The U.S. Food and Drug Administration (FDA) has cleared Minovia Therapeutics' second Investigational New Drug (IND) application for MNV-201, paving the way for a Phase II clinical trial in pediatric patients with Pearson Syndrome, a rare and fatal mitochondrial disease. The therapy has also received Rare Pediatric Disease Designation.
MNV-201 represents a novel approach to treating mitochondrial diseases, consisting of autologous hematopoietic stem cells enriched with allogeneic mitochondria. This second-generation mitochondrial cell therapy aims to restore mitochondrial function in patients' stem cells, potentially addressing the underlying cause of the disease.
Novel Approach to a Fatal Pediatric Disease
Pearson Syndrome is a devastating multisystem progressive mitochondrial disease caused by single large-scale deletions of mitochondrial DNA. The condition typically presents in the first year of life with bone marrow failure and exocrine pancreatic dysfunction. Patients suffer from macrocytic sideroblastic anemia that often requires blood transfusions, along with thrombocytopenia and neutropenia.
"The FDA's clearance of our IND marks an important achievement for Minovia, allowing us to clinically evaluate our allogeneic mitochondrial cell therapy approach and proceed with the Phase II clinical program for this first-in-class allogeneic mitochondrial therapy for Pearson Syndrome patients," said Natalie Yivgi Ohana, PhD, CEO of Minovia.
Currently, there are no effective treatments for Pearson Syndrome, which is universally fatal. The disease progressively affects multiple organ systems, including the pancreas, kidneys, liver, adrenal glands, and heart.
Clinical Trial Design and Preliminary Evidence
The Phase II trial is designed as an open-label, single-dose study to evaluate both safety and efficacy in pediatric patients with Pearson Syndrome. The primary endpoint will focus on change in growth (height SDS), based on promising data from the company's first-generation product, MNV-101.
According to natural history data published by Dr. Rebecca Ganetzky from Children's Hospital of Philadelphia (CHOP), Pearson Syndrome patients typically experience an annual reduction of 0.5 units in height SDS and do not respond to growth hormone therapy. In contrast, patients treated with MNV-101 showed stabilization or improvement, with no decline in height SDS at 6 and 12-month follow-up.
Importantly, these growth improvements correlated with enhanced scores on the International Pediatric Mitochondrial Disease Scale (IPMDS), which measures quality of life and function (R²=0.9; p=0.0036).
"We are pleased to have safely dosed three Pearson patients enrolled in an ongoing study under the Israeli Ministry of Health," Dr. Ohana noted. "We look forward to treating additional patients under this IND, as well as to learning about the potential of MNV-201 to improve growth in this patient population."
The study is expected to enroll three additional patients for a total of six participants.
Broader Applications of Mitochondrial Therapy
Beyond Pearson Syndrome, Minovia is exploring the potential of its mitochondrial augmentation technology in other conditions. MNV-201 is currently being studied in a Phase Ib trial for low-risk Myelodysplastic Syndrome, with preliminary clinical data demonstrating both safety and efficacy.
The company's proprietary Mitochondrial Augmentation Technology (MAT) produces mobilized peripheral blood, autologous CD34+ cells enriched with allogeneic, cryopreserved placental-derived mitochondria. This approach aims to address mitochondrial dysfunction in both pediatric patients with primary mitochondrial diseases and adults with age-related diseases.
"We are pleased that our cumulative interactions with the FDA enabled alignment on requirements for the entire MNV-201 program, including preclinical, CMC, and clinical aspects," said Noa Sher, PhD, CSO of Minovia. "Early clinical and regulatory experience with MNV-101 shaped the current program and enabled a successful IND submission."
Scientific Rationale and Manufacturing Considerations
Preclinical research suggests MNV-201 has potential for safe dosing with low immunogenicity risk. The manufacturing process is designed to be scalable, potentially addressing the needs of a significant number of eligible patients.
The therapy works by enriching hematopoietic stem cells with healthy and functional mitochondria, aiming to restore stem cell function in patients suffering from mitochondrial dysfunction. This approach targets the fundamental cellular energy deficits that underlie mitochondrial diseases.
To date, Minovia has successfully dosed five patients with single-large scale mtDNA deletion syndromes, including both Pearson Syndrome and Kearns-Sayre Syndrome, demonstrating the potential breadth of application for this therapeutic approach.
For Pearson Syndrome specifically, MNV-201 aims to reduce disease-associated symptoms and the risk of disease progression and death, potentially improving both lifespan and quality of life for affected children.
