First in human clinical study provides proof–of–concept for mitochondrial augmentation therapy platform, which enables use of healthy mitochondria to improve mitochondrial function and mitigate effects of large–scale mitochondrial DNA (mtDNA) deletion syndromes

Study showed improved quality of life measures in children with Pearson Syndrome and Kearns–Sayre Syndrome spectrum

No treatment–related adverse effects reported in study

WOBURN, Mass. and HAIFA, Israel, Dec. 21, 2022 (GLOBE NEWSWIRE) — Minovia Therapeutics, a clinical–stage global biotechnology company, today announced that the findings of the first clinical use of mitochondrial augmentation therapy (MAT) platform to treat pediatric patients with primary mitochondrial diseases have been published in Science Translational Medicine. The study was conducted in collaboration with global leaders in the field of hematology and primary mitochondrial disease at Sheba Medical Center (Tel Hashomer, Israel).

Single, large deletions in mitochondrial DNA (mtDNA) can lead to a variety of devastating diseases, including Pearson Syndrome and Kearns–Sayre Syndrome (KSS). These mtDNA deletion syndromes are sporadic, uncurable and ultimately fatal. Pearson syndrome is a bone marrow failure disease that usually begins in infancy. In addition to presenting with sideroblastic anemia, patients are characterized by exocrine pancreas dysfunction. About half of patients die in infancy or childhood, while many who survive go on to develop KSS, a progressive multisystem disorder.

"These findings demonstrate that mitochondrial augmentation therapy is feasible in children with mitochondrial DNA deletion syndromes and that autologous CD34+ cells augmented with mitochondria derived from maternal blood may potentially deliver some functional improvement for patients living with these debilitating diseases for which there are no available therapies," said Elad Jacoby, M.D., Ph.D., Hemato–oncology Pediatric department, Sheba Medical Center.

MAT is designed to rescue mitochondrial function and metabolic activity in diseased cells through enrichment with healthy mitochondria. This builds upon Minovia's previous demonstration that MAT provides long–term functional benefit in an immunocompromised mouse model, and that mitochondria can transfer between hematopoietic stem cells (HSCs) in vivo (Jacoby et al 2021). Preclinical studies showed that hematopoietic stem and progenitor cells (HSPCs) can transfer normal mitochondria to hematopoietic and non–hematopoietic cells and improve disease features (Rocca et al., 2017).

Minovia is developing MAT to treat Primary Mitochondrial Diseases such as Pearson syndrome, as well as other mitochondrially–related sideroblastic anemias. The Company's lead investigational candidate, MNV–101 (MNV–BM–BLD), has been granted the Fast–Track, Orphan Drug and Rare Pediatric Disease designations by the U.S. Food and Drug Administration.

The latest study reported results from six patients ranging from 2 to 7 years of age: four with Pearson syndrome and two with KSS spectrum. All six patients suffered from significant failure to thrive and advanced multi–organ disease, which was either immediately or potentially life–threatening, requiring multiple ongoing supportive care interventions.

Key Findings

• No treatment–related adverse events were reported. Adverse events related to the leukapheresis procedure were managed with standard medical care. Adverse events that occurred following treatment were expected due to the patient's underlying disease and resolved spontaneously or with appropriate treatment.
• Higher levels of normal mitochondrial DNA were observed in the blood of four out of six patients, indicating a reduction of mitochondria with large DNA deletions.
• Clinical improvement in aerobic function was observed in some patients, and five of six patients experienced weight gain.
• Quality of life measurements showed improvement in most patients. Changes in the general well–being of children and physical activity were reported, along with increased time spent awake and in play.
• A series of aerobic and endurance tests were performed on two patients. Both patients demonstrated improvement in leg muscle strength and endurance at 6 and 12 months post treatment.
• One patient, who at baseline was unable to walk any distance, was able to walk 10 meters at 12 months and had improvement on the 30–second sit–to–stand test.
• Another patient demonstrated improvement in muscle function in some tests and a sustained improvement in others, including the six–minute walk test and sit–to–stand capacity at 6 and 12 months.

"We are tremendously encouraged by evidence of improvement to the quality of life and well–being of the children treated with MAT, including clinical improvements in aerobic function, weight gain and increased strength and endurance,” said Natalie Yivgi Ohana, Ph.D., co–founder and CEO of Minovia. “We believe these findings lay important groundwork for further development of MAT and future clinical trials to demonstrate the effectiveness and safety of MAT in patients with primary mitochondrial disorders and other diseases. Our excellent collaboration with the clinicians and teams at the Sheba Medical Center, as well as with patient advocacy groups, will enable us to accelerate the clinical development plans for Pearson Syndrome patients.”

About Primary Mitochondrial Diseases (PMD) and Mitochondrial Dysfunction
Primary Mitochondrial Diseases (PMDs) are chronic, genetic disorders that occur when mitochondria fail to produce enough energy for the body to function properly. Mitochondrial diseases affect about one in 5,000 people globally and can be sporadic or inherited and onset can occur at any age. Mitochondrial diseases can affect almost any part of the body, including the cells of the brain, nerves, muscles, kidneys, heart, liver, eyes, ears or pancreas. Mitochondrial dysfunction also plays an important role in more prevalent diseases, such as Alzheimer's disease, muscular dystrophy, amyotrophic lateral sclerosis and diabetes.

About Minovia
Minovia Therapeutics is a clinical–stage global biotechnology company committed to the discovery and development of novel approaches to treating diseases caused by mitochondrial dysfunction. Minovia's Mitochondrial Augmentation Therapy (MAT) platform is designed to extend and enhance human lives by restoring mitochondrial function using autologous stem cells enriched with healthy, functional mitochondria. This unique approach capitalizes on the natural ability of mitochondria to transfer between cells. The company's initial clinical focus is on primary mitochondrial diseases, such as Pearson syndrome, a fatal pediatric disease, and hematological disorders that include mitochondrial dysfunction. Minovia was founded by leading researchers in mitochondrial biology and is headquartered in Haifa, Israel, with operations in Massachusetts. For more information, visit http://minoviatx.com/.

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