Ann: Release of Shares from Voluntary Escrow, page-10

The orphan designation just announced is very significant as it recognises a new disease and potentially offers a new pathway to commercialisation for Revascor.
The FDA appears to want to combat the role of endothelial dysfunction created by abnormal blood vessels in the gut which constrict and put resultant pressure on the heart muscle.
With endothelial dysfunction,vasodilation is impaired and the arteries begin to lack the ability to dilate properly. The endothelium is a thin membrane which helps regulate blood clotting ,immune function and controls vascular relaxation and contraction.
It would appear that MLC’s in Revascor express the right payload of Angiopoietin -1 (suppresses vascular leakage and modulates the Ang 2 cells), Hepatocyte Growth Factor (HGF) (act as a multi functional cytokines on both epithelial and endothelial cells) , Vascular endothelial growth factor (VGEF), Matrix metalloproteinasis ( regulates chemokines in the stroma cells and promotes wound healing) and of course SDF-1.
Whilst the orphan designation from the FDA specifically targets “Prevention of Gastrointestinal Bleeding in Patients With Left Ventrical Assist Devices” ...I am sure some bright spark has realised ,that the ability to meaningfully reduce endothelial dysfunction , is something that could offer significant breakthrough in many diseases which which adversely affect our immune systems. Some very big off label opportunities spring to mind !

If i am right , I would expect the US analysts to take much greater interest in Mesoblast because this represents an accelerated pathway to significant potential revenues. The question now , is , will we have the confirmatory trial agreed as part of a conditional approval for LVAD use , or do we have to wait for the confirmatory trial to finish ? We will probably get guidance on that issue, post the FDA meeting in July. Whichever way the decision goes, it represents a fast tracking of revenues which will please shareholders. This is big news. “MESO” Nasdaq did not peak at $6.03 offered overnight for no reason. The sophisticated biotech investor will need no reminding of the following information provided by The Scientist Magazine:

https://www.the-scientist.com/features/how-orphan-drugs-became-a-highly-profitable-industry-64278

For example, AbbVie’s Humira, which was FDA-approved in 2003 to treat rheumatoid arthritis, a condition that affects around 1 million adults in the U.S. alone, later gained additional approvals for multiple indications with orphan designation, including juvenile rheumatoid arthritis and pediatric Crohn’s disease—giving the company market exclusivity for some of these conditions until the early 2020s. Peter Saltonstall, president of the National Organization for Rare Disorders, told KHN in 2015 that Humira is “not a true orphan drug.” In fact, Humira is currently one of the world’s best-selling medications: in 2017, it raked in $18 billion in sales.

Another technique is to identify additional populations to gain orphan drug approvals in a practice dubbed “salami slicing,” in which a more common condition is divided into smaller, biomarker-defined categories. A 2016 study found that 13 of the 84 drugs approved with orphan designation between 2009 and 2015 were for subsets of more prevalent diseases and that some of those medications were also approved for other, related conditions (PLOS Med, 14:e1002190, 2017). For example, pharma firm Boehringer Ingelheim received FDA approval for afatinib (Gilotrif) to treat non-small cell lung cancer (NSCLC) patients with an EGFR mutation in 2013. Then, in 2016, the company received approval to use the same drug to treat NSCLC patients with squamous histology. The firm was awarded seven years of market exclusivity for both of the specified indications.

Interesting times ahead ! GLA