DualityBio announced on August 28, 2026 a collaboration and license agreement with Genentech, a member of the Roche Group, to develop antibody-drug conjugates (ADCs) built on its DUPAC payload platform. DualityBio receives US$45 million upfront and is eligible for more than US$1 billion in aggregate development, regulatory and commercial milestones across all programs, plus tiered royalties on annual net sales.
The companies describe the collaboration as directed at patients whose tumors have progressed on ADCs carrying topoisomerase I (TOP1) inhibitor payloads, a population the announcement calls a large and growing unmet need.
Terms
DualityBio will generate and develop ADCs against oncology targets defined by Genentech, using DUPAC payloads, and will lead discovery and early global clinical development. Genentech receives an exclusive worldwide license and takes sole responsibility for development and commercialization after Phase 1a.
Neither company disclosed the number of targets, the royalty rates, or the allocation of the milestones, and no candidates were named. The upfront is the only disclosed committed payment; the rest of the headline figure is contingent on programs not yet public.
The payload platform
DUPAC (DualityBio Unique Payload Antibody Conjugate) is one of four ADC platforms the company has disclosed, alongside DITAC, DIMAC and DIBAC. It comprises several payloads with novel mechanisms of action, including DUP5, DUP9 and DUP10, paired with linkers the company says are designed for systemic stability and tumor-specific release.
The rationale rests on mechanism. DUP5, the payload described in most detail publicly, has been presented as an mRNA translation inhibitor, unrelated to the DNA damage through which topoisomerase inhibitors kill. Whether that translates into benefit after TOP1 payload failure is untested. The same translational literature that documents TOP1 mutations also implicates efflux transporter upregulation and bypass survival pathway activation, mechanisms that can blunt a payload regardless of how it acts.
Preclinical data the company says show activity in tumor models relatively insensitive to topoisomerase inhibitor payloads, plus non-human primate tolerability, were presented at AACR 2025 (Abstract 5454), AACR-NCI-EORTC 2025 (Abstracts B129 and B130) and AACR 2026 (Abstract 2657). No clinical data for any DUPAC-based ADC have been reported.
The resistance evidence
Six approved ADCs deliver TOP1 inhibitor payloads. Three are approved in the United States and Europe, trastuzumab deruxtecan and datopotamab deruxtecan, both carrying deruxtecan, and sacituzumab govitecan, carrying SN-38, and all three have moved into earlier lines of therapy; trastuzumab deruxtecan is the highest-selling ADC on the market. Three more have been approved in China since late 2024: sacituzumab tirumotecan, trastuzumab rezetecan and izalontamab brengitecan. Genentech’s own approved ADCs, trastuzumab emtansine and polatuzumab vedotin, carry microtubule inhibitors instead.
A translational study published in Clinical Cancer Research in 2025 used plasma-based genotyping to identify four acquired TOP1 mutations in 12.9% of patients (4 of 31) assessed at progression on an ADC, against 0.7% (3 of 420) in metastatic breast cancer patients who had not received ADCs and 0.5% in The Cancer Genome Atlas. The 0.7% figure comes from a separate comparison cohort, not pre-treatment sampling of the same patients, and the incidence rests on four patients. Median duration on the first ADC was 455 days, against 52 days on the second. Three of the four mutant proteins were characterized, each showing reduced enzymatic activity and resistance to SN-38 and deruxtecan.
At ESMO Breast Cancer 2026 in Berlin, two prospective studies reported limited activity for TOP1 inhibitor-based ADCs after prior exposure to the same payload class. A phase II study of patritumab deruxtecan (Abstract 422RO) reported response rates of 39% and 25% in ADC-naive HR-positive/HER2-negative and triple-negative disease (n=60), falling to 5% with prior TOP1 ADC exposure (n=40) and 5% in HER2-positive patients who had progressed on trastuzumab deruxtecan (n=21).
The phase II SATEEN trial (LBA4), testing sacituzumab govitecan with trastuzumab in 27 heavily pretreated HER2-positive patients after prior trastuzumab deruxtecan, reported a 3.7% response rate, median progression-free survival of 2.3 months and median overall survival of 9.2 months; it missed its primary endpoint and was stopped for futility at interim analysis.
You can read more on the SATEEN Trial on OncoDaily.
Dr. Thomas Grinda of Gustave Roussy, commenting in the ESMO Daily Reporter, cautioned that the cohorts were small and not definitive evidence against sequential TOP1 inhibitor-based ADCs, while calling them a consistent signal that switching the ADC target alone is unlikely to overcome resistance when the payload is unchanged.
Company background
DualityBio (HKEX: 09606) listed on the Hong Kong Main Board on April 15, 2025, raising about US$211 million, and closed its first day up 116.7%. On June 12, 2026, the Shanghai Stock Exchange accepted its application for an RMB share issue on the Science and Technology Innovation Board, which remains subject to further approvals and may not proceed. Chinese trade publication VCBeat reported the shares had fallen more than two-thirds from their high as of June 2026.
In its 2025 annual results, DualityBio reported out-licensing and collaboration agreements with partners including BioNTech, BeOne, Adcendo, GSK and Avenzo, with total transaction value exceeding US$6 billion, contingent potential rather than cash received, and trials in 17 countries with more than 3,200 patients enrolled; the August announcement put the footprint at nearly 20 countries and 3,500 patients.
What remains unresolved
The claim that DUPAC retains antitumor activity where TOP1 inhibitor payloads have failed rests on preclinical models, presented in conference abstracts rather than full peer-reviewed publications. The first clinical test will be Phase 1a response data in patients previously treated with topoisomerase inhibitor-based ADCs. Neither company has disclosed a timeline for entering the clinic.
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