8-K

 

 

UNITED STATES

SECURITIES AND EXCHANGE COMMISSION

WASHINGTON, D.C. 20549

 

 

FORM 8-K

 

 

CURRENT REPORT

Pursuant to Section 13 or 15(d)

of the Securities Exchange Act of 1934

Date of Report (Date of Earliest Event Reported): November 18, 2019

 

 

SURFACE ONCOLOGY, INC.

(Exact name of registrant as specified in its charter)

 

 

 

Delaware   001-38459   46-5543980

(State or other jurisdiction

of incorporation)

 

(Commission

File Number)

  (I.R.S. Employer
Identification No.)
50 Hampshire Street, 8th Floor
Cambridge, MA
  02139
(Address of principal executive offices)   (Zip Code)

Registrant’s telephone number, including area code: (617) 714-4096

Not Applicable

Former name or former address, if changed since last report

 

 

Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions:

 

Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)

 

Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)

 

Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))

 

Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))

Securities registered pursuant to Section 12(b) of the Act:

 

Title of each class

 

Trading

Symbol(s)

 

Name of each exchange

on which registered

Common stock, $0.0001 par value per share   SURF   Nasdaq Global Market

Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).

Emerging growth company  ☒

If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act.  ☒

 

 

 


Item 7.01.

Regulation FD Disclosure.

On November 18, 2019, Surface Oncology, Inc. will present at its Research and Development Day. The slide presentation to be presented at the Research and Development Day is furnished as Exhibit 99.2 to this Form 8-K and is incorporated by reference herein.

The information responsive to Item 7.01 of the Form 8-K, including Exhibit 99.1 and Exhibit 99.2 attached hereto, is intended to be furnished and shall not be deemed “filed” for purposes of Section 18 of the Exchange Act, or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act or the Exchange Act, except as expressly set forth by specific reference in such filing.

 

Item 9.01.

Financial Statements and Exhibits.

(d) Exhibits

 

99.1    Press Release of Surface Oncology, Inc. dated November 18, 2019
99.2    Presentation dated November 18, 2019

 

2


SIGNATURE

Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.

 

Date: November 18, 2019     SURFACE ONCOLOGY, INC.
    By:  

/s/ J. Jeffrey Goater

      J. Jeffrey Goater
      President and Chief Executive Officer
EX-99.1

Exhibit 99.1

Surface Oncology Announces Filing of IND for CD39 Targeted Antibody Candidate, SRF617, at Inaugural R&D Day

Details clinical plans for phase 1/1b clinical studies of SRF617 and SRF388 in patients with advanced solid tumors

Shares preclinical data for new, CD112R targeted antibody candidate, SRF813, and its ability to promote NK/T cell activation

CAMBRIDGE, Mass., Nov. 18, 2019 — Surface Oncology (Nasdaq: SURF), a clinical-stage immuno-oncology company developing next-generation immunotherapies that target the tumor microenvironment, today announced that it has submitted an Investigational New Drug (IND) application to the U.S. Food and Drug Administration (FDA) to support the initiation of a phase 1/1b clinical study of SRF617 (targeting CD39). At an inaugural R&D day today, the Company will share progress across its portfolio including clinical development plans for SRF617 and SRF388 (IL-27), and preclinical data supporting its new development candidate, SRF813, which targets the recently identified checkpoint protein CD112R to promote natural killer (NK) and T cell activation.

“We welcome this opportunity to dive into the compelling data underpinning our lead programs’ differentiated approaches to overcoming the immunosuppressive tumor microenvironment, as we work to break through and bring the benefits of immunotherapy to more patients suffering with cancer,” said Jeff Goater, chief executive officer of Surface Oncology. “We look forward to furthering the incredible scientific work of our team with the initiation of our phase 1 clinical trials for both SRF617 and SRF388 in early 2020.”

SRF617 is a fully human anti-CD39 antibody designed to promote anti-tumor immunity through a dual mechanism of reducing immunosuppressive adenosine and driving the extracellular accumulation of immunostimulatory ATP within the tumor microenvironment. Due to this dual mechanism, Surface Oncology believes CD39 is the most promising therapeutic target on the adenosine axis, a notable immunosuppressive pathway. The Company’s planned phase 1/1b study will evaluate SRF617 in patients with advanced solid tumors both as a monotherapy and in combination with other cancer therapies.

