subslover
3月前
CytomX Therapeutics Announces 2025 Financial Results and Provides Business Update
- Announced Positive Data from Phase 1 Dose Expansion Study of varsetatug masetecan (“Varseta-M”) EpCAM PROBODY® ADC in Patients with Advanced Colorectal Cancer (CRC) -
- FDA interactions targeted for mid-year with goal to align on potential Varseta-M registrational trial design in late line CRC -
- Varseta-M Phase 1 study evaluating combination with bevacizumab initiated; Phase 1b/2 chemotherapy combination study to be initiated by the end of 2026 -
- Initial CX-801 PROBODY Interferon-alpha-2b Phase 1 combination data with KEYTRUDA® (pembrolizumab) in melanoma expected by the end of 2026 -
- Company to host conference call today at 8 a.m. ET / 5 a.m. PT -
SOUTH SAN FRANCISCO, Calif., March 16, 2026 (GLOBE NEWSWIRE) -- CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, today announced 2025 financial results and provided a business update.
“Today’s encouraging Varseta-M Phase 1 update underscores the program’s intentional design and broad potential in CRC as well as other EpCAM-expressing indications. CytomX’s top priority in 2026 is to align with the FDA on a registrational path for Varseta-M in late-line CRC. We also plan to accelerate Varseta-M combination studies to benefit CRC patients in earlier lines of treatment,” said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX.
“Our continued and exciting progress with Varseta-M reinforces our leadership in the field of masking and CytomX’s ability to unlock true innovation. Our highly focused portfolio strategy is also illustrated by our second clinical program, CX-801. This masked version of Interferon-alpha-2b is being developed initially in advanced melanoma and, we believe, has the potential to become a new centerpiece of combination immunotherapy across multiple cancers. The CX-801 translational and biomarker data presented to date have been very encouraging, and we expect to share initial proof of concept data for the combination with KEYTRUDA® later this year.”
Pipeline Program Updates:
Varsetatug masetecan (EpCAM PROBODY Topo-1 ADC, CX-2051)
Announced positive data update from Phase 1 dose expansion study of Varseta-M in patients with advanced colorectal cancer (CRC).
The Company aims to align with the FDA in 2026 on a potential registrational study design for Varseta-M monotherapy in advanced CRC.
Additional Phase 1 follow-up data are also expected to be presented at major medical meeting(s) in 2026.
A Phase 1 Varseta-M combination study with bevacizumab in CRC has been initiated and a Phase 1b/2 study in combination with bevacizumab and chemotherapy is expected to start by the end of 2026.
Initiation of Phase 1 expansion cohort(s) in additional indications is planned for 2H 2026.
CX-801 (PROBODY Interferon alpha-2b)
The CX-801 Phase 1 study is progressing with a focus in advanced melanoma. The CX-801 monotherapy dose escalation portion of the study has reached the fourth dose level.
CX-801 monotherapy has been well tolerated at dose levels exceeding the approved dose of unmasked IFNa2b.1
In May 2025, Phase 1 dose escalation of CX-801 in combination with KEYTRUDA® (pembrolizumab) was initiated. Dose escalation of CX-801 in combination with KEYTRUDA® is currently enrolling the 2nd dose level.
Biomarker data from the CX-801 monotherapy study in advanced melanoma were presented at the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting, reinforcing CX-801’s mechanism of action and supporting the ongoing combination trial with KEYTRUDA®.
Initial clinical data for CX-801 in combination with KEYTRUDA® in advanced melanoma is projected by the end of 2026.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Corporate and Financial:
Financial: CytomX ended 2025 with $137.1 million of cash, cash equivalents and investments with expected cash runway to the second quarter of 2027.
Research Pipeline and Collaborations: CytomX has research collaborations with Bristol Myers Squibb, Amgen, Regeneron, and Moderna. Multiple drug discovery programs continue across our research collaborations with a focus on bispecific immunotherapies, including T-cell engagers.In March 2026, Astellas chose to not advance the remaining preclinical research programs under the alliance resulting in a termination of the collaboration effective in the second quarter of 2026.
Full Year 2025 Financial Results:
Cash, cash equivalents and investments totaled $137.1 million as of December 31, 2025, compared to $100.6 million as of December 31, 2024.
Total revenue was $76.2 million for the year ended December 31, 2025, compared to $138.1 million in 2024. The decrease in revenue was driven primarily by the completion of our performance obligations in our collaboration with Bristol Myers Squibb in April 2025 as well as a lower estimated percentage of performance obligation completion for 2025 compared to 2024 in the Moderna, Astellas, and Regeneron collaborations.
In 2025, CytomX remained focused on controlling costs and efficiently progressing its pipeline programs. Total operating expense for 2025 was $98.6 million compared to $113.1 million for 2024, a decrease of $14.5 million.
Research and development expenses decreased by $14.7 million during the year ended December 31, 2025, to $68.7 million compared to $83.4 million for 2024. Research and development expenses decreased primarily due to lower general research and development expenses as a result of our January 2025 restructuring and reduced expenses for CX-904, partially offset by increased manufacturing and clinical spend on Varseta-M.
General and administrative expenses increased by $0.1 million during the year ended December 31, 2025, to $29.8 million, compared to $29.7 million for 2024. The general and administrative expenses for 2025 included $1.1 million of one-time restructuring expenses partially offset by reduced personnel related expenses and legal and consulting related expenses.
About CytomX Therapeutics, Inc.
