REINVENTING THERAPEUTIC

ANTIBODIES FOR CANCER

June 2017

1© 2017 CytomX Therapeutics, Inc.

Forward Looking Statements

Special Note Regarding Forward-Looking Statements

This presentation may contain projections and other forward-looking statements regarding future events. All statements

other than statements of historical facts contained in this presentation, including statements regarding our future

financial condition, technology platform, development strategy, prospective products, preclinical and clinical pipeline and

milestones, regulatory objectives, expected payments from and outcomes of collaborations, and likelihood of success,

are forward-looking statements. Such statements are predictions only and involve known and unknown risks,

uncertainties and other important factors that may cause our 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 and uncertainties include, among others, the costs, timing and results of preclinical studies

and clinical trials and other development activities; the uncertainties inherent in the initiation and enrollment of clinical

trials; expectations of expanding on-going clinical trials; availability and timing of data from clinical trials; the

unpredictability of the duration and results of regulatory review; market acceptance for approved products and

innovative therapeutic treatments; competition; the potential not to receive partnership milestone, profit sharing or

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and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of

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This presentation concerns products that have not yet been approved for marketing by the U.S. Food and Drug

Administration (FDA). No representation is made as to their safety or effectiveness for the purposes for which they are

being investigated.

2

Goals in Clinical Oncology Today

3

% S

urv

ival

Time

SOC

Chemo/TKI

IO Monotherapy

Ipi/nivo Combo

Next Wave of

Combos and

Innovation

Response (particularly CR)

Toxicity

Durability of response

Survival

Options for PD-(L)1 progressors

Important Progress in Last Five Years;

Still Much Room for Improvement

Probody Therapeutics are Designed to be Activated

in the Tumor Microenvironment

4

ANTI-CANCER

ANTIBODY

LINKER

MASKING PEPTIDE

PROTEASES

Reinventing Therapeutic Antibodies for Cancer

5

• Innovative antibody platform designed to enhance tumor targeting and

create/widen therapeutic window

• Built on deep scientific know-how, more than a decade of research

• >200 CytomX-owned patents and patent applications

PROBODY is a trademark of CytomX Therapeutics, Inc. All other brands and trademarks referenced herein are the property of their respective owners.

Innovative

Probody™

Platform

• Potential best-in-class immunotherapies against clinically-validated targets

- CX-072 (PD-L1), CX-188 (PD-1)

- CTLA-4 in collaboration with Bristol-Myers Squibb

• First-in-class therapeutics directed against novel, difficult-to-drug targets

- CX-2009 (CD166-PDC)

- CX-2029 (CD71-PDC) co-development with AbbVie

Advancing

Pipeline

Well-Funded

• $162.5 million cash balance as of March 31, 2017

• Additional $200 million from Bristol-Myers Squibb received in May 2017

• 2017 ending cash expected to be $285-305 million; funding at least

through 2019

• CX-2009 study initiation (IND cleared 5/17)

• CX-072 and CX-2009 Phase 1 clinical data (2018)

• CTLA-4 trial initiation (early 2018)

• CX-2029 (CD71-PDC) IND filing (2018)

2017/2018

Milestones

PRODUCT CANDIDATE DISCOVERY LEAD OPTIMIZATION IND-ENABLING PHASE 1

CX-072

CX-2009

CTLA-4 Probody Tx

CX-2029

CX-188

T-cell Bispecifics

Additional PDCs

Immunotherapy

Discovery

6

Broad Probody Therapeutic Pipeline Poised for Proof

of Concept and Value Creation

PIPELINE

CD166 PDC

CTLA-4

PD-L1

CD71 PDC

PD-1

Multiple programs

IND Anticipated in 2018

Trial Initiation by early 2018

IMMUNO-ONCOLOGY

PROGRAMS

CX-072 (ANTI-PD-L1)

ANTI-CTLA-4 (BMS)