Surface Oncology also anticipates the filing of an IND for SRF388 before the end of 2019, with the subsequent initiation of a phase 1/1b clinical study in early 2020. The Company has identified particular tumor types, including hepatocellular and renal cell carcinoma, where IL-27 appears to play an important role in tumor progression. Furthermore, Surface Oncology has identified a potential biomarker associated with IL-27 that may be useful in helping identify patients most likely to respond to SRF388, which has the potential to be the first IL-27 targeted antibody to enter clinical trials.

“The Surface team is energized by the compelling preclinical datasets across our programs, and is excited about advancing SRF617 and SRF388 into clinical development,” said Rob Ross, M.D., chief medical officer of Surface Oncology. “Both SRF617 and SRF813 have best-in-class potential related to targeting the adenosine axis and NK cells, respectively, and we believe SRF388 has the ability to inhibit the highly immunosuppressive cytokine IL-27, which gives it the potential to be a potent therapeutic. We look forward to providing clinical updates from the SRF388 and SRF617 programs in late 2020.”

Surface Oncology’s preclinical data demonstrates that SRF813 increases NK and T cell activity, has strong, differentiated preclinical efficacy and promotes immunological memory. Currently, there are no


therapeutic strategies to overcome resistance to T cell checkpoint inhibitor blockade, and emerging data highlights the potential of NK cell-based therapies, such as SRF813, to overcome checkpoint inhibitor resistance.

Surface Oncology recently presented data from a number of its programs, including SRF388 and SRF617, at the Society for the Immunotherapy of Cancer’s (SITC) 34th Annual Meeting in National Harbor, MD. These can be viewed on the Pipeline page of the Surface Oncology corporate website.

The R&D Day presentations and a live broadcast will be viewable from 8:15am ET at investors.surfaceoncology.com.

About Surface Oncology:

Surface Oncology is an immuno-oncology company developing next-generation antibody therapies focused on the tumor microenvironment with lead programs targeting CD73, CD39, IL-27 and CD112R. Surface’s novel cancer immunotherapies are designed to achieve a clinically meaningful and sustained anti-tumor response and may be used alone or in combination with other therapies. The Company has a pipeline of six novel immunotherapies and a strategic collaboration with Novartis focused on NZV930 (CD73). For more information, please visit www.surfaceoncology.com.

Cautionary Note Regarding Forward-Looking Statements:

Certain statements set forth in this press release constitute “forward-looking” statements within the meaning of the Private Securities Litigation Reform Act of 1995, as amended. Forward-looking statements can be identified by terms such as “believes,” “expects,” “plans,” “potential,” “would” or similar expressions and the negative of those terms. These forward-looking statements are based on Surface Oncology’s management’s current beliefs and assumptions about future events and on information currently available to management.

Forward-looking statements involve known and unknown risks, uncertainties and other factors that may cause Surface Oncology’s actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. These risks include, but are not limited to, risks and uncertainties related to Surface Oncology’s ability to successfully develop SRF388, SRF617, SRF813 and its other product candidates through current and future milestones or regulatory filings on the anticipated timeline, if at all, the therapeutic potential of Surface Oncology’s product candidates, the risk that results from preclinical studies or early clinical trials may not be representative of larger clinical trials, the risk that Surface Oncology’s product candidates, including SRF388, SRF617 and SRF813, will not be successfully developed or commercialized, and the risks related to Surface Oncology’s dependence on third parties in connection with its manufacturing, clinical trials and preclinical studies. Additional risks and uncertainties that could affect Surface Oncology’s future results are included in the section titled “Risk Factors” in our Annual Report on Form 10-K for the year ending December 31, 2018, which is available on the Security and Exchange Commission’s website at www.sec.gov and Surface Oncology’s website at www.surfaceoncology.com.

Additional information on potential risks will be made available in other filings that Surface Oncology makes from time to time with the Securities and Exchange Commission. In addition, any forward-looking statements contained in this press release are based on assumptions that Surface Oncology believes to be reasonable as of this date. Except as required by law, Surface Oncology assumes no obligation to update these forward-looking statements, or to update the reasons if actual results differ materially from those anticipated in the forward-looking statements.


