CytomX Therapeutics : 39th Annual J.P. Morgan Health Care Conference

39th Annual J.P. Morgan Healthcare Conference

Sean McCarthy, D.Phil.

President, Chief Executive Officer, and Chairman

JANUARY 14, 2021

© 2021 CytomX Therapeutics, Inc.

Conditionally-Active Antibody Therapeutics

for the treatment of cancer

© 2020 CytomX Therapeutics, Inc.

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; the uncertainties associated with the COVD-19 pandemic; 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.

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Company Snapshot

Conditionally-Active Antibodies

Key 2021 Milestones

Clinical-Stage

Oncology Focused

Biopharma Company

• Innovative targeting strategy
• Leverages tumor microenvironment
• Opens previously undruggable target space
• Leaders in field

• CX-2009initial Phase 2 data in breast cancer
• CX-2029initial Phase 2 expansion cohort data
• Next IND filings

Foundational Partnerships	Strong Balance Sheet
•	AbbVie, Amgen, Astellas & BMS	•	$321M cash at end of Q3 2020
•	Retained certain US rights	•	No debt

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Experienced Leadership

Sean A. McCarthy, D. Phil.

President, Chief Executive Officer and Chairman

>20 years of experience in biotech with roles in R&D, business development, financing and general management

Amy C. Peterson, M.D.

EVP, Chief Development Officer

>15 years of leadership experience in oncology drug development

Alison L. Hannah, M.D.

SVP, Chief Medical Officer

>30 years of experience in investigational cancer therapy development

Carlos Campoy

SVP, Chief Financial Officer

>30 years of financial and leadership experience, mostly with publicly-held healthcare and biopharmaceutical companies

Marcia P. Belvin, Ph.D.

SVP, Head of Research

>20 years of experience in preclinical pipeline discovery and development in oncology

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Broad Clinical and Preclinical Pipeline with Multiple Phase 2 Readouts 2021+

CONDITIONAL ADCs

IMMUNO- ONCOLOGY

PRODUCT	PROBODY	INDICATION	IND-ENABLING	PHASE 1	PHASE 2	COMMERCIAL RIGHTS
CANDIDATE	TARGET

		Breast	Arm A: monotherapy in advanced, metastatic HR+/HER2 non-amplified BC	Initial Data
CX-2009	CD166-DM4	Arm B: monotherapy in advanced, metastatic TNBC	Expected
Cancer
		Arm C: in combination with CX-072 in advanced, metastatic TNBC	Q4 2021

			Cohort 1: sqNSCLC	Initial Data	Initial
		Multiple	Cohort 2: HNSCC
CX-2029	CD71-MMAE	Expected
Cohorts	Cohort 3: Esophageal cancer
		Cohort 4: DLBCL	Q4 2021	2021
CX-2043	EpCAM-	Solid	Target IND 2021
DM21	Tumors
BMS-986249	CTLA-4	1L	Randomized: + nivolumab vs. ipilimumab + nivolumab vs. nivolumab
Melanoma
BMS-986288	CTLA-4	Solid	Dose escalation: +/- nivolumab
	a-Fucosylated	Tumors
	EGFR + CD3
CX-904	T-Cell	TBA	Target IND 2021
	Bispecific

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The Probody® Therapeutic Platform:

Conditionally-Active Antibodies

Less

Binding in

Normal

Tissues

Protease

Substrate	Protease
linker
Mask

More

Binding

in Tumors

Target

"Masking" limits ability of conditionally-active	Proteases in tumor microenvironment "unmask" conditionally-active antibody,
antibody to bind to healthy tissues	allowing more binding to tumor cells
Antibody-	Immune Modulator/	T-Cell
Drug Conjugate	Checkpoint Inhibitor	Bispecific
Linker-payload							Healthy Tissue
						Anti-Tumor	Anti-CD3

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Antibody-Drug Conjugates for Cancer are a Major Opportunity

Recent Approvals and Transactions Underscore High Potential of Class

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Probody Drug Conjugates Expand ADC Target Landscape

Antibody-	Limited
druggable space
drug
for conventional
conjugates
ADCs

					Broad	Convert
					opportunity	undruggable
					target to
					for new
					druggable target
					first in class
					by opening
					therapies
CytomX PDCs	therapeutic
						window