CytomX is a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel conditionally activated, masked PROBODY® therapeutics designed to be localized to the tumor microenvironment. By pioneering a novel pipeline of localized biologics, powered by its PROBODY therapeutic platform, CytomX’s vision is to create safer, more effective therapies for the treatment of cancer. CytomX’s robust and differentiated pipeline comprises therapeutic candidates across multiple treatment modalities including antibody-drug conjugates (“ADCs”), cytokines and T-cell engagers. CytomX’s clinical-stage pipeline includes varsetatug masetecan (Varseta-M; CX-2051) and CX-801. Varseta-M is a masked, conditionally activated ADC armed with a topoisomerase-1 inhibitor payload and directed toward epithelial cell adhesion molecule (EpCAM). EpCAM is a highly expressed tumor antigen that has previously been undruggable due to expression on normal tissues. Varseta-M is designed to open a therapeutic window for this high potential target and is initially being developed for the treatment of metastatic colorectal cancer. Varseta-M was discovered in collaboration with ImmunoGen, now part of AbbVie. CX-801 is a masked interferon alpha-2b PROBODY® cytokine with broad potential applicability in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. CX-801 is initially being developed for the treatment of metastatic melanoma. CytomX has established strategic collaborations with multiple leaders in oncology, including Amgen, Bristol Myers Squibb, Regeneron and Moderna. For more information about CytomX and how it is working to make conditionally activated treatments the new standard-of-care in the fight against cancer, visit www.cytomx.com and follow us on LinkedIn and X (formerly Twitter).
CytomX Therapeutics Forward-Looking Statements
This press release includes forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that are difficult to predict, may be beyond CytomX’s control, and may cause the actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied in such statements, including those related to the future potential of partnerships or collaboration agreements and projected cash runway. Accordingly, you should not rely on any of these forward-looking statements, including those relating to the potential benefits, safety and efficacy or progress of CytomX’s or any of its collaborative partners’ product candidates, including varsetatug masetecan (Varseta-M; CX-2051) and CX-801, the potential benefits or applications of CytomX’s PROBODY® therapeutic platform, CytomX's planned interactions with the U.S. Food and Drug Administration and the ability to align on a potential registrational study design and regulatory pathway for varsetatug masetecan, CytomX’s or its collaborative partners’ ability to develop and advance product candidates into and successfully complete clinical trials, including the ongoing and planned clinical trials of varsetatug masetecan and CX-801 and the timing of initial
INV4
1年前
CytomX Therapeutics Announces First Quarter 2025 Financial Results and Provides Business Update
May 12 2025
CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, today announced first quarter 2025 financial results and provided a business update.
“Our positive interim clinical results announced today for CX-2051 in advanced colorectal cancer are highly encouraging and provide a significant opportunity for CytomX. As an EpCAM-directed ADC, CX-2051 was intentionally designed to address the high unmet need in CRC. CX-2051 remains the Company’s top strategic priority and is positioned to rapidly advance towards later stage development. Just one year into the clinic, CX-2051 dose expansions are already in progress with a goal to initiate a Phase 2 study in advanced CRC in the first half of 2026. This excellent progress underscores the intense focus of the CytomX team on diligent execution for the benefit of the patients we serve,” said Sean McCarthy, D.Phil., chief executive officer and chairman of CytomX.
Pipeline Program Updates:
CX-2051 (EpCAM PROBODY Topo-1 ADC)
Announced positive interim data from ongoing Phase 1 dose escalation study of EpCAM Antibody Drug Conjugate (CX-2051) candidate in patients with advanced colorectal cancer (CRC).
Initiated CX-2051 dose expansions at the 7.2 mg/kg, 8.6 mg/kg, and 10 mg/kg doses, administered every three weeks (Q3W).
Phase 1 data update in advanced CRC in at least 70 patients is expected to be presented by Q1 2026.
Planning Phase 2 study initiation in 1H 2026
CX-801 (PROBODY Interferon alpha-2b)
Phase 1 dose escalation continues with a focused early development strategy in metastatic melanoma and with the goal of initiating combination therapy with CX-801 and KEYTRUDA® in 2025.
The Phase 1 study is currently in the fourth monotherapy dose escalation cohort where the dose of CX-801 exceeds the approved dose of the unmasked peginterferon alfa-2b (SYLATRON™)1.
Initial Phase 1a translational and biomarker data in advanced melanoma is expected in the second half of 2025.
KEYTRUDA® is a registered trademark of Merck Sharp & Dohme LLC, a subsidiary of Merck & Co., Inc., Rahway, NJ, USA
Corporate and Financial:
Financial:
Focused clinical development priorities and cost reductions implemented in Q1 2025 have extended the Company’s cash runway into the second quarter of 2026. CytomX ended the first quarter of 2025 with $79.9 million of cash, cash equivalents and investments.
Research collaborations:
Milestone achieved in Astellas T-cell engager collaboration: In February 2025, Astellas advanced the second program to GLP toxicology studies, triggering a $5.0 million milestone payment to CytomX.
Presented preclinical data for mRNA encoded masked IL-12 molecule in collaboration with Moderna at AACR Annual Meeting showing potent anti-tumor activity with significantly enhanced tolerability vs. unmasked IL-12 molecule.
Multiple drug discovery programs continue across our research collaborations with a focus on T-cell engagers. CytomX has research collaborations with Bristol Myers Squibb, Amgen, Astellas, Regeneron, and Moderna.
First Quarter 2025 Financial Results:
Cash, cash equivalents and investments totaled $79.9 million as of March 31, 2025, compared to $100.6 million as of December 31, 2024.
Total revenue was $50.9 million for the quarter ended March 31, 2025, compared to $41.5 million for the quarter ended March 31, 2024. The increase in revenue was driven primarily by a higher percentage of completion for research programs in the Bristol Myers Squibb collaboration and the acceleration of revenue recognition in the Amgen collaboration due to the decision to not further develop the CX-904 program, partially offset by lower Astellas milestones and Moderna revenue.
