TCR Vβ sequencing• 78 y/o male• Non‐GCB DLBCL• Prior lines of therapy: 

1. R‐EPOCH/R‐CEOP (CR)2. PI3Kd inhibitor (PR)3. SYK inhibitor (CR)4. IRAK4 inhibitor (PD)

• Dose 0.8 mg/kg • Achieved PR at Weeks 8, 16, 24; CR 

Week 36 by PET/CT

• 5 pre‐existing T cell clones increased in frequency at every time point between week 1 and 32.

• At week 40,  these 5 clones were still expanded (bolded orange dots), while expansion of new clones was also observed (orange dots along the Y‐axis).

Cohort 1 

Cohort 2 

Cohort 3 

Cohort 4 

Cohort 5

Cohort 6 

n=4

n=3

n=4; 1 active (1 CR)

n=4; (1 PR) 

n=4; (1 PR)

n=8; 1 active (3 PRs)

0.05, 0.05, 0.1 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, 8.0, 8.0 mg/kg 

Cohort 7  n=4; 3 active12.0, 12.0, 12.0 mg/kg 

2018 2019 2020

O NJ A SJ FD J M A M J J O NA S D FJ M A M J J O NA S D

Cohort 8  n=2; 2 active18.0, 18.0, 18.0 mg/kg 

Cohorts 1 – 8 status as of 3 November 2020n = subjects at Week 3; some time points may have fewer subjects

Figure 5. Target Lesion Response   

Figure 6. Response Onset and Duration   

DLBCL0.05

DLBCL8

DLBCL0.3

DLBCL1

DLBCL8

HL0.3

DLBCL8

HL0.1

FL0.8

DLBCL0.1

HL0.8

DLBCL4

DLBCL12

CTCL8

CTCL8

HL4

DLBCL8

PTCL2

PTCL8

DLBCL4

HL2

DLBCL0.8

‐100‐75‐50‐250

255075

100

Target Lesion Ch

g (%

)

CR PR SD PD

Lymphoma(mg/kg)

*

*  Partial Metabolic Response1) Lesion measures in 9 patients are missing due to 1) Not Assessed (n=5: 3 off study due to clinical PD, 1 off study to start CAR‐T; 1 withdrawal of consent), 2) Pending Assessments (n=4)  2) New lesion observed concurrently with target lesion reductions Note: Dose levels shown represent the highest dose level each patient received 

**

2

22

Figure 4. Median Platelets Week 1 and Pre‐dose Thereafter  A. Week 1 Median Platelets  

B. Weekly Pre‐Dose Median Platelets  

50100150200250300350

1 2 3 4 5 6 7 8 9

Platelets (x109

/L)

Days

Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Cohort 6 Cohort 7

50

100

150

200

250

300

350

1 2 3 4 5 6 7 8 9 10 11 12

Platelets (x109

/L)

Weeks

AllPatients

n

Response Evaluable Pts

n1CRn

PRn

ORn

ORR in Evaluable Pts

(%)31 22 1 5 6 27

Total Patients

n

Response n Tmt Duration in Responders (days)med (min‐max)

Time to Response(days)

med (min‐max)CR PR OR

31 1 5 6 113 (92‐534) 49 (45‐51)

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)

Abdominal pain 4 (13) 2 (6) 4 (13) 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)

Back pain 3 (10) 1 (3) 3 (10) 1 (3)

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

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

Fall 3 (10) 3 (10)

Insomnia 3 (10) 3 (10)

Leukocytosis 3 (10) 1 (3) 3 (10) 1 (3)*A = All AEs, R = Related AEs

Adverse Eventsn (%)

Total n=31 All AEs Related AEs

10 20 30 40 50

*ARARARARARARARARARARARARARARAR

Patients (%)

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

→Ongoing

(0.8 mg/kg)

270 360 450 540

*****

*

PDPD

PD following 3 week treatment interruption due to unrelated AEPD

Off study due to intercurrent illness→  Ongoing (12 mg/kg)

→  Ongoing (12 mg/kg)→  Ongoing (12 mg/kg)

→  Ongoing (8 mg/kg)

Off study to pursue CAR‐T (12 mg/kg)

