Targeting the Wnt pathway to regenerate tissues and organs

BiospliceBiosplice, formerly Samumed, is developing drugs for multiple degenerative diseases, including osteoarthritis, alopecia (baldness), and degenerative disc disease. While these therapies differ from each other, they all focus on restoring the Wnt signaling pathway.

The Wnt pathway is fundamental in stem cell differentiation. It allows for ordinary tissue repair and upkeep, and it provides for wound healing and recovery from injuries. However, like many other pathways, it becomes deregulated with age. By restoring this pathway, Biosplice intends to replenish deteriorating tissues with the body’s own cells, staving off age-related diseases.

Biosplice has multiple therapies in human clinical trials, two of which have returned positive results from Phase 2 testing. If these therapies succeed in Phase 3 trials and are found to be effective in clinical practice, they will demonstrate the viability of targeting signaling pathways, potentially paving the way for a broad range of similar therapies.

Biosplice has launched a number of Phase 3 trials of lorecivivint (SM04690) for the treatment of knee osteoarthritis (OA), which will study the effects of lorecivivint on patient-reported outcomes and disease progression, with results expected in H2 2021. A Phase 2b trial met its primary endpoints in Pain NRS (daily pain measurement) and OMERACT-OARSI Strict Response.

Lorecivivint Phase 2b results: A Phase 2b randomized trial of lorecivivint, a novel intra-articular CLK2/DYRK1A inhibitor and Wnt pathway modulator for knee osteoarthritis & Individual Participant Symptom Responses to Intra-Articular Lorecivivint in Knee Osteoarthritis: Post Hoc Analysis of a Phase 2B Trial

Another drug, dalosirvat (SM04554), is in a Phase 2/3 trial for androgenetic alopecia (hair loss), with results expected later in 2021. An earlier Phase 2 trial led to a statistically significant increase in total follicle count versus placebo.


Yazici, Y., McAlindon, T. E., Gibofsky, A., Lane, N. E., Clauw, D., Jones, M., … & Tambiah, J. (2020). Lorecivivint, a Novel Intraarticular CDC-Like Kinase 2 and Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A Inhibitor and Wnt Pathway Modulator for the Treatment of Knee Osteoarthritis: A Phase II Randomized Trial.

Deshmukh, V., Hu, H., Barroga, C., Bossard, C., Kc, S., Dellamary, L., … & Seo, T. (2018). A small-molecule inhibitor of the Wnt pathway (SM04690) as a potential disease-modifying agent for the treatment of osteoarthritis of the knee. Osteoarthritis and cartilage, 26(1), 18-27.

Yazici, Y., McAlindon, T. E., Fleischmann, R., Gibofsky, A., Lane, N. E., Kivitz, A. J., … & Tambiah, J. R. S. (2017). A novel Wnt pathway inhibitor, SM04690, for the treatment of moderate to severe osteoarthritis of the knee: results of a 24-week, randomized, controlled, phase 1 study. Osteoarthritis and cartilage, 25(10), 1598-1606.

Website: Biosplice