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By 2025, the global ADC (Antibody-Drug Conjugate) market size will exceed $30 billion, yet the confusion among oncologists remains—half of the patients develop resistance during treatment, 15% experience severe side effects due to off-target effects, not to mention the dual payload ADCs that can attack tumors simultaneously, most of which are still stuck in the “unable to produce, high toxicity” laboratory stage.
Until CrossBridgeBio from Houston introduced a dual payload ADCCBB-120, everything opened up new possibilities. Founded in 2023, this biotech company advanced its technology to the IND-enabling stage in just 18 months through a combination of “protease-resistant linker + click chemistry,” and plans to initiate non-human primate safety testing in 2025. More importantly, it has solved three major issues that the ADC industry has struggled with for 30 years, transforming dual payloads from an “ideal” to a “practical therapy.”
Today, we will dissect:What makes CrossBridge’s dual payload technology so strong? What new pathways does the “Houston model” provide for academic transformation?
-01-
The Three Major Issues of ADCs Have Been Fully Resolved by Two Technical Details
“Previously, making dual payload ADCs was like building blocks on a tightrope—either they were unstable (low purity), or once built, they fell apart (linker degradation), or the blocks fell on people (high toxicity).” A complaint from a senior industry R&D personnel encapsulates the difficulties of ADC innovation. CrossBridge’s solution lies in two seemingly simple technical details.
Issue1: Linkers fall apart as soon as they enter the bloodstream—protease-resistant design withstands degradation
The core of ADCs is “antibodies carrying drugs to precisely attack tumors,” but the linker (the “rope” connecting the antibody and the drug) often fails. Traditional linkers can be “cut” by neutrophil proteases as soon as they enter the bloodstream, leading to premature drug release, harming healthy cells and wasting efficacy.
CrossBridge’s response is to give the linker a “bulletproof vest”—developing a proprietary neutrophil protease-resistant linker. Simply put, this linker can “withstand attacks” in the bloodstream until the antibody finds the tumor cells to release the drug. As CEO Michael Torres puts it, “We no longer have to worry about the drug prematurely ‘exploding’ before reaching the target.”
Even better, this linker also comes with a “hydrophilic buff.” Traditional linkers are often hydrophobic materials, which can accumulate in organs like the liver and kidneys, causing toxicity; whereas CrossBridge’s linker, with its high hydrophilicity, “avoids” non-target tissues, reducing the risk of side effects from the source. For patients, this means less vomiting, less bone marrow suppression, and finally being able to effectively combat cancer while maintaining quality of life.
Issue2: Pure products of dual payloads cannot be produced—click chemistry achieves “modular assembly”
If the linker solves the “delivery” problem, then click chemistry addresses the “production volume” challenge. Previously, making dual payload ADCs was like manually assembling a clock; connecting two different drugs precisely to the antibody was not only inefficient (with yields often below 60%) but also prone to “wrong parts” heterogeneity, making large-scale production impossible.
CrossBridge transformed this process into “LEGO blocks”—using click chemistry to build a modular platform, where the linker and two drugs are like standardized blocks, allowing for the rapid assembly of pure dual payload ADCs while “minimizing waste and side reactions.” Torres emphasized in an interview, “We can quickly create a library of dual payload ADCs to find the optimal design, which was previously unimaginable.”
How critical is this efficiency improvement? For patients, it means that in the future, dual payload ADCs will not be hard to find due to insufficient production capacity; for the industry, it opens the door to “multi-drug synergistic cancer therapy”—for example, equipping CBB-120 with a drug that “kills tumor cells” and another that “blocks tumor blood vessels,” allowing both mechanisms to work together, naturally reducing resistance issues.
Issue3: Toxicity accumulation of dual payloads—CBB-120 targets TROP-2 positive solid tumors
Having solved the “delivery and production volume” issues, it also needs to pass the “toxicity hurdle.” The biggest concern with dual payloads is the toxicity accumulation of “1+1>2,” but CrossBridge’s strategy is clever—risk control starts from the indication. Its first dual payload CBB-120 targets TROP-2 positive solid tumors, including colorectal cancer, ovarian cancer, and non-small cell lung cancer, which are areas “lacking good drugs.”
How difficult are the existing treatments for these cancers? For example, in colorectal cancer, the resistance rate for late-stage patients using single-agent ADCs exceeds 40%, while CBB-120, through dual payload synergy, is expected to reduce the resistance rate to below 20% (specific data pending clinical validation). More importantly, thanks to the stable linker and high hydrophilicity design, CBB-120 has not shown toxicity accumulation in early cell experiments, and the non-human primate safety tests starting in 2025 will further validate its safety.
-02-
18 Months from Lab to IND: Three Key Aspects of the Houston Model
CrossBridge’s technological breakthroughs are impressive, but what deserves more attention is the “Houston model” behind it—advancing the academic technology of UTHealth Houston to the IND-enabling stage in just 18 months, nearly half the industry average of 24-30 months. The core of this model is the triple synergy of “academia + capital + entrepreneurship”; lacking any one of these elements slows down progress.
1. Academic Source: Top Journal Technology Foundation, Not Building “Castles in the Air”
The roots of CrossBridge’s technology lie in the laboratories of the University of Texas Health Science Center (UTHealth Houston). The teams of Zhiqiang An and Kyoji Tsuchikama have been deeply engaged in “therapeutic antibodies and linker technology” for years, with their research published twice in top journals such as “Nat. Rev. Clin. Oncol.” and “Nat. Commun.”, including the protease-resistant linker later transformed by CrossBridge.