90 180

DLBCLDLBCLDLBCLCTCLCTCL

DLBCLPTCL

DLBCLFLFL

DLBCLDLBCL

HLFL

DLBCLPTCLHL

DLBCLHL

CTCLHL

DLBCLDLBCLAITL

DLBCLMCLHL

DLBCLDLBCLDLBCLDLBCL

Days

CR PR SD PD NA Pending

* Response start

//

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

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

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

Week 1

Wee

k 40

Differential Abundance of T cell clones at week 40 vs week 1

1

Figure 1

Lin et al. AACR 2018

TTI-622

contro

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BRIC126

2D3

CC2C6

B6H12 5F

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mIgG1mIgG2b

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CD47 mAbs ControlmAbs

Figure 1. CD47 Pathway in Cancer and TTI‐622 Structure

Figure 2. Binding of TTI‐622 or CD47 mAbs to RBCs

• CD47 is an innate immune checkpoint that binds signal regulatory protein alpha (SIRPα) and delivers a "don’t eat me" signal to suppress macrophage phagocytosis. 

• Overexpression of CD47 serves as a mechanism of immune surveillance evasion and has been found to be associated with poor prognosis in both hematologic and solid malignancies. 

• TTI‐622 is a fusion protein consisting of the CD47‐binding domain of human SIRPα linked to the Fc region of human IgG4. It is designed to enhance phagocytosis and antitumor activity by preventing CD47 from delivering its inhibitory signal as well as generating a moderate pro‐phagocytic signal via IgG4 Fc. 

• Unlike anti‐CD47 antibodies, TTI‐622 binds minimally to human RBCs.

• Results of human RBC binding study show mean fluorescence intensity of saturating concentrations of TTI‐622 and Anti‐CD47 antibodies for 43 human donors, measured by flow cytometry.

Figure 1.  

Figure 2. 

2

Figure 3. Dose Escalation   

Cohort 1 

Cohort 2 

Cohort 3 

Cohort 4 

Cohort 5

Cohort 6 

Cohort 7 

Cohort 8 

n=4

n=3

n=4; 1 active (1 CR)

n=4; (1 PR) 

n=4; (1 PR)

n=8; 1 active (3 PRs)

0.05, 0.05, 0.1 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, 8.0, 8.0 mg/kg 

n=4; 3 active12.0, 12.0, 12.0 mg/kg 

2018 2019 2020

O NJ A SJ FD J M A M J J O NA S D FJ M A M J J O NA S D

n=2; 2 active18.0, 18.0, 18.0 mg/kg 

Cohorts 1 – 8 status as of 3 November 2020

• 31 R/R lymphoma patients enrolled to Cohorts 1–7, includingDLBCL (n=16), HL (n=5), FL, PTCL and CTCL w LCT (n=3, each),and MCL (n=1), are included in this presentation.

• Median age was 66 (range, 24–86); 13 males and 18 females.

• Majority of patients had advanced stage disease: IV (n=20), III(n=8), I‐II (n=2), or not specified (n=1). Patients received amedian of 3 prior lines of systemic therapy (range 1‐9); 10patients received prior cellular therapy including 8 with HSCTand 6 with CAR‐T.

• Additionally, 2 patients had been enrolled and treated with 18mg/kg in the ongoing Cohort 8.

Study DesignDose escalation was based on a modified 3+3 scheme escalating weekly doses through dose levels of 0.05 – 18 mg/kg. The dose limiting toxicity (DLT) period was 3 weeks. During the first 2 weeks, patients in Cohort 1‐5 (doses 0.05 – 4 mg/kg) received a lower 'run in' dose followed by the higher planned dose at week 3. Starting with Cohort 6, all doses are administered at a flat dose.

Patients

Abbreviations: R/R ‐ Relapsed/Refractory; DLBCL – Diffuse Large B Cell Lymphoma; HL – Hodgkin Lymphoma; FL – Follicular Lymphoma; PTCL – Peripheral T Cell Lymphoma; CTCL w LCT – Cutaneous T Cell Lymphoma with Large Cell Transformation; MCL – Mantel Cell Lymphoma Based on the data in clinical database as of 3 Nov 2020; data are subject to change prior to final database lock

3

Adverse Events Design• All & related AEs were predominantly Gr 

1‐2.• Common related AEs: thrombocytopenia (16%); neutropenia (13%); nausea, anemia and fatigue (10%), each.

