The Tumor Microenvironment Company

Transcription

1 The Tumor Microenvironment Company June 2018

2 Legal Disclaimer This presentation includes forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. All statements contained in this presentation other than statements of historical facts, including statements regarding future results of operations and financial position of Surface Oncology, Inc. ( we, us or our ) our business strategy and plans, the preclinical and clinical development of our product candidates and our objectives for future operations, are forward-looking statements. The words anticipate, believe, continue, estimate, expect, intend, may, will and similar expressions are intended to identify forward-looking statements. We have based these forward-looking statements largely on our current expectations and projections about future events and financial trends that we believe may affect our financial condition, results of operations, business strategy, clinical development, short-term and long-term business operations and objectives and financial needs. These forward-looking statements are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward looking statements. These risks and uncertainties include the timing, progress, and results of preclinical studies and clinical trials for SRF231 and our other product candidates, the timing and likelihood of regulatory approvals and those risks identified and discussed in the section titled Risk Factors, set forth in our Quarterly Report on Form 10-Q and in our other SEC filings. Moreover, we operate in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for our management to predict all risks, nor can we assess the impact of all factors on our business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements we may make. Although we believe that the expectations reflected in the forward-looking statements are reasonable, we cannot guarantee future results, levels of activity, performance, achievements or events and circumstances reflected in the forward-looking statements will occur. We are under no duty to update any of these forward-looking statements after the date of this presentation to conform these statements to actual results or revised expectations, except as required by law. You should, therefore, not rely on these forward-looking statements as representing our views as of any date subsequent to the date of this presentation. Moreover, except as required by law, neither we nor any other person assumes responsibility for the accuracy and completeness of the forward-looking statements contained in this presentation. By attending or receiving this presentation you acknowledge that you will be solely responsible for your own assessment of the market and our market position and that you will conduct your own analysis and be solely responsible for forming your own view of the potential future performance of our business. 2

3 Company Overview 3

4 Next-Generation Immunotherapies Targeting the Tumor Microenvironment to Bring Hope to Those Affected by Cancer 4

5 Company Highlights Robust Product- Generating Capabilities Deep understanding of tumor microenvironment biology Robust antibody generation and translational capabilities Broad Immuno-Oncology Pipeline Multi-faceted approach to targeting the tumor microenvironment Seven next-generation immunotherapy programs SRF231 (CD47) and SRF373 (CD73) are both in Phase 1 Strong Financial Position and Partners Strong cash position, ~$203 million 1 as of Mar 31, 2018, no debt Transformative strategic partnership with Novartis ~$175 million 2 received to date Total potential payments to Surface of up to ~$1.2 billion, plus tiered royalties Outstanding Team Strong leadership team with significant product development experience World-class scientific advisors highly engaged with internal team (1) Net proceeds of ~$112 million from IPO and concurrent private placement in April (2) Includes aggregate equity investments of $25 million. 5

6 A Broad Approach To Target the Immunosuppressive Tumor Microenvironment Activate Macrophages (CD47) Block Suppressive Metabolites and Cytokines (CD73, CD39, IL-27) Deplete Regulatory T Cells Activate Natural Killer Cells 6

7 Scientific Advisory Board World-Class and Highly Engaged Sasha Rudensky, PhD Professor & Chair of Immunology Director Ludwig Center for Immunotherapy, MSKCC Arlene Sharpe, MD, PhD Professor, Harvard HMS, Dana Farber, CoStim co-founder Elliott Sigal, MD, PhD Former CSO, EVP of BMS Venture Partner & Senior Advisor, NEA David Tuveson, MD, PhD Professor and Director, NCI-Designated Cancer Center at Cold Spring Harbor Laboratory John Wherry, PhD Professor & Director, Institute for Immunology, University of Pennsylvania John Stagg, PhD Professor, Cancer Institute of Montreal Christopher Hunter, PhD Professor, University of Pennsylvania Carla Rothlin, PhD Associate Professor, Yale University 7

8 Broad Portfolio Targeting the Tumor Microenvironment Four Clinical-Stage Programs Anticipated by 2020 TME Component Discovery In vivo Validation Toxicology Phase 1 Worldwide Rights CD47 SRF231 Surface Macrophages Surface CD73 SRF373 Novartis 1 Cytokines & Metabolites CD39 SRF617 Surface IL-27 SRF388 Surface 2 Regulatory T Cells Surface 2 Natural Killer Cells Surface (1) Novartis has WW development and commercial rights to this program. (2) Novartis has the right to purchase an option for this program. 8

9 World Class Leadership Team Management Team With A Strong Track Record of Success Jeff Goater Vito Palombella, PhD Chief Executive Officer Chief Scientific Officer Bob Steininger Rob Ross, MD Jessica Fees Pam Holland, PhD SVP, CMC Vice President, Finance Dave Konciak Vice President, BD & Strategy Chief Medical Officer Vice President, Cancer Biology Lisa McGrath Vice President, Human Resources 9

10 Targeting CD47 To Activate Macrophages Within The TME SRF231 10

11 Lead Candidate SRF231 - an Antibody Targeting CD47 High affinity, fully human antibody against human CD47 Promotes robust tumor cell phagocytosis Potent in vivo anti-tumor activity in preclinical models, both as monotherapy and in combination No observed RBC hemagglutination in vitro Initial Phase 1 data expected in H1:2019 Program wholly owned by Surface 11