Total operating expense in the first quarter of 2025 was $28.3 million compared to $29.8 million in the first quarter of 2024, a decrease of $1.5 million. Operating expenses in the first quarter of 2025 included $2.9 million of one-time expenses related to the Company’s January 2025 restructuring.
Research and development expenses were $18.9 million for the three months ended March 31, 2025, a decrease of $3.2 million compared to the corresponding period of 2024. Reduced research and development expenses were primarily due to reduced pre-clinical activities in wholly owned and partnered programs and decreased manufacturing activities for CX-801, partially offset by increased clinical trial activities related to CX-2051 and CX-801, and $1.8 million of restructuring expenses.
General and administrative expenses were $9.4 million for the three months ended March 31, 2025, an increase of $1.7 million compared to the corresponding period of 2024. The increase in general and administrative expenses was primarily driven by $1.1 million of restructuring expenses as well as other personnel-related expenses.
____________________________
1 SYLATRON Prescribing Information
About CytomX Therapeutics
CytomX is a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel conditionally activated, masked biologics designed to be localized to the tumor microenvironment. By pioneering a novel pipeline of localized biologics, powered by its PROBODY® therapeutic platform, CytomX’s vision is to create safer, more effective therapies for the treatment of cancer. CytomX’s robust and differentiated pipeline comprises therapeutic candidates across multiple treatment modalities including antibody-drug conjugates (ADCs), T-cell engagers, and immune modulators such as cytokines. CytomX’s clinical-stage pipeline includes CX-2051 and CX-801. CX-2051 is a masked, conditionally activated ADC directed toward epithelial cell adhesion molecule (EpCAM), armed with a topoisomerase-1 inhibitor payload. CX-2051 has potential applicability across multiple EpCAM-expressing epithelial cancers, including CRC, and was discovered in collaboration with ImmunoGen. CX-801 is a masked interferon alpha-2b PROBODY® cytokine with broad potential applicability in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. CytomX has established strategic collaborations with multiple leaders in oncology, including Amgen, Astellas, Bristol Myers Squibb, Regeneron and Moderna. For more information about CytomX and how it is working to make conditionally activated treatments the new standard-of-care in the fight against cancer, visit www.cytomx.com and follow us on LinkedIn and X (formerly Twitter).
CytomX Therapeutics Forward-Looking Statements
This press release includes forward-looking statements. Such forward-looking statements involve known and unknown risks, uncertainties and other important factors that are difficult to predict, may be beyond our control, and may cause the actual results, performance, or achievements to be materially different from any future results, performance or achievements expressed or implied in such statements, including those related to CX-2051. Accordingly, you should not rely on any of these forward-looking statements, including those relating to the potential benefits, safety and efficacy or progress of CytomX’s or any of its collaborative partners’ product candidates, including CX-2051 and CX-801, the potential benefits or applications of CytomX’s PROBODY® therapeutic platform, CytomX’s or its collaborative partners’ ability to develop and advance product candidates into and successfully complete clinical trials, including the ongoing and planned clinical trials of CX-2051 and CX-801 and the timing of initial and ongoing data availability for our clinical trials, including CX-2051 and CX-801, and other development milestones. Risks and uncertainties that contribute to the uncertain nature of the forward-looking statements include: the unproven nature of CytomX’s novel PROBODY® therapeutic technology; uncertainties around the Company’s ability to raise sufficient funds to carry out its planned research and development; CytomX’s clinical trial product candidates are in the initial stages of clinical development and its other product candidates are currently in preclinical development, and the process by which preclinical and clinical development could potentially lead to an approved product is long and subject to significant risks and uncertainties, including the possibility that the results of preclinical research and early clinical trials, including initial CX-2051 results, may not be predictive of future results; the possibility that CytomX’s clinical trials will not be successful; the possibility that current preclinical research may not result in additional product candidates; CytomX’s dependence on the success of CX-2051 and CX-801; CytomX’s reliance on third parties for the manufacture of the Company’s product candidates; possible regulatory developments in the United States and foreign countries, including China and the European Union; and the risk that we may incur higher costs than expected for research and development or unexpected costs and expenses or may not obtain expected savings from our announced restructuring. Additional applicable risks and uncertainties include those relating to our preclinical research and development, clinical development, and other risks identified under the heading "Risk Factors" included in CytomX’s Quarterly Report on Form 10-Q filed with the SEC on May 12, 2025. The forward-looking statements contained in this press release are based on information currently available to CytomX and speak only as of the date on which they are made. CytomX does not undertake and specifically disclaims any obligation to update any forward-looking statements, whether as a result of any new information, future events, changed circumstances or otherwise.
PROBODY is a U.S. registered trademark of CytomX Therapeutics, Inc. All other trademarks are the properties of their respective owners.
Company Contact:
Chris Ogden
SVP, Chief Financial Officer
cogden@cytomx.com
Investor Contact:
Precision AQ (formerly Stern Investor Relations)
Stephanie Ascher
Stephanie.Ascher@precisionaq.com
Media Contact:
Redhouse Communications
Teri Dahlman
teri@redhousecomms.com
https://ih.advfn.com/stock-market/NASDAQ/cytomx-therapeutics-CTMX/stock-news/96035605/cytomx-therapeutics-announces-first-quarter-2025-f
$CTMX
INV4
1年前
CytomX Therapeutics Announces Pricing of $100 Million Underwritten Offering of Common Stock
May 12 2025
CytomX Therapeutics, Inc. (NASDAQ:CTMX), a leader in the field of masked, conditionally activated biologic therapeutics, today announced the pricing of an underwritten offering of 76,923,076 shares of its common stock at an offering price of $1.30 per share, before underwriting discounts and commissions. All of the shares are being offered by the Company. The gross proceeds from the offering are expected to be approximately $100 million before deducting underwriting discounts and commissions and other offering expenses. The offering is expected to close on May 13, 2025, subject to customary closing conditions.
