Rondo Therapeutics has unveiled promising preclinical data for RNDO-564, their novel CD28 x Nectin-4 costimulatory bispecific antibody, demonstrating significant potential in treating advanced bladder cancer. The findings were presented at the 2025 American Society of Clinical Oncology (ASCO) Genitourinary Cancers Symposium in San Francisco.
Breakthrough in T Cell-Mediated Cancer Treatment
The experimental therapy represents a significant advancement in immunotherapy approaches, specifically designed to enhance T cell-mediated tumor killing while addressing the challenge of T cell exhaustion in solid tumor microenvironments. RNDO-564 works through a dual mechanism, targeting both CD28 and Nectin-4 to stimulate anti-tumor immune responses.
"CD28 co-stimulatory bispecific antibodies are designed to boost T cell-mediated tumor killing and overcome T cell exhaustion in the solid tumor microenvironment," explained Thomas Manley, CMO of Rondo Therapeutics. "In preclinical studies, RNDO-564 demonstrated robust anti-tumor activity in vivo and in vitro, including in an antibody drug conjugate (ADC)-resistant bladder cancer model."
Key Preclinical Findings
The preclinical studies revealed several promising aspects of RNDO-564's performance:
- Demonstrated ability to elicit robust Nectin-4 and signal-1 dependent T-cell mediated killing of Nectin-4-expressing tumor cells
- Successfully restored tumor cell killing function in serially stimulated T cells
- Showed effective tumor inhibition both as monotherapy and in combination with checkpoint therapy
- Maintained cytotoxicity against ADC-resistant bladder cancer cells
- Preliminary toxicology studies indicated favorable safety profile supporting clinical evaluation
Innovative Platform Technology
Rondo Therapeutics' proprietary platform features CD28-targeting binders with varying co-stimulatory potencies, designed to be tailored to specific tumor targets and indications. This approach moves beyond traditional "one size fits all" strategies, potentially offering more personalized and effective treatment options for solid tumors.
Path to Clinical Development
Based on these encouraging results, Rondo Therapeutics is advancing RNDO-564 through IND-enabling studies. The company has announced plans to initiate a Phase 1/b trial in patients with relapsed/refractory, locally advanced/metastatic bladder cancer by the end of 2025. This development represents a potential new treatment option for patients who have developed resistance to existing therapies, including ADCs.