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CX-2009(Praluzatamab ravtansine)

Anti-CD166 Conditional ADC for HER2 non-Amplified Breast Cancer

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Substantial Unmet Need Remains in Breast Cancer

30% ~42k

Breast cancer is the 2nd leading cause of cancer deaths in women1

of all cancer in females with an estimated ~276k new cases and

deaths in the United States in 2020

• ~80% of breast cancer is HER2 non-amplified
• Despite recent advances, new therapies are needed, especially in the metastatic setting
• CD166 is broadly and highly expressed in HER2 non-amplified breast cancer

1. Cancer Statistics, 2020; Siegel CA Cancer J Clin 2020;70:7-30

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CX-2009: A Probody Drug Conjugate Targeting CD166 (ALCAM*)

CX-2009

DM4 PAYLOAD	ANTIBODY

SUBSTRATE

LINKER

MASK

PROTEASE
DAR ~ 4	CD166
	CANCER CELL

CD166

Expression

by IHC

• CD166 expression in normal cells limits development of a conventional ADC (e.g., Lung, GI tissues, Liver)
• CX-2009is a first-in-classanti-CD166 Probody conjugated to the maytansinoid cytotoxic payload DM4
• Designed to target CD166 towards tumor tissue, away from healthy tissue
• CD166 expressed on many other cancer types → future opportunity (e.g., Ovarian, Lung, HNSCC)

Breast Cancer

Lung Cancer

Ovarian Cancer

* ALCAM - Activated Leukocyte Cell Adhesion Molecule

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Phase 1 Enrolled 39 Patients with Breast Cancer at Doses 0.25-10 mg/kg

CD166 Expression (H-Score) in

Breast Cancer Patients

High

Low

HR+/HER2- : Hormone Receptor positive and HER2 non-amplified breast cancer;

TNBC: Triple negative breast cancer

Data presented SABCS 2020, ASCO 2020

Data Cutoff: August 2020

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Change in Target Lesions Size (%)

Observed Clinical Activity in Breast Cancer with CX-2009 at Doses ≥4 mg/kg Q3W

Breast cancer patients with measurable disease who received ≥ 4 mg/kg CX-2009 and had a post-baseline assessment

HR+/Her2-	(%)
BaselinefromBurdenTumorin
TNBC
Change			**Dose reduced (to 4 Q2W).
				*Patient still on study.
	Percent	**		#PD in non-target/new lesions.
	**
Best Response in Target Lesions					CR in target lesions
			Weeks Since Treatment Initiation

	Evaluable* Breast Cancer Patients
	Overall	HR+/HER2-	TNBC
Parameter	(n=32)	(n=22)	(n=10)
CBR16	13 (41%)	9	4
CBR24	9 (28%)	5 (2 cPR)	4 (3 uPR)

CBR= clinical benefit rate (CR, PR or SD for 16 or 24 wks); cPR= confirmed partial response;

uPR= unconfirmed Partial Response

Data presented SABCS 2020

*Includes those with non-measurable but evaluable (e.g. bone-only) disease

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Partial Response to CX-2009 in Patient with TNBC Refractory to Pembrolizumab+Paclitaxel and to Sacituzumab Govitecan

BASELINE

Week 8

Week 16

• 41-year-oldtreated at 8 mg/kg
• Prior treatment for metastatic disease:
• • Pembrolizumab + paclitaxel (best response = PD)
  • Sacituzumab govitecan (best response = PD)
• Baseline: ulcerating skin lesions on chest wall and axillary nodal metastasis
• First scan (Week 8): 48% reduction in target lesions
• Dose interruption (week 9 -16) for keratitis (resolved), disease progressed before treatment could be re-initiated

Data presented SABCS 2020

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CX-2009: Phase 1 Tolerability Supports Phase 2 Dose of 7 mg/kg

			RP2D
		< 6	7 mg/kg	8 mg/kg		9 mg/kg	10
		mg/kg		mg/kg
		(n=12)	(n=22)		(n=9)
		(n=38)		(n=8)
TRAE (Grade 3+)		16%	33%	64%		56%	50%
TEAE leading to		13%	8%	14%		22%	13%
Discontinuation
DLT (n)		0	0	1		0	0
TR SAEs		0	17%	27%		22%	13%
Ocular Toxicity (any		26%	25%	59%		56%	75%
grade)*
Ocular Toxicity		3%	0	14%		33%	13%
(Grade 3+)
RP2D= Recommended Phase 2 Dose
*Ocular prophylaxis was optional; future studies will incorporate mandatory ocular prophylaxis