The Company intends to use the net proceeds from this offering for research and development, general corporate purposes and working capital needs.
The offering was led by Longitude Capital and also included participation from OrbiMed, Venrock Healthcare Capital Partners, Vivo Capital, RTW Investments, and a large investment management firm, among other funds. Jefferies and Piper Sandler are acting as joint book-running managers for the offering.
The securities described above are being offered pursuant to an effective shelf registration statement that was filed with the U.S. Securities and Exchange Commission (SEC) on August 9, 2024. This offering is being made only by means of a prospectus supplement and the accompanying prospectus which forms a part of the effective shelf registration statement.
A prospectus supplement related to the offering (including the accompanying prospectus) will be filed with the SEC and will be available on the SEC’s website located at www.sec.gov. Copies of the prospectus supplement related to the offering and the accompanying prospectus may be obtained, when available, by visiting the SEC’s website or by contacting: Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10022, by telephone at (877) 821-7388, or by email at prospectus_department@jefferies.com; or Piper Sandler & Co., Attention: Prospectus Department, 800 Nicollet Mall, J12S03, Minneapolis, MN 55402, or by telephone at (800) 747-3924, or by email at prospectus@psc.com.
This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, the securities in this offering in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of such state or jurisdiction.
About CytomX Therapeutics
CytomX is a clinical-stage, oncology-focused biopharmaceutical company focused on developing novel conditionally activated, masked biologics designed to be localized to the tumor microenvironment. By pioneering a novel pipeline of localized biologics, powered by its PROBODY® therapeutic platform, CytomX’s vision is to create safer, more effective therapies for the treatment of cancer. CytomX’s robust and differentiated pipeline comprises therapeutic candidates across multiple treatment modalities including antibody-drug conjugates (ADCs), T-cell engagers, and immune modulators such as cytokines. CytomX’s clinical-stage pipeline includes CX-2051 and CX-801. CX-2051 is a masked, conditionally activated ADC directed toward epithelial cell adhesion molecule (EpCAM), armed with a topoisomerase-1 inhibitor payload. CX-2051 has potential applicability across multiple EpCAM-expressing epithelial cancers, including CRC, and was discovered in collaboration with ImmunoGen. CX-801 is a masked interferon alpha-2b PROBODY® cytokine with broad potential applicability in traditionally immuno-oncology sensitive as well as insensitive (cold) tumors. CytomX has established strategic collaborations with multiple leaders in oncology, including Amgen, Astellas, Bristol Myers Squibb, Regeneron and Moderna.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Certain statements contained in this press release, including those relating to the timing and completion of the offering and the satisfaction of customary closing conditions related to the offering, the anticipated total gross proceeds from the offering and the planned use of proceeds of the offering, are forward-looking statements that involve a number of risks and uncertainties that could cause actual results to differ materially from those in the forward-looking statements. These risks and uncertainties include, but are not limited to, risks and uncertainties associated with the consummation of the offering, the satisfaction of customary closing conditions related to the offering, the completion of the offering on the anticipated terms or at all, general economic conditions and other risks identified from time to time in the reports the Company files with the SEC, including its Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, Current Reports on Form 8-K, and the prospectus supplement and accompanying prospectus related to the offering to be filed with the SEC, which are available at www.sec.gov. The forward-looking statements in this press release speak only as of the date of this document, and the Company undertakes no obligation to update or revise any of the statements. The Company’s business is subject to substantial risks and uncertainties, including those referenced above. Investors, potential investors, and others should give careful consideration to these risks and uncertainties.
Company Contact:
Chris Ogden
SVP, Chief Financial Officer
cogden@cytomx.com
Investor Contact:
Precision AQ (formerly Stern Investor Relations)
Stephanie Ascher
Stephanie.Ascher@precisionaq.com
Media Contact:
Redhouse Communications
Teri Dahlman
teri@redhousecomms.com
https://ih.advfn.com/stock-market/NASDAQ/cytomx-therapeutics-CTMX/stock-news/96035773/cytomx-therapeutics-announces-pricing-of-100-mill
$CTMX
Helter Skelter
2年前
CytomX Therapeutics, Inc. (NASDAQ:CTMX) Q1 2024 Earnings Call Transcript
Insider Monkey Transcripts
Thu, May 9, 2024, 1:17 PM PDT24 min read
In This Article:
CTMX
-2.94%
CytomX Therapeutics, Inc. (NASDAQ:CTMX) Q1 2024 Earnings Call Transcript May 8, 2024
CytomX Therapeutics, Inc. beats earnings expectations. Reported EPS is $0.1669, expectations were $-0.03. CytomX Therapeutics, Inc. isn’t one of the 30 most popular stocks among hedge funds at the end of the third quarter (see the details here).
Operator: Good day, and thank you for standing by. Welcome to the CytomX Therapeutics First Quarter 2024 Financial Results Conference Call. At this time, all participants are in a listen only-mode. After the speaker's presentation there will be a question-and-answer session. [Operator Instructions] Please be advised that, today's conference is being recorded. I would now like to turn the conference over to your speaker today, Chris Ogden, CytomX's Senior Vice President, Finance and Accounting. Please go ahead.
Chris Ogden: Thank you. Good afternoon and thank you for joining us. Before we begin, I would like to remind everyone that, during this call, we will be making forward-looking statements. Because forward-looking statements relate to the future, they are subject to inherent uncertainties and risks that are difficult to predict and many of which are outside of our control. Important risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. We undertake no obligation to update any forward-looking statements, whether as a result of new information, future developments or otherwise. Earlier this afternoon, we issued a press release that includes a summary of our first quarter 2024 financial results and highlights recent progress at CytomX.
