Biosplice Begins NCI-Sponsored AML and MDS Trial

Biosplice Therapeutics, Inc. has announced that the U.S. Food and Drug Administration (FDA) has cleared the National Cancer Institute (NCI)-sponsored Investigational New Drug (IND) application for cirtuvivint. This clearance will allow for a new clinical trial of cirtuvivint, a small molecule inhibitor of CDC-like kinases (CLK) and Dual-specificity tyrosine phosphorylation-regulated (DYRK) kinases, to begin. The drug is being developed for the treatment of hematological malignancies and solid tumors. The trial will investigate cirtuvivint both as a standalone treatment for patients with relapsed/refractory Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS) and in combination with ASTX727 for patients with frontline high-risk MDS.

The clinical study, known as NCI protocol 10674 (NCT06484062), will be sponsored by the NCI, part of the National Institutes of Health (NIH). Dr. Maximilian Stahl from the Dana-Farber Cancer Institute will serve as the principal investigator. The study will be conducted at participating centers within the NCI’s Experimental Therapeutics Clinical Trials Network, including the Dana-Farber Cancer Institute and Memorial Sloan Kettering Cancer Center. The trial aims to enroll up to 52 patients and will be carried out under the Cooperative Research and Development Agreement (CRADA) between Biosplice and the NCI.

Dr. Yusuf Yazici, Chief Medical Officer of Biosplice, expressed excitement about the FDA clearance and the start of the Phase 1 trial. He emphasized the significance of this milestone in advancing treatments that target CLKs and DYRKs. Dysregulated alternative splicing is often implicated in AML and MDS, and cirtuvivint’s ability to regulate this process through CLK and DYRK inhibition offers a promising new therapeutic pathway. Based on previous compelling anti-tumor activity observed in both solid and liquid tumors through in vitro and in vivo models, as well as data from two prior Phase 1 trials in solid tumors, cirtuvivint holds promise for significantly improving patient outcomes in these underserved areas.

This development underscores the ongoing collaboration between Biosplice and the NCI’s Cancer Therapy Evaluation Program (CTEP) through the NCI Experimental Therapeutics (NCI-NExT) program. Following extensive evaluation, cirtuvivint was selected for inclusion in the NExT program after a competitive review process. The NCI-NExT program collaborates with external researchers and leading scientific experts to fast-track the development of promising therapies from early-stage research to regulatory approval.

Biosplice Therapeutics is a leader in the study and regulation of Cdc2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs). These kinases are crucial in cell cycle regulation, splicing, and neurodevelopment, making them vital targets for therapeutic intervention in various diseases, including cancer, neurological disorders, diabetes, and osteoarthritis. Using advanced technologies, Biosplice has developed a robust platform for discovering and developing highly selective kinase inhibitors.

Cirtuvivint, a small molecule inhibitor of CLK and DYRK kinases, is recognized for its potential to reduce the expression of genes essential for tumor growth, survival, and drug resistance by modulating alternative pre-mRNA splicing. The compound has demonstrated broad anti-tumor activity in both solid and liquid tumors through extensive preclinical studies. Cirtuvivint has also been evaluated in two clinical trials for the treatment of advanced solid tumors. The first trial, SM08502-ONC-01 (NCT03355066), focused on evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced solid tumors. The second trial, SM08502-ONC-03 (NCT05084859), assessed the efficacy of cirtuvivint in combination with standard treatments for patients with advanced castration-resistant prostate cancer, advanced non-small cell lung cancer, and advanced colorectal cancer.