Dr. Silviu ItescuProfessor Silviu Itescu is the Chief Executive and founder of Mesoblast, an Australian publicly-listed company since 2004 and now the world’s largest regenerative medicine company. Professor Itescu has established an outstanding international reputation as a physician scientist in the fields of stem cell biology, autoimmune diseases, organ transplantation, and heart failure. He is currently an active faculty member of Melbourne and Monash universities in Australia and was previously a faculty member of Columbia University in New York.


 

SFLF: How does Mesoblast’s strategy for development of allogeneic or off-the-shelf cell therapy products using its proprietary adult Mesenchymal Precursor Cells (MPCs) sit with regulatory bodies?

Dr. Itescu: The only way to ensure that cell therapy products become a mainstream component of patient treatment protocols is to adhere to existing regulatory frameworks around the world which are designed to protect patient welfare and ensure maximal integrity by both clinicians and product developers. Mesoblast’s approach has been to ensure rigorous science is performed using our purified cell populations with an understanding of mechanisms of action in each indication for which our cell products are being developed, and appropriate preclinical translational studies prior to embarking on clinical trials. Mesoblast’s clinical trials have all been sanctioned by regulatory bodies whose review ensures that the data has demonstrated scientific and regulatory rigor.

SFLF: By the end of this year, you will be in the midst of or have completed at least eight Phase 2 or 3 clinical trials. Can you elaborate on these?

Dr. Itescu: Mesoblast’s strategic product development focus is in three major and distinct areas. Our intravenous MPC product is being developed as an immunomodulatory agent to treat prevalent systemic disorders caused by excessive inflammation and activation of multiple immune pathways, including type 2 diabetes and end-stage kidney disease, rheumatoid arthritis, and inflammatory lung diseases. For degenerative diseases of the lumbar spine, we are developing two products, one for inducing bony fusion in end-stage disease patients, and a second for non-surgical disc repair in earlier stage patients with low back pain. We are also very excited about the potential for the catheter-based delivery of our cells to either prevent heart failure after a major heart attack or to retard disease progression in patients with established heart failure.

SFLF: Can you tell us about your upcoming Phase 3 program in congestive heart failure?

Dr. Itescu: Mesoblast has an important strategic partnership with Teva Pharmaceutical Industries with Teva providing Phase 3 trial expertise, proven capability to obtain product regulatory approvals, and global distribution strength.

In Mesoblast’s Phase 2 trial for heart failure, patients treated with a single intra-cardiac injection of the highest dose of MPCs have to date had no hospitalization events for decompensated heart failure or cardiacrelated deaths, over a mean follow-up period approaching three years.

On the basis of these results, Teva and Mesoblast have been working closely together on a Phase 3 trial design for congestive heart failure. The trial is expected to commence during 2013 with an early interim analysis for evidence of efficacy.

SFLF: From your vantage point, what would be the greatest help in moving adult stem cell research and therapies forward?

Dr. Itescu: The greatest benefit to the industry will come from forward- thinking and committed investors willing to support the leading technology innovators in embarking on appropriately-powered, well-designed, controlled Phase 3 trials. Successful outcomes of these trials will demonstrate to the wider community the power and effectiveness of cell therapy products.

SFLF: As a pioneer in translating science from the lab into the clinic, what has been your greatest challenge?

Dr. Itescu: The challenges in translating the science of adult stem cells to a clinical reality have in essence been those inherent to any new industry which attempts to change existing paradigms and the prevailing business perceptions. Cell therapy offers the potential to provide holistic approaches to tissue regeneration and repair via activation of multiple endogenous pathways, in contrast to conventional drug development which targets single individual pathways. The concept of using cells as therapies was previously met with some skepticism from investors, regulatory bodies, and pharmaceutical companies. Quality science, meticulous attention to manufacturing, and rigorous clinical trials are the answer to the sceptics, and as Mesoblast has achieved these outcomes there has been a discernible shift and acceptance by the wider community.