We also issued a press release today announcing positive initial Phase 1a dose escalation data for monotherapy CX-904 which will be the primary focus of today's call. We encourage everyone to read today's press releases and the associated materials, which have been filed with the SEC. Additionally, the press release, a recording of this call and our SEC filings can be found under the Investors and News section of our website. With me on the call today is Dr. Sean McCarthy, CytomX’s Chief Executive Officer and Chairman; Dr. Wayne Chu, CytomX's Chief Medical Officer. Sean will provide an update on the overall pipeline and also outline CytomX's broader strategy for mast T-cell engagers. Wayne will then give an update on the CX-904 Phase 1 dose escalation study before Sean provides closing comments and we open up the call for Q&A.
With that, I'll now turn the call over to Sean.
Sean McCarthy: Thanks, Chris, and good afternoon, everyone. It's a pleasure to be here today to share considerable progress during Q1, including our initial findings from our Phase 1 study of our EGFR targeted PROBODY T-cell engager CX-904. CytomX is highly focused on addressing major unmet needs in oncology using our PROBODY therapeutic platform, a proprietary antibody masking strategy designed to improve the therapeutic window for multiple antibody modalities through tumor localized activation. We are leveraging our PROBODY therapeutic platform to discover and develop new cancer therapies based on masked T-cell engagers, masked ADCs, and masked cytokines. Our broad and deep pipeline encompasses more than 15 active programs, including three clinical stage molecules and significant retained commercial rights.
Strategic partnering is a long standing components of our corporate strategy, and we're proud to be working closely with Bristol Myers Squibb, Amgen, Astellas, Regeneron, and Moderna on multiple PROBODY Therapeutic Programs. We continue to be in a strong financial position with $150 million of cash at the end of Q1, which provides cash runway to the end of 2025, not including any milestone payments under our existing collaborations or any potential new partnership funding. CytomX is very strong organizationally with integrated R&D capabilities, continued investment in our core technology, and a deeply experienced team dedicated to our vision of transforming lives with safer, more effective therapies. Moving to Slide 6, the CytomX product design strategy using our PROBODY Therapeutic platform is informed by more than a decade of experience and seeks to balance target selection, masking strategy and effective function to make meaningful impact in key areas of unmet need in oncology.
CX-904 brings the EGFR target together with T-cell engagement via CD3 with the goal of T-cell mediated killing of EGFR positive tumor types, potentially including those for which conventional antibodies have not shown activity. CX-2051 is our masked conditionally activated ADC that integrates the high potential of EpCAM as a cancer cell target with the potency of a topo-1 inhibitor payload ideally suited we believe to high EpCAM expressing tumors like colorectal cancer. CX-801 leverages the potent activity of the cytokine interferon alpha, which in this case is the effective mechanism itself. Our marked interferon is designed to locally activate the anti-tumor immune microenvironment with potential to drive responses across multiple cancer types, including melanoma, renal cell carcinoma and head and neck squamous cell carcinoma.
Q1 was an extremely productive quarter for CytomX. We are executing to our plans, and we're making progress across the full breadth of our pipeline. Today, we're announcing positive initial Phase 1a dose escalation data for monotherapy CX-904, our EGFR CD3 T-cell engager in solid tumors, and this is the main topic of our update here today. In addition to our exciting progress with CX-904, during Q1, the first dose cohort cleared in the Phase 1 clinical study of 2051, our ADC targeting EpCAM. This study is focused largely in colorectal cancer. And we anticipate initial data in the first half of 2025. Also during Q1, Phase 1 study initiation activities continued for CX-801, our masked interferon alpha, including the execution of an agreement with Merck to supply KEYTRUDA for combination with CX-801, and we announced that agreement last night.
Initial data from the 801 program is also anticipated in 2025. We continue to make excellent progress across our collaborations, including earning $10 million of milestones under our T-cell engaging bispecific collaboration with Astellas that was to preclinical progress on the first two programs in the alliance. We're also delighted to welcome Dr. Zhen Su to our board during Q1. So, a really productive start to 2024 for CytomX on all fronts and our current clinical pipeline is really gaining momentum and we have a very exciting 12 to 24 months ahead of us. Moving now to our T-cell engager strategy, T-cell engaging bispecific antibodies, of course, have enormous potential for the treatment of cancer and first demonstrated meaningful clinical benefit in hematologic malignancies.
Looking at the solid tumor landscape for T-cell engagers, however, it's taken time to see meaningful clinical progress. And for this modality to really breakthrough in solid tumors, there are some significant challenges to overcome. Notably, T-cell engagers bring very high potency and this potency can lead to toxicities in normal tissues, where the tumor antigen of interest may also be present. Another key limitation for T-cell engagers in solid tumors is cytokine release syndrome, resulting from systemic binding to CD3 on T-cells and also neurotoxicity in the form of ICANS. At CytomX, we have a broad based program focused on masking T-cell engagers to decrease tumor adjuvant binding in normal tissues and also decrease CD3 binding in the periphery, thereby improving therapeutic index.
In addition to our internal programs, we're working with partners Amgen, Astellas, Regeneron, and BMS in this exciting space. CX-904 is our lead program in the T-cell engager area, and I'd like to spend a few minutes now walking through the history and structure of this molecule. We've had a longstanding interest in EGFR CytomX, our seminal publication of the first ever successful antibody masking was focused on the EGFR binding antibody cetuximab, for which we showed a marked reduction in systemic skin rash for the masked antibody compared to the unmasked version. These findings set the stage for the evolution of the monospecific EGFR PROBODY into our CX-904 bispecific T-cell engager. We've reasoned that EGFR as a target has so much more potential to be realized and the realization of this potential would require a more potent effect of mechanism leading us to the concept of the mass EGFR CD3 strategy encompassed in CX-904.
