New Hope for Fragile X as Mirum Launches Pivotal Phase II Trial

ESCONDIDO, CA – January 09, 2026 – A significant milestone has been reached in the quest for a treatment for Fragile X syndrome (FXS), the most common inherited cause of intellectual disability. Mirum Pharmaceuticals, in partnership with Enthorin Therapeutics, has initiated the BLOOM Phase 2 clinical study for MRM-3379, an investigational oral drug designed to target the underlying biology of the neurodevelopmental disorder. The trial's launch marks a moment of profound hope for a community that has long awaited a therapy capable of addressing more than just symptoms.

Affecting approximately 1 in 4,000 males and 1 in 8,000 females, Fragile X syndrome stems from a mutation in the FMR1 gene, which disrupts the production of a protein critical for brain development and function. This leads to a range of challenges, including developmental delays, learning disabilities, severe anxiety, and autistic-like behaviors. To date, no treatments have been approved to specifically address the core genetic cause, leaving patients and families to rely on supportive care and medications for co-occurring conditions. The advancement of MRM-3379 into mid-stage human trials represents a potential paradigm shift in this landscape.

A Decade-Long Journey to a Targeted Therapy

The path to the BLOOM study has been a marathon, not a sprint, representing the culmination of over a decade of dedicated scientific work. The compound, MRM-3379, was originally discovered by scientists at Dart Neuroscience (DNS), a team that includes many current members of Enthorin Therapeutics. It was at DNS that the drug, then known as ENT-3379, was advanced through initial safety trials in healthy volunteers.

Enthorin Therapeutics, a private biotechnology company focused on restoring brain circuit function, was founded to carry this legacy forward. The company’s announcement acknowledged the "diligent scientific research and development by the clinicians and scientists at Enthorin and DNS," highlighting the perseverance required to bring a novel central nervous system drug from the laboratory bench to patient trials.

For the estimated 50,000 males in the U.S. and Europe living with Fragile X, the start of this trial is more than a corporate milestone; it is a tangible sign of progress. Patient advocacy groups like the FRAXA Research Foundation have been instrumental in funding early-stage research and raising awareness about potential therapeutic pathways, including the one MRM-3379 now pursues. This long-term collaboration between scientists, companies, and the patient community has been essential in reaching this critical juncture.

The Science of Rebuilding Brain Circuits

At the heart of MRM-3379's potential is its innovative mechanism of action. The drug is a highly selective phosphodiesterase-4D (PDE4D) inhibitor. In simple terms, the PDE4D enzyme acts as a brake on a key signaling molecule in the brain called cyclic AMP (cAMP). By inhibiting this enzyme, MRM-3379 is designed to "release the brake," elevating cAMP levels.

This is crucial because cAMP plays a vital role in synaptic plasticity—the ability of brain cells to form and strengthen connections, which is fundamental to learning and memory. In Fragile X syndrome, these neural signaling networks are significantly impaired. The scientific hypothesis is that by boosting cAMP, MRM-3379 can help rebuild these essential communication pathways and restore more normal synaptic function.

Preclinical studies have provided a strong foundation for this theory. In mouse models genetically engineered to mimic Fragile X syndrome, the compound demonstrated the ability to improve cognition and alleviate behavioral deficits across multiple domains. Furthermore, its design as an orally available drug that can effectively penetrate the brain makes it a practical candidate for a chronic condition.

While promising, MRM-3379 is not alone in the race to treat FXS. Shionogi is advancing zatolmilast, another PDE inhibitor, which has received multiple special designations from the FDA. Meanwhile, Harmony Biosciences, following its acquisition of Zynerba Pharmaceuticals, is conducting a Phase 3 trial for its own investigational treatment. This competitive activity underscores the scientific community's belief that targeting the core biology of FXS is a viable and urgent goal.

A Strategic Partnership to Accelerate Development

The journey of MRM-3379 also exemplifies a powerful trend in the biopharmaceutical industry: strategic partnerships that pair the discovery engines of smaller biotechs with the clinical and commercial muscle of larger companies. Enthorin Therapeutics, with its deep expertise in translational neurobiology, successfully shepherded the drug through its foundational stages. However, advancing a drug through costly and complex late-stage trials requires significant resources and specialized experience.

This is where Mirum Pharmaceuticals enters the picture. A commercial-stage company with a proven track record in developing and marketing treatments for rare diseases, Mirum is well-positioned to carry the torch. The company already has three approved medicines for rare liver and metabolic disorders—Livmarli, Cholbam, and Ctexli—and reported impressive revenues of $336.9 million in 2024. With a strong cash position of over $293 million at the end of last year, Mirum has the financial stability to fund the demanding road ahead.

The licensing agreement reflects this synergy. Mirum made an upfront payment of $7.5 million to Enthorin and DNS and has committed to potential future milestone payments of up to $217.5 million, plus royalties on sales if the drug is approved. For Mirum, this deal marks a strategic expansion from rare liver diseases into genetically-defined neurological disorders, a field with immense unmet need. For Enthorin, the partnership validates its discovery platform and provides non-dilutive funding to advance its other pipeline assets, such as a PDE2A inhibitor for intellectual disabilities and treatments for Parkinson's disease.

The Road Ahead: The BLOOM Study and Beyond

The BLOOM study is a Phase 2, multi-center trial designed to evaluate the efficacy, safety, and tolerability of MRM-3379 in adolescent and adult males with Fragile X syndrome. The primary phase of the study will assess males aged 16 to 45, with a separate open-label cohort planned for younger boys aged 13 to 16. The trial will measure changes in cognitive function, behavior, and overall daily functioning, providing the first critical data on whether the drug’s promise in preclinical models translates to meaningful benefits for patients.

The initiation of this trial is a crucial inflection point. Success in Phase 2 would not only pave the way for larger, pivotal Phase 3 studies but would also provide powerful validation for the PDE4D inhibitor approach in neurodevelopmental disorders. The entire Fragile X community, from researchers and clinicians to families and caregivers, will be watching the results with cautious optimism. While the path through clinical development is fraught with uncertainty, the start of the BLOOM study represents a concrete step forward and a renewed sense of hope for a brighter future for those affected by Fragile X syndrome.