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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
royalty payments; the possible impairment of, inability to obtain and costs of obtaining intellectual property rights; and
possible safety or efficacy concerns, general business, financial and accounting risks and litigation. Because forward-
looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified
and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of
future events. More information concerning us and such risks and uncertainties is available on our website and in our
press releases and in our public filings with the U.S. Securities and Exchange Commission. We are providing this
information as of its date and do not undertake any obligation to update or revise it, whether as a result of new
information, future events or circumstances or otherwise. Additional information may be available in press releases or
other public announcements and public filings made after the date of this presentation.
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
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