Gliachem is developing a small molecule therapeutic whose first clinical opportunity will be Rett Syndrome, a rare, pediatric disease with limited treatment options.

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‍UNMET NEED

Rett Syndrome is a rare, X-linked genetic neurological and developmental disorder that affects the way the brain develops. With approximately 350,000 patients worldwide, it manifests primarily in young girls, presenting with a wide range of disabilities and often misdiagnosed as general autism, cerebral palsy, or other conditions of pervasive developmental delay. Limited treatment options exist for these patients, most of which are off-label treatments for symptom management & occupational therapy. There is one approved drug (Trofinitide, Acadia Pharmaceuticals; approved 2023) which has a small effect size and tolerability issues, leaving significant room for improvement.

Rett Syndrome is caused by mutations of the MECP2 gene. In Rett patients, the brain fails to properly mature, remains under-developed throughout life, and functions inefficiently.  While the errant function of many systems contributes to these neural impairments, the hypoactivity of mTOR represents a key convergence point of pathogenic processes. Strategies to improve mTOR activity represent potential treatments for Rett Syndrome. The Transient Receptor Potential Cation Channel Subfamily M Member 2 (TRPM2) is one system that negatively regulates mTOR, and is over-expressed in the Rett Syndrome brain. We have developed new molecules that block TRPM2. These small molecules display high affinity and selectivity for TRPM2, and represent a first-in-class approach to engage TRPM2 for translational development in Rett Syndrome.  

‍APPLICATION/UTILITIES
The first clinical indication for our small molecule will be Rett Syndrome. However, TRPM2 has been implicated in other indications beyond Rett. We will look to validate additional clinical indications once we have the compounds to build the pipeline.

‍INVESTMENT & OBJECTIVES

‍We are currently looking to raise a $2.9M seed round, which will enable us to complete our hit to lead activities and select our lead candidate in ~12-18 months. This includes proof of concept in a mouse model and a comparison study of our lead vs. Trofinitide. A follow-on round of ~$5M will support Lead Optimization and a Series A of ~$5M will advance us through IND-enabling studies.

‍MARKET SIZE
350,000 patients worldwide, including major markets of EU (13k), USA(11k), Canada (4k) & Japan (1k). With only one approved drug (Trofinitide)which has a small effect size and tolerability issues, there is an opportunity to capture a significant segment of this market.

‍IP PORTFOLIO
Composition patent applications pending (NCEs).

CURRENT READINESS LEVEL
‍Hit to lead

‍SCIENTIFIC FOUNDER(S)
This new initiative is a collaboration among distinguished researchers at the Krembil Brain  Institute:

- Dr. Mark Reed, expertise in medicinal chemistry, chemical biology & CNS drug discovery, and leads UHN’s Centre for Medicinal Chemistry and Drug Discovery

- Dr. James Eubanks, epigenetic and mitochrondrial diseases expert, and a Rett Syndrome KOL.