CytomX Therapeutics Presents Preclinical Data for mRNA Encoded Masked IL-12 Molecule in Collaboration with Moderna at AACR Annual Meeting

Rhea-AI Summary

CytomX Therapeutics and Moderna have unveiled promising preclinical data for their collaborative development of an mRNA-encoded masked IL-12 molecule at the AACR Annual Meeting in Chicago.

The breakthrough combines CytomX's PROBODY® masking technology with Moderna's mRNA expertise to create a novel cancer treatment approach. The key innovation lies in developing an IL-12 therapeutic that can be selectively activated within the tumor microenvironment while minimizing systemic activity.

Key highlights:

• Successfully demonstrated proof of concept for mRNA encoded masked molecule in cancer treatment
• Achieved enhanced tolerability while maintaining anti-tumor efficacy
• Addresses previous limitations of IL-12's clinical use due to inflammatory toxicity

The research findings will be presented in Poster #3127/12 on April 28, 2025, highlighting how this innovative combination of technologies could potentially overcome traditional IL-12 therapy limitations.

Positive

• Successful proof of concept demonstrated for new mRNA encoded masked IL-12 molecule in preclinical studies
• Strategic collaboration with Moderna combines CytomX's PROBODY® masking technology with Moderna's mRNA expertise
• Novel therapeutic shows potent anti-tumor activity while improving systemic tolerability
• Technology designed to be selectively activated within tumor microenvironment, limiting systemic side effects

Negative

• Data is only preclinical stage, indicating long path to potential commercialization
• No specific efficacy metrics or comparative data provided in the release

Insights

Biotechnology Analyst

CytomX and Moderna demonstrate proof-of-concept for combining mRNA and masking technologies to improve IL-12's therapeutic profile in preclinical cancer studies.

The preclinical data presented by CytomX and Moderna represents an innovative approach to addressing a long-standing challenge in cytokine-based cancer immunotherapy. IL-12 has been recognized for decades as a potent anti-tumor cytokine, but its clinical development has been severely limited by systemic inflammatory toxicity when administered as a conventional protein therapeutic.

The technical approach combines two distinct platform technologies: CytomX's PROBODY® masking technology, which uses protease-cleavable masks to restrict activity to the tumor microenvironment, and Moderna's mRNA delivery platform, which enables in vivo production of therapeutic proteins. The data demonstrated this masked IL-12 maintained anti-tumor efficacy while improving systemic tolerability in preclinical models.

This represents a significant technical achievement at the preclinical stage. The selective activation mechanism addresses IL-12's primary clinical limitation by restricting its inflammatory effects to the tumor site, potentially widening its therapeutic window. If this approach translates to human studies, it could potentially revitalize clinical development for this cytokine class.

While still at an early research stage, this proof-of-concept demonstrates the feasibility of combining these platform technologies, which could extend beyond IL-12 to other potent but toxicity-limited cancer immunotherapy agents.

Healthcare Investment Analyst

Preclinical proof-of-concept validates CytomX-Moderna technology collaboration but remains years from potential commercialization with no financial impact metrics.

The announcement marks a technology validation milestone for the CytomX-Moderna collaboration, demonstrating successful integration of their respective platforms in a preclinical setting. For CytomX, whose core technology focuses on masked biologics, this data supports their platform's applicability to mRNA-encoded proteins, potentially expanding its utility beyond antibody therapeutics.

For Moderna, this represents advancement in their oncology pipeline diversification strategy, showing their mRNA technology can deliver complex masked protein therapeutics beyond vaccines. The IL-12 program addresses an established cancer target with known clinical challenges.

From a development perspective, this remains at the preclinical stage in the R&D continuum, meaning potential clinical trials, regulatory review, and commercialization would be several years away at minimum. The press release contains no mention of financial terms, milestone payments, or commercial rights allocation between the companies.

The data demonstrates technological feasibility rather than clinical or commercial validation at this stage. For investors, this represents incremental positive progress in platform validation and pipeline development for both companies, without immediate revenue implications. The collaboration's continued progress indicates productive execution on previously announced strategic priorities.

Novel engineering approach to developing an mRNA-encoded masked IL-12 therapeutic demonstrates potent anti-tumor activity with significantly enhanced tolerability

SOUTH SAN FRANCISCO, Calif., April 28, 2025 (GLOBE NEWSWIRE) -- CytomX Therapeutics, Inc. (Nasdaq: CTMX), a leader in the field of masked, conditionally activated biologics, today announced new preclinical data in collaboration with Moderna on an mRNA encoded masked IL-12 molecule. The data will be presented at the American Association for Cancer Research (AACR) Annual Meeting, being held in Chicago, IL on April 25-30, 2025.

“We are excited to share new preclinical data at AACR, establishing proof of concept for an mRNA encoded masked molecule in the treatment of cancer,” said Marcia Belvin, Ph.D. SVP, Chief Scientific Officer of CytomX Therapeutics. “IL-12 has shown promising anti-tumor activity, but its clinical use has been limited due to its inflammatory toxicity and narrow therapeutic window. By combining CytomX’s proprietary PROBODY^® masking technology and Moderna’s mRNA technology, we have created an mRNA therapeutic encoding a masked IL-12, designed to be selectively activated within the tumor microenvironment (TME), with limited systemic activity. The data presented at AACR show proof of concept for this unique technology combination, a key initial goal of the CytomX-Moderna collaboration.”

Details for the poster presentation are as follows:
Presentation Title: An mRNA-encoded masked IL-12 improves systemic tolerability while maintaining anti-tumor efficacy in preclinical studies
Poster Number: 3127/12
Section 24
Session Date and Time: April 28, 2025, 2:00 pm – 5:00 pm CT

About CytomX Therapeutics, Inc.
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, 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. 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 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 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 and CX-801 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; 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-K filed with the SEC on March 6, 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

FAQ

What is the new mRNA IL-12 treatment announced by CytomX (CTMX) and Moderna in April 2025?

CytomX and Moderna announced a novel mRNA-encoded masked IL-12 molecule that shows strong anti-tumor activity with better tolerability. The treatment combines CytomX's PROBODY masking technology with Moderna's mRNA technology to create a therapy that activates specifically within tumors.

How does CytomX (CTMX) masked IL-12 technology improve cancer treatment safety?

The masked IL-12 technology improves safety by being selectively activated only within the tumor microenvironment (TME), limiting systemic activity. This addresses the traditional limitations of IL-12 treatments, which have shown promising anti-tumor effects but were restricted by inflammatory toxicity.

When will CytomX (CTMX) present their mRNA IL-12 cancer treatment data at AACR 2025?

CytomX will present their mRNA IL-12 preclinical data at the AACR Annual Meeting in Chicago on April 28, 2025, from 2:00 PM to 5:00 PM CT. The presentation is listed as Poster Number 3127/12 in Section 24.

What makes the CytomX-Moderna collaboration unique for cancer treatment?

The collaboration uniquely combines CytomX's PROBODY masking technology with Moderna's mRNA technology to create a masked IL-12 treatment that is more targeted and better tolerated than traditional IL-12 therapies, while maintaining anti-tumor effectiveness.

What are the key benefits of CytomX (CTMX) masked IL-12 cancer therapy?

The key benefits include potent anti-tumor activity, significantly enhanced tolerability, and selective activation within the tumor microenvironment. This addresses the narrow therapeutic window that has historically limited IL-12's clinical use in cancer treatment.