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 |
4
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
5
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 |
9
CX-2009(Praluzatamab ravtansine)
Anti-CD166 Conditional ADC for HER2 non-Amplified Breast Cancer
10
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 | 11 |
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 | 12 |
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 | 13 |
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 | 14 |
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 | 15 |
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 | 16 |
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 | 17 |
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 |
20
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
26
CX-2043
Anti-EpCAM(TROP-1) Conditional ADC
27
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 | 28 |
Alliances and Financials
29
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 |
30
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
31
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. | 34 |
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CytomX Therapeutics Inc. published this content on 14 January 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 14 January 2021 21:05:03 UTC