We did actually publish an early lead molecule from this program in cancer research to demonstrate preclinical proof-of-concept, and we subsequently refined the structure using the depth of our platform and in collaboration with our partner Amgen. The next slide shows the molecular architecture of 904. CX-904 has one CD3 binding domain and one EGFR binding domain. Both domains are masked with unique peptides. Furthermore, the protease clinical substrates are different in each binding domain, reflecting our preclinical fine tuning strategy for optimization of therapeutic window. CX-904 also has an Fc region and so it would be expected to have an antibody like half life. This overall structure is somewhat similar to Amgen's Tarlatamab that has shown impressive results in small cell lung cancer.
Shown on the right of this slide is a recap of the therapeutic concept for CX-904 and for our platform generally. The concept is that masking reduces drug binding to target in normal tissues, whereas in tumor tissue, the masks are removed by activated tumor proteases. This tumor localization leads to the improvement or creation of a therapeutic window. For the EGFR CD3 antigen pair, it's been shown previously that the unmarked bispecific is highly toxic in preclinical models. So, our marketing strategy is, we believe, essential for creating a therapeutic window. In terms of the toxicities we're looking to mitigate, EGFR antibodies are well known to cause rash and gastrointestinal side effects. And so, we've been specifically looking out for our marketing strategy to really limit serious EGFR toxicities, particularly Grade 3 and above.
With regard to CD3, our marketing strategy is of course designed to limit CRS and ICANS. Before handing over to Wayne, let me review the high-level goals and achievements to date for our Phase 1 study of CX-904. Given the really high potency of T-cell engagers and the widespread expression of EGFR, goal number one for this study has been to evaluate the safety of 904, and we've made excellent progress as you will see from Wayne's presentation. We've explored non-step and step dosing. We were very pleased to see very limited CRS with non-step dosing, we believe because of successful CD3 masking. And in step dosing cohorts, rather remarkably, we've seen no CRS at all. We've also seen no evidence of ICANS at any dose level or schedule. Furthermore, while we have seen some EGFR toxicities, these have been manageable and have not limited us in achieving therapeutically active doses.
Again, this shows the success we believe of our EGFR marking strategy, and this success of EGFR marking is consistent with our prior published work that I mentioned earlier. Goal number 2 of our Phase 1 study has, of course, been to look for initial signs of anti-tumor activity. As we've said in recent months, any evidence of tumor stabilization or tumor shrinkage in this first in human study will be very encouraging. I want to emphasize that the patient population we've enrolled to date in this Phase 1 study is heavily pretreated and is a range of tumor types and is unselected for EGFR. All that said, we're delighted to announce today very encouraging early signs of anticancer activity for 904, including confirmed resist responses in pancreatic cancer, a very difficult to treat tumor type that is not typically responsive to EGFR inhibition or for that matter to immunotherapy.
Moreover, our initial assessments of pharmacodynamics are supportive of the mechanism of action of CX-904 as a mask T-cell engager, providing crucial platform proof-of-concept with read through, we believe, to the many other programs we're working on at CytomX. Importantly, this Phase 1 study is ongoing. We're continuing to dose escalate and enroll multiple tumor types, but our next goal is to determine recommended Phase 2 dose and to define plans for Phase 1b expansions. We see the data that we're sharing today as a very promising initial step in the development of CX-904, and this work positions CytomX at the forefront of the T-cell engager field. Now, let me hand over to Wayne to review the data in some detail.
Wayne Chu : Thanks Sean, and thanks everyone for the opportunity to share our early clinical and translational observations in the ongoing dose escalation study. This slide summarizes the dose escalation scheme, key eligibility criteria, and study objectives. Patients with tumors with known EGFR expression were enrolled. However, patients were not selected based on EGFR expression. Dose escalation was initiated using a non-step dosing schedule in which CX-904 was dosed once every two weeks. Doses starting from 7 micrograms through 6 milligrams were tested. As we will discuss in the subsequent slides, dose escalation of CX-904 continued using a step dosing schedule with an initial target dose of 5 milligrams. Various step dosing schedules were tested, after which the target dose was administered every two weeks.
The data presented today represents safety and efficacy data from a total of 13 dose escalation cohorts through the 10 milligram target dose. And as Sean mentioned, dose escalation continues with the current enrollment testing, the 15 milligram target dose. Selected baseline characteristics for enrolled patients are shown in this slide. The majority of patients enrolled in non-step dosing escalation cohorts were those with microsatellite stable or MSS colorectal cancer, which I will perm CRC from here on out, which has been demonstrated to be unresponsive to immune therapies, such as in checkpoint inhibitors. With step dosing escalation cohorts, we have begun to focus on patients with tumors with early evidence of clinical activity as well as other tumor types with known EGFR expression.
A researcher in a lab coat observing a microscope, studying molecules in the companys antibody therapeutics.
A researcher in a lab coat observing a microscope, studying molecules in the companys antibody therapeutics.
As is typical for a Phase I first in human dose escalation study, patients had advanced late line disease. Enrolled patients received a median of four prior cancer therapies, many were refractory to their last prior therapy, and a considerable proportion received prior EGFR and or PD-1 and PD-L1 directed therapy. Early clinical pharmacokinetic data from the non-step dosing schedule was consistent with the CX-904 PROBODY T-cell engager design. The graph on the left shows that total CX-904 exposure increases linearly with increasing dose, indicating no apparent change in dose dependent clearance or evidence of target mediated drug disposition. The graph on the right shows the cycle 1 PK profile of CX-904 at the 3 milligram dose level. The three curves show circulating analyte concentrations of intact or masked CD3, intact EGFR and total PROBODY.