Contacts:

Endurance Advisors

Pete Rahmer

prahmer@enduranceadvisors.com

415-515-9763

Ten Bridge Communications

Tom Donovan

tom@tenbridgecommunications.com

857-559-3397

EX-99.2

Slide 1

Analyst and Investor R&D Day November 18, 2019 Exhibit 99.2


Slide 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, SRF388, SRF617 and SRF813, 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 Annual Report on Form 10-K 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.


Slide 3

Today’s Agenda 8:15 – 8:35am Welcoming remarks and overview of corporate updates, strategy and vision Jeff Goater, President & CEO 8:35 – 9:30am Immunotherapy in Cancer: Immune Profiling, Mechanisms and Therapeutic Opportunities John Wherry, Ph.D. 9:30 - 9:45am Break 9:45 – 10:15am SRF617: A novel, potential best-in-class, anti-CD39 antibody with a dual mechanism of action Robert Ross, M.D., Chief Medical Officer 10:15 – 10:45am SRF388: A first-in-class antibody targeting genetically distinct tumors Vito Palombella, Ph.D., Chief Scientific Officer 10:45 – 11:00am Introduction of new antibody targeting CD112R Pamela Holland, Ph.D., VP, Cancer Biology 12:05pm Conclusion/Lunch 12:00pm Closing Remarks Jeff Goater, President & CEO 11:00am – 12:00pm Q&A All Speakers


Slide 4

Recent Corporate Highlights Filed IND for SRF617 (CD39) SRF388 (IL-27) IND on track to be filed by end of this year New clinical candidate announced: SRF813, targeting CD112R Multiple poster presentations at SITC annual meeting Cash at end of Q3 2019: $111.8 million


Slide 5

BREAK THROUGH Financial resources and strategic partners provide STRONG FOUNDATION On a mission to dramatically IMPROVE CURE RATES FOR CANCER Proven leadership and UNIQUELY COLLABORATIVE SCIENTIFIC ADVISORS Deep biological expertise across the TUMOR MICROENVIRONMENT Focus on differentiated targets bridging ADAPTIVE AND INNATE IMMUNITY


Slide 6

Block Suppressive Metabolites and Cytokines Activate Macrophages Deplete Regulatory T Cells Activate Natural Killer Cells Broad Approach Targeting the Immunosuppressive Tumor Microenvironment


Slide 7

Characteristics of a Great Next-Generation I/O Target 1. Broad immune system engagement (innate & adaptive) 2. Biologic relevance and activity in the TME 3. Targeted translational approach


Slide 8

Deep Collaboration With Renowned Advisors Oncology Immunology Translational science Clinical development A break through philosophy Transformative impact for patients Collective learning SCIENTIFIC ADVISORY BOARD SURFACE TEAM Deep expertise in: Commitment to: Sasha Rudensky, PhD Carla Rothlin, PhD John Stagg, PhD Stephen Hodi, MD Arlene Sharpe, MD, PhD David Tuveson, MD, PhD Christopher Hunter, PhD Elliott Sigal, MD, PhD John Wherry, PhD


Slide 9

Genome- & Disease-wide database analysis Strategic screening of new targets Target identification & validation SOSAS Workflow SOSAS: Proprietary Computational Tool for Target ID Surface Oncology Survival Analysis Suite Proprietary statistical methodology for new target discovery Leverages large datasets of gene expression and clinical outcomes Allows for systematic screening of diverse target classes, improving prioritization of translational strategies  


Slide 10

Broad Portfolio Targeting the Tumor Microenvironment (1) (1) Novartis has option remaining on the program


Slide 11

Overview of Ongoing Phase 1 Trial NZV930 Single Agent Dose Escalation NZV930 with PDR001 (Anti-PD-1) NZV930 with NIR178 (A2AR antagonist) NZV930, NIR178 & PDR001 (1) NSCLC, TNBC, Ovarian Cancer, MSS Colorectal, Pancreatic Ductal Adenocarcinoma, Renal Cell Carcinoma Enrollment spanning three combination expansion arms Overview of NZV930 Potential Best-in-Class CD73 Targeted Antibody Phase 1 initiated in June 2018 Target enrollment ~344 patients  Currently enrolling in 7 countries Currently targeting 6 solid tumor types(1) Novartis licensed WW development & commercial rights in January 2016 Potent inhibitor of CD73 enzymatic activity Significant reduction of adenosine and increased proliferation of T cells Total cumulative milestones of $500M+ Tiered royalties on annual net sales ranging from high single-digit to mid-teens percentages