• Related Gr ≥3 AEs: neutropenia (13%); thrombocytopenia and anemia (3%), each. 

• DLT: Gr4 thrombocytopenia in Cohort 6 (8 mg/kg); resolved following prophylactic transfusion without bleeding. 

• Treatment interruptions of 1‐2 weeks occurred in 3 patients: neutropenia (n=2) and thrombocytopenia (n=1). 

• Generally moderate platelet decreases occurred on dosing days with recovery over initial and subsequent weeks.  Based on the data in clinical database as of 3 Nov 2020; data are subject to change prior to final database lock

Table 2. Adverse Events in 3 or More Patients  Figure 4. Median Platelets Week 1 and Pre‐dose Thereafter  

50100150200250300350

1 2 3 4 5 6 7 8 9Days

Cohort 1 Cohort 2 Cohort 3 Cohort 4Cohort 5 Cohort 6 Cohort 7

Week 1

50100150200250300350

1 2 3 4 5 6 7 8 9 10 11 12

Weeks

Platelets (x10^

9/L) Weeks 1‐12

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)

Abdominal pain 4 (13) 2 (6) 4 (13) 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)

Back pain 3 (10) 1 (3) 3 (10) 1 (3)

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

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

Fall 3 (10) 3 (10)

Insomnia 3 (10) 3 (10)

Leukocytosis 3 (10) 1 (3) 3 (10) 1 (3)*A = All AEs, R = Related AEs

Adverse Eventsn (%)

Total n=31 All AEs Related AEs

10 20 30 40 50

*ARARARARARARARARARARARARARARAR

Patients (%)

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

Platelets (x10^

9/L)

4

Objective Responses• Objective responses per Lugano criteria were achieved in 6/22 (27%) response evaluable patients (across all dose levels) including:

• 1 CR in DLBCL

• 5 PRs: • CTCL n=2• DLBCL n=2• PTCL n=1

• The lowest dose level where a response was seen was at 0.8 mg/kg

• Objective responses achieved in 6/17 (35%) response evaluable patients at dose levels ≥0.8 mg/kg

DLBCL0.05

DLBCL8

DLBCL0.3

DLBCL1

DLBCL8

HL0.3

DLBCL8

HL0.1

FL0.8

DLBCL0.1

HL0.8

DLBCL4

DLBCL12

CTCL8

CTCL8

HL4

DLBCL8

PTCL2

PTCL8

DLBCL4

HL2

DLBCL0.8

‐100

‐75

‐50

‐25

0

25

50

75

100

Target Lesion Ch

g (%

)

CR PR SD PD

Lymphoma(mg/kg)

*

*  Partial Metabolic Response1) Lesion measures in 9 patients are missing due to 1) Not Assessed (n=5; 3 off study due to clinical PD, 1 off study to start CAR‐T, 1 withdrawal of consent), 2) Pending Assessments (n=4)  2) New lesion observed concurrently with target lesion reductions Note: Dose levels shown represent the highest dose each patient received 

*

*

2

22

Figure 5. Target Lesion Response

AllPatients  

n

ResponseEvaluable Pts

n1CRn

PRn

ORn

ORR in Evaluable Pts 

(%)

31 22 1 5 6 27

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

5

Response Onset and Duration

• The median (min‐max) time to response was 49 days (45‐51)

• The median duration of treatment in responders was 113 days (92‐534)

• The CR patient was ongoing at 534 days and in CR for 289 days

• The response assessment for 12 mg/kg was pending for 3 patients as of November 3, 2020

Figure 6. Response Onset and Duration

Total Patients

n

Response n

Tmt Duration in Responders (days)med (min‐max)

Time to Response(days)

med (min‐max)CR PR OR

31 1 5 6 113 (92‐534) 49 (44‐51)

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

→Ongoing

(0.8 mg/kg)

270 360 450 540

*****

*

PDPD

PD following 3 week treatment interruption due to unrelated AEPD

Off study due to intercurrent illness→  Ongoing (12 mg/kg)

→  Ongoing (12 mg/kg)→  Ongoing (12 mg/kg)

→  Ongoing (8 mg/kg)

Off study to pursue CAR‐T (12 mg/kg)

90 180

DLBCLDLBCLDLBCLCTCLCTCL

DLBCLPTCL

DLBCLFLFL

DLBCLDLBCL

HLFL

DLBCLPTCLHL

DLBCLHL

CTCLHL

DLBCLDLBCLAITL

DLBCLMCLHL

DLBCLDLBCLDLBCLDLBCL

Days

CR PR SD PD NA Pending

* Response start

//

6

Figure 8. TTI‐622 Mean Concentration Profiles 

Figure 9. 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 8). 

