Mirum Pharmaceuticals to Launch Phase 2 Trial of MRM-3379 for Fragile X Syndrome

Key Insights

• Mirum Pharmaceuticals plans to initiate a Phase 2 clinical trial of MRM-3379, an oral treatment for fragile X syndrome, in 2025.
• MRM-3379 selectively blocks phosphodiesterase 4D (PDE4D), an enzyme involved in nerve cell communication, aiming to increase cAMP levels in the brain.
• Fragile X syndrome affects approximately 50,000 males in the U.S. and EU, and currently has no approved treatments.

Mirum Pharmaceuticals is set to begin a Phase 2 clinical trial in 2025 to evaluate MRM-3379, an investigational oral therapy for fragile X syndrome. The announcement was made in conjunction with Mirum's recent financial results and business update.

Mirum acquired the global rights to MRM-3379, previously known as ENT-3379, from Enthorin Therapeutics and Dart Neuroscience in October. The agreement included an upfront payment of $7.5 million, potential milestone payments up to $217.5 million, and royalties on future sales.

Targeting PDE4D to Enhance Nerve Cell Communication

MRM-3379 is designed to selectively inhibit phosphodiesterase 4D (PDE4D), an enzyme highly active in brain regions crucial for learning, memory, and emotional regulation. PDE4D breaks down cAMP, a key signaling molecule between nerve cells, which is found at lower levels in individuals with fragile X syndrome. By blocking PDE4D, MRM-3379 aims to elevate cAMP levels and rebuild neural networks affected by the disease, potentially alleviating fragile X symptoms.

Unmet Need in Fragile X Syndrome

Fragile X syndrome, a neurodevelopmental disorder caused by mutations in the FMR1 gene, affects an estimated 50,000 males in the U.S. and European Union. The condition results in a range of symptoms, including developmental delays, learning difficulties, anxiety, and hyperactive or autistic behaviors. Currently, there are no approved treatments specifically targeting the underlying causes of fragile X syndrome, highlighting a significant unmet medical need.

Promising Preclinical and Phase 1 Data

According to Mirum, preclinical studies have shown that MRM-3379 achieves brain concentrations five times higher than blood levels. The therapy has also demonstrated efficacy in preclinical models of memory. In Phase 1 clinical trials, MRM-3379 was well-tolerated in both single and multiple ascending dose regimens.

"With the addition of the Phase 2-ready MRM-3379 candidate, Mirum’s growing commercial portfolio of treatments for rare neurological diseases with a genetic cause is taking shape," said Chris Peetz, Mirum’s CEO.