Breaking through for patients with cancer

March 2021

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 otherthan 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 expectationsand 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-termbusiness 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 andadversely 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 forSRF617, SRF388 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,” setforth 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 notpossible 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 todiffer 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 eventsand 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 conformthese 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 datesubsequent 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-lookingstatements 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 ownanalysis and be solely responsible for forming your own view of the potential future performance of our business.

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Company Highlights

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Outstanding team of experienced company builders & oncology drug developers

Wholly-owned SRF617 (CD39) in Phase 1/1b, targeting promising adenosine axis

SRF388 first-ever IL-27 targeted therapy in Phase 1, compelling translational hypothesis

Cash runway through 2023 ($175M in cash as of Dec 31st)

Detailed clinical update for both SRF617 & SRF388 to be presented in the first half of 2021

Leading Pipeline Targeting the Tumor Microenvironment

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Adaptive

Engaging Both the Adaptive and Innate Immune ResponsesDifferentiated antibody programs with strong translational hypotheses

Four programs that relieve immune suppressionTwo programs targeting the adenosine axis

Innate

ATP

AMP

Adenosine

Stimulation

CD39

CD73

Suppression

5

Suppression

CCR8 Suppression

Suppression

IL-27

PVRIG

6

NZV930

• WW development & commercial rights (January 2016)

• Status: Phase 1 development targeting multiple solid tumor types

• Financials:

• Upfront payment of $70M, total cumulative milestones up to $525 million

• Tiered royalties on annual net sales (high single-digit to mid-teens %)

POTENTIAL BEST-IN-CLASS CD73 TARGETED ANTIBODY

SRF813

• WW development & commercial rights (December 2020)

• Status: Planned IND filing in 2021

• Financials:

• Upfront payment of $85 million, total cumulative milestones up to $730 million

• Tiered royalties on annual net sales (high single-digit to mid-teens %)

POTENTIAL BEST-IN-CLASS PVRIG TARGETED ANTIBODY

Licensed Programs Partnerships validate strong IO drug discovery capabilities

SRF617Targeting CD39 for

Immune System Activation

SRF617

Antibody Targeting

CD39

High-affinity, fully human IgG4 antibody against human CD39

Potent inhibitor of enzymatic activity

Phase 1 trial ongoing

Dual mechanism of action: Significant reduction of adenosine and increased levels of ATP leads to increased T cell proliferation and dendritic cell maturation

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Detailed clinical update to be presented at a medical conference in the first half of 2021

Targeting CD39 Can Activate Innate & Adaptive Immunity

ATP

AMP

Adenosine

Cell stress/ damage/ death

CD39

CD73

Innate and adaptive immune response

(adaptive)

(innate)

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NK cell

T cell

Myeloid cell

Macrophage

Dendritic cell

CD39 Inhibition Demonstrates Potent Anti-tumor Activity

Days on Study

10/18 CR

4/16 CR (Rechallenge)

SRF617 Single Agent Activity in Xenograft MOLP8 In Vivo Model

Murine Anti-CD39 Surrogate Cooperates with Anti-PD-1 in CT26

Model, Increasing Cures

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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

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Anti-Murine-CD39 Shows Efficacy as Single Agent and in Combination with Gemcitabine in a Subcutaneous Pancreatic Cancer Model

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Data provided by John Stagg Lab*Similar results observed in MOLP-8 Xenograft model with SRF617 + Paclitaxel and SRF617 + Doxorubicin combinations

CD39 Expression in KPC Tumor Stroma

Fibroblast Macrophage

CD8+ TILs Increase With Anti-MuCD39 TreatmentDay 12 tumors

KPC Ova Gluc injected on day 0 (0.1 x 10^6 cells per mouse s.c.)Gemcitabine: days 7 and 10 (100 mg/kg i.p.)Anti-muCD39 or isotype control: days 7,10, 14,17,21 and 24 (400 μg/mouse i.p.)Anti-muCD39 = VX26102

Anti-MuCD39 + Gemcitabine in KPC Ova Model*

CONFIDENTIAL

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CD39 and CD73 Expression Are Both Increased in Malignant vs. Normal Pancreas

CD39

n=34

n=34

Tumors exhibit predominantly stromal (non-tumor cell) CD39 expression

Tumors show both stromal and tumor cell CD73 expression

CD73

Strategic bioassays for early detection of biologic activity:

• PBMC target occupancy: binding of SRF617 to PBMCs is highly correlated to enzymatic inhibition and plasma PK

• CD39 enzymatic activity by IHC: allows for direct measurement of CD39 inhibition within the TME