CX-2009 was generally well tolerated at doses ≤ 7 mg/kg (toxicity profile consistent with payload: ocular, neuropathic and hepatic)

Ocular toxicities appeared dose dependent in frequency and severity

Selection of 7 mg/kg Q3W as RP2D is supported by activity, tolerability and PK/PD modeling

Data presented SABCS 2020

Data cut-off: August 2020

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CX-2009 Breast Cancer Phase 2 Study Design

Monotherapy (7mg/kg Q3W) and Combination with Pacmilimab (CX-072;anti-PD-L1)

In Advanced, HER2 non-Amplified Breast Cancer

Key Eligibility

Ocular prophylaxis required

HR+/HER2 non-amplified

• 0 - 2 prior cytotoxics for advanced disease
• Measurable disease required
• No active corneal disease

TNBC

• CD166 High
• ≥ 1 and ≤ 3 priors for advanced disease
• Measurable disease required
• Treated/stable brain metastases allowed
• No active corneal disease
• Arm C exclusion criteria:
• • PD-L1negative/unknown
  • I/O refractory
  • History of or active autoimmune condition

Breast Cancer SubType

Arm A

HR+/HER2 non-amp (n~40*)

CX-2009

Arm B

TNBC (n~40*)

CX-2009

Arm C

TNBC (n~40*)

CX-2009 + CX-072**

Endpoints

Primary: Overall Response Rate (ORR) by central review

Secondary: ORR (Inv), PFS, DCR, CBR24, DoR, OS, Safety, PK, ADA

Exploratory: Biomarker correlation with outcome

Readout: Initial data expected Q4 2021

*Evaluable, **https://meetinglibrary.asco.org/record/186711/abstract

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CX-2029

Anti-CD71 (Transferrin Receptor) Conditional ADC

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CD71 (Transferrin Receptor)

• Highly expressed tumor antigen
• "Professional internalizer" ideally suited to delivery of cytotoxic payloads to cancer cells
• Undruggable target with conventional antibody approaches due to normal tissue biology
• Probody strategy - open therapeutic window by limiting normal tissue binding
• Potentially paradigm shifting anti-cancer agent with first in class potential

Elliott and Head. J Cancer Ther. 2012;3:278-311.

LUNGHNSCC

ESOPHAGEAL LYMPHOMA

CD71

Expression

by IHC

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CX-2029: Potentially Paradigm Shifting Anti-Cancer Agent

DAR = 2

• Unmasked ADC is lethal in preclinical models at sub-therapeutic doses
• Therapeutic range for CX-2029 conditional ADC predicted in patients 2-4 mg/kg
• Hematologic toxicity dose limiting in preclinical studies

Tumor Volume (mm3) Mean +/- SEM

2500HNSCC

2000

1500	Vehicle
1000
500	CX-2029

0

0	20	40	60	80
	Days Post 1st Dose

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Phase 1 Dose Escalation Study Evaluated CX-2029 Q3W in 45 Patients with Solid Tumors

5 mg/kg n=4

4 mg/kg n=6

3 mg/kg n=12

2 mg/kg n=8

0.1-1.0 mg/kg n=15	Below Dose Predicted
to be Biologically Active

Key Eligibility Criteria

• Metastatic or locally advanced unresectable solid tumor
• Archival tissue or biopsy available for tissue analyses
• Stable brain metastases permitted

Exclusions:

• Transfusion-dependentanemia or iron metabolism disorders
• Grade 2 or higher neuropathy

Key Patient Demographics	All Cohorts
	(n=45)
Age, median (min, max)	60 (31, 75)
Baseline ECOG 0 / 1, %	29 / 71
CD71 IHC staining, n (%)
High expression [2+/3+]	15	(33)
Low expression [0/1+]	16	(36)
Unknown	14	(31)
Tumor types, n (%)
NSCLC	9 (20)
Squamous NSCLC	4	(9)
HNSCC	8 (18)
Colorectal cancer	7 (16)
Other*	21	(46)
Median priors (min, max)	3 (1, 16)

*Other tumor types include sarcoma (4), Prostate (3), parotid gland (3); ovarian (2); melanoma (n=1); endometrial (1); hepatocellular (1); mesothelioma (1); ocular melanoma (1); pancreatic (1); perivascular epithelioid (1); thymoma (1); thyroid (1).

