Roche’s Genentech has entered into a collaboration and licensing agreement with Shanghai-based DualityBio to develop antibody-drug conjugates (ADCs) intended for patients whose cancers progress after treatment with existing ADC therapies.
Under the agreement, Genentech will pay DualityBio $45 million upfront. The deal also includes the possibility of more than $1 billion in development, regulatory, and commercial milestone payments. DualityBio will additionally be eligible to receive tiered royalties on net sales of any approved products.
Collaboration Focuses on Patients With Limited Options After ADC Treatment
The partnership centers on an emerging need among patients treated with currently approved ADCs. Products such as AstraZeneca and Daiichi Sankyo’s Enhertu and Gilead’s Trodelvy use cytotoxic topoisomerase inhibitor payloads to target cancer cells expressing specific receptors.
As these therapies move into earlier treatment settings, including first-line use, a growing number of patients are progressing after treatment and becoming less responsive to topoisomerase inhibitor-based approaches.
To address this challenge, Genentech is gaining access to DualityBio’s Dupac platform. The platform was developed to create payloads designed to retain activity in tumors that progress on existing topoisomerase-based ADCs.
Under the terms of the collaboration, DualityBio will generate and develop ADC candidates using Dupac payloads against oncology targets selected by Genentech. DualityBio will lead discovery and early global development efforts, while Genentech will assume sole responsibility for further development after Phase 1a studies.
Dupac Payload Research and Development Activities
DualityBio has published several scientific abstracts related to Dupac payloads during the past 16 months.
Last year, the company presented two abstracts on DUP5, an mRNA translation inhibitor payload. The abstracts described how the asset could improve on the efficacy of Blenrep, GSK’s BCMA-directed ADC.
The company has also reported data on an ecteinascidin derivative, showing its potential to improve on TA-MUC1-targeting ADCs such as Daiichi’s DS-3939a. Additional research demonstrated that the DUP9 payload kills cells expressing EGFR and DLL3.
DualityBio plans to file next year to begin human testing of its TA-MUC1 ADC. The company also has a third Dupac payload, DUP10, although it has not yet published preclinical data on that molecule.
Agreement Expands Use of DualityBio’s ADC Technologies
At the center of the collaboration is DualityBio’s proprietary Dupac platform, which was developed to generate payloads with mechanisms intended to address resistance to payload classes used in currently approved ADCs.
As stated in the company’s announcement, the collaboration will develop “next-generation ADCs built on DualityBio’s Dupac novel payload platform,” according to DualityBio.
The Genentech agreement adds to a series of partnerships involving DualityBio’s ADC technologies. In 2023 and 2024, BioNTech, GSK and BeiGene, now known as BeOne Medicines, entered into agreements covering DualityBio ADCs. Those deals focused on the company’s topoisomerase-based platform.
Under the agreement, DualityBio will receive $45 million upfront and could receive more than $1 billion in development, regulatory, and commercial milestone payments, along with tiered royalties on annual net sales of approved products.
A Strategic Move in ADC Development
The collaboration brings together a large pharmaceutical company’s global development capabilities with a biotechnology company’s specialized antibody-drug conjugate technology. The goal is to create new candidates that may work differently from existing ADC treatments.
Understanding Payload Resistance
Many existing ADCs rely on payload mechanisms such as topoisomerase inhibitors. When cancer cells become less responsive to these mechanisms, treatment effectiveness can decline. The new platform is designed around alternative payload mechanisms that could potentially maintain activity against resistant tumors.
The Role of DUPAC
DUPAC is a platform containing several novel payload technologies, including DUP5, DUP9, and DUP10. These payloads are intended to provide different mechanisms of action compared with payload classes used by currently approved ADCs.
Discovery and Early Development
Under the collaboration, DualityBio will lead discovery research and early global clinical development. The resulting candidates are expected to advance through Phase 1a development before the larger partner assumes responsibility for further development and commercialization.
Financial Structure
The agreement includes a $45 million upfront payment, more than $1 billion in potential development, regulatory, and commercial milestones, and tiered royalties on annual net sales of approved products.
Potential Impact on Oncology
If successful, the programs could offer new treatment possibilities for patients whose tumors progress after earlier ADC therapy. However, these candidates remain in development, so their ability to overcome resistance will need to be established through clinical studies.
A Broader Technology Platform
DualityBio has developed several ADC technology platforms and continues to build a pipeline covering different targets and therapeutic approaches. The partnership demonstrates how specialized biotechnology platforms can be combined with global pharmaceutical development resources to advance complex oncology programs.
What Comes Next
The next major milestones will involve candidate selection, preclinical development, and early clinical testing. Results from these studies will determine whether the novel payload approaches can deliver meaningful advantages over existing therapies.
Addressing Resistance in Cancer Treatment
The collaboration targets an important challenge in oncology: patients whose tumors stop responding to antibody-drug conjugates that use topoisomerase inhibitor payloads. As these therapies move into earlier lines of treatment, resistance could become an increasingly important clinical problem.
Novel Payload Mechanisms
The DUPAC platform contains multiple payloads built around different antitumor mechanisms. One highlighted payload, DUP5, is an mRNA translation inhibitor that has shown tumor-regression activity in preclinical models, including models with limited response to deruxtecan-based ADCs.
Combining Targeting and Payload Innovation
The effectiveness of an ADC depends on more than its antibody target. Payload activity, linker behavior, drug release, cellular internalization, and tumor biology can all influence treatment performance. The collaboration brings these elements together to explore new ADC designs.
Development Responsibilities
DualityBio will generate ADC candidates against oncology targets selected by Genentech and lead discovery and early global clinical development. Genentech will receive exclusive worldwide rights and is expected to assume further development and commercialization responsibilities after Phase 1a.
Significant Financial Commitment
The agreement includes a $45 million upfront payment and more than $1 billion in potential development, regulatory, and commercial milestones, plus tiered royalties on annual net sales of approved products. The milestone payments remain dependent on successful development and commercialization.
Broader ADC Competition
The deal comes during a period of intense competition in ADC research. Pharmaceutical and biotechnology companies are exploring new antibodies, payloads, linkers, and mechanisms to improve efficacy and address resistance.
DualityBio already has several ADC collaborations, including partnerships with BioNTech and other pharmaceutical companies, demonstrating growing interest in its technology platforms.
What Happens Next
The collaboration will need to progress through candidate discovery, preclinical testing, and early clinical studies. Safety, pharmacokinetics, antitumor activity, and evidence of effectiveness against resistant tumors will be important measures of success.