Slide 12

Overview of Lead, Wholly-Owned Product Programs to be Reviewed Today SRF617 (CD39) Potent inhibitor of CD39 enzymatic activity Best target on the adenosine axis Dual mechanism: reduction of immuno-suppressive adenosine and increased levels of immunostimulatory extracellular ATP IND filed in November 2019 SRF388 (IL-27) Pioneering new biology Highly immuno-suppressive cytokine in TME Targeted translational hypothesis in RCC and HCC IND filing anticipated in December 2019 SRF813 (CD112R) Increased activity of NK cells and T cells Strong, differentiated preclinical activity in vitro and in vivo Strong T cell memory response seen in preclinical models


Slide 13

Overview of Lead, Wholly-Owned Product Programs to be Reviewed Today SRF617 (CD39) Potent inhibitor of CD39 enzymatic activity Best target on the adenosine axis Dual mechanism: reduction of immuno-suppressive adenosine and increased levels of immunostimulatory extracellular ATP IND filed in November 2019 SRF388 (IL-27) Pioneering new biology Highly immuno-suppressive cytokine in TME Targeted translational hypothesis in RCC and HCC IND filing anticipated in December 2019 SRF813 (CD112R) Increased activity of NK cells and T cells Strong, differentiated preclinical activity in vitro and in vivo Strong T cell memory response seen in preclinical models


Slide 14

Overview of Lead, Wholly-Owned Product Programs to be Reviewed Today SRF617 (CD39) Potent inhibitor of CD39 enzymatic activity Best target on the adenosine axis Dual mechanism: reduction of immuno-suppressive adenosine and increased levels of immunostimulatory extracellular ATP IND filed in November 2019 SRF388 (IL-27) Pioneering new biology Highly immuno-suppressive cytokine in TME Targeted translational hypothesis in RCC and HCC IND filing anticipated in December 2019 SRF813 (CD112R) Increased activity of NK cells and T cells Strong, differentiated preclinical activity in vitro and in vivo Strong T cell memory response seen in preclinical models


Slide 15

Emerging Trends and Observations in T cell Exhaustion and the Tumor Microenvironment   John Wherry, Ph.D. Professor, University of Pennsylvania Chair, Department of Systems Pharmacology and Translational Therapeutics Richard and Barbara Schiffrin President’s Distinguished Professor Director, Institute for Immunology Co-Director of the Parker Institute for Cancer Immunotherapy at Penn Surface Oncology scientific co-founder, member of SAB


Slide 16

Immunotherapy in Cancer: Immune Profiling, Mechanisms and Therapeutic Opportunities John Wherry, Ph.D.


Slide 17

Break 9:30 – 9:45


Slide 18

SRF617 (CD39): Engaging Innate and Adaptive Immunity IND filed Planned Phase 1/1b clinical study to enroll patients with advanced solid tumors Initial clinical update in late 2020


Slide 19

Characteristics of a Great Next Generation I/O Target 1. Broad immune system engagement (innate & adaptive) 2. Biologic relevance and activity in the TME 3. Targeted translational approach


Slide 20

SRF617 Engages Both the Innate and Adaptive Immune System ATP AMP Adenosine Cell stress/ damage/ death CD39 CD73 Innate and adaptive immune response (adaptive) SRF617 SRF617 Reduces Plasma Adenosine Levels in Tumor-Bearing Mice


Slide 21

21 ATP AMP Adenosine Cell stress/ damage/ death CD39 CD73 Innate and adaptive immune response (adaptive) SRF617 SRF617 Mediated CD39 Blockade is Immunostimulatory SRF617 Stimulates Dendritic Cells, A Key Component of the Innate Immune System


