This presentation may contain forward-looking statements, which reflect Trillium's current expectation regarding future events. These forward-looking

Transcription

1 Q1/2016

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 preclinical 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 developing a next generation immune checkpoint inhibitor Lead program SIRPαFc targets CD47, a do not eat signal tumor cells exploit to escape destruction by the innate immune system Phase 1a/1b trial in patients with advanced hematologic malignancies ongoing Raised ~$85M (Since 12/2013) from premier US healthcare funds to support clinical development 3

4 Experienced Leadership & Veteran Board of Directors MANAGEMENT Executive Title Joined Trillium Dr. Niclas Stiernholm President & Chief Executive Officer 2002 Dr. Robert Uger Chief Scientific Officer 2003 Dr. Eric Sievers Chief Medical Officer 2015 Dr. Penka Petrova Chief Development Officer 2003 Mr. James Parsons Chief Financial Officer 2003 Ms. Elizabeth Wieland Senior Director, Clinical Operations 2015 BOARD OF DIRECTORS Executive Affiliation Executive Affiliation Dr. Calvin Stiller, Chair Chair Dr. Robert Kirkman CEO Dr. Henry Friesen Chair (former) Dr. Thomas Reynolds CMO (former) Dr. Niclas Stiernholm CEO Mr. Luke Beshar CFO (former) Dr. Michael Moore CEO (former) 4

5 SIRPaFc Checkpoint Inhibitor Program KEY ATTRIBUTES SIRPaFc inhibits the CD47 DO NOT EAT signal allowing macrophages to engulf and destroy tumor cells Follows in the footsteps of CTLA-4 and PD-1 checkpoint inhibitors Operates through macrophages (innate immune system) and may exert downstream effects on the adaptive immune system (T cells) Holds great promise as both monotherapy and combination therapy with other immunological agents Has broad clinical potential in both hematological and solid tumors Mobilizes the immune system to attack bulk cancer cells and cancer stem cells 5

6 SIRPaFc Development Strategy Advanced hematologic malignancies in Phase I... With broad clinical potential Planned Expansion Cohorts (n=12-15) First indication: lymphoma Approximately 36 patients 3+3 design 1 st patient to be dosed in Q1 5 US sites Cohort Expansion Acute Myeloid Leukemia Myelodysplastic syndrome Chronic lymphocytic leukemia Hodgkin lymphoma Indolent B cell lymphoma Aggressive B cell lymphoma T-cell lymphoma Multiple myeloma 6

7 CD47 Delivers a Do Not Eat Signal to Macrophages Through SIRPa Widely expressed cell surface glycoprotein Associates with integrins, binds multiple ligands Involved in diverse cellular functions IgSF cell surface glycoprotein Expressed on myeloid cells and neurons Transmits inhibitory signal 7

8 CD47 is Highly Expressed by Many Tumors Acute myeloid leukemia Acute lymphoblastic leukemia Chronic lymphocytic leukemia Chronic myeloid leukemia Diffuse large B cell lymphoma Follicular lymphoma Mantle cell lymphoma Multiple myeloma Bladder cancer Breast cancer Colon cancer GBM Leiomyosarcoma Liver cancer Melanoma Ovarian cancer Pancreatic cancer Prostate cancer CD47 expression is correlated with poor outcome in many cancers 8

9 SIRPaFc (TTI-621): Inducing Anti-Tumor Responses Through Blockade of the CD47 Do Not Eat Signal Audra Geras 9

10 P h a g o c y to s is In d e x SIRPaFc Enables Macrophages to Kill Human Tumor Cells E C 50 = 4 n M No Treatment Control Fc (1 mm) SIRPαFc (1 mm) S IR P a F c (L o g n M ) Human AML cells labeled green Human macrophages labeled red Phagocytosis assessed by confocal microscopy after 2 hr co-culture 10

11 SIRPaFc is Active Against a Diverse Panel of Primary Human Hematopoietic Tumor Samples TTI-621 enhances macrophage phagocytosis of 97% (32/33) of samples tested 11

12 SIRPaFc Induces Tumor Cell-Specific Phagocytosis Phagocytosis Index CD47 Exp 381 * SIRPaFc Control Fc 0 AML + SIRPαFc Normal cells + SIRPαFc AML cells Normal monocytes Results consistent with a model in which CD47 blockade enables macrophages to kill only target cells that express pro-phagocytic signals (i.e, tumor cells) 12