Notably, the three curves are essentially superimposable, indicating that CX-904 exists in circulation in predominantly intact or matched form. Preliminary estimates of CX-904 half life are between 2.8 to 5.3 days. This slide summarizes treatment related adverse events observed with CX-904 in the non-step dosing schedule. It is important to mention that during the CX-904 escalation, no corticosteroids or other prophylactic medication was administered for systemic toxicity such as CRS and ICANS. The safety and tolerability data shown here with non-step dosing, therefore, reflect the ability of the masking to mitigate CRS in ICANS. With that, the virtual absence of CRS in ICANS is quite striking. Through the 3 milligram dose level, no CRS or ICANS of any grade were observed.
Even at the 6 milligram dose level, where two patients had dopamine toxicity of grade 3 tinnocinibitis and grade 3 rash, no patients experienced eye cancer of any grade and only grade 1 CRS characterized by transient fever without any other signs or symptoms associated with CRS was observed. Low grade musculoskeletal adverse events, such as arthralgia and arthritis were observed in addition to the one grade 3 tinnocinibitis at the 6 milligram dose level. Musculoskeletal events overall appear to be associated with a dose dependent increase in circulating IL-6 as shown in the graph. This is in direct contrast with CRS, where the association with circulating IL-6 levels was much less evident. Similarly, except for the Grade 3 rash observed at the 6 milligram dose level, only Grade 1 rash was observed.
Overall, the data presented here quite convincingly demonstrate the benefit of masking on effectively eliminating CRS and ICANS, which constitute dose limiting toxicities with many T-cell engagers. Based on the observations during dose escalation on the non-step dosing schedule, which demonstrated that CRS and ICANS are effectively mitigated by the masking of CX-904, step dosing schedules and tocilizumab prophylaxis were used specifically to mitigate emerging musculoskeletal adverse events, maintain a broad therapeutic index, and allow continuation of escalation to higher and potentially more efficacious target doses. These measures enabled escalation to higher CX-904 target doses while continuing to maintain an acceptable safety and tolerability profile.
Impressively, no CRS or ICANS of any grade was observed. Moreover, the incidence and severity of musculoskeletal adverse events did not substantially increase with higher CX-904 target doses, no related grade 3 rashes were reported, and no treatment related adverse events resulted in CX-904 treatment discontinuation. Overall, the safety profile of CX-904 continues to be favorable and importantly enable CX-904 administration and management of adverse events in an outpatient setting. In this regard, per protocol, no mandatory hospitalization is required for monitoring at clear dose levels, and the safety profile observed to date has not necessitated a change to this practice. In the context of a favorable safety profile, we observed compelling signs of CX-904 anti-tumor activity highlighted by activity observed to date in patients with advanced pancreatic adenocarcinoma.
The responses observed with CX-904 are highly encouraging given that outcomes in patients with recurrent metastatic pancreatic cancer remain extremely poor with current available therapies. Shown here is the waterfall plot of six efficacy evaluable patients treated across a range of target doses on both non-step and step dosing schedules. Confirmed partial responses per RECIST 1.1 criteria were observed in 2 of the 6 patients. One was treated with 6 milligrams on a non-step dosing schedule and had an 83% reduction in measurable tumor burden and a second patient was treated on a step dosing schedule with a target dose of 5 milligrams and had a 51% reduction in tumor burden. Furthermore, of note, all 6 patients had disease control. Of the 6 patients, 2 remain on study treatment and we will now discuss these patients in greater detail.
The first case describes a confirmed partial response in a 49-year old patient with metastatic pancreatic adenocarcinoma. Prior therapies included surgery, radiation therapy, and three lines of prior chemotherapy. The patient received CX-904 on a step dosing schedule with 1.5 milligrams administered on day one and the target dose of 5 milligrams administered one week later and then two weeks thereafter every two weeks thereafter. The patient did not experience cytokine relief syndrome or ICANS. The patient experienced Grade 3 related arthralgia, but this resolved to Grade 1 after a one cycle delay in administration of corticosteroids. As shown in the CT scan images, the patient achieved a partial response with deeper reduction in tumor burden observed at the confirmatory CT scan.
And as I mentioned, this patient remains on CX-904 treatment, having received over three months of treatment to date. This next case illustrates durable, stable disease with CX-904 in a 59-year old patient with metastatic pancreatic adenocarcinoma who had received three prior lines of systemic chemotherapy. The patient received CX-904 on a step dosing schedule with 1.5 milligrams administered on day 1, 5 milligrams on day 8, and 10 milligrams on day 15 every two weeks thereafter. The patient tolerated CX-904 treatment well with no CRS, ICANS, or musculoskeletal events and only grade 1 papulopustular rash, which resolved with topical treatment. The patient was able to maintain stable disease with no evidence of measurable tumor growth and additional information supporting continued clinical benefit included a greater than 50% reduction in serum CA19 levels and overall improvement of performance status from baseline.
This patient remains on CX-904 treatment, having received over 3.5 months of treatment to date. Preliminary translational data indicates T-cell pharmacodynamic activity that is consistent with the mechanism of action of CX-904 in pancreatic adenocarcinoma. The figure on the left is an immunofluorescence image from a biopsy obtained prior to CX-904 treatment in a patient with pancreatic cancer who achieved a deep partial response. The colors indicate T-cell markers in red, dark blue, and magenta and cancer cells in light blue. And as you can see, the pretreatment biopsy showed a high level of CD8 positive T-cells within the tumor microenvironment, indicating their contribution to T-cell engager anti-tumor activity. The figure on the right shows the reduction of peripheral CDA positive T-cells as it relates to RESIST-1.1 response.