7

Full Potential for Combination Immunotherapy is

Limited by Toxicities

8

*Treatment-related **Not reported

1. Larkin et al., NEJM, July 2015. 2. Chapman et, al. NEJM, 2011. 3. Hamid, Society for Melanoma Research

2015

Opdivo

alone

Yervoy

Alone

Yervoy+

Opdivo1

ORR 44% 19% 58%

Grade 3-4

AEs*16% 27% 55%

Stopped Drug 8% 15% 36%

MELANOMA

DERMATITIS

PNEUMONITIS

HEPATITIS

THROMBOEMBOLIC

OCULAR TOXICITY

HYPOPHYSITIS

THYROIDITIS

COLITIS, DIARRHEA

NEUROPATHY

*

Vemurafenib

alone2

Atezolizumab+

Vemurafenib3

ORR (CR) 48% (1%) 67% (33%)

Grade 3-4 AEs* 38% 67%

Stopped Drug NR** 100%

MELANOMA

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22

9

*CytomX analysis of available data through ASCO and ESMO 2016

Emerging Clinical Data:

Increased Efficacy at the Cost of Increased Toxicity*

EFFICACY PD-(L)1 Agent SOC Agent Combo

SAFETY PD-(L)1 Agent SOC Agent Combo

CTLA-4 CHEMO IDO BRAF &/or MEK VEGF EGFR

CTLA-4 CHEMO IDO BRAF &/or MEK VEGF EGFR

Ove

rall R

es

po

ns

e R

ate

(O

RR

)G

rad

e 3

/4 T

rea

tme

nt-

Re

late

d A

E’s

Rationale for Probody Therapeutics in

Immuno-Oncology

Studies indicate localizing

immunotherapies to the tumor can

achieve efficacy without

toxicity1,2,3,4,5

Probody Therapeutics are

designed to achieve localized

effects with conventional

administration

1. Marabelle, A., et. al., Clin Cancer Res; 19(19) October 1, 2013

2. Ray, A., et. al., Oncotarget; 7(39) July 2016

3. Wang. C., et. al., NanoLetters; 16(4), 2016

4. Van Hooren, L., et. al., Eur. J. Immunol. 2016. 00: 1–9

5. Fransen, M., et. al., Clin Cancer Res; 19(19) October 1, 2013

DERMATITIS

PNEUMONITIS*

HEPATITIS

Patient Treated with

Traditional Antibody Tx

Patient Treated with

Probody Tx

Tumor *Examples of Toxicities

10

Active Antibody Tx Masked Probody Tx

Non-binding

Control Antibody

Parent PD-L1

Antibody

CX-072 PD-L1

Probody Tx

Tumor

11

CX-072 Preclinical Proof of Concept

TUMOR GROWTH SAFETYInduction of Autoimmunity

Prevents Binding in Periphery

Autoimmunity ReducedSimilar Efficacy

Localizes to Tumor

Tx

CX-072 Has the Potential to Become

the PD-L1 Combination Agent of Choice

12

CX-072PD-L1 PROBODY

THERAPEUTIC

Checkpoint

Inhibitors

Traditional

Chemotherapy

Other Cancer

Immuno-

therapies

Kinase

InhibitorsADCs

• Validated target

• Well-established

efficacy & safety

for class

CX-072 (.03 – 30 mg/kg)

D: MONOTHERAPYEXPANSION COHORT(S)

PROCLAIM-072 (PD-L1)

Phase 1/2 Clinical Trial Design

13

CX-072 (starting dose:0.3 mg/kg) + 3 MPK IPI

concomitant schedule

D O S E

E S C A L A T I O N

D O S E E S C A L A T I O N

B1: IPILIMUMAB COMBO

1H’17 2H’17 2018

E N R O L L M E N T E N R O L L M E N T & F O L L O W U P

CX-072 (starting dose: 3 mg/kg) + 3 MPK IPI

phased schedule

B2: IPILIMUMAB COMBO

CX-072 (starting dose: 1 mg/kg) + 960 MG VEM

A: MONOTHERAPY

C: VEMURAFENIB COMBO

Presence of Target &

Protease Activity

Translational Strategy for CX-072

PD-1 Pathway

Inhibition

89Zr-PET Imaging

of CX-072Western CE/MSIHZ/QZ

Target Engagement by

Probody

IHC

Cleavage of

Probody in Tumors

IHC

mRNA Nanostring

14

During Treatment

Before Treatment

Resp

on

se

T-CellON

T-CellReceptor Antigen

PD-1

TumorCell

PD-L1

Chem

ilum

inescence

12 40

MW (kDa)

