Callio Therapeutics is actively developing a pipeline of promising dual-payload ADCs featuring rationally designed payload combinations for hard-to-treat tumors
CLIO-8221 is the first program from Callio Therapeutics dual-payload ADC pipeline to enter the clinic; Phase I trial is ongoing in Australia and the U.S., with planned expansion to China; IND clearance received from the U.S. Food and Drug Administration
SEATTLE and SINGAPORE, March 24, 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 that the first patient has been dosed in a Phase I clinical trial evaluating CLIO-8221 in patients with advanced HER2-expressing solid tumors. CLIO-8221 is a novel, first-in-class dual-payload ADC targeting HER2, engineered for targeted delivery of two payload classes: a topoisomerase 1 (Topo1) inhibitor and an ATR inhibitor, to HER2-expressing tumors.
The Phase I clinical trial (NCT07300943) is ongoing in Australia and the U.S., with Callio Therapeutics having received IND clearance from the U.S. Food and Drug Administration (FDA) this month. The IND is also under review by the China National Medical Products Administration (NMPA), and the trial is expected to expand to multiple sites in China.
“Dosing the first patient in the Phase I trial in Australia and receiving IND clearance from the U.S. FDA are significant steps in our commitment to advancing dual-payload ADCs for patients with cancer,” said Piers Ingram, Ph.D., Chief Executive Officer of Callio Therapeutics. “CLIO-8221 is the first program from Callio’s dual-payload ADC pipeline to enter the clinic, achieved in just a year from our launch. We believe this dual-payload ADC approach represents a promising new modality for multi-mechanism targeted cancer treatment.”
“CLIO-8221 uses a potent combination of two complementary anti-cancer payloads to address a common mechanism that causes resistance to single-payload ADCs. In preclinical models, CLIO-8221 demonstrated compelling anti-tumor activity, with a single dose leading to tumor regression in both Topo1 inhibitor-insensitive and -refractory models and was significantly more effective than single-payload ADCs,” said Jerome Boyd-Kirkup, Ph.D., Chief Scientific Officer of Callio Therapeutics. “Callio is actively developing a pipeline of promising dual-payload ADCs with rationally selected payload combinations. We are excited to move this pipeline into clinical trials in the upcoming months.”
“We are committed to improving treatment options for patients and are excited to take this step with CLIO-8221,” said Naomi Hunder, M.D., Chief Medical Officer of Callio Therapeutics. “CLIO-8221 represents a major advance in ADC technology, combining the validated cytotoxic payload exatecan with an ATR inhibitor payload. For patients whose cancers have become resistant or do not respond to existing Topo1 inhibitor-based ADCs, this dual-payload approach offers a new potential treatment option. Patients may also benefit from improved safety, as our next-generation linker platform is designed to reduce toxicities, consistent with the broad therapeutic window observed in preclinical 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 I 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.
Contacts
Media:
Crystal Ho
media@calliotx.com
Alexis Feinberg – ICR Healthcare
alexis.feinberg@ICRHealthcare.com
(203) 939-2225
Investors:
ir@calliotx.com
Stephanie Carrington – ICR Healthcare
stephanie.carrington@ICRHealthcare.com
(646) 277-1282
