Agreement Reached to Develop MMP-13 Inhibitors to Treat Myeloma

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by Vanda Pinto, PhD |

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SteroTherapeutics has entered into an exclusive license agreement with Moffitt Cancer Center and Florida Atlantic University Research Corporation to develop matrix metalloproteinase 13 (MMP-13) inhibitors for treating multiple myeloma.

“This partnership with Moffitt Cancer Center and the Research Institute of Florida Atlantic University will allow us to further develop this novel line of highly selective MMP-13 inhibitors for the treatment of multiple myeloma to fulfill our strategic intent to bring revolutionary breakthroughs and innovations that significantly impact the lives of patients with orphan diseases as well as potentially larger indications with unmet needs,” Manohar Katakam, PhD, CEO of SteroTherapeutics said in a press release.

Multiple myeloma is a rare blood cancer marked by malignant plasma cells proliferating in the bone marrow. The exact causes of multiple myeloma are still unknown and there is no cure.

Extensive research has gone into matrix metalloproteinases, a family of enzymes involved in degrading and remodeling the extracellular membrane in cells, as targets for cancer therapy. Preclinical studies have shown the destruction of the basement membrane in tumors allows malignant cells to escape and establish metastases in other tissues in the body.

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Matrix metalloproteinases are also involved in bone remodeling, a vital process necessary to maintain the skeleton’s structural integrity. In bone remodeling, specialized bone cells, called osteoclasts, break down old bone. At the same time, these osteoblasts produce new bone. People with multiple myeloma have overactive osteoclasts which causes osteolysis, a condition where bone tissue is destroyed.

In myeloma mouse models, MMP-13 inhibition improved overall survival, which supported the development of MMP-13 inhibitors as a treatment for this disorder and for osteolysis. However, a few of the recently produced selective MMP-13 inhibitors showed poor solubility, metabolic stability, and bioavailability (the fraction of a medication that reaches circulation).

According to SteroTherapeutics, new compounds, or small molecules, that can potently and selectively inhibit MMP-13 have been developed. These new MMP-13 inhibitors also showed a robust modulation of osteoclast production and excellent solubility and stability. The company expects the new compounds to be highly effective add-on therapies to the current standard of care.

“We are delighted to work with [SteroTherapeutics] to further develop this novel line of highly selective MMP-13 inhibitors for the treatment of multiple myeloma. We anticipate that the inhibition of MMP-13 will not only reduce tumor burden but also protect against myeloma induced bone destruction, a painful aspect of this disease that greatly diminishes patient quality of life,” Conor Lynch, PhD, a senior member of the Tumor Biology Department at Moffitt Cancer Center, said.

“The teaming up of Florida Atlantic University, Moffitt Cancer Center and SteroTherapeutics will facilitate the bench-to-bedside path for a new class of chemical compounds that represent disease-modifying agents for treatment of cancer,” Gregg Fields, PhD, co-director of the Memorial Cancer Institute/Florida Atlantic University Cancer Center of Excellence, said.