12 CD47 Overexpression is an Important Tumor Immune Escape Mechanism Key tumor immune escape mechanism tumor cells overexpress CD47 on their surface to avoid macrophage phagocytosis Macrophage o CD47 interacts with SIRPa, as well as other proteins such as thrombospondin and integrins By blocking CD47, the tumor cell is vulnerable to macrophage attack SIRPa CD47 Tumor 12

13 SRF231 Reduces Tumor Burden in Ovarian Cancer Model Tumor Burden Overall Survival Isotype d52 SRF231 d52 Reduced tumor burden in SRF231-treated mice NOTE: SRF231 is NOT active in the model when tumor is implanted s.c. All SRF231-treated mice alive at day 70 SRF231: 100 mg/mouse i.p. 3x/wk for 3 wk SKOV3-luc tumors implanted IP 13

14 SRF231 Has Demonstrated Anti-Tumor Activity as a Monotherapy and in Combination with Rituximab AML 1 Multiple Myeloma 2 Burkitt Lymphoma 3 DLBCL 4 Combination Monotherapy Control SRF231 Rituximab Rituximab + SRF231 (1) MV-411 model (2) RPMI-8226 model (3) Raji model (4) SU-DHL-4 model. 14

15 SRF231 Does Not Appear to Induce Hemagglutination Hemagglutination Positive Control Aggregation (%) Antibody A SRF231 1 Antibody (mg/ml) Negative Control (1) Antibody A is an analog of a competitor antibody. 15

16 SRF231 Phase 1 Trial Design Multiple Myeloma T-Cell Lymphoma Monotherapy Expansions (20 patients per cohort) AML/MDS Ovarian Cancer Single Agent Dose Escalation (estimated patients) Combination Expansions (to be added once MTD is determined) Solid Tumor Biopsy Cohort Several Combinations Are Being Considered With Currently Approved Cancer Therapies We are conducting this trial in multiple sites in the United States and Canada 16

17 Targeting the Adenosine Axis for Immune System Activation SRF373 and SRF617 17

18 Targeting the Adenosine Axis to Activate Immune System Extracellular adenosine suppresses tumor immunity Extracellular ATP stimulates innate immunity ATP AMP Adenosine NK Cell Cell Stress T Cell Cell Damage CD39 TUMOR CD73 Myeloid Cell Macrophage Cell Death Dendritic Cell 18

19 SRF373 an Antibody Targeting CD73 High affinity, fully human antibody against human CD73 Potent inhibition of CD73 enzymatic activity Significant reduction of adenosine and increased proliferation of T Cells Strong synergistic preclinical in vivo anti-tumor activity in combination with checkpoint inhibitors (PD-1) IND submitted in February 2018 Licensed worldwide rights to Novartis 19

20 Compelling Synergistic Activity With PD-1 Treatment Control PD-1 CD73 Combination Tumor volume (mm 3 ) Days after inoculation CT26 Syngeneic Model No tumor growth when cured animals are re-challenged with tumor 20

21 SRF617 an Antibody Targeting CD39 High affinity, fully human antibody against human CD39 Significant reduction of adenosine and increased levels of ATP leads to increased T Cell proliferation and dendritic cell maturation Potent inhibitor of enzymatic activity Initiation of IND-enabling studies anticipated in 2018 Program wholly owned by Surface 21

22 SRF617 Inhibits CD39 Enzymatic Activity & Stimulates Dendritic Cell Maturation Inhibition Of Enzymatic Activity Dendritic Cell Maturation Donor 1 Donor 2 Donor 3 Assays performed on Human MOLP8 Myeloma Cells Dendritic cell maturation was determined by measuring levels of CD86 22

23 Targeting IL-27 to Enhance Immune Activity in the TME SRF388 23

24 Overview of SRF388 a Potentially First-in-Class Antibody Targeting IL-27 SRF388 identified from a panel of high affinity, fully human antibodies against both subunits of IL-27 Reduction of IL-27 driven immunosuppression Strong translational hypothesis in some tumor types Initiation of IND-enabling studies anticipated in 2018 Novartis has right to purchase an option 24

25 IL-27 Plays an Important Role in Immunosuppression T Reg Function Dendritic Cell T Cell Exhaustion OR IL-27 T Cell Repression Macrophage Dendritic Cell Suppression 25

26 SRF388 Blocks IL-27 Induced Immune Exhaustion PD-L1 In Monocytes TIM3 In Monocytes PD-L1 In CD8 + T Cells Mean Fluorescence Intensity Control IL-27 IL-27 + SRF388 Positive Expression (%) Control IL-27 IL-27 + SRF388 Mean Fluorescence Intensity Control IL-27 IL-27 + SRF388 26

27 SRF388 Plus PD-1 Inhibition Increases Inflammatory Cytokine Production TNFa IL-6 Concentration % (pg/ml) Concentration % (pg/ml) Control PD-1 SRF388 SRF388 + PD-1 Control PD-1 SRF388 SRF388 + PD-1 27

28 Upcoming Milestones & Summary 28

29 Upcoming Milestones Four Clinical-Stage Programs Anticipated by 2020 Program Candidate Key Near Term Milestones CD47 SRF231 Initial Phase 1 Results CD73 SRF373 Initial Phase 1 Results CD39 SRF617 Initiate IND-enabling Studies IL-27 SRF388 Initiate IND-enabling Studies Novartis Option Purchase 29

30 Summary Robust Product-Generating Capabilities Broad Immuno-Oncology Pipeline Strong Financial Position and Partners Outstanding Team 30