Slide 22

22 Cell stress/ damage/ death (innate) ATP AMP Adenosine CD39 CD73 Innate and adaptive immune response SRF617 SRF617 Monotherapy or Combination with Gemcitabine Leads to Increased ATP Levels in Human Pancreatic Cancer Cultures * SRF617 Engages Both the Innate and Adaptive Immune System


Slide 23

SRF617 Stimulates Key Components of the Innate Immune System 23 Cell stress/ damage/ death (innate) ATP AMP Adenosine CD39 CD73 Innate and adaptive immune response SRF617 SRF617 Engages Both the Innate and Adaptive Immune System


Slide 24

SRF617 Modulates Macrophage Trafficking and Tumor Infiltrate 24 Tumor macrophage infiltration MOLP8 Xenograft Model F4/80 IHC Cell stress/ damage/ death (innate) ATP AMP Adenosine CD39 CD73 Innate and adaptive immune response SRF617 SRF617 Engages Both the Innate and Adaptive Immune System


Slide 25

Conclusion: A Highly Active Mechanism 25 SRF617 Single Agent Activity in Xenograft MOLP8 In Vivo Model Murine Anti-CD39 Surrogate Cooperates with Anti-PD1 in CT26 Model, Increasing Cures Days on Study 10/18 CR 4/16 CR (Rechallenge)


Slide 26

Clear Approach to Measuring Both CD39 Target Occupancy and Enzymatic Inhibition by SRF617 in Circulation 26 Enzymatic Inhibition + SRF617 Target Occupancy % Target Occupancy % Enzymatic Inhibition


Slide 27

SRF617 Inhibits CD39 Enzymatic Activity in TME of Treated Mice – Key Assay for Human POC 27 Untreated 4 h 24 h 72 h + SRF617


Slide 28

Key Phase 1 Bioassays to Assess Biologic POC 28 PBMC Target Occupancy CD39 Enzymatic Activity by IHC Allows for Direct Measurement of CD39 Inhibition within the TME Binding of SRF617 to PBMCs is Highly Correlated to Enzymatic Inhibition


Slide 29

Patterns of CD39 TME Expression Lead to Translational Hypotheses in Tumor Types with High Clinical Need CD39 TIL expression CD39/CK Gastric CA CD39 CD39 stromal expression Pancreatic CA CD39/CK 29


Slide 30

Stromal Expression – Targeting Chemo Combinations in Tumor Types with High Stromal Staining SRF617 + Doxorubicin In MOLP-8 SRF617 + Paclitaxel In NSCLC Xenograft Intense CD39 Stromal Staining in NSCLC Patient Sample Courtesy of Kurt Schalper, MD *p<0.05 30 * Dosing Ended


Slide 31

TIL Expression - CD39 is Highly Expressed on TILs From Multiple Tumor Types and Associated with an Exhausted, Dysfunctional State % CD39 + PBMC CRC RCC PBMC – N=6 (Healthy Donors) CRC – N=4 RCC – N=5 31 CD39 Expression Increases in TILs CD39+ TILs are Exhausted and Dysfunctional CD39 Expression Duhen et. al., Nature Communications, July 2018 Li et. al. Cell, February 2019


Slide 32

TIL Expression – CD39 Expression Increases After PD-(L)1 Exposure *Surface data 5 individual PBMC donors -/+ Nivolumab at 10ug/ml 96-Hour incubation Cell types and %CD39 expression determined by flow *Clinical data, Corvus, SITC 2017 CD39 expression analysis from RCC and NSCLC screening biopsies Resistant pts treated > 3 months with anti-PD-(L)1 (atezolizumab) CD73 and A2AR also elevated in resistant population (not shown) 32 From Patients… In Vitro…


Slide 33

Our Approach is to Identify and Revitalize These T Cells Revitalize Identify Combo with A2A 10/18 CR 4/16 CR Combo with PD-1 33 Endometrial CA Gastric CA


Slide 34

SRF617 Clinical Development Plan Phase 1/1b 34 Dose Escalation: Patients with advanced solid tumors Establish safe monotherapy dose (accelerated & 3+3 design) Establish safe combination therapy dose(s); anticipate staggered start after monotherapy Biopsy Expansion Cohort: Evaluate on-target tumor tissue changes in enzymatic activity SFR617 Monotherapy Dose Escalation Biopsy Expansion Cohort SRF617 + Gem/Abraxane Combination SRF617 + αPD-1 Combination Additional combination cohorts to be considered RP2D Enables start of RP2 in Pancreatic Cancer Enables start of RP2 in Gastric Cancer Phase 2 RP2D RP2D


