Mitochondrial Augmentation Therapy (MAT)

Enriching patient's hematopoietic & progenitor cells with healthy mitochondria isolated from
a healthy donor

For us, no disease is too rare.

The MAT Process

Manufacturing

Manufacturing of a qualified mitochondria product derived from healthy donor cells

mobilized

Patient’s hematopoietic stems cells are mobilized to the peripheral blood to allow cell collection by apheresis

Autologous

Autologous CD34+ HSPCs are selected from the apheresis product

Cells

Selected cells are enriched with healthy mitochondria

mitochondrial-augmented

The mitochondrially augmented cells are then reinfused back to patient’s bloodstream

* MAT is an investigational therapy that is undergoing clinical study to verify its safety and effectiveness.
Additional information can be found on ClinicalTrials.gov.

Primary Mitochondrial Diseases

A heterogeneous group of disorders caused by mutations or deletions in nuclear or mitochondrial DNA (mtDNA), displaying a wide range of severity and phenotypes. These complex, multi-systemic and rare group of diseases occur as a result of mitochondrial dysfunction.

Mitochondrial diseases can be inherited (mitochondrial inheritance) or non-inherited (de-novo). The latter also include rare paediatric diseases caused by a mutation or deletion in mtDNA, which develop into a systemic multi organ disease and can be fatal. Currently, there are no approved disease modifying drugs for mitochondrial diseases and patients are treated with supportive care only.

Primary Mitochondrial Diseases

Clinical Development

Minovia is currently evaluating MAT platform to treat both inherited and non-inherited primary mtDNA diseases.

In our first clinical study of MAT, Pearson syndrome patients are treated with autologous hematopoietic stem cells enriched with healthy, functional mitochondria, derived from maternal blood. This personalized therapy with our MNV-BM-BLD investigational product may have the potential to treat all non-inherited mitochondrial disorders.

For patients affected with an inherited mitochondrial disease, an allogeneic source of healthy mitochondria will be used for MAT. For this purpose, we have chosen the placenta, a young, healthy, ephemeral organ rich in mitochondria to augment patient’s autologous cells and developed MNV-BM-PLC to be the investigational product.

Clinical Development

Our Pipeline

Our current focus is on non-inherited and inherited primary mitochondrial diseases:

Product

Indication

Discovery

Pre-Clinical

Phase I/II

Phase III

Caused by single large mtDNA deletions: Pearson syndrome, which affects about 100 patients, & Kearns- Sayre Syndrome spectrum (KSS), which affects ~6,000 patients across the US, Europe & Japan.

Non-Inherited
diseases

Table 2
Mobile table

Caused by mutations in mtDNA: for example mt-tRNA mutation causing different mitochondrial diseases such as Mitochondrialm encephalomyopathy, lactic acidosis, and stroke-like episodes(MELAS) and Myoclonic epilepsy and ragged-red fibers (MERRF) with an estimated prevalence of 50,000 patients across the US, Europe and Japan.

Inherited
diseases

Minovia pipe-line
Mobile table

FDA Orphan Drug Designation

FDA Rare Pediatric Disease Designation

Fast-track Designation

Q & A

Q & A
Why did we select Pearson Syndrome as our lead program focus?

Pearson syndrome is an ultra-rare, fatal disease. Usually the main symptom at diagnosis is associated with the bone marrow, therefore HSPCs are the right modality to treat this disease. It is not inherited, allowing the mother to be a donor of healthy mitochondria to her child.

How do we address inherited mitochondrial diseases specifically in situations when the mother cannot be the mitochondria donor?

For patients affected with an inherited mitochondrial disease, an allogeneic source of healthy mitochondria will be used for MAT. For this purpose, we have chosen the placenta, a young, healthy, ephemeral organ rich in mitochondria. Feasibility and safety studies are conducted to test matching requirements of allogeneic mitochondria carrying different haplotypes to personalize the therapy.

How many times do patients require MAT?

The current clinical trials protocols include single treatment. We will continue to follow-up on all patients, using specific biomarkers as well as the patient’s well-being and overall clinical condition.

What happens with the damaged mitochondria? Are they cleared away?

Mitochondrial Augmentation Therapy does not require an active step of eliminating damaged mitochondria. Instead, by enriching the cells with healthy mitochondria, we increase the total mtDNA copy number and normal mitochondria content, which result in a shift in the metabolism of the recipient cell. The hypothesis is that the quality control of the cell maintains the normal mitochondria and eliminate damaged mitochondria through mitophagy.