13 SIRPaFc Has Potent Anti-leukemic Activity in an AML Patient Xenograft Model Injected Bone Marrow Non-Injected Bone Marrow Spleen Patient #90543 % AML Engraftment p=3x10-8 SIRPaFc Control Fc % AML Engraftment p=0.003 SIRPaFc Control Fc % AML Engraftment p=0.02 SIRPaFc Control Fc Patient #90191 % AML Engraftment Injected Bone Marrow p=0.008 SIRPaFc Control Fc % AML Engraftment Non-Injected Bone Marrow p=0.003 SIRPaFc Control Fc % AML Engraftment Spleen p= SIRPaFc Control Fc Human SIRPaFc treatment: 8 mg/kg IP 3x/wk for 4 wks, starting 21d after engraftment 13

14 T u m o r V o l u m e ( m m 3 ) SIRPaFc Has Potent Anti-leukemic Activity in a CD20 lo Rituximab-Resistant B Lymphoma Xenograft Model (Raji) C o n t r o l F c R it u x im a b S I R P a F c D a y p o s t - E n g r a f t m e n t Mouse SIRPaFc treatment: 10 mg/kg IP 5x/wk for 3 wks, starting 3d after engraftment 14

15 A Second Clinical Pathway: SIRPaFc Combination Therapy SIRPαFc-mediated enhancement of innate immunity could be synergistic with other immune therapies, such as: Approved cancer antibodies (e.g., Rituxan ) T cell checkpoint inhibitors (e.g., anti-pd-1) Cancer vaccines Oncolytic viruses CAR T cells Preliminary evidence suggests that CD47 blockade can enhance the potency of anti-cancer antibodies and promote T cell responses We are evaluating SIRPαFc in preclinical combination studies 15

16 Competition Trillium is the only group developing a SIRPαFc fusion protein and has developed IP around this approach Three others are pursuing anti-cd47 antibodies: Stanford, through a non-commercial entity (CIRM grant) Celgene (licensed from Inhibrx) Novimmune (bispecific anti-cd47/anti-cd19 antibody) Trillium s SIRPαFc has much lower binding to human RBCs compared to anti-cd47 mabs potential best in class through: Lower hemotoxicity More favorable PK (no RBC antigen sink ) Non-interference with blood typing 16

17 SIRPaFc Has a Favorable Low Binding Profile to Human RBCs Compared to CD47 Antibodies Mean Fluorescence Intensity SIRPaFc Fc control BRIC126 2D3 CC2C6 B6H12 5F9 CD47 mabs migg1 migg2b mab Controls Donor Characteristics (n=43) Male (n=32) Female (n=11) Type A blood group (n=11) Type B blood group (n=13) Type AB blood group (n=5) Type O blood group (n=14) Rh+ blood group (n=20) Rh- blood group (n=13) Binding of SIRPαFc and anti-cd47 mabs to human RBCs (n=43 donors) 17

18 2015 Highlights Completed GMP manufacturing and GLP toxicology studies with TTI-621 Filed and cleared IND Initiated two clinical sites Completed US$55 million financing from major US healthcare funds Released preclinical data supporting trials in additional hematologic indications Expanded management and R&D staff 18

19 2016 Activities Clinical: Provide update on phase 1 trial Prepare for trial in solid tumors Manufacture clinical supply for future trials Preclinical: Characterize the effect of SIRPaFc on various macrophage subsets and dendritic cells Explore the impact of SIRPaFc on the generation of tumor-specific adaptive immune responses Assess the effect of SIRPaFc in combination with other therapies 19

20 Capitalization and Intellectual Property SHARES OUTSTANDING 10.7M Common & Preferred (assuming full conversion) 15.2M fully diluted CURRENT CASH $89.1M (CAD) as of September 30, 2015 INSTITUTIONAL OWNERSHIP ~85% INTELLECTUAL PROPERTY Two patent families covering method of use and composition of matter through 2030 and

21 Trillium Therapeutics Inc. (NASDAQ:TRIL/TSX:TR) is an immuno-oncology company dedicated to the discovery and development of novel and innovative cancer therapies.