Overview

Velcura Therapeutics is dedicated to developing therapies for the treatment of multiple myeloma, bone metastases, rheumatoid arthritis and osteoporosis. We particularly focus on therapies that restore bone homeostasis.

Velcura’s discovery process leverages a platform of proprietary and industry-standard technologies to elucidate the intimate linkages between bone formation and resorption. This integrated approach to bone metabolism utilizes primary human cells that, as a result, allows the rapid identification and optimization of robust human-focused targets and therapies. To date, Velcura has applied its technologies to identify novel therapeutics that restore bone homeostasis. Its lead compound, VEL-0230, is currently in phase 1 clinical trials.

Human Bone Function Studies: Osteoblasts and Osteoclasts

Ex Vivo Human Bone Formation: Velcura’s Three-dimensional Osteoblast Development

Velcura has demonstrated that osteogenic growth factor treatment of human bone cells derived from multiple sources results in the formation of three-dimensional tissue like aggregates, the up-regulation of bone proteins such as osteonectin and alkaline phosphatase and the formation of human bone This core technology allows the rapid (3-5 days) growth of human bone in tissue culture (also known as ex vivo bone formation). Human bone cells (osteoblasts) grown in the presence of an osteogenic compound (small molecule or osteogenic growth factors) form three-dimensional tissue-like aggregates and produce micro-crystalline bone that is indistinguishable from that seen in vivo (Nature Biotech. 18, 954-958 2000)

In addition, Velcura has used this platform coupled with genomic analysis of gene expression following induction of bone formation to understand the critical pathways and processes leading to bone formation. Analysis of these pathways has revealed known but also previously unknown modulators of human bone formation. This transcriptional profiling also allowed determination of the molecular response of human osteoblasts to induction of bone formation with osteogenesis promoting compounds. From this, genes that are regulated in a similar manner by all of the bone stimulatory factors were identified. We believe these 165 genes represent a molecular signature of bone formation. Pathway mapping has identified novel pathways and networks not previously associated with bone formation. These pathways and their regulators provide key entry points for RNA interference (RNAi)-based reverse genetics to further identify new targets for bone therapy.

Human Osteoclast Analysis

Velcura has developed a robust process to differentiate and functionally characterize human osteoclasts in vitro with the aim of identifying molecules that effectively inhibit bone resorption. These consist of industry-standard assays of osteoclast mobility, resorption, protein expression and immunophenotyping.