A Phase 2 clinical trial has began of DS-1211 in individuals with Pseudoxanthoma Elasticum (PXE), a rare multisystem genetic disease that causes calcium deposits in soft tissue leading to considerable morbidity. DS-1211 is a possible first-in-class small molecule developed through a research collaboration between Daiichi Sankyo and Sanford Burnham Prebys.
Calcification is a necessary, tightly regulated process in skeleto-dental tissues. But when the method goes awry and occurs in ‘soft’ tissues-;referred to as ectopic calcification-;it might be extremely dangerous. There’s an unmet medical need for treatments to forestall ectopic calcification, and this drug could help meet that need.”
José Luis Millán, Ph.D., Professor at Sanford Burnham Prebys
PXE affects roughly one in 25,000 people. It causes tissues within the body to improperly accumulate minerals, which results in changes in skin texture, problems with vision, and heart problems within the later stages. PXE is a progressive disease and not using a cure, which suggests that for most individuals, the disease only tends to worsen.
“The foundational science for DS-1211 comes from the pioneering research of Dr. Millan, whose work led to a molecular and cellular understanding of how physiological mineralization is controlled,” says Michael Jackson, Ph.D., senior vp of drug discovery and development on the Institute’s Conrad Prebys Center for Chemical Genomics (Prebys Center).
The Prebys Center played a key role in the event of DS-1211 by leading the drug discovery effort, from assay development and chemical-library screening to guide optimization, which ultimately resulted in a potent selective inhibitor of tissue-nonspecific alkaline phosphatase (TNAP) that showed efficacy in an animal model of PXE. This system was licensed to Daiichi Sankyo in 2015, and a compound, DS-1211, was chosen as a clinical candidate.
In 2017, DS-1211 was tested in Phase 1 clinical trials of healthy volunteers. The Phase 2 study will test dosing, safety and pharmacological properties of the investigational drug in individuals diagnosed with PXE.
“This may very well be the primary drug of its kind that may goal ectopic calcification without impairing physiological skeletal and dental mineralization and that may be very exciting,” says Millán. “While we do not know what the final result of the trial will probably be, it could make a serious difference within the lives of individuals with PXE and other ectopic calcification disorders.”