MeiraGTx Announces Poster Presentation on a Potential Treatment for MC4R Genetic Deficiency at the 2024 Society for Neuroscience Conference

MeiraGTx Holdings plc (Nasdaq: MGTX), a vertically integrated, clinical stage genetic medicine company, today announced a poster presentation at the 2024 Society for Neuroscience Conference (SfN), which is being held from October 5-9, 2024, in Chicago, IL.

“We are pleased to share data at this year’s Society for Neuroscience Conference on the remarkable efficacy of our AAV-BDNF treatment in diet-induced obesity animal models,” said Alexandria Forbes, Ph.D., president and chief executive officer of MeiraGTx. “We leveraged our proprietary vector design platform to create a highly potent construct with the potential to treat children with severe early-onset obesity caused by MC4R genetic deficiency via the local delivery of a small dose of AAV-BDNF to a specific site in the ventromedial hypothalamus. This represents a powerful mechanism to treat these severely affected patients with no current treatment options available.”

The poster is available on the Posters and Publications page of the Company’s website on October 9, 2024.

The details of the poster presentation are as follows:

Poster Number: 5090Abstract Title: A CNS-targeted gene therapy for the treatment of severe pediatric obesityDate: October 9, 2024Time: 1pm CT

In the ventromedial hypothalamus, the leptin-proopiomelanocortin pathway interprets energy signals from the periphery to initiate feeding or fasting through two opposing neuronal populations. In a fed state, elevated leptin signals a decrease in food intake via the release of brain derived neurotrophic factor (BDNF) from Melanocortin 4 receptor (MC4R) expressing neurons. Loss-of-function mutations along this pathway, including in MC4R or BDNF, cause severe obesity in humans. MC4R deficiency leads to a severe form of early-onset pediatric obesity that is characterized by an increased drive to eat and impaired satiety. Hyperphagia and food-related distress have been reported in patients as young as 8 months old. Current therapeutic approaches such as bariatric surgery and glucagon-like peptide 1 (GLP1) agonists do not result in significant, durable treatment for persons with MC4R deficiency. MC4R agonists are being developed, but this approach will not benefit patients with homozygous mutations. Therefore, there remains a need to develop a therapeutic that results in healthy weight loss that can be maintained throughout life. With this aim, we developed an adeno-associated virus (AAV)-based gene therapy to deliver BDNF to the ventromedial hypothalamus to treat patients with MC4R deficiency. Here, we show that our optimized BDNF gene therapy, designed by altering various cis-regulatory components, achieves significantly higher expression compared to a previously published construct. In head-to-head comparisons in primary mouse cortical neurons and various immortalized neural cell lines, the optimized vector achieved 4-fold greater expression. As a demonstration of our synthetic promoter, expression of a fluorescent protein was as strong as the CAG promoter while off-target expression in the liver and heart was much lower, highlighting the specificity of our promoter. Furthermore, AAV-mediated delivery of our optimized BDNF gene therapy to the hypothalamus caused significant weight loss in a diet-induced obesity (DIO) mouse model within 21 days. Our BDNF gene therapy expresses 143-fold greater than basal levels of BDNF in vivo, which is in excess of the 10-fold increase required to prevent weight gain in the DIO model. By designing a highly expressing BDNF gene therapy, we can drive efficacy at lower viral vector doses and potentially lower immune responses and decrease safety risks. Taken together, these results indicate a potent and effective gene therapy for the treatment of patients with MC4R deficiency.

About MeiraGTx

MeiraGTx (Nasdaq: MGTX) is a vertically integrated, clinical-stage genetic medicine company with a broad pipeline of late-stage clinical programs supported by end-to-end manufacturing capabilities. MeiraGTx has an internally developed manufacturing platform process, internal plasmid production for GMP, two GMP viral vector production facilities as well as an in-house Quality Control hub for stability and release, all fit for IND through commercial supply. MeiraGTx has core capabilities in viral vector design and optimization and a potentially transformative riboswitch gene regulation platform technology that allows for the precise, dose-responsive control of gene expression by oral small molecules. MeiraGTx is focusing the riboswitch platform on delivery of metabolic peptides including GLP-1, GIP, Glucagon and PYY using oral small molecules, as well as cell therapy for oncology and autoimmune diseases. Although initially focusing on the eye, central nervous system, and salivary gland, MeiraGTx has developed the technology to apply genetic medicine to more common diseases, increasing efficacy, addressing novel targets, and expanding access in some of the largest disease areas where the unmet need remains great.

For more information, please visit www.meiragtx.com

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