San Diego, California, USA, and Suzhou, China, September 9, 2026
Adagene Inc. and Exelixis Inc. have achieved a new preclinical milestone in their collaboration to develop SAFEbody® antibody-drug conjugate (ADC) candidates, advancing the companies’ efforts to develop tumor-targeted therapies designed to improve the therapeutic index of highly potent cancer medicines. The milestone is associated with XB404, a SAFEbody-based ADC candidate targeting ROR1/2-expressing tumors, and triggered a $2 million milestone payment to Adagene. An additional payment was also triggered following candidate selection for another SAFEbody ADC program.
$2 Million Milestone Advances XB404 Development
The latest milestone represents progress in the ongoing Adagene-Exelixis collaboration and license agreement, which uses Adagene’s proprietary SAFEbody precision-masking technology to generate masked antibody candidates for ADC development. The achievement is specifically linked to a preclinical milestone event for XB404, demonstrating continued advancement of the program beyond initial antibody engineering and candidate-generation activities. Under the collaboration, XB404 is designed to deliver a cytotoxic payload to tumors expressing ROR1 or ROR2 while reducing on-target, off-tumor effects. ROR1 and ROR2 are tumor-associated targets that have attracted interest in oncology drug development because their expression patterns may provide opportunities for targeted therapeutic approaches. The ability to selectively activate an ADC within the tumor environment is intended to address one of the major challenges associated with highly potent cytotoxic payloads: achieving sufficient tumor exposure while limiting damage to healthy tissues. The milestone triggered a $2 million payment from Exelixis to Adagene, providing further non-dilutive financial support for Adagene’s technology platform. The companies did not disclose the specific nature of the preclinical milestone event beyond its association with XB404.
SAFEbody Technology Designed for Tumor-Selective Activation
Adagene’s SAFEbody technology uses precision masking to temporarily shield an antibody’s binding domain, with activation designed to occur within the tumor microenvironment. The approach is intended to enable more selective targeting of cancer cells while potentially reducing binding to healthy tissues. This strategy is particularly relevant to ADC development, where potent cytotoxic payloads can create significant safety and tolerability challenges if delivered to non-target tissues. The technology forms part of Adagene’s Dynamic Precision Library (DPL) platform, which also includes its NEObody and POWERbody technologies. The company is applying SAFEbody across multiple antibody-based therapeutic modalities, including ADCs, Fc-enhanced antibodies and bispecific or multispecific T-cell engagers. The Exelixis collaboration began in 2021, when the companies entered into a collaboration and license agreement under which Exelixis could nominate targets for development of masked antibody candidates using SAFEbody technology. Exelixis assumes responsibility for subsequent clinical development, manufacturing and commercialization of resulting programs, while Adagene is eligible for development, regulatory and commercial milestones and royalties on potential product sales. The collaboration was expanded in 2025 to include a third novel SAFEbody ADC program, further broadening the application of the platform within Exelixis’ oncology pipeline.
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Additional SAFEbody ADC Program Reaches Candidate Selection
Beyond XB404, the September 2026 announcement also disclosed that candidate selection for another SAFEbody ADC program triggered an additional payment to Adagene. The companies did not disclose the target, candidate identity or financial value associated with this additional payment. The development provides further evidence that the collaboration is progressing across multiple programs rather than being limited to a single ADC candidate. Adagene remains eligible for future development and commercialization milestone payments and royalties on net sales from products arising from the collaboration. XB404 and the additional SAFEbody ADC program remain in the preclinical stage, meaning their safety and efficacy have not yet been established in human clinical trials. The milestone therefore represents advancement in drug discovery and preclinical development rather than a regulatory approval or clinical efficacy result. Nevertheless, the progress highlights continued industry interest in precision-masked ADC technologies as pharmaceutical companies seek approaches that could improve tumor selectivity and therapeutic windows for targeted cancer therapies.
Source: Adagene, Exelixis press release