Both pancreatic patients with confirmed partial response had among the greatest reduction of peripheral CD8 positive T-cells following CX-904 treatment, consistent with the trafficking of T-cells from the periphery to tumor site as a mechanism of action of T-cell engagers. Taking a step back from the early but compelling activity of CX-904 patients with pancreatic adenocarcinoma, shown here is the waterfall plot for efficacy evaluable patients treated with CX-904 at target doses greater than or equal to 0.75 milligrams. While no objective responses were observed in patients with other tumor types, reductions in measurable disease burden were observed in a total of 8 patients, including the 2 pancreatic cancer patients with partial responses.
Reductions in measurable disease burden were also observed in patients with CRC, esophageal carcinoma, and non-small cell lung cancer. We believe that the early signals of CX-904 activity in pancreatic cancer are compelling and that currently tested target doses are efficacious. As a result, study enrollment moving forward, in addition to continuing to enroll patients with pancreatic cancer, will focus on patients with other EGFR positive tumor types, including lung cancer, upper GI cancers, and head and neck cancers. This slide summarizes the time on study treatment for patients treated with CX-904, again highlighting the patients with pancreatic adenocarcinoma that continue to derive clinical benefit with ongoing CX-904 treatment. Importantly, while CX-904 has had minimal clinical activity to date in patients with CRC, CX-904 retains its pharmacodynamic activity as illustrated in this slide, which are immunofluorescence images of biopsies taken from a patient with MSS CRC at baseline and while on CX-904 treatment.
As you can clearly see at baseline, the tumor's tumor is notable for the almost complete absence of CD8 positive T-cells within the tumor. In contrast, the on treatment biopsy showed a substantial increase in the number of CD8 positive T-cells within the tumor. This observation is a clear demonstration of the CX-904 mechanism of action and demonstrates potential combination strategies for the treatment of CRC. In summary, we are very encouraged by this early clinical data of CX-904 in the ongoing Phase 1 dose escalation. CX-904 has a favorable safety profile, which given the broad expression of EGFR in normal tissues in addition to cancers, is indicative of the ability of masking to maintain a meaningful therapeutic index. Second, CX-904 has promising early efficacy in pharmacodynamic activity, highlighted by the confirmed partial responses in patients with metastatic pancreatic adenocarcinoma and early demonstration of CX-904 mechanism of action, including in colorectal cancer.
The clinical and translational observations have been extremely valuable in demonstrating not only the early clinical activity of CX-904, but also provide clear direction to plans to ultimately determine the recommended Phase 2 dose. And this includes continued enrollment in pancreatic cancer and enrollment in other EGFR positive tumor types that are also more responsive to immune therapies based on prior clinical experience. Together, these data will inform future development of CX-904, which include considerations of combination strategies. And with that, I will now turn it back to Sean for concluding remarks.
Sean McCarthy: Great. Thanks, Wayne. So staying with CX-904 for a moment, we're excited by our progress to date developing this very novel drug candidate. EGFR is such a high potential target with expression on many tumor types, and we're just at the beginning of learning what CX-904 can do for patients. We clearly have a drug candidate with confirmed monotherapy activity, and we're redoubling our efforts to generate data in additional tumor types as we more broadly explore 904. Our data also unlocks potential strategies for future combinations, as Wayne mentioned. Focusing for a moment on pancreatic cancer, this is one of the greatest areas of unmet need oncology today, and it's notoriously difficult to treat. Second line response rates were in the single digits and PFS and overall survival in just a matter of months.
To reiterate the importance of our data shared today, pancreatic cancer does not respond to either anti-EGFR antibodies or to immunotherapy alone. What we have shown today is that when we combine these two powerful strategies in bispecific form, enabled by our PROBODY masking technology, we can elicit meaningful responses in late stage pancreatic cancer patients. CX-904 brings these two mechanisms together into an integrated and unique pharmacology that could impact this very difficult to treat disease, showing how masked PROBODY T-cell engagers can be a new frontier in the war on cancer. These results are the embodiment of exactly what CX-904 was designed to do, and we plan to aggressively pursue this signal for the benefit of people afflicted with this devastating tumor type.
Now zooming back out to our full pipeline and looking ahead to the rest of this year and also into 2025, we anticipate a great deal of additional progress at CytomX. We see the data we're sharing today on 904 as a promising initial step in developing this asset and also our T-cell engager portfolio overall. T-cell engagers are starting to break through in solid cancers and it's exciting to be playing our part here at CytomX in this highly promising field, not only with 904, but also the many T-cell engager programs we're advancing through preclinical discovery and development. And we look forward to providing an additional CX-904 update later this year. Now, of course, today's update has been very 904 focused, but before I wrap up, I'd like to remind everyone to also keep our other programs in mind.
We're making a lot of progress on multiple fronts. CX-2051 and CX-801 are wholly owned assets, and we anticipate Phase 1a data for both in 2025. We're already in our second Phase 1 cohort with 2501, our masked anti-EpCAM ADC clinical initiation for CX-801, our masked interferon, is imminent. I'd like to close by thanking everyone involved in this work for their commitment to our vision. The CytomX team is intensely focused on delivering an innovative pipeline for the benefit of people living with cancer, and it's truly a privilege to work with such a talented team. I also want to sincerely thank the patients who joined our studies, their families, and our investigators. And with that, operator, let's go ahead and open up the call for questions.
Operator: [Operator Instructions] And for your first question, it comes from the line of Peter Lawson from Barclays. Please go ahead.
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