GYS1

PHILADELPHIA--(BUSINESS WIRE)-- Aro Biotherapeutics, a clinical stage biotechnology company pioneering the development of tissue-targeted genetic medicines, today announced upcoming data presentations highlighting the therapeutic potential of its proprietary CD71 Centyrin – Gys1 siRNA conjugate ABX1100, for the treatment of Pompe Disease. The presentations will take place at the WORLD Symposium 2024 in San Diego, CA, from February 4-6, 2024. In the upcoming presentations, Bartholomew Pederson, PhD, Aro collaborator and Professor of Medical Education at Ball State University, will present new data in the Pompe Disease mouse model that demonstrates potent and specific reduction of Gys1 mRNA, glycogen synthase activity and glycogen in muscle tissues, and improved impaired treadmill performance in male mice. “We are excited for the opportunity to share our promising data with the Lysosomal Storage Disease and Pompe communities,” said Steven Nadler, Ph.D., Senior Vice President of Translation Research of Aro Biotherapeutics. “Dr. Pederson is a leading expert in the field of glycogen biology, and working with him affords us the ability to better understand the mechanism of action and the potential disease-modifying impact of our CD71 Centyrin - Gys1 siRNA conjugate for treatment of Pompe disease.” Dr. Nadler will also present data from non-human primate studies, detailing the preclinical development work supporting progression of ABX1100 into first in human studies, which are now ongoing. Following are additional details about the conferences and presentations: Title: A novel Centyrin - siRNA targeting and delivery platform inhibits glycogen synthesis and reduces glycogen levels in skeletal and cardiac muscle in a mouse model of Pompe Disease Presentation Type: Oral Presenter: Bartholomew Pederson, Ph.D., Professor of Medical Education at Ball State University Date: February 6th, 2024 at 10:30am PST Title: A novel Centyrin - siRNA targeting and delivery platform inhibits glycogen synthesis and reduces glycogen levels in skeletal and cardiac muscle in a mouse model of Pompe Disease Presentation Type: Poster Presenter: Bartholomew Pederson, Ph.D., Professor of Medical Education at Ball State University Date: February 6th, 2024 at 3:00pm PST Title: Nonclinical studies in non-human primates on ABX1100: A Centyrin – siRNA conjugate for the treatment of Pompe disease Presentation Type: Poster Presenter: Steven Nadler, PhD, SVP Translational Research at Aro Biotherapeutics Date: February 6th, 2024 at 3:00pm PST About ABX1100 ABX1100, a novel potential treatment for Pompe Disease, is comprised of a CD71 receptor binding Centyrin conjugated to a small interfering RNA (siRNA) which specifically interferes with expression of Gys1 mRNA, thereby reducing levels and overall activity of the Gys1 enzyme in muscle tissues. ABX1100 demonstrated a favorable safety pro GLP toxicology studies, with durable reductions in Gys1 mRNA in muscles supporting the potential for monthly or quarterly dosing. ABX1100 has received Orphan Drug Designation and Rare Pediatric Disease status from the United States Food and Drug Administration. About Aro Biotherapeutics Based in Philadelphia, Aro Biotherapeutics is a biotechnology company pioneering the development of tissue-targeted genetic medicines with a platform based on a proprietary protein technology called Centyrins. The company is developing a wholly owned pipeline of Centyrin-based therapeutic candidates for tissue-specific targeting of therapeutics for a diverse set of diseases. For more information, visit .

Looking to get its hands on a promising rare disease candidate, Sanofi has agreed to acquire California-based Inhibrx. The deal hinges on Inhibrx's phase 2 Alpha-1 Antitrypsin Deficiency (AATD) asset, INBRX-101. AATD is an inherited rare disease characterized by low levels of AAT protein, predominantly affecting the lung with progressive deterioration of the tissue. INBRX-101 is designed to reduce inflammation and prevent further deterioration of lung function in affected individuals, with less frequent (monthly vs. weekly) dosing. As part of the deal, Sanofi will spin off all non-INBRX-101 assets — three sdAb-based therapeutic candidates currently being evaluated in trials against various cancers — into a new publicly traded company, New Inhibrx. Per the deal, Sanofi will acquire all outstanding shares of Inhibrx for $30.0 per share in cash, representing an equity value of approximately $1.7 billion. The other pieces of the deal, which include Sanofi assuming inhibrx's outstanding debt and retaining an 8% equity interest in New Inhibrx, add up to a total transaction value of approximately $2.2 billion. Looking to build its rare disease portfolio, Sanofi had signed a potential $750 million deal with Maze Therapeutics Back in May , to pick up its glycogen synthase 1 program, including its lead clinical candidate currently in development for the treatment of Pompe disease. Sanofi later abandoned the deal in December , following the FTC's move to block the acquisition.

Pictured: Exterior view of Sanofi office in Gentilly, France/iStock, HJBC Sanofi on Monday announced it is abandoning a proposed licensing agreement with California biotech Maze Therapeutics, targeting the rare, genetic and often fatal disorder Pompe disease, in response to an FTC administrative complaint and authorization for a lawsuit in federal court. The deal’s termination follows the FTC’s challenge, filed earlier Monday, seeking to block the transaction on antitrust grounds. According to the regulator, the licensing agreement between Maze and Sanofi would “eliminate a nascent competitor” to Sanofi’s Pompe disease treatments Lumizyme (alglucosidase alfa) and Nexviazyme (avalglucosidase alfa-ngpt)—and would ultimately preserve Sanofi’s monopoly in the therapeutic space. The agreement, which involves Maze’s glycogen synthase 1 inhibitor MZE001, would deny patients and doctors access to more affordable Pompe treatments as well as curtail innovation and competition to develop new drugs, the FTC contends. Nate Soderstrom, acting deputy director of the FTC’s Bureau of Competition, said in a statement that “Sanofi’s acquisition of Maze’s Pompe disease drug threatens to deprive patients of a new, innovative treatment and maintain a status quo of exorbitant pricing for essential life-saving medicines.” Sanofi in a Monday statement said that it was “disappointed” by the FTC’s decision to block the Maze deal, adding that it disagrees with the regulator’s assertions. The pharma argued that the FTC’s actions would delay advancements that could potentially yield beneficial treatments for Pompe patients. “The delay associated with a long litigation has led Sanofi to conclude that it would not be in the best interests of patients to contest this litigation and Sanofi will therefore be terminating the agreement with Maze in accordance with its terms,” the company said in its announcement. Pompe disease is a rare genetic disorder that arises from mutations in the gene encoding for the acid alpha-glucosidase (GAA) enzyme. Under normal conditions, GAA works to break down glycogen polymers into its smaller glucose components. Dysfunctional activity of this enzyme leads to the toxic accumulation of glycogen in the muscles, triggering the hallmark symptoms of Pompe, such as heart defects and severe and progressive muscle weakness. Sanofi sought to address the underlying cause of Pompe with the Maze partnership in May 2023, for which the pharma paid $150 million upfront and pledged up to $600 million in milestones. At the center of the deal was MZE001, Maze’s lead asset—an oral inhibitor of the GYS1 protein—which is a central player in the production of glycogen. The company has two FDA approved therapies for Pompe. The first, Lumizyme, was approved by the FDA in 2010 and joined Sanofi’s fold when it bought Genzyme in 2011. The second, Nexviazyme, was approved in August 2021. While MZE001 is a twice-daily oral tablet, Lumizyme and Nexviazyme are administered via lengthy biweekly intravenous infusions. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.