The first patient has been dosed in a Phase 2 clinical trial evaluating cirtuvivint as a monotherapy for patients with advanced soft-tissue sarcomas, Biosplice Therapeutics announced today. The multicenter, open-label trial is being conducted at eight clinical sites across Spain under the sponsorship of the Sarcoma European and Latin American Network (SELNET).
Led by Principal Investigator Dr. Javier Martin Broto, the study will evaluate approximately 30 patients with specific sarcoma subtypes whose disease has progressed following initial standard of care treatment. The trial aims to assess both safety and efficacy of cirtuvivint in this difficult-to-treat patient population.
"This trial represents a critical step forward for patients with advanced soft-tissue sarcomas, who currently face limited therapeutic options after first-line treatment," said Dr. Yusuf Yazici, Chief Medical Officer of Biosplice. "We are grateful to SELNET and the participating investigators for their partnership in evaluating cirtuvivint in this patient population."
Addressing an Unmet Need in Sarcoma Treatment
Soft-tissue sarcomas (STS) comprise a heterogeneous group of rare cancers originating in connective tissues. Treatment-resistant forms of the disease present significant challenges for clinicians and patients alike, with limited effective options available after first-line therapy failure.
SELNET elected to sponsor this investigator-initiated trial following a comprehensive review of preclinical data, which demonstrated compelling activity of cirtuvivint across multiple soft-tissue sarcoma cell lines and xenograft models that were refractory to other treatments.
The trial is registered on euclinicaltrials.eu (EUCT 2024-511987-10-00) and represents a key milestone in Biosplice's oncology program.
Cirtuvivint's Novel Mechanism of Action
Cirtuvivint is a small molecule inhibitor targeting CDC-like kinases (CLK) and dual-specificity tyrosine phosphorylation-regulated kinases (DYRK), which are increasingly recognized as key drivers of various cancers. The compound's mechanism involves modulating alternative pre-mRNA splicing, which reduces the expression of genes vital for tumor growth, survival, and drug resistance.
The drug has demonstrated broad anti-tumor activity across a range of solid and liquid tumors in extensive preclinical studies. Prior clinical investigation includes a first-in-human dose escalation study (SM08502-ONC-01, NCT03355066) evaluating safety, tolerability, pharmacokinetics, and pharmacodynamics in patients with advanced solid tumors.
A subsequent Phase 1b trial (SM08502-ONC-03, NCT05084859) assessed cirtuvivint in combination with standard treatments for patients with advanced castration-resistant prostate cancer, advanced non-small cell lung cancer, and advanced colorectal cancer.
Expanding Clinical Development Program
Beyond the current sarcoma trial, Biosplice is exploring cirtuvivint's utility across multiple tumor types. The National Cancer Institute is sponsoring a study to investigate the compound in Acute Myeloid Leukemia (AML) and Myelodysplastic Syndromes (MDS).
"Cirtuvivint has shown compelling activity in preclinical sarcoma models, and this study is a key milestone in our efforts to bring new therapeutic options to patients with high unmet need," Dr. Yazici added.
About Biosplice Therapeutics
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 across multiple disease areas.
The company's pipeline includes lorecivivint for knee osteoarthritis (completed Phase 3) and cirtuvivint for numerous cancers, with additional preclinical programs in Alzheimer's disease, diabetes, and other degenerative conditions.
With its robust chemical platform for kinase inhibition and deep understanding of kinase signaling pathways, Biosplice leverages cutting-edge technologies to discover and develop highly selective kinase inhibitors for conditions with significant unmet medical needs.