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

• Dose‐dependent increase in serum trough levels (Figure 9).

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

Pharmacokinetics

7

Figure 10. Receptor Occupancy   

• Receptor Occupancy (RO) on peripheral blood T cells was determined using a flow cytometry‐based competitive binding assay (Figure 10).

• Increased peripheral T cell clonality and expansion of new and existing T cell clones observed in a patient achieving a CR (subject 006‐001; Figure 11).

Figure 11. TCR Vβ sequencing

• 78 y/o male• Non‐GCB DLBCL• Prior lines of therapy: 

1. R‐EPOCH/R‐CEOP (CR)2. PI3Kd inhibitor (PR)3. SYK inhibitor (CR)4. IRAK4 inhibitor (PD)

• Dose 0.8 mg/kg • Achieved PR Weeks 8, 16, 24; 

CR Week 36 by PET/CT

• 5 pre‐existing T cell clones increased in frequency at every time point between week 1 and 32

• At week 40,  these 5 clones were still expanded (bolded orange dots), while expansion of new clones was also observed (orange dots along the Y‐axis)

Translational Assessments

• 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.

8

• TTI‐622 administered weekly IV was well tolerated at doses up to 12 mg/kg. Related thrombocytopeniaof Grade 3‐4 intensity had occurred in only 3% of patients.

• Dose‐dependent increases in TTI‐622 serum exposure support continued dose escalation beyond 12mg/kg.

• Dose‐dependent increases in peak RO and RO durability were observed.

• Objective responses in 6/22 (27%) response evaluable patients [6/17 (35%) at dose levels ≥0.8 mg/kg]occurred within the first 8 weeks across multiple lymphoma indications and included 5 PRs and a CR; theCR patient was ongoing through Day 534.

• Further dose escalation is ongoing at 18 mg/kg.

Preliminary Conclusions

• The patients who participated in this study and their families• Members of the sponsor and CRO study team• The following investigational study site staff members who contributed to the conduct of the study 

9

• Swedish Cancer Institute • Memorial Sloan Kettering Cancer Center

• University of Tennessee • Lombardi Comprehensive Cancer Center

• Colorado Blood Institute • Karmanos Cancer Institute/Wayne State University

• Sarah Cannon Research Institute • University of Texas MD Anderson Cancer Center

Disclosures: KP has consultancy relationships with AstraZeneca, Pharmacyclics, Janssen, Genentech, BeiGene, Kite, Bristol‐Myers Squibb, Morphosys; speakers’ bureau relationship with Genentech, Bristol‐Myers Squibb, Pharmacyclics/Janssen; and research funding from AstraZeneca; RR has consultancy relationships with Seattle Genetics, Sandoz‐Novartis, Pharmacyclics/Janssen, Bristol‐Myers Squibb; and research funding from Merck, Seattle Genetics, Janssen and Genentech; AL has consultancy and Honoraria relationships with BMS, GenMab, Juno, Takeada; and research funding from BMS, Genentech, Janssen; and patents and royalties with Serametrix Inc.; GvK has research funding from Pharmacyclics, Genentech, and Bayer; BC has consultancy relationships with Abbvie, Janssen and Pharmacyclics; JZ has a consultancy relationships with Caelum, Intellia, Amgen, Takeada, Janssen, Regeneron, Alnylam, Oncopeptides; research funding from Celgene and BMS; ES has membership on a Board of Directors or advisory committees for Janssen/Pharmacyclics, Karyopharm; and has research funding from Karyopharm, Bristol‐Myers Squibb, Genentech, Incyte, Merck, and Seattle Genetics; TC, GL, BU, PP, KR, and YS are employees of Trillium Therapeutics Inc.; SI has research funding from Arog, Bristol‐Myers Squibb, Genentech/Roche, Incyte and Seattle Genetics; MM has no disclosures.

The authors would like to thank: 

Please direct correspondence to ASH2020@trilliumtherapeutics.com