A transcript from the Questions Dan answered at Bloom BurtonQuestion (19:08): I think you talked about phase II studies on bunionectomies and tummy tucks. Can you talk about the number of operations that would be done in the US on those 2 markets, per year?
Dan (19:20): They're not that hard to recruit for, I don't know actually know Bob, how many, but these are incredibly popular (mumbles, laughs) let's say unfortunately my wife has bunions, but uh, they're just generally known not to be difficult to recruit for. Our phase 2 recruiting in total, will probably be 3 months or so. But it's in the millions.
Question (19:48): Mesalamine, you're adding hydrogen sulfide to that, step 1 is it a generic and step 2 by itself are there shortcomings you're hoping to improve by adding hydrogen sulfide?
Dan (20:01): Yes, mesalamine is generic. Mesalamine is known as a very safe drug, but not particularly effective. We're trying to render our drug much more effective. IBD is a very, very complex disease, intimately involved in the biome and all the interactions of all the bacteria in the biome. It's going to be another 50 years before we fully understand inflammatory bowel disease. But that's why we get such great data (in animals of course) with the addition of that molecule that releases hydrogen sulfide. You also have to pay a lot of attention to the formulation because you want essentially, topical all along the intestinal tract.
Question (20:59): This AST elevation you have in the liver, is probably due to the chemical moeity on your molecule, you added a biocarboxamide and that labels protein, that labels GSH, could that be the liability, and whaddya gonna do about it?
Dan (21:14): It's a great question, and I know a fair amount about it, but I'm not a scientist and I'm also happy to follow you up with our scientists.
We are working with a group called ?Dillysen? they were funded by a consortium of 9 of the 10 biggest pharma. They're heavily respected by the FDA. We're spending a million dollars a year with them in North Carolina, deeply figuring this out. All NSAIDS cause AST and ALT rises in the neighbourhood of 2-4% of people. Tylenol causes 39%, but Tylenol would never be approved today. Historically we've been at about a 9% average and it's too much. We've finally think we've actually figured it out. It's clear that it's coming from reactive oxygen species from naproxen, all NSAIDS cause them and we think it's from the reactive oxygen species. In a small number of people, this 9%, everyone of whom has pre-existing liver damage, but common damage, so it's still something we have to deal with, we can't just exclude them. What is happening, and this is still a hypothesis, but this is pretty considered hypothesis. In the past 2 years, other scientists have discovered, have realized that every cell in our body makes hydrogen sulfide, but the liver specifically makes hydrogen sulfide additionally in the glutathione production process. And the liver uses both glutathione and hydrogen sulfide to protect against, among other things reactive oxygen species. And in the small number of people, over the longer term, we think the liver is essentially saying "wow free lunch!" Free hydrogen sulfide, and they're slowing down their own production of it. So it's not toxic, for these people it's too much of a good thing. And we think that the solution is going to be a sophisticated regimen control and so we're working on that. Yeah, yeah, hydrogen sulfide, there's huge scavenging systems in the body for it, so it dissipates relatively quickly compared to the naproxen which doesn't, so it has those reactive oxygen species. So we think that we're going to solve it now that we understand it. But we don't face it on acute pain.