US preclinical trials for Mesoblast's stem cells

Melbourne-based stem cell specialist Mesoblast (ASX:MSB) has entered into agreements with Colorado State University to perform preclinical dose-escalation trials of its universal donor adult stem cell technology for the treatment of long bone fractures, and a new indication, intervertebral spinal fusion.

The trials, to be conducted in 40 to 50 sheep each, are expected to commence prior to the end of August and preliminary results should be available five months later.

Mesoblast uses proprietary technology to extract purified mesenchymal precursor cells from bone marrow. Adult mesenchymal stem cells can differentiate into a range of cell types for in situ tissue repair or regeneration, without inducing a rejection reaction from the recipient's immune system.

The large animal studies in the US will use an unrelated donor population of stem cells which are extracted, grown and injected into the sheep.

"Primarily, it is testing our allogeneic model, to demonstrate that central manufacturing of the stem cells in a large scale production is valid," said Mesoblast's chief scientific adviser, Silviu Itescu.

The second purpose of the trials is to demonstrate the safety of extremely high doses of stem cells in different applications, he said.

With plans to gain US Food and Drug Administration (FDA) approvals for use of its universal donor adult stem cells in patients needing bone repair/regeneration, these preclinical trials form an important milestone for Mesoblast.

"The bone regeneration for those applications is easy, and it's obvious and it's the quickest way to market," said Itescu.

The data from the preclinical trials will be provided to the FDA parallel with autologous trials, where the patient's own stem cells are extracted, grown and then injected back into the original donor, planned to begin in Australia in the next few months.

"The actual isolation of the cells and expansion is identical, irrespective of whether they're the patient's own cells or whether they're universal donor cells," said Itescu. "We want to limit it to the patient's own cells, just to remove one variable."

The autologous trials in Australia are for orthopaedics, specifically non-healing tibial fractures, and angina. The first patient for Mesoblast's clinical trials in angina has been recruited and the company is awaiting ethics approval for the orthopaedics trial. Mesoblast is also awaiting internal validation of cell manufacturing process used at the Peter MacCallum Cancer Institute, said Itescu.

"They've got to do three runs to make sure they get uniformity of scalability of the cells, and we're ready to go," he said.

As part of the trials in the US and Australia, Mesoblast is currently in discussions with a number of major pharmaceutical companies about the potential of using their products, such as ceramic carriers for use in bone regeneration, in these trials and in the future.

"If they're part of the animal studies, and the human studies, then they become part of the FDA dossier," said Itescu.