Unlike many academic technologies that are “innovative for the sake of innovation,” this linker technology has been aimed at clinical pain points from the start. Professor An specifically mentioned in his paper, “The linker of ADCs must not only be stable but also release drugs precisely,” this “practical orientation” in research saved a lot of modification time for later industrialization.
2. Capital Support: CPRIT Funding, Crossing the “Valley of Death”
To bring academic technology to market, the most crucial element is the “first funding.” CrossBridge was fortunate to receive special funding from the Cancer Prevention and Research Institute of Texas (CPRIT), which was directly used for the IND-enabling research of CBB-120, helping it cross the most dangerous “valley of death” for biotech companies.
CPRIT is not an ordinary VC; it is a cancer-specific agency established by the Texas government, with the mission of “transforming academic cancer technologies into therapies that patients can use.” This model of “government endorsement + targeted funding” understands the value of early-stage technology better than market financing and is more patient in accompanying companies through the lengthy preclinical cycle.
3. Entrepreneurial Leadership: “Transformers” from Accelerators
If academia is the “foundation” and capital is the “cement,” then CEO Michael Torres is the “builder.” He previously worked at the Texas Medical Center Innovation Accelerator, which is itself a CPRIT-funded project designed to help university professors turn their technologies into companies.
This experience allowed Torres to accurately hit the “balance point between academia and industry.” In 2023, after seeing An’s team’s linker technology, he did not simply take a license but directly invited the academic team to co-found the company, ensuring that the research direction remained aligned with “feasible, usable, and practical” clinical needs. Eighteen months later, CBB-120 advanced to the IND-enabling stage, a speed far exceeding the industry average, confirming the value of the deep binding between “entrepreneurs and academic teams.”
-03-
The Next Decade of the ADC Industry: From Target Point Competition to Technological Innovation
CrossBridge’s story is not just about a company’s comeback; it also signals a shift in the competitive logic of the ADC industry. Previously, everyone focused on popular targets like HER2 and TROP-2, competing on who could launch first and who could offer lower prices; now, smart players have shifted to “technological innovation,” competing on who can solve resistance and who can effectively produce dual payloads.
1. The End of Target Point Competition is Technological Differentiation
By 2025, there will be three approved drugs targeting TROP-2 ADCs, with price wars raging, some annual treatment costs dropping by 40%. However, CrossBridge refuses to join this frenzy; it chooses the TROP-2 target but differentiates itself with “dual payload + stable linker”—while others compete on “whose single-agent effect is better,” it competes on “who can prevent patients from developing resistance and suffering less.”
CSO Dan Pereira’s judgment is clear: “At the moment, what really differentiates us in the ADC world is multi-payload.” This veteran, who has developed five FDA-approved cancer antibodies, knows that in an era of target point competition, only technological innovation can ensure longevity.
2. From “Single Agent” to “Synergy”: The Next Stop for ADCs
CrossBridge’s ambition goes beyond CBB-120. It has already planned to “couple our technology with bispecific antibodies,” simply put, combining “dual antibodies” with “dual payload ADCs”—the dual antibodies are responsible for precisely locating tumors, while the dual payloads efficiently eliminate them. This combination can cover more complex tumor types, such as highly heterogeneous pancreatic cancer and cholangiocarcinoma.
This is precisely the future of the ADC industry: no longer limited to “one drug targeting one point,” but using “multi-technology integration” to solve clinical challenges. As Torres said, “What we aim to create is not another ADC, but an anti-cancer therapy that can truly change patients’ destinies.”
3. Risk Warning: The “Ideal and Reality” of Dual Payloads
Of course, we cannot ignore the risks. The clinical phase III failure rate for ADCs is as high as 30%. Although CBB-120 has shown impressive preclinical performance, the non-human primate safety tests in 2025 and subsequent human clinical trials may encounter unexpected issues. Moreover, the manufacturing cost of dual payload ADCs is still 20% higher than that of single agents, and how to balance efficacy and price is also a challenge that CrossBridge must face.
But these risks are precisely the necessary path of innovation. Just like 30 years ago when ADCs first appeared, no one believed they could replace traditional chemotherapy; now, dual payload ADCs are also breaking through skepticism with technology, bringing the dream of “precise cancer treatment with less suffering” closer to patients.
Ending Interaction
While the ADC industry is still fighting over target points, CrossBridge has opened a gap with its dual payload technology. It proves that innovation in anti-cancer drugs is not about “who is faster,” but about “who understands patients’ pain better”—understanding their fear of resistance, their suffering from side effects, and their desire to “live well.”
Do you think dual payload ADCs will become mainstream in cancer treatment within five years? If you know cancer patients, would you recommend they wait for this new type of therapy or choose existing options? Let’s discuss your thoughts in the comments and let more people see the new possibilities of ADC innovation～
References
1. CrossBridgeBio official website (crossbridgebio.com) public technical materials;2. “Nat. Rev. Clin. Oncol.” 2024 An/Zsuchikama team linker technology research3. “Nat. Commun.” 2021 An/Zsuchikama team antibody technology research.
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