Biosplice Therapeutics Announces Initiation of AML & MDS Trial Sponsored by the National Cancer Institute

Biosplice Therapeutics, Inc. recently announced the US FDA has cleared the NCI-sponsored Investigational New Drug (IND) application for cirtuvivint. This small molecule inhibitor of CLK and DYRK kinases is in development for the treatment of hematological malignancies and solid tumors. This clearance allows for the initiation of a new clinical trial of cirtuvivint, both as a standalone treatment for patients with relapsed/refractory AML and MDS as well as in combination with ASTX727 for patients with frontline high-risk MDS.

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

“We are thrilled that the NCI has received FDA clearance to launch this groundbreaking new Phase 1 trial of cirtuvivint in liquid tumors, both as monotherapy and in combination with ASTX727,” stated Dr. Yusuf Yazici, Chief Medical Officer of Biosplice. “This milestone is a major step forward in our efforts to advance innovative treatments targeting CLKs and DYRKs. Given that dysregulated alternative splicing is commonly implicated in AML and MDS, cirtuvivint’s ability to regulate alternative splicing via CLK and DYRK inhibition may provide a promising new therapeutic pathway for patients. Based on compelling anti-tumor activity across both solid and liquid tumors in in vitro and in vivo models, as well as data from two prior Phase 1 trials in solid tumors, cirtuvivint promises to greatly improve outcomes for patients in these critical and underserved areas.”

This milestone highlights the ongoing collaboration between Biosplice and the NCI’s Cancer Therapy Evaluation Program (CTEP) through the NCI Experimental Therapeutics (NCI-NExT) program. After extensive evaluation, cirtuvivint was chosen for inclusion by NCI in the NExT programs following a competitive review. NCI-NExT partners with external researchers and leading scientific experts to accelerate the development of the most promising and innovative therapies, guiding them from early-stage research through to regulatory approval.

Biosplice stands at the forefront of research concentrating on the study and regulation of Cdc2-like kinases (CLKs) and dual-specificity tyrosine-regulated kinases (DYRKs). These kinases play pivotal roles in cell cycle regulation, splicing, and neurodevelopment, marking them as critical targets for therapeutic intervention in a range of diseases, including osteoarthritis, cancer, neurological disorders, and diabetes. With a robust chemical platform for kinase inhibition and a deep understanding of kinase signaling pathways, Biosplice leverages cutting-edge technologies to discover and develop highly selective kinase inhibitors. Biosplice’s drugs in clinical development include lorecivivint for osteoarthritis (completed Phase 3) and cirtuvivint for numerous cancers, with a broad preclinical pipeline that encompasses Alzheimer’s disease, diabetes and other degenerative conditions.

Cirtuvivint is a small molecule inhibitor of CLK and DYRK kinases, which are increasingly recognized as key drivers of various cancers. By targeting these kinases, cirtuvivint modulates alternative pre-mRNA splicing, which may reduce the expression of genes vital for tumor growth, survival, and drug resistance. The compound has shown broad anti-tumor activity across a range of solid and liquid tumors in extensive preclinical studies.

Cirtuvivint has also been investigated for the treatment of advanced solid tumors in two clinical trials. The first, SM08502-ONC-01 (NCT03355066), was a first-in-human dose escalation study designed to evaluate safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced solid tumors. The second, SM08502-ONC-03 (NCT05084859), was a Phase 1b trial assessing 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.