Slide 35

SRF617 – A Potent Inhibitor of the Adenosine Axis 1. Broad immune system engagement (innate & adaptive) 2. Biologic relevance and activity in the TME 3. Targeted translational approach Intrinsic properties of SRF617 Single-digit nanomolar monovalent affinity to human CD39 Potent inhibitor of hu/cyno CD39 enzymatic activity Reduces adenosine and stabilizes ATP within the TME, leading to broad immune system activation Functional properties of SRF617 Augments T cell proliferation and DC maturation in the presence of ATP Monotherapy and combination activity in murine xenograft models Promotes macrophage infiltration Blocks tumor CD39 enzymatic activity and reduces adenosine Assays in place to demonstrate biologic POC early in development SRF617 Bench to Bedside Patterns of CD39 expression lead to clear clinical hypotheses Strong stromal expression - chemotherapy combinations Strong TIL expression - I/O combinations Evidence of CD39 activity in PD-(L)1 pre-treated population Multi-arm, single agent and combination Phase 1 to assess these hypotheses rapidly 35


Slide 36

SRF388 (IL-27): Potent Inhibition of an Immunosuppressive Cytokine With Potential Prognostic Biomarker IND expected by end of 2019 Biology supports highly targeted clinical strategy Initial clinical update in late 2020


Slide 37

Five Key Takeaways from Today’s Presentation The cytokine IL-27 is a regulator of immune suppression Strong translational hypotheses in RCC and HCC SRF388 is a novel, first-in-class anti-IL-27 antibody SRF388 was selected by leveraging a deep understanding of IL-27 and TME biology  IND to be filed this Quarter 2019


Slide 38

IL-27 is a Cytokine Involved in Resolving T-cell Mediated Inflammation IL-27 Receptor p28 Jak2 Jak1 STAT3 STAT1 Inflammatory Cytokines TNF⍺ +IL-27 Control EBI3 IL-27 Ligand Inhibitory Receptors on Immune Cells T N F ⍺ p g /m L Chihara et al, Nature 558, 2018 DeLong et al, Immunohorizons 3, 2019


Slide 39

Pregnancy, an Immune-tolerant State, is Associated with Elevated IL-27 Coulomb L’Hermine 2007 Detection of EBI3 in Serum Detection of Localized IL-27 Heterodimer in Placenta


Slide 40

p28 is the Limiting Subunit for IL-27 Activity Serum derived EBI3 pairs with p28 to form bioactive IL-27 Only the p28-EBI3 heterodimer binds to IL-27RA with high affinity; biological activity of either subunit by itself has not been observed p28 EBI3 IL-27


Slide 41

p28 is the Limiting Subunit for IL-27 Activity Media EBI3 Norm Serum Preg Serum EBI3 Norm Serum Preg Serum + p28 rIL-27 Serum derived EBI3 pairs with p28 to form bioactive IL-27 Only the p28-EBI3 heterodimer binds to IL-27RA with high affinity; biological activity of either subunit by itself has not been observed p28 EBI3 IL-27 pSTAT1 Signaling in U937 cells


Slide 42

EBI3 and p28 mRNA are Expressed in Tumors HNSCC p28/EBI3 dual ISH with RNAscope EBI3 p28


Slide 43

Levels of EBI3 are Elevated in Serum from Cancer Patients


Slide 44

Levels of EBI3 are Elevated in Serum from Cancer Patients


Slide 45

Gene Signature and Plasma EBI3 Protein Levels in Renal Cell Carcinoma Patients Predicts Poor Outcome IL-27 T cell gene signature identified in a subset of RCC patients RCC U. Montreal Cohort- J. Stagg 187 RCC Plasma samples


Slide 46

All Components of the IL-27 Complex are Associated with Poor Prognostic Outcomes in Renal Cell Carcinoma RCC (KIRC) Genome-wide Survival Statistics Genome-wide Hazard Ratios Better Worse