5

C1:22

C1:18

ab2 ab pb

Chem

ilum

inescence

0

5,000

10,000

15,000

20,000

200

400

600

800

8 13 18

ab pb

Antibody

Protease

Substrate Linker

Mask

Original Collaboration Terms

BMS Alliance: Building on Success

Collaboration Outline

• Twelve target collaboration; Ten oncology and two non-oncology targets

• $275 million in upfront payments received

• Invested $10 million in CytomX IPO

• $4.8 billion in potential milestones, tiered royalties up to low-double digits

• CTLA-4 Probody in IND enabling studies, clinical trial initiation anticipated by early

2018

• Multiple additional programs in lead optimization

• BMS responsible for all costs associated with research, development, and

commercialization

• BMS not eligible to select CytomX targets currently in discovery, preclinical research

or clinical development

• Deal does not include CytomX wholly owned assets, CX-072, CX-2009, CX-188

15

Preclinical Proof of Concept Achieved for CTLA-4 Probody:

Similar Anti-Tumor Efficacy with Less Activity on

Peripheral T-Cells than Ipilimumab

16

C o n tro l

0 1 0 2 0 3 0 4 0 5 0

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

D a y s P o s t Im p la n ta tio n

Tu

mo

r V

olu

me

(m

m3

/2)

Ip il im u m a b

0 1 0 2 0 3 0 4 0 5 0

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

D a y s P o s t Im p la n ta tio n

Tu

mo

r V

olu

me

(m

m3

/2)

Ip il im u m a b P ro b o d y

0 1 0 2 0 3 0 4 0 5 0

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

D a y s P o s t Im p la n ta tio n

Tu

mo

r V

olu

me

(m

m3

/2)

Control

0/10 Tumor Free

Ipilimumab

7/10 Tumor Free

Ipilimumab Probody

6/10 Tumor Free

Tumor T-Cell Activation

Perc

en

tag

e o

f K

i-67+

CD

4+

T-c

ell

s Vehicle Anti-CTLA-4

(ipilimumab)

Pretest Day 8 Day 150

5

10

15

20

25

3

0

35

40

45

50

Perc

en

tag

e o

f K

i-67+

CD

8+

T-c

ell

s

Pretest Day 8 Day 150

5

10

15

20

25

30

35

40

45

50

Anti-CTLA-4-

Probody-Tx

Vehicle Anti-CTLA-4

(ipilimumab)

Anti-CTLA-4-

Probody-Tx

PROBODY DRUG

CONJUGATE

PROGRAMS

CX-2009 (ANTI-CD166)

CX-2029 (ANTI-CD71)

17

Probody Technology Enables Selection of Better

Antibody Drug Conjugate Targets

18

PDC Targets May Have More

Attractive Attributes:

CD166 CD71

Her2

CD30 Mesothelin

Folate Receptor

CD166

PDC Targets

ADC Targets

ADC Targets are Limited Based on

Healthy Tissue Expression:

• More patients

• More indications

Source: Human Protein Atlas

CD166

• Higher Expression

• Uniform Expression

Her2

Validation of CD166: An Attractive Target for

a Probody Drug Conjugate

19

CD166 is expressed at high levels in many solid tumors

CX2009

CD166

AntibodyDM4 Payload

V1

V2

C1

C2

C3

Cancer Cell

Lung cancerOvarian cancerBreast cancer

0

1000

2000

3000

4000

5000

6000

BT

-54

9

H2

92

PC

3

SK

OV

3

HC

C1

80

6

ZR

75

H1

97

5

HP

AC

SC

C2

5

MD

AM

B2

31

HP

AF

II

HC

T-1

16

HC

C1

95

4

OvC

AR

3

MD

AM

B4

68

HS

766T

CA

L51

co

lo2

05

H2

40

5

DL

D-1

PA

NC

-1

LS

411

N

lovo

HC

T-1

5

HT

-29

AS

PC

1

BT

20

Mia

pa

ca

SW

48

0

CX2009 is Efficacious Across Many Models and a Wide Expression Range

Bm

ax

(MF

I)