SFR617 MonotherapyDose Escalation

SRF617 + Gem/AbraxaneCombination

SRF617 + AB928 Combination**

SRF617 + PembroCombination*

Biopsy ExpansionCohort

PD-1 Relapsed Combo cohort

Safety Expansion

Safety Expansion

Enables start of RP2 in Pancreatic Cancer

Enables start of RP2in Gastric Cancer

Enables start of SAP2in Prostate Cancer

Safety Expansion

*Clinical collaboration with Merck **Clinical collaboration with Arcus Biosciences

RP2D

RP2D

RP2D

RP2D

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

Phase 2

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SRF617 Clinical Development Plan

Data from nine patients treated across three dose levels(20 mg, 70 mg, and 200 mg)

Well tolerated to date without dose limiting toxicities

Prolonged stable disease (>5 mos) has been seen in one patient with NSCLC who had progressed on prior anti-PD-1 treatment

Target occupancy on PBMCs has increased in a dose-dependent manner. Sustained target occupancy achieved within the 200 mg cohort

SRF617

Clinical Update

As of 11/13/20

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Detailed clinical update to be presented at a medical conference in the first half of 2021

SRF388Targeting IL-27 to

Enhance Immune Activity in the TME

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Overview of SRF388

Potential First-in-Class

Antibody Targeting

IL-27

High-affinity, fully human IgG1 antibody against p28 subunit of IL-27

IL-27 is a highly immunosuppressive cytokine upregulated during pregnancy and associated with maternal-fetal tolerance

Targeted translational hypothesis: RCC & HCC

IL-27 serves as a “master switch” of checkpoint protein expression

Potential for patient selection using a blood test

Phase 1 trial ongoing

Detailed clinical update to be presented at a medical conference in the first half of 2021

IL-27 Upregulates Checkpoint Receptors, Downregulates Proinflammatory Cytokines

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IL-27 Receptor

p28

Jak2 Jak1

STAT3 STAT1

Inflammatory Cytokines

EBI3 IL-27 Ligand

Inhibitory Receptors on Immune Cells

Chihara et al, Nature 558, 2018DeLong et al, Immunohorizons 3, 2019

TNF⍺Downregulates Pro-Inflammatory Cytokines

Upregulates Checkpoint ReceptorsIL-27

T N

F ⍺

p g

/m L

+IL-27 Control

Perc

enta

ge p

ositi

ve

CD

8+T

Cel

ls

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

Similar effects observed with IL-17 and TNFα

Anti-PD-1

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Evidence for IL-27 Pathway Activation in HCC and RCC

U. Montreal Cohort - J. Stagg 180 RCC Plasma Samples

Overall Survival

Elevated risk of HCC in those with High Levels of Circulating IL-27

From combined prospective cohorts of healthy volunteers from Shanghai and Singapore Yuan et al, AACR 2020

0

100

200

300

1st Tertile 2nd Tertile 3rd Tertile

Serum IL-27 Levels

Hepatitis B Negative Hepatitis B Positive

1.0

24.766.1

10.7

265.2

45.5

Odd

s R

atio

of H

CC

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SRF388 Inhibits Tumor Growth in an Orthotopic Modelof Hepatocellular Carcinoma

SRF388 was dosed IP BIW x 2Starting day 5Tumor growth was measured by bioluminescent imaging

Hepa1-6-Luc Tumors

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SRF388 Significantly Modulated Gene Expression in the Hepa1-6 Mouse Model of Hepatocellular Carcinoma (HCC)

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SRF388 modulates gene expression in Hepa1-6 tumors

SRF388 reduces the expression of immune-inhibitory receptors and TGF related genes

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SRF388 Clinical Development Plan

Strategic bioassays for early detection of biologic activity and patient selection biomarker:

• Phospho-STAT inhibition as a direct assessment of on target activity in whole blood

• Assessment of circulating IL-27/EBI3 as a patient selection biomarker

• Subset of patients with RCC and HCC will undergo pre and on-treatment paired tumor biopsies

Renal Cell Cancer Monotherapy

Single arm Phase 2

SRF388 + Pembrolizumab Doublet

Pilot expansion in RCC and HCC

Hepatocellular CancerMonotherapy

Single arm Phase 2

Potential to explore combinations in RCCDose Escalation:

Monotherapy dose escalation in patients with advanced solid tumors

• Establish a safe dose

• Accelerated and standard 3+3 design

RP2D

RP2D

RP2D

Crossover to DoubletOption for RCC & HCC

patients progressing on SRF388 monotherapy

Potential to explore combinations in HCC

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SRF388

Clinical Update

As of 11/13/20

Data from nine patients treated across 5 dose levels (0.003, 0.03, 0.1, 0.3 and 1 mg/kg)

Well tolerated without dose limiting toxicities

Prolonged stable disease (>6 mos) noted in one patient with kidney cancer who had progressed on prior anti-PD-1 treatment