Slide 47

IL-27 Induces the Expression of PD-L1 on Renal Cell Carcinoma Tumor Cells PD-L1 Surface Expression ACHN line (RCC) treated with IL-27 for 72 h


Slide 48

Elevated mRNA Expression of p28 in Hepatocellular Carcinoma P28 Expression (TCGA)


Slide 49

Elevated mRNA Expression of p28 in Hepatocellular Carcinoma Liver P28 Expression (TCGA)


Slide 50

Vision Statement for SRF388 SRF388, a first-in-class anti-IL-27 antibody, will substantially improve efficacy outcomes in patients with clear cell RCC and HCC who have high levels of circulating EBI3.


Slide 51

Our Clinical Candidate: Anti-p28 Antibody SRF388 Single-digit picomolar affinity to p28 subunit of IL-27 Prevents IL-27 from engaging with IL-27R Blocks IL-27 mediated Stat1 phosphorylation Blocks IL-27 driven immunosuppression ü SRF388 IL-27 IL-27 Binding and Downstream Signaling ü ü ü


Slide 52

SRF388 Restores Cytokine Production in Combination with αPD-1 in Presence of rIL-27 in Healthy Donor PBMCs IFNγ, TNFα, IL-17 T cell PD1 Control ⍺PD-1 IL-27 + ⍺PD-1 Anti-PD-1 IL-27 Similar effects observed with IL-17 and TNFa


Slide 53

IL-27 SRF388 Restores Cytokine Production in Combination with αPD-1 in Presence of rIL-27 in Healthy Donor PBMCs IFNγ, TNFα, IL-17 T cell PD1 Control ⍺PD-1 IL-27 + ⍺PD-1 IL-27 + ⍺PD-1 + SRF388 Anti-PD-1 SRF388 Anti-PD-1 Similar effects observed with IL-17 and TNFa


Slide 54

SRF388 Blocks IL-27 Induced Inhibitory Receptor Expression in Primary Immune Cells TIGIT PD-L1 TIM3 LAG3 IL-27R Similar effects with other inhibitory receptors on T cells & monocytes SRF388 IL-27 TIGIT PD-L1 TIM3 LAG3 Leukocyte


Slide 55

SRF388 Inhibits Tumor Growth in an Orthotopic Model of Hepatocellular Carcinoma SRF388 (50 mg/kg) was dosed IP BIW x 2 Starting day 5 Tumor growth was measured by bioluminescent imaging Hepa1-6-Luc Tumors


Slide 56

Potential to explore combinations in RCC Single arm Phase 2 in RCC SRF388 Clinical Development Plan Renal Cell Cancer Monotherapy dose expansion (Mandatory pre & post-treatment biopsies) Hepatocellular Cancer Monotherapy safety Potential to explore combinations in HCC Monotherapy dose escalation in patients with advanced solid tumors Establish a safe dose Accelerated and standard 3+3 design RP2D RP2D


Slide 57

EBI3 Immunoassay Immunohistochemistry Elevated expression of IL-27 pathway components Elevated levels of serum EBI3 Translational Hypotheses with Patient Selection Potential Tumor Biopsy Blood/ Serum Correlation with patient response mRNA Expression IL-27 gene expression signature


Slide 58

Five Key Takeaways from Today’s Presentation ü ü ü ü ü The cytokine IL-27 is a regulator of immune suppression Strong translational hypotheses in RCC and HCC SRF388 is a novel, first-in-class anti-IL-27 antibody SRF388 was selected by leveraging a deep understanding of IL-27 and TME biology  IND to be filed this Quarter 2019


Slide 59

SRF813 (CD112R): Unique Approach to New Checkpoint Inhibitor  Our first NK cell targeting program Potential to overcome PD-1 resistance and reactivate NK and T cell immunity


Slide 60

Summary: An Immunotherapy With PD-1 Refractory Potential T cell based immunotherapies have been transformative but resistance is emerging Currently there are no therapeutic strategies to overcome resistance to T cell checkpoint inhibitor blockade Emerging data highlights the potential of NK based therapies to overcome PD-1 resistance SRF813 is an anti-CD112R antibody that promotes NK/T cell activation via a distinct mechanism Targeting CD112R represents a new therapeutic approach designed to enhance NK activation in the TME