Positive xenograft study

Tested in vitro onlySubstrate Linker

Mask

Protease

CX-2009 is Highly Active in Preclinical Tumor Models

20

0 2 0 4 0 6 0

0

5 0 0

1 0 0 0

1 5 0 0

2 0 0 0

H C C 1 8 0 6 tu m o r m o d e l (T N B C )

s tu d y d a y

Me

an

Tu

mo

r V

olu

me

(m

m3

) v e h ic le c o n tro l

C D 1 6 6 P D C ; 3 m p k

C D 1 6 6 A D C ; 5 m p k

0 1 0 2 0 3 0

0

5 0 0

1 0 0 0

1 5 0 0

H 2 9 2 tu m o r m o d e l (N S C L C )

s tu d y d a y

Me

an

Tu

mo

r V

olu

me

(m

m3

)

is o ty p e -D M 4 ; 5 m p k

C D 1 6 6 P D C ; 5 m p k

C D 1 6 6 A D C ; 5 m p k

0 5 1 0 1 5 2 0

0

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

O v a ria n P D X m o d e l

s tu d y d a y

Me

an

Tu

mo

r V

olu

me

(m

m3

)

is o ty p e -D M 4 ; 5 m p k

C D 1 6 6 P D C ; 5 m p k

C D 1 6 6 A D C ; 5 m p k

IV dosing on days 0 and 7

Tumor regressions at expected clinical dose (5 mpk)

CD166 IHC

CX-2009 (CD166): Clinical Strategy

21

1H 2H

2017

1H 2H

2018

Phase 1/2 StudyIND Cleared

Biomarker, safety and efficacy data in 2018

Dose escalation and potential expansion cohorts in

CD166-positive tumor types:

• Non-small cell lung cancer

• Breast cancer

• Ovarian cancer

• Endometrial cancer

• Cholangiocarcinoma

• Head and neck cancer

• Castration-resistant prostate cancer

CD71 is a Highly Desirable

Antibody Drug Conjugate Target

• Ubiquitously expressed on dividing, normal

and malignant cells

• Mediates iron uptake required for cell division

• A professional internalizing protein: often used

as a positive control in ADC experiments

• Expression in normal dividing cells prohibits

development of a traditional ADC

22

J. Cancer Ther. (2012)

CD71-Probody Drug Conjugate

Preclinical Proof of Concept

23

TUMOR GROWTH TOLERABILITY IN NON-HUMAN PRIMATES

Toxicity ReducedSimilar Efficacy

0 1 0 2 0 3 0 4 0

0

2 0 0

4 0 0

6 0 0

8 0 0

1 0 0 0

D a y s P o s t D o s e

Tu

mo

r V

olu

me

mm

3

Cell Line-Derived Xenograft

IgG control ADC

CD71-ADC

CD71-PDC

NCI-H292 (Lung)

Status: IND expected in 2018

AbbVie licensed SGEN’s validated MMAE payload

SUMMARY

24

PRODUCT CANDIDATE DISCOVERY LEAD OPTIMIZATION IND-ENABLING PHASE 1

CX-072

CX-2009

CTLA-4 Probody Tx

CX-2029

CX-188

T-cell Bispecifics

Additional PDCs

Immunotherapy

Discovery

25

Broad Probody Therapeutic Pipeline Poised for Proof

of Concept and Value Creation

PIPELINE

CD166 PDC

CTLA-4

PD-L1

CD71 PDC

PD-1

Multiple programs

IND Anticipated in 2018

Trial Initiation by early 2018

Sean McCarthy, D.Phil., MBA

President and CEO

W. Michael Kavanaugh, M.D.

Chief Scientific Officer

Rachel Humphrey, M.D.

Chief Medical Officer

Debanjan Ray, MBA

Chief Financial Officer &

Head of Corporate Development

Cynthia Ladd, JD

General Counsel

Danielle Olander

SVP, Talent & Administrative Operations

Experienced Leadership Team

26

Execu

tive T

eam

Reinventing Therapeutics Antibodies for Cancer

27

Innovative

Probody Platform

Strong Execution

Since IPO

Validating

Pharma Partners

Well-Funded

2017/2018

Milestones

• Clinical trial initiation on two wholly owned assets

• More than $250 million in non-dilutive capital raised

• Enhanced tumor targeting for therapeutic antibodies

• Strong cash position to advance broad pipeline

• CX-072 and CX-2009 Phase 1 readouts (100% owned)

• CTLA-4 and CX-2029 clinical initiation (partnered)

• Partner milestone payments

Broad Probody Therapeutic Pipeline Poised for

Proof of Concept and Value Creation

28