- Callio Therapeutics is developing novel dual-payload antibody-drug conjugates (ADCs) designed to address resistance to existing cancer therapies, using proprietary linker and ADC platform technologies
- CLIO-8221 is a first-in-class dual-payload ADC combining a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, currently in a Phase 1 clinical trial for HER2-expressing solid tumors
- At AACR 2026, Callio Therapeutics will present preclinical data demonstrating that CLIO-8221 provides a wide therapeutic window with strong durable activity, supporting its potential to deliver clinical benefit in patients with tumors resistant to existing Topo1 inhibitor-based ADCs
SEATTLE and SINGAPORE, April 15, 2026 (GLOBE NEWSWIRE) -- Callio Therapeutics, a biotherapeutics company advancing dual-payload antibody-drug conjugates (ADCs) with a targeted, multi-mechanism approach to cancer treatment, today announced a poster presentation on CLIO-8221 at the American Association of Cancer Research (AACR) Annual Meeting 2026 (April 17-22, San Diego). CLIO-8221, currently being evaluated in an ongoing Phase 1 trial, is a first-in-class dual-payload ADC, engineered for targeted delivery of two payload classes, a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, to HER2-expressing tumors.
“CLIO-8221 is the first program from Callio’s dual-payload ADC pipeline to enter the clinic, just one year after our launch, underscoring our commitment to advancing innovative dual-payload ADCs for cancer. By combining two complementary anti-cancer payloads, CLIO-8221 may offer a new treatment option for patients whose cancers are resistant to existing single-payload Topo1 inhibitor-based ADCs,” said Jerome Boyd-Kirkup, Ph.D., Chief Scientific Officer of Callio Therapeutics. “Our preclinical studies support the high potency and enhanced tolerability of CLIO-8221, enabled by our next generation linker platform and ADC technologies, and we look forward to presenting these data at AACR.”
At AACR 2026, Callio Therapeutics will present data that highlight the potential of CLIO-8221 as a therapeutic option for HER2-expressing cancers:
- CLIO-8221 is a dual-payload ADC carrying a Topo1 inhibitor and an ATR inhibitor (DAR 4:4 ratio), selected to maximize anti-tumor efficacy and overcome Topo1 inhibitor resistance
- CLIO-8221 uses proprietary linker and ADC technologies to reduce systemic toxicity and enable co-delivery of both payloads to drive strong tumor cell killing
- CLIO-8221 demonstrated potent anti-tumor activity across varying HER2 expression levels and drove tumor regression after a single dose in both trastuzumab deruxtecan-sensitive and -insensitive models
- CLIO-8221 has a broad therapeutic window with no toxicological findings observed at doses up to 70 mg/kg in NHP studies
About CLIO-8221
HER2 is a clinically validated target for antibody-drug conjugates (ADCs), with multiple approved therapies demonstrating meaningful benefit across tumor types, however, most patients eventually progress on treatment despite retaining HER2 expression. Mechanistic resistance to cytotoxic payloads has emerged as a key reason for treatment failure. CLIO-8221 is a novel, first-in-class dual-payload ADC targeting HER2, designed to address this challenge.
CLIO-8221 delivers two mechanistically complementary payloads, a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, directly to HER2-expressing tumors. While Topo1 inhibitors have shown strong clinical activity, activation of the DNA damage response following Topo1 inhibitor-induced replication stress represents a potential major driver of resistance. By simultaneously inhibiting Topo1 and blocking the DNA damage response through ATR inhibition, CLIO-8221 is engineered to overcome payload insensitivity and sensitize tumors to Topo1 inhibition. Developed using proprietary linker and ADC platform technologies, CLIO-8221 aims to maximize anti-tumor activity while reducing systemic toxicity, offering the potential for deeper and more durable responses in patients who have progressed on existing HER2-targeted therapies.
About Callio Therapeutics
Callio Therapeutics is a clinical-stage biotherapeutics company advancing dual-payload antibody-drug conjugates (ADCs) with a targeted, multi-mechanism approach to cancer treatment. The company’s dual-payload ADC platform rapidly translates ideas into promising drug candidates, with the potential to achieve deeper and more durable treatment responses. The modular and highly adaptable platform features differentiated payload and linker technologies designed to maximize therapeutic benefit while improving tolerability. Headquartered in Seattle and Singapore, Callio Therapeutics’ lead program is CLIO-8221, a HER2-targeted dual-payload ADC currently in Phase 1 clinical development. Launched with technology and programs exclusively licensed from Hummingbird Bioscience and backed by top life science investors, Callio Therapeutics is built to discover and deliver with an experienced team with a track record of success. For more information, visit www.calliotx.com and follow Callio Therapeutics on LinkedIn.