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Observed Clinical Activity with CX-2029 at Doses ≥2 mg/kg Q 3 Weeks

Patients with measurable disease who received ≥ 2 mg/kg CX-2029 and had a post-baseline assessment

* * *

* Denotes patients still on treatment

*Confirmed Partial Responses in HNSCC and sqNSCLC

Best Response in Target Lesions

CRC=Colorectal Cancer, HCC=Hepatocellular carcinoma, aNSC=Non-small cell lung adenocarcinoma, TC=Thyroid carcinoma MPM=Malignant pleural mesothelioma, HN=Head and neck squamous cell carcinoma, PAC=Pancreatic cancer, PEC=Perivascular epithelioid cell tumor, sNSC=Non-small cell lung squamous carcinoma

Data cut-off: August 2020	22

Observed Clinical Activity in sqNSCLC and HNSCC with CX-2029

at Doses ≥2 mg/kg Q 3 Weeks

sqNSCLC or HNSCC patients with measurable disease, received ≥ 2 mg/kg CX-2029, and had a post-baseline assessment

Lesions

(%)

Dose Level:		2 mg/kg		3 mg/kg		5 mg/kg

TumorBurden (%)

Dose Level:		2 mg/kg		3 mg/kg		5 mg/kg

Response: PR SD PD

in Sum of Target	from Baseline
Change

HNSCC

HNSCC HNSCC

sqNSCLC HNSCC

HNSCC

HNSCC

sqNSCLC

Best Response in Target Lesions

sqNSCLC

HNSCC

Change in	from Baseline
Percent

*Denotes patients still on treatment

Weeks Since Treatment Initiation

1 patient with sqNSCLC was dosed at 1 mg/kg; 1 patient with HNSCC came off study without a post-baseline assessment

Data cut-off: August 2020	23

CX-2029 Case Study: Patient with HNSCC

• Nasopharyngeal carcinoma (Diagnosed in February 2018)
• Prior therapies: docetaxel/5FU/cisplatin with radiation; high-dose cisplatin; investigational agent (sEphB4-HSA) + pembrolizumab (best response was PD)
• CX-2029treatment initiated (January 2020)
• Partial response at Week 8 confirmed 8 weeks later. Dose reduced to 2 mg/kg; additional shrinkage of liver target lesion seen.

18 Dec 2019	13 Mar 2020 (43% ↓)	28 Aug 2020 (84% ↓)
Baseline	Week 8	Week 27

Data cut-off: August 2020.	24

CX-2029 Phase 1 Tolerability Supports Phase 2 Dose of 3mg/kg

Generally Well Tolerated to 3 mg/kg with Manageable Adverse Events

			RP2D
Treatment-Related	1.0	2.0	3.0	4.0	5.0
Grade 3+ AEs	• > 90% masking maintained in circulation
mg/kg	mg/kg	mg/kg	mg/kg	mg/kg
(≥2 patients)
(n=3)	(n=8)	(n=12)	(n=6)	(n=4)
	• Most frequent Grade 3+ AE was anemia
Anemia	33%	63%	58%	83%	100%	- Managed with red blood cell
						transfusions, growth factor support
Neutropenia	0	0	33%	50%	75%	and/or dose delays/reductions
						- Likely multi-factorial including CD71
Leukopenia	0	0	8%	33%	50%	biology and MMAE payload

Infusion-related					•	3 mg/kg Q3W selected as Phase 2 dose
0	13%	0	17%	0
reaction

Data cut-off: August 2020	25

Phase 2 Expansion Underway to Evaluate CX-2029 in Four Cohorts

Monotherapy at 3 mg/kg Q3W

Eligibility

Cancer Type

Endpoints

sqNSCLC, HNSCC and esophageal

• Prior therapy must include prior platinum and a checkpoint inhibitor (alone or in combination; if approved by the local Health Authority).
• For esophageal: squamous, adenocarcinoma or GE junction; prior HER2-targeted therapy if tumor is HER2+
• Documented progression after at least one prior regimen for advanced disease

