Development of the novel small-molecule anti-osteoclastic drug ELP-004 to alleviate the symptoms of osteogenesis imperfecta (OI) - we are working on a new drug, called ELP-004, to treat osteogenesis…

The National Institute of Arthritis and Musculoskeletal and Skin Diseases awarded $172,164 to Exesalibero Pharma, Inc. on August 15, 2026, to develop ELP-004, a novel small-molecule anti-osteoclastic drug intended to alleviate symptoms of osteogenesis imperfecta (OI). The award is made under the Arthritis, Musculoskeletal and Skin Diseases Research program (CFDA 93.846), a Project Grant.

OI is a rare genetic primary bone dysplasia characterized by increased bone fragility, low bone mass, and susceptibility to fractures, with an incidence of 1:10,000–20,000 live births. Ninety percent of cases result from monoallelic variants in the COL1A1 and COL1A2 genes, the focus of this work. Current antiresorptive treatments, including bisphosphonates and denosumab, carry significant side effects and limited effectiveness in some patients. ELP-004 targets a common pathway in cellular infiltrates that damage bones, offering an alternative mechanism to existing therapies.

Work is performed in Morgantown, West Virginia. The period of performance runs from August 15, 2026, through July 31, 2028.

Development of the novel small-molecule anti-osteoclastic drug ELP-004 to alleviate the symptoms of osteogenesis imperfecta (OI) - we are working on a new drug, called ELP-004, to treat osteogenesis imperfecta (OI)-induced bone disease based on a common pathway in the cellular infiltrates that damage bones. OI is a rare, genetic, primary bone dysplasia characterized by increased bone fragility, low bone mass, and susceptibility to bone fractures. The incidence of forms recognizable at birth is 1:10,000-20,000. Thus, OI meets the definition of an "orphan disease". The clinical severity of OI is heterogeneous; however, bone fragility is the most clinically relevant characteristic of all types of OI, which manifests as multiple spontaneous fractures. At least five clinically distinct types of OI have been identified, with some sources listing up to 18 different types. The differentiation between the different types depends on the defective gene/protein. However, 90% of cases are caused by monoallelic variants in the COL1A1 and COL1A2 genes, which is the focus of this application. OI is incurable and survival is dependent of the type of OI. For example, type i, which has an autosomal dominant mutation of the COL1A1 (Α1) gene, is mild, while type II, which has different autosomal dominant mutations of the COL1A1 (Α1) or COL1A2 (Α2) gene, is lethal in the perinatal period. Several antiresorptive drugs are currently used to control osteoclastogenesis in OI patients. The most widely used drug class are bisphosphonates (BP). However, BPS have several side effects, including a long half-life (which may even last for several years after discontinuing the treatment) and their scarce or limited effectiveness in some OI patients make the BP less than ideal. Denosumab, an anti-rankl antibody, has shown positive effects in controlling osteoporosis; however, IT has several concerning side effects. Denosumab controls osteogenesis by inhibiting rankl (receptor activator of NF-ΚB) binding, which is essential for normal osteoclastogenesis. Long-term use of denosumab in children results in hypercalcemia and hypercalciuria. Discontinuing denosumab also resulted in a rapid decrease in lumbar spine bone mineral density z-scores in patients with type VI OI. ELP-004 would be classified as an 'antiresorptive' in the context of OI because of its ability to control osteoclastogenesis. ELP-004 has none of the side effects noted above for BP and denosumab. ELP-004 blocks the activity of canonical transient receptor potential (trpc) channels, which function as CA2+ permeable plasma membrane channels with varying CA2+ selectivity at concentrations congruent with in vivo dose levels that prevent bone erosion (preliminary data). We propose that pharmacologically suppressing the osteoclast development via the trpc channels with ELP004 will prevent bone disease associated with OI. ELP-004 will thus increase the quality of life of patients with OI. The overall goals of the project will be accomplished with one aim: aim 1: evaluate the potential of ELP-004 in treating type III OI symptoms using the +/OIM mouse model.