Biosplice to Present Positive Lorecivivint Phase 3 Data for Knee Osteoarthritis at OARSI

Alternative splicing is a complex and tightly regulated process that allows a single gene to give rise to multiple protein variants, which is essential for the proper development and function of various tissues in the human body. This process is fundamental to the proteome's diversity and plays a critical role in determining tissue fate and function. However, when alternative splicing is disrupted, it can lead to a variety of diseases, including developmental disorders, tissue degeneration, and cancer.

Biosplice Therapeutics is a clinical-stage biotechnology company that has been pioneering innovative therapeutics based on the modulation of alternative splicing. Their approach involves targeting the CLK/DYRK family kinases, which are key regulators of RNA splice-site selection and are implicated in tissue-specific and disease-specific processes. By modulating the activity of these kinases, Biosplice aims to develop treatments that can correct the dysregulation of alternative splicing, potentially offering new therapeutic options for a range of diseases.

The company's lead drug candidate, lorecivivint, is being developed for the treatment of osteoarthritis (OA), a condition that affects millions of people worldwide and can cause significant pain and disability. Biosplice recently completed two Phase 3 clinical trials for lorecivivint: the OA-07 study, which focused on the long-term effects on joint structure, pain, and function, and the OA-21 study, which assessed short-term pain relief.

The final analysis of the OA-07 study showed that lorecivivint provided a statistically significant improvement in joint structure, as evidenced by X-ray measurements, and also led to a significant reduction in pain and improvement in function, as measured by standardized assessment tools. These results suggest that lorecivivint has the potential to be a first-in-class, structure-modifying drug for OA, offering patients a new treatment option that goes beyond just managing pain.

However, the preliminary results from the OA-21 study indicated that the drug did not achieve the primary endpoint of reducing pain at 12 weeks. The high placebo response observed in this trial was unusual and is currently being analyzed to understand the reasons behind this outcome, which contrasts with the positive results seen in the OA-07 study and previous trials.

Despite the mixed results, Biosplice remains committed to developing lorecivivint as a novel treatment for OA. The company plans to consult with regulatory agencies, including the US Food and Drug Administration (FDA), to discuss the path forward for marketing approval. Biosplice's broader pipeline includes other drug candidates targeting CLK/DYRK kinases for the treatment of various diseases, such as cancer, neurological disorders, and diabetes, reflecting the company's expertise in kinase inhibition and signaling pathways.

Biosplice's focus on the study of CLKs and DYRKs, which are involved in cell cycle regulation, splicing, and neurodevelopment, positions the company at the forefront of research into these important cellular processes. With a robust chemical platform and a deep understanding of kinase signaling, Biosplice is well-equipped to discover and develop highly selective kinase inhibitors that could potentially transform the treatment landscape for a variety of diseases.