DLBCL

• Progression after at least 2 prior regimens (one of which must be anti-CD20 based therapy); not a candidate for stem cell transplant

sqNSCLC

n~25*

HNSCC

n~25*

Esophageal/GEJ

n~25*

DLBCL

n~25*

*Evaluable

Primary: Overall Response Rate (ORR) by local investigator

Secondary: PFS, DCR, CBR24, DoR, OS, Safety, PK, ADA, TTR

Exploratory: Biomarker correlation with outcome

Readout: Initial data expected Q4 2021

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CX-2043

Anti-EpCAM(TROP-1) Conditional ADC

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CX-2043: Conditional ADC Targeting EpCAM/TROP-1

CX-2043

DM21 linker- payload

DAR ~ 4

EPCAM

• CX-2043generated in collaboration with Immunogen
• CytomX retains WW development and commercial rights

Target Background

• Epithelial cell marker; Highly expressed on solid tumors
• EpCAM-targetedtherapies can be active when delivered locally
• On-target /off-tumor toxicities limit systemic delivery

CX-2043:EpCAM-targeting PDC

• Next-generationlinker-payload system with enhanced stability and improved bystander activity
• Probody platform alleviates on-target /off-tumor toxicity (pancreatitis, GI tox)

Presented at EORTC-NCI-AACR 2020

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Alliances and Financials

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Strong Alliances Advancing Multiple Programs and Probody Formats

CHECKPOINT INHIBITORS	PROBODY	T-CELL	T-CELL
DRUG CONJUGATES	BISPECIFICS	BISPECIFICS
LEAD PROGRAMS: Expanding	LEAD PROGRAM: CD71 (CX-2029)	LEAD PROGRAM: CX-904	Conditional T-Cell Bispecifics
Therapeutic Window for CTLA-4
	Global co-development alliance	EGFR-CD3 conditional T-Cell	Alliance formed March 2020
BMS-986249 ipilimumab		bispecific
Probody in melanoma Phase 2	CytomX retained US rights (35%)		$80 million upfront
	and >20% royalties ex-US	IND enabling studies for
BMS-986288non-fucosylated		potential 2021 IND
ipilimumab Probody in Phase 1

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Strong Balance Sheet to Support Pipeline and Operations

$321M in cash as of Sept. 30th 2020

$130M of non-dilutive capital in 2020

• $80M upfront from Astellas
• $40M CX-2029 milestone from AbbVie
• $10M anti-CTLA-4 milestone from BMS

No debt

46.2M shares outstanding

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Leadership in Conditionally-Active Antibodies with Validated Platform

Summary

• Versatile, multi-modality platform
• Five clinical stage assets
• 2 conditional ADCs in Phase 2
• • CX-2009,CX-2029
• 2 conditional checkpoint inhibitors in Phase 2
• • CX-072(+ CX-2009)
  • BMS-986249
• Emerging T-cell bispecifics
• Robust platform and preclinical pipeline
• Strong alliances

2021

Priorities

• Patient enrollment into CX-2009 Ph 2 study
• • HR+/HER2 non-amplified breast cancer
  • TNBC +/‒ CX-072
  • Initial data expected Q4 2021
• Patient enrollment into CX-2029 Ph 2 expansions
• • sqNSCLC, HNSCC, esophageal, DLBCL
  • Initial data expected Q4 2021
• IND submission
• • CX-2043
  • CX-904
• Continued progress within partnerships

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CytomX Therapeutics Inc.

Our	Our	Our	Our
VISION	PLATFORM	PRODUCTS	TOMORROW

Create

a new approach to the treatment of cancer by improved tumor targeting

Lead

in conditional activation of antibody-drug conjugates and other modalities

Advance	Build
a broad clinical pipeline of	a long-term, commercial
anti-cancer therapies in areas	stage, multi-product
of significant unmet need	enterprise

PROBODY is a U.S. registered trademark of CytomX Therapeutics, Inc. All other brands and trademarks referenced
herein are the property of their respective owners.	33

Questions and Answers

© 2021 CytomX Therapeutics, Inc.

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