-Well-characterized mechanism of action significantly reduces risk of translation to human therapeutics for CNS diseases

– Apertura’s TfR1 capsids demonstrate broad CNS biodistribution and transduction and liver de-targeting at dose levels 40-fold lower than current CNS therapies

NEW YORK, NY, USA I January 04, 2023 I Apertura Gene Therapy, a biotechnology company opening opportunities in genetic medicine for treating debilitating diseases with limited options, today unveiled its proprietary engineered Adeno-Associated Virus (AAV) capsids that bind to the human Transferrin Receptor 1 (TfR1). This transportation mechanism mediates crossing of the blood-brain barrier (BBB) to enable gene therapy delivery throughout the central nervous system (CNS).

Human TfR1 is broadly expressed across the brain capillary endothelium. TfR1 binds iron attached to transferrin to mediate iron transport across the BBB, a highly selective, tightly associated layer of endothelial cells that regulates the transfer of solutes and chemicals between the circulatory system and the CNS. While the BBB is critical for protecting the brain, it poses challenges for the development and delivery of drugs to treat neurological disorders.

Apertura’s TfR1 capsids are based on technology developed in conjunction with the Vector Engineering Lab led by Dr. Ben Deverman at the Stanley Center for Psychiatric Research at the Broad Institute of MIT and Harvard. These novel capsids bind to the apical domain of TfR1 without interfering with transferrin binding, resulting in receptor-mediated transcytosis of the capsid into the CNS. Administered intravenously, Apertura’s second-generation capsids cross the BBB, demonstrating broad distribution and transduction in both neurons and astrocytes while also reducing distribution of the capsids to the liver. Apertura’s TfR1 capsids have demonstrated high efficiency at crossing the BBB at dose levels 40-fold lower than current CNS-targeted gene therapies.

“This milestone serves as an important advancement in our differentiated approach to designing next-generation gene therapies. Our capsids are the first-of-their-kind to be engineered through their native structure to target TfR1 to cross the blood-brain barrier,” said Joseph La Barge, Chief Executive Officer of Apertura. “Our TfR1 capsids, with their well-characterized mechanism of action, offer the unique advantage of significantly reducing human translation risk – a major historical challenge of engineering novel AAV capsids. These capsids hold exciting promise for patients with devastating and currently intractable CNS diseases. We are leveraging this technology to advance our own pipeline of next-generation gene therapies to widen the scope of treatable genetic diseases.”

Launched in 2021, Apertura is building a next-generation gene therapy company by utilizing an integrated, machine learning-enabled, data-driven approach to improving delivery and gene expression. Apertura is currently advancing two programs utilizing its TfR1 capsids for undisclosed neurologic conditions and is leveraging its platform technologies to engineer novel payloads to regulate genetic expression and develop additional AAV capsids targeting specific human receptors.

About Apertura Gene Therapy

Apertura is a biotechnology company opening opportunities for treating currently intractable diseases. We are uniquely positioned to develop genetic medicines by simultaneously engineering AAV capsids, genetic regulatory elements, and payloads to overcome limitations in cellular access, gene expression, pre-existing immunity, and manufacturability. Apertura is committed to growing the field of gene therapy and believes that together we maximize our impact by working with corporate and academic partners, patients, and foundations. Founded on technologies from the Broad Institute and Harvard Medical School, and with support from Deerfield Management Company, the company is based at the Cure, Deerfield’s innovation campus in New York City. For more information, please visit our website at www.aperturagtx.com and follow us on LinkedIn and Twitter.

SOURCE: Apertura Gene Therapy