Govorestat (AT-007) Receives Orphan Medicinal Product Designation from the EMA for Treatment of SORD Deficiency

• EMA Orphan Designation reflects high unmet need in SORD Deficiency and benefit of govorestat treatment in reducing toxic sorbitol levels
• New data published in Journal of Clinical Investigation further elucidates the molecular pathophysiology of SORD neuropathy and the role of sorbitol in neuronal toxicity

NEW YORK, May 25, 2023 (GLOBE NEWSWIRE) -- Applied Therapeutics, Inc. (Nasdaq: APLT), a clinical-stage biopharmaceutical company developing a pipeline of novel drug candidates against validated molecular targets in indications of high unmet medical need, today announced that AT-007 (govorestat) has been granted orphan medicinal product designation by the European Medicines Agency (EMA) for treatment of Sorbitol Dehydrogenase (SORD) Deficiency. Additionally, the Company announced that new data has been published in the Journal of Clinical Investigation on govorestat treatment in models of SORD Deficiency.

EMA Orphan Medicinal Product Designation of AT-007 (govorestat) in SORD Deficiency

“We are pleased that the EMA has recognized the high unmet medical need in SORD Deficiency, and the benefit of govorestat treatment in reducing toxic sorbitol levels in patients with SORD Deficiency as well as preventing disease progression in the animal model of disease,” said Shoshana Shendelman, PhD, Founder and CEO of Applied Therapeutics. “Orphan designation for govorestat marks an important step towards advancing our regulatory initiatives in Europe.”

Orphan medicinal product designation provides certain benefits and incentives in the EU, including protocol assistance, fee reductions, and ten years of market exclusivity once the medicine is on the market. Applied Therapeutics has partnered govorestat for treatment of SORD Deficiency as well as Galactosemia in Europe with ADVANZ Pharma.

Sorbitol reduction via govorestat ameliorates synaptic dysfunction and neurodegeneration in sorbitol dehydrogenase deficiency
Yi Zhu, Amanda G. Lobato, Adriana P. Rebelo, Tijana Canic, Natalie Ortiz-Vega, Xianzun Tao,
Sheyum Syed, Christopher Yanick, Mario Saporta, Michael Shy, Riccardo Perfetti, Shoshana
Shendelman, Stephan Züchner, R. Grace Zhai
Journal of Clinical Investigation: May 22, 2023 Volume 8 Issue 10

The new data on govorestat treatment in models of SORD Deficiency was recently published in the Journal of Clinical Investigation. The article can be accessed here.

https://insight.jci.org/articles/view/164954/pdf

The molecular and cellular pathophysiology of SORD neuropathy was investigated through use of patient-derived cells and a drosophila model of disease, finding reduced adenosine triphosphate (ATP) production and reactive oxygen species (ROS) accumulation in the central nervous system (CNS) and muscle, indicating mitochondrial dysfunction as a result of increased sorbitol accumulation. Govorestat treatment significantly reduced sorbitol levels in patient-derived fibroblasts, patient iPSC-derived motor neurons, and SORD-deficient drosophila. Govorestat treatment in the SORD drosophila model mitigated synaptic degeneration and significantly improved synaptic transduction, locomotor activity, and mitochondrial function. Moreover, govorestat treatment significantly reduced ROS accumulation in patient derived cells and drosophila CNS and muscle. These findings uncover the molecular and cellular pathophysiology of sorbitol toxicity in SORD neuropathy, and govorestat provides a potential treatment strategy for patients with SORD Deficiency.