Ann: MSB Presents Commercial Plans at 2020 Biotech Showcase, page-49

Surely the best strategy to increase the number of early responders would be to move Ryoncil™ ahead of steroids? Children’s GI systems are still in development, even in adolescence and, among other differences, they have a larger mucosal area. Mucosal healing is the key (as in IBD) and in GvHD, the earlier the better. Steroids are not known for healing the mucosa. SI has used the word ‘cure’. This imo carries particular weight at this stage as we prepare to enter clinical practice in the US. I wonder if the recent spike in Temcell sales is because doctors have seen how patients who have had Temcell are doing long term compared with those who had a durable effect from steroids. .

The application in Crohn’s Disease has been mentioned. I don’t know whether initially our product would be reimbursed for off label bowel rescue in ulcerative colitis because colectomy is curative; however, Ryoncil™ could be reimbursed for refractory IBD cases where the patient is unlikely to survive surgery. Surgeons are wary of operating on CD because it can go crazy, particularly in adolescents where it’s driven by hormones.

IBD (particularly UC) is strongly associated with the liver disease primary sclerosing cholangitis. Laborda et al (2019) say, "PSC is common in children with inflammatory bowel disease (IBD), affecting at least 10% of children with ulcerative colitis...Within ten years of diagnosis, 50% of children will develop clinical complications including 30% requiring liver transplantation"

The Merlin project in Europe is studying bone marrow mscs for PSC. Deneau et al (2013) published a study in epidemiology in autoimmune hepatitis (AIH), Primary sclerosing cholangitis (PSC) and autoimmune sclerosing cholangitis (ASC) in children in the state of Utah. Authors estimated that for all three conditions there were under 4000 cases in the USA.. Bear in mind, though, the authors analysed data from 2005-2011 and during the past decade there has been a big increase in cases of IBD, which is being diagnosed at increasingly younger age, particularly in Canada; there are also few pediatric studies in PSC as Ricciuoto et al (2019) say.

PSC may not be so rare. Perhaps earlier and increased testing, better imaging could identify cases likely to progress and there could be intervention before scarring occurs? I'm not great at figures and estimates and we don't know what the price will be, but if Ryoncil™ is used in these three conditions to potentially save the livers of 1000 children, then we could see significant revenue from this off label use alone. I also considered the context of what’s currently available; from the reading I’ve done, the consensus is that for PSC there’s currently no effective treatment.

MSCs being Immunomodulatory and the most severe disease responding best to our cells (proven by p3 results in aGvHD, surely the most severe cytokine storm) has pediatric autoimmune illnesses written all over it. If I could see this almost three years ago Post #: 31731838 then doctors in acute medicine will too. SLE, for example, takes a more aggressive course in children and adolescents (Tucker et al, 2008) and patients of African descent (Lewandowski et al (2017) It can damage not only the kidneys but other organs.

Evidence is mounting of the importance of the microbiome, not just in autoimmune illnesses (including PSC) but other diseases too, such as CHF and mental illness. I bought Gershon's book, 'The Second Brain' based on an articulate review that questioned whether we were treating the correct brain. I used to wonder how the gut could affect the brain. Now I think how can it not? Anything that heals the gut well is of immense value and likely to have a positive effect on the microbiome, as I suggested in my post here:Post #: 37166233

I believe MSB's cells are the obvious next generation biologics and the pediatric market for that is huge.

ALL IMO GLTAH