Astellas Pharma has ended a six-year-old collaboration with CytomX Therapeutics designed to both expand the pharma giant’s pipeline of next-gen immuno-oncology treatments and generate up to $1.68 billion-plus for the South San Francisco, CA, developer of antibody therapeutics.
Through the collaboration, launched in March 2020, Astellas said it planned to apply CytomX’s Probody® therapeutic tech platform, bispecific formats, and CD3 molecules to discover, research, develop, and commercialize novel T-cell engaging bispecific antibodies designed to fight cancer by targeting CD3 and tumor surface cell antigens.
The companies’ collaboration agreement allowed Astellas to select up to four targets to develop, with an option to expand to six before the third anniversary of the partnership, an option that has expired. Astellas selected its initial four targets, programs for three of which remain active.
The collaboration’s first public sign of trouble came in the first quarter of 2025, when Astellas opted not to continue IND enabling activities it had initiated for the companies’ first collaboration target—choosing instead to prioritize their second nominated collaboration target by initiating GLP toxicology studies for the molecule, triggering a $5 million milestone payment to the company from Astellas.
“CytomX is currently assessing options to advance select targets previously covered under the Astellas collaboration as part of its ongoing research and development strategy,” CytomX disclosed in its Form 10-K annual report for 2025, filed Monday with the U.S. Securities and Exchange Commission (SEC).
The companies have not disclosed details about any of their targets under development.
Astellas paid CytomX $80 million upfront and agreed to pay up to $1.6 billion-plus in payments tied to achieving preclinical, clinical, and commercial milestones—as well as tiered royalties from high-single digit to mid-teen percentage royalties from potential future sales. Astellas also agreed to pay CytomX tiered royalties on global net sales that range from high-single digits to mid-teens.
“We are excited about the use of our technology to assist Astellas in unlocking the potential of T-cell engaging bispecifics in the treatment of solid tumors, building on the growing proof of concept we have established for our platform,” Sean McCarthy, DPhil, CytomX’s CEO and chairman stated in announcing the collaboration.
$20M in milestones paid out
In addition to the upfront payment, Astellas paid out $20 million in milestone payments:
- $5 million in 2023 after Astellas nominated the first clinical candidate under the collaboration.
- $10 million in 2024, consisting of $5 million after Astellas nominated the second collaboration target, and $5 million after GLP toxicology studies began for the first target.
- $5 million last year after Astellas initiated GLP toxicology studies for the second target.
Probody T-cell engaging bispecifics are antibody constructs capable of directing cytotoxic T-cells to tumor microenvironments, leading to cell-mediated anti-cancer activity. According to CytomX, Probody therapeutics are designed to reduce toxicities and create safer, more effective therapies by remaining inactive until they are activated by proteases in the tumor microenvironment, and by binding selectively to tumors while minimizing binding to healthy tissue.
CytomX has additional collaborations in progress with biopharma giants that include Amgen, Bristol Myers Squibb (BMS), Moderna, and Regeneron Pharmaceuticals.
The end of the collaboration with Astellas was not an apparent factor in CytomX shares rocketing 75% from Friday’s close of $4.68 to a 52-week high of $8.20 as of 11:15 a.m. ET Monday before closing at $6.75 and settling for a 44% gain—a surge that Jefferies equity analyst Roger Song, MD, attributed to positive data from a Phase I dose expansion study assessing varsetatug masetecan (varseta-M) in advanced colorectal cancer.
Varseta-M is a Probody-developed masked, conditionally activated antibody–drug conjugate (ADC) armed with a topoisomerase-1 inhibitor payload (licensed from drug co-discoverer ImmunoGen, acquired by AbbVie for $10.1 billion) and directed toward epithelial cell adhesion molecule (EpCAM). Varseta-M achieved an overall response rate of 32% (best in disease, Song wrote in a Monday research note) and a median progression-free survival (mPFS) of 7.1 months at the high dose of 10 mg/kg.
The ends of the Astellas partnership was disclosed as part of CytomX’s release of fourth quarter and full year 2025 results. CytomX finished last year by swinging to a $17.368 million net loss from $31.869 million in net income in 2024.
CytomX also saw its revenues tumble by 45% in 2025, to $76.201 million from $138.103 million a year earlier—a drop the company blamed on the completion of work in its collaboration with Bristol Myers Squibb in April 2025, and less work completed in 2025 versus 2024 in the Astellas, Moderna, and Regeneron collaborations.
CytomX ended 2025 with $137.052 million of cash, cash equivalents and investments, a cash runway that the company anticipates will stretch to the second quarter of 2027. The cash and equivalents is nearly 5% below the $143.626 million reported at the end of the fourth quarter, but 36% above the $100.623 million stated for fourth quarter 2024.
