Mesoblast Limited

Mesenchymal Lineage Cells

Mesoblast currently has two drug therapies in late-state clinical testing for five areas of medical need. The company has already received full regulatory approval for drugs developed from its platform in both Japan and Europe, and has licensed out those therapies to suitable partners in those markets. All the drug candidates from Mesoblast’s technology platform are based on mesenchymal lineage cells. 

Mesenchymal lineage cells are rare cells found around blood vessels in the bone marrow that are essential for maintaining, repairing, and regenerating blood vessels. These cells have special properties that stimulate reduced inflammation in the body to allow proper healing. Mesenchymal lineage cells also have a few key features that allow for efficient commercialization to treat a broad range of complex diseases.

Mesenchymal lineage cells are obtained from the bone marrow of healthy adults and from there are capable of expansion from within a lab culture. These cells have reproducible properties that allow for commercial scaling from limited donors. Furthermore, whereas other transplant-related therapies require donor-patient matching or recipient immune suppression, Mesoblast’s mesenchymal-based therapies can be effectively administered without. When combined with Mesoblast’s proprietary manufacturing processes, the result is a cryopreserved, off-the-shelf cellular medicine, to treat multiple diseases that are readily available to patients in need.

Mesoblast’s product candidates are derived from two mesenchymal lineage cell therapy technology platforms: Remestemcel-L and Rexlemestrocel-L. 

Remestemcel-L

Remestemcel-L is Mesoblast’s first-generation product platform that is based on mesenchymal lineage stromal cells, which are cells that can become connective tissue cells of any organ. Remestemcel-L is currently in late-state clinical testing for Steroid Refractory Acute Graft Versus Host Disease, Moderate to Severe Acute Respiratory Distress Syndrome (ARDS) due to COVID-19 Infection, and Inflammatory Bowel Disease (IBD) – Ulcerative Colitis (UC) and Crohn’s Colitis. 

Graft Versus Host disease is a life-threatening condition that occurs after a bone marrow transplant where the donor cells attack the recipient, causing inflammation and tissue damage in the liver, stomach, and skin. Of the 30,000 people receiving bone marrow transplants worldwide each year, up to 60% develop the condition. In the US, there are no FDA-approved treatments for the condition in children under 12, and only one for other patients. Mesoblast’s initial Biologics License Application (BLA) to the FDA for Remestemcel-L in pediatric patients was denied in 2020 for data deficiencies, and they are now preparing for resubmission after working with the FDA to address outstanding items. 

Mesoblast is also working with the FDA for the potential emergency use of Remestemcel-L in ventilator-dependent patients with moderate or severe ARDS due to COVID-19. ARDS causes a severe inflammatory reaction, causing significant damage to the lungs and other organs and is a major cause of immortality in COVID-19 patients. Although initial trials have shown that Remestemcel-L could be a viable treatment for this condition, producing a reduced mortality rate of 48% for patients under 65, Mesoblast is collaborating with Vanderbilt University Medical Center to jointly trial an additional clinical study to meet FDA requirements for an Emergency Use Authorization (EUA). 

Inflammatory bowel disease affects up to 1.6 million people in the USA alone, with around 30% unresponsive to currently available drug treatments. For those with Crohn’s disease, 80% will require surgical treatment at some point, which can negatively impact quality of life. Remestemcel-L is currently in phase 2 trials for patients with medically refractory Crohn’s disease and ulcerative colitis. 

Rexlemestrocel-L

Rexlemestrocel-L is Mesoblast’s second-generation platform that produces therapies from mesenchymal lineage precursor cells. Rexlemestrocel-L is currently in late-stage clinical testing for Chronic Heart Failure and Chronic Low Back Pain (CLBP) associated with Degenerative Disc Disease (DDD). 

Chronic heart failure affects about 6.2 million people in the United States, inflicting immense economic costs of up to $60.2 billion when identified as the primary diagnosis. Positive data from testing of Rexlemestrocel-L on chronic heart failure patients has resulted in Mesoblast obtaining a regenerative medicine advanced therapy (RMAT) designation for the drug from the FDA for treatment of chronic heart failure with left ventricular systolic dysfunction in patients with an left ventricular assist device (LVAD). Mesoblast is now preparing to meet with the FDA for the potential use of Rexlemestrocel-L across a broader spectrum of chronic heart failure instances. 

An estimated 7 million people in the US suffer from CLBP with DDD, with all non-surgically available therapies addressing only disease symptoms and not the underlying cause. Disc damage results in an inflammatory response from ingrowth of nerves, causing chronic pain. The mesenchymal lineage cells in Rexlemestrocel-L have shown anti-inflammatory effects and other beneficial impacts. In accordance with the FDA after reviewing the first phase 3 clinical trial results for treatment of CLBP patients who have DDD with Rexlemestrocel-L, Mesoblast is gearing up for an additional phase 3 clinical trial in the US. 

Operational Overview

Mesoblast has yet to generate any revenue from product sales and has primarily funded operations through the sale of equity on the ASX and Nasdaq Global Select Market, debt financing, collaboration agreements, licensing revenues, royalties, and grants. The company will need considerable additional capital to continue operating, much of which is likely to come from further equity offerings or debt financing, which could adversely affect stock ownership interest.

Final Thoughts

Mesoblast’s mesenchymal lineage technology platform has proven enormous potential in broad treatment across areas of medical need, with platform-derived products already in use in the two major markets of Japan and Europe, and two late-stage pipeline drug candidates making their way towards FDA approval.

With an extensive patent portfolio of approximately 1,000 patents covering all major markets through 2040, Mesoblast is primed to take advantage of its mesenchymal lineage cell product candidates. If approved for widespread commercial use, it’s clear this technology could have tremendous impacts, promoting extended longevity and increased life outcomes for people suffering from painful inflammatory diseases.