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Fighting degenerative disease
NEW YORK—As Dr. Silviu Itescu, CEO of Mesoblast Limited, notes: “Disease is about multiple pathways being turned on and off. Mesoblast was established more than 10 years ago to use the precursors of mesenchymal lineage adult stem cells (MLCs)—cells present in all of us next to blood vessels—that respond to stress or damage to tissues and that release multiple factors to undo that damage without inducing an immune response against themselves.”
Using technology licensed from Australian biologists, Mesoblast has leveraged its proprietary technology platform based on MLCs to establish a broad portfolio of late-stage, allogeneic, off-the-shelf cell product candidates to treat advanced stages of degenerative diseases with high, unmet medical needs. Included are cardiovascular diseases, orthopedic disorders, oncology and hematology diseases and immune-mediated and inflammatory conditions.
According to the company, mesenchymal precursor cells (MPCs) are extracted from a healthy volunteer. Antibodies with magnetic particles attached are introduced and bind to the MPCs. Using magnets, the MPCs are then isolated and separated. The purified MPCs are grown and expanded in the lab into billions of cells. MPCs are divided into doses, frozen in vials and shipped to medical facilities for use in patients.
In February, Mesoblast’s proprietary MPC product candidate, MPC-300-IV, was determined to be safe and resulted in early and sustained clinical responses in the first cohort of its ongoing Phase 2 trial in rheumatoid arthritis (RA) patients who have previously failed one or more biologic agents. The clinical trial involved a single intravenous infusion of the lower dose of the product candidate in 48 patients.
RA, a chronic autoimmune disease of unknown etiology, affects approximately 1 percent of the global population. The disease is attributed to chronic inflammation affecting the synovial membrane of multiple joints, which eventually leads to cartilage and bone destruction. Major advances using biologic agents in the treatment of RA have substantially increased the market size to $15.7 billion in 2014, with the market expected to grow to $18.4 billion in 2024. Still, about one-third of patients either do not sufficiently respond or cannot tolerate these agents, creating a need for safe and effective treatment without the potential risk of opportunistic infections or malignancies.
The prevalence of type 1 diabetes (T1D) continues to increase in people under age 20, making innovative new treatments a major strategic focus for the pharmaceutical industry. T1D remains a disease with significant morbidity and mortality despite use of insulin and other glucose-lowering agents.
Mesoblast has exclusively licensed patented technology developed at Harvard Medical School to modify MLCs to enhance their natural homing properties to sites of excessive inflammation. MLCs modified using this proprietary cell targeting technology, called ex-vivo fucosylation, have successfully induced durable reversal of T1D in a preclinical study. The cell targeting technology increased by threefold the numbers of MLCs reaching the inflamed pancreas in autoimmune diabetic mice following intravenous infusion, compared with unmodified MLCs, resulting in an increased number of mice who reverted to having normal blood glucose and in durable reversal of T1D.
Itescu projects that the company’s first commercial product, which would treat the complications of bone marrow transplants, could be available in about 18 months. Half of the time, the transplanted bone marrow attacks the body, which can result in death. The product, which has been fast tracked by the U.S. Food and Drug Administration, can “provide first-line therapy when steroids have failed,” Itescu says.
Other products in late or advanced stage also “answer big unmet medical needs,” Itescu adds. In addition to RA, there is a product to treat chronic low back pain from degenerative disc disease. Patients in clinical trials have failed all conservative measures including opioids. They have seen significant benefit from a single injection with no need for surgery, according to Itescu.
Injection of the Mesoblast cells in patients with chronic heart failure demonstrates significant improvement. A Phase 3 study slated to conclude in 2017 indicates that the treatment can eliminate hospital stays.
“We’re excited to see results in disparate disease states,” Itescu concludes. “These cells are safer than small molecules and more effective than single agents that target one pathology. The promise of stem cells has been around for quite awhile. Now we’re seeing the maturity of the industry and the ability to treat patients at the sickest end of the spectrum where other medications have failed.”