Maximal inhibition of the IL-27 signaling pathway achieved starting at the 0.3 mg/kg dose (as measured in whole blood)

Detailed clinical update to be presented at a medical conference in the first half of 2021

SRF114Targeting CCR8 To Deplete

Immunosuppressive Regulatory T cells in the TME

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Overview of SRF114

Antibody Targeting CCR8

High-affinity, fully human IgG1 antibody against CCR8

Binds and induces ADCC of CCR8+ tumor Treg cells

Highly specific for binding CCR8 and no other target proteins

Enhanced killing observed as an afucosylated variant

Potential for IND filing in 2022

CCR8 is Predominantly Expressed on Tumor Infiltrating Treg Cells

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Surface dataSimilar findings reported by Villarreal D et al, Cancer Res 2018

Anti-CCR8 Antibody Treatment Results InDecreased Tumor Growth

****

CCR8 Ab: TIW, 2.5 wk

CCR8 Expression is More Selective than CCR4

RNA seq read counts from human T cell subsetst: breast tumor infiltratingb: normal blood

CC

R8

Cou

nts

AACR 2015 (R. Rudensky)

CCR4CCR8

SRF114 Depletes Human Tumor Treg cells

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Tumors: 3 NSCLC, 1 BreastPan tumor CD4+ Foxp3+/-

Isolated Treg co-cultured with NK cells +/-indicated Abs

0

25

50

75

100

125

SRF114 Results in Significant Reduction of Tumor-infiltrating Treg Cells

% o

f CD

3+ce

lls

Treg cells

Non-Treg CD4+ cells

Rob Ross, MDIncoming Chief Executive Officer

Vito Palombella, PhDChief Scientific Officer

Jessica FeesSenior Vice President, Finance

Bob SteiningerSenior Vice President, CMC

Liisa NogeloChief Legal Officer

Management Team with Proven Track Record of Success

Wendy DwyerChief Business Officer

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Lisa McGrathSenior Vice President, Human Resources

Alison O’Neill, MDSenior Vice President, Clinical Development

Outstanding Board of Directors & Scientific Advisory Board

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Board of Directors Scientific Advisory Board

Sasha Rudensky, PhD (co-Chair)Memorial Sloan-Kettering Cancer Center

Arlene Sharpe, MD, PhD (co-Chair)Harvard Medical School

Stephen Hodi, MDDana-Farber/Brigham and Women’s Cancer Center

John Wherry, PhDUniversity of Pennsylvania

David Tuveson, MD, PhDCold Spring Harbor Laboratory

John Stagg, PhDUniversity of Montreal

Christopher Hunter, PhDUniversity of Pennsylvania

Carla Rothlin, PhDYale School of Medicine

(1) Also serves on SAB

Dan Lynch (Chair)bluebird bio, Blueprint Medicines, Translate Bio, SpringWorks

Jeff Goater (Incoming Chair)CEO, Surface Oncology

David Grayzel, MDPartner, Atlas Venture

Ramy Ibrahim, MDCMO, bit.bio

Geoffrey McDonough, MDCEO, Generation Bio

Armen Shanafelt, PhDFormer General Partner, Lilly Ventures

Elliott Sigal, MD, PhD(1)

Former Pres of R&D, CSO of Bristol-Myers Squibb

Laurie StelzerCFO, Arena Pharmaceuticals

Strong Financial Position and Near-term Clinical Milestones

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Wholly-owned SRF617 (CD39) in Phase 1/1b, targeting promising adenosine

SRF388 first-ever IL-27 targeted therapy in Phase 1, compelling translational hypothesis

Two strategic partnerships (Novartis & GSK) validate strong IO drug discovery capabilities

Cash runway through 2023 ($175M in cash as of Dec 31st)

Detailed clinical update for both SRF617 & SRF388 to be presented in the first half of 2021

For More Information:

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• Jessica Fees, SVP Finance• jfees@surfaceoncology.com

• Matt Lane, Gilmartin Group• matt@gilmartinir.com

Breaking through for patients with cancer

SRF617 Engages the Adaptive Immune System by Reducing Adenosine Levels, Stimulating T Cell Responses

SRF617 Mediated CD39 Blockade is

Immunostimulatory

ATP

AMP

Adenosine

Cell stress/damage/death

CD39

CD73

(adaptive)

(innate)

SRF617 Reduces Plasma Adenosine Levels in Tumor-Bearing Mice

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SRF617 Monotherapy or Combo with Gemcitabine Leads to Increased ATP

Levels in Human Pancreatic Cancer

Cultures

SRF617 Engages the Innate Immune System By Increasing Extracellular ATP, Stimulating Dendritic Cells

SRF617 Stimulates Key Components of the

Innate Immune System

ATP

AMP

Adenosine

Cell stress/damage/death

CD39

CD73

(adaptive)

(innate)

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