Slide 61

Dendritic cell NK Cells are Critical for Optimal Antitumor Responses Tumor cell NK cell Lytic granules MHC-deficient Inhibitory receptors Activating receptors Inhibitory ligands Stimulatory ligands + - Chemokines T Cell TCR IL-12 Antigen presentation


Slide 62

NK Focused Immunotherapies Provide a Strategy to Overcome T Cell-Associated Tumor Immune Resistance Freeman, et al Cell Reports, 28, 2019 Genes that when depleted are associated with increased sensitivity to NK mediated killing Tumor cell NK cell MHC I low NK sensitivity Genes that when depleted promote resistance to T cell killing Unbiased genome-wide CRISPR screens identify transcriptional networks that are: Associated with PD-1 resistance Increased tumor cell sensitivity to NK cell killing Shared genes between screens, P <0.01 Genes for: Antigen Presentation Machinery IFN Signaling


Slide 63

NK cell CD112R is an Inhibitory Receptor Expressed on NK and T Cells CD112R expression increased on activated NK/T cells anti-CD3 stimulation NK Cells Tumor cell CD112 CD112R CD226 CD112 CD16


Slide 64

NK cell CD112R is an Inhibitory Receptor Expressed on NK and T Cells CD112R expression increased on activated NK/T cells CD8 T Cells NK Cells Tumor cell CD112 CD112R CD226 CD112 CD16 TCR T Cell CD226 CD112R anti-CD3 stimulation


Slide 65

NK cell CD112R is an Inhibitory Receptor Expressed on NK and T Cells Tumor cell CD112 TCR T Cell CD112R CD226 CD112 CD16 CD226 CD112R Upregulated on CT26 tumor infiltrating NK/T cells


Slide 66

The CD112R Blocking Antibody SRF813 Promotes NK Cell Activation NK cell Tumor cell CD112 CD16 CD112R CD226 PBMC-NK activation assay K562 Cells NK degranulation assay Raji.CD112 Cells


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The CD112R Blocking Antibody SRF813 Promotes NK Cell Activation PBMC-NK activation assay NK degranulation assay Raji.CD112 Cells K562 Cells NK cell Tumor cell CD112 CD16 IgG4 Abs CD112R CD226


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The CD112R Blocking Antibody SRF813 Promotes NK Cell Activation PBMC-NK activation assay NK degranulation assay Raji.CD112 Cells K562 Cells NK cell Tumor cell CD112 Ab-A IgG1 CD16 CD112R CD226


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The CD112R Blocking Antibody SRF813 Promotes NK Cell Activation NK cell Tumor cell CD112 PBMC-NK activation assay NK degranulation assay Raji.CD112 Cells K562 Cells SRF813 + + activation + + + CD16 CD112R CD226


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CD112R is a Negative Regulator of T Cell Activation T cell Tumor cell IL-2 CD112 CD112R TCR CD112R overexpression abrogates T cell activation SRF813 enhances T cell activation SRF813


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CD112R Antibody Delays Tumor Growth and Promotes Immunological Memory Anti-muCD112R 25 mg/kg, starting day 4 (BIW x 3) Anti-tumor activity as a single agent Naive Re-challenged Tumor free re-challenged display immunological memory Activity is NK and T cell dependent Isotype anti-muCD112R


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SRF813 Activity is Dependent on CD16 Engagement In vitro NK cell activity assay K562 Cells CD16 CD112R Distinct epitope and isotype important for functional activity Competitor Model for SRF813 binding CD112 SRF813 + Tumor cell NK Cell CD226 + - CT26 syngeneic tumor model muIgG1 = low affinity binding muIgG2a = high affinity binding


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SRF813 – an Antibody Targeting CD112R High affinity, fully human IgG1 antibody against human CD112R Binds distinct epitope and blocks CD112-CD112R interaction Enhances NK/T cell activation and cytotoxicity CD112R blockade promotes antitumor immunity in mice SRF813 represents a new therapeutic approach designed to enhance NK/T cell activation in the TME


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Q&A 11:00 am – 12:00 pm


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Final Remarks from Jeff Goater, President & CEO 12:05 PM


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Thank You