17th Annual BIO CEO & Investor Conference February 9-10, 2015 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 pre-clinical 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. 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 Investment Highlights Immuno-oncology company developing a next generation immune checkpoint inhibitor Over a decade of immunotherapy research; validated by several revenue-generating partnerships – Genentech, Biogen, Medarex etc. Lead program targets CD47, a “do not eat” signal tumor cells exploit to escape destruction by the innate immune system Raised $30M (12/2013) from premier US healthcare funds to support clinical development IND in Q3/15; $90 million valuation 3 2014 Highlight Capitalization Listed on NASDAQ (TRIL) and TSX (TR) 6.7M Common & Pref. shares (as converted) ~70% institutional ownership 12M shares fully diluted ~$90M market cap (including Pref. shares) Raised $30M in Dec 2013 $22M cash at December 31, 2014 5 Experienced Leadership Management Dr. Niclas Stiernholm – President & Chief Executive Officer (2002) Dr. Robert Uger – Chief Scientific Officer (2003) Dr. Penka Petrova – Vice President, Drug Development (2003) Mr. James Parsons – Chief Financial Officer (2003) Mr. Scott Duncan – Director, Patents and Licensing (2003) Board of Directors Affiliation Dr. Calvin Stiller, Chair (2011) Dr. Henry Friesen (2011) Dr. Niclas Stiernholm (2011) Dr. Michael Moore (2013) Dr. Robert Kirkman (2013) Dr. Thomas Reynolds (2014) Mr. Luke Beshar (2014) Chair, Ontario Institute for Cancer Research President, Medical Research Council of Canada (former) CEO, Trillium CEO, Piramed (former) CEO, Oncothyreon CMO, SeattleGenetics (former) CFO, NPS Pharmaceuticals 6 SIRPaFc Checkpoint Inhibitor Program A pre-IND immunotherapy program targeting CD47 SIRPaFc inhibits the ‘DO NOT EAT’ signal of CD47 allowing macrophages to engulf and destroy tumor cells 7 Key Attributes of the SIRPaFc Program SIRPαFc is a biologic cancer immunotherapy targeting the CD47 “do not eat” signal Follows in the footsteps of CTLA-4 and PD-1 checkpoint inhibitors Operates through macrophages (innate immune system) but can 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 8 SIRPaFc: A Novel Biologic that Blocks the CD47 “Do Not Eat” Signal 9 SIRPaFc Enables Macrophages to Kill Human Tumor Cells CD47 Exp 377 Phagocytosis Index 500 100 Human AML cells labeled green Human macrophages labeled red Phagocytosis assessed by confocal microscopy after 2 hr co-culture SIRPaFc (nM) 10 00 10 00 0 10 0 ro l 10 0 Co nt * * 200 1 SIRPαFc (10 mM) * 300 0 0. 00 1 Control Fc (10 mM) 400 Fc No Treatment * *p<0.01 10 SIRPaFc is Active Against a Diverse Panel of AML Samples Phagocytosis Assay SIRPaFc Control Fc 300 * ** 200 ** * ** ** ** * 100 *** NS *p<0.05 **p<0.01 ***p<0.001 0 80 55 80 9 56 90 7 17 90 4 54 90 3 59 90 6 65 90 0 7 10 65 01 10 16 06 10 22 08 57 Phagocytosis Index 400 AML Patient Characteristics AML Patient Patient Age Sex FAB Subtype Blast % 80559 68 M M5a 20 80567 69 F M5a 90 90174 41 M M4 NA 90543 33 M M2 82 90596 69 M M0 97 90650 67 M M1 90 90765 94 F M2 90 100116 66 F M4 NA 100622 65 F M4Eo 40 100857 73 M M2 10 11 SIRPaFc Induces Tumor Cell-Specific Phagocytosis CD47 Exp 381 Phagocytosis Index 300 250 * SIRPaFc Control Fc 200 150 100 50 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 Evaluating SIRPaFc Efficacy In Vivo Xenografts in NOD.SCID mice: the “gold standard” model in AML Intrafemoral injection AML cells from cancer patient SIRPαFc Measure leukemia by flow cytometry treatment NOD.SCID mouse Isolate bone marrow & spleen 13 SIRPaFc Has Potent Anti-leukemic Activity In Vivo Injected Bone Marrow % AML Engraftment 50 25 p=3x10-8 75 50 25 p=0.003 0 0 SIRPaFc SIRPaFc Control Fc Injected Bone Marrow % AML Engraftment % AML Engraftment 50 25 SIRPaFc Control Fc p=0.008 0 SIRPaFc Control Fc Control Fc Spleen 8 100 75 p=0.02 Non-Injected Bone Marrow 100 Patient #90191 1.1 1.0 0.9 0.8 0.7 0.6 0.5 0.4 0.3 0.2 0.1 0.0 % AML Engraftment % AML Engraftment 75 % AML Engraftment 100 100 Patient #90543 Spleen Non-Injected Bone Marrow 75 50 25 p=0.003 7 6 5 4 3 2 1 p=0.0004 0 0 SIRPaFc Control Fc SIRPaFc Control Fc Human SIRPaFc treatment: 8 mg/kg IP 3x/wk for 4 wks, starting 21d after engraftment 14 SIRPaFc Has Strong Anti-leukemic Activity Even At Low Doses 100 6 75 50 p<0.001 25 p<0.001 0 50 40 30 20 10 p<0.001 p<0.001 p<0.001 1 mg/kg SIRPaFc 5 mg/kg Control Fc 5 4 3 2 1 p<0.001 p<0.001 p<0.001 0.2 mg/kg 1 mg/kg 5 mg/kg Control Fc 0 0 0.2 mg/kg % AML Engraftment 60 % AML Engraftment % AML Engraftment Spleen Non-Injected Bone Marrow Injected Bone Marrow 0.2 mg/kg 1 mg/kg 5 mg/kg Control Fc SIRPaFc SIRPaFc Mouse SIRPaFc treatment: 0.2, 1 or 5 mg/kg IP 3x/wk for 4 wks, starting 21d after engraftment Mouse (NOD) SIRPαFc binds both human and mouse CD47 (antigen sink effect) 15 SIRPaFc Pre-Clinical Development Plan 2013 Q3 Q4 2014 Q1 NHP Study Q2 Q3 Q4 2015 Q1 Q2 Q3 Q4 NHP Study AML Xenograft Studies In Vitro Pharmacology Studies Manufacturing (CMC) Pre-IND GLP Toxicology IND Phase I Solid and Other Hematological Tumor Xenograft Studies 16 SIRPaFc Has Broad Clinical Potential Many different tumors express high levels of the CD47 “do not eat” signal High CD47 levels are often associated with disease progression Blood cancers AML ALL CLL CML DLBCL Follicular lymphoma Mantle cell lymphoma Multiple myeloma Solid cancers Bladder Brain Breast Colon Leiomyosarcoma Liver Melanoma Ovarian Prostate Pre-clinical program has been expanded to other liquid and solid oncology indications 17 SIRPaFc Triggers Macrophage-mediated Phagocytosis of Many Different Human Blood Cancer Cell Lines 100 120 100 80 60 * 40 20 *** 150 100 *** 50 NS * E N L -1 C1R J u rk a t *** 60 40 * P h a g o c y to s is In d e x P h a g o c y to s is In d e x Ly1 N a m a lw a R a ji *** 60 ** 40 NS *** 20 A M L -2 H L -6 0 K G -1 T H P -1 T F -1 SIRPaFc Control Fc 70 80 *** 60 50 40 ** 30 *** 20 NS 10 0 0 K562 80 M u lt ip le M y e lo m a CML 20 *** 0 0 0 P h a g o c y to s is In d e x 200 *** P h a g o c y to s is In d e x P h a g o c y to s is In d e x 140 AML B Lym phom a ALL K U812 M M 1 .s 8226 H929 ***p<0.0001 **p<0.01 *p<0.05 U266 18 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 will be evaluating SIRPαFc in preclinical combination studies 19 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”) 20 SIRPaFc Binds Very Poorly to Human RBCs Compared to CD47 Antibodies RBCs CD47 mAbs 2000 1500 1000 500 CD47 mAbs 350 Geometric Mean Geometric Mean 2500 AML-2 300 250 200 150 100 50 R IC 12 6 C C 2C 6 SI R Pa Fc 12 0 B 6H B c 6 c 6 aF 12 lF 2C P o C C I R tr C R SI B on C 6H 12 B 3 2D 2D 3 0 Binding of commercially available anti-CD47 mAbs and SIRPαFc to human RBCs (n=14 donors) and AML-2 cells 21 Upcoming Milestones AACR presentation – Q2’14 GMP master cell bank generation – Q3’14 CMC engineering run – Q3’14 NASDAQ listing Q4’14 Pre-IND meeting with the FDA – Q4’14 (scheduled Jan 2015) Initiate GLP toxicology studies – Q1’15 Production of GMP lot – Q2’15 IND filing – Q3’15 Preclinical data supporting additional clinical indications – Q4’15 22 Trillium Therapeutics Inc. (NASDAQ:TRIL/TSX:TR) is an immuno-oncology company dedicated to the discovery and development of novel and innovative cancer therapies.
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