Can you discuss the purpose of establishing the CAHtalog Registry, and how the insights gleaned from this database help us better understand the burden of CAH, and how it highlights the unmet need for better therapies for CAH?
So in order to sort of demonstrate the relevance of the data coming out of the Catalyst and Catalyst pediatric trials, uh there was a need to, Kind of benchmark these patients compared to Joe average patient out there or Jane average patient, and so the catalog registry was started to capture the clinical information from a large swath of patients with congenital adrenal hyperplasia, uh, primarily about what their laboratory data were, what dose of glucocorticoids they were taking, and what comorbidities they were suffering from. And, you know, you can think of people as falling into four quadrants. If you have on one axis androstendiion control, which you can use 170-hydroxyprogesterone or testosterone, whatever you want to, as a measure of control from a blood sample that we can do in the lab as a Objective biomarker, and then on the other axis, glucocorticoid dose, and that is the sort of resistance to uh control that the patients have. So people kind of parse out into four groups. Uh, the, the place you want people to be is with the androstendiion under control and the glucocorticoid dose in the physiologic range, but it turns out there's only 10, 15% of people that are in that group. And then you can imagine people with high androstendiome with that physiologic glucocorticoid dose, or people with normal androstendiome but at a high glucocorticoid dose. And then of course the worst quadrant is the patients who a lot of them were in the catalyst studies were the people who are on high doses of glucocorticoid above physiologic, yet Still, despite that, their androcenediione is above goal, and so it winds up that, you know, people are scattered between these three groups, and they transition between these three groups throughout their life for reasons we don't fully understand. I mean, you can imagine children as they go through puberty, they will outgrow their dose. They may have difficulty taking hydrocortisone multiple. Times a day, there's also the factors of changes in hydrocortisone metabolism that occurred during puberty. So you know people will shift from one group to another, but it is rare for people to stay in that quadrant that we want everybody to be in, you know, for a substantial period of time. And so, you know, we see people toggling good control. But then they're on a high dose glucocorticoid, and then they go into the bad control despite the high dose, and then they kind of finally come down into good control, but at the higher dose or somebody drops their dose and their control deteriorates. So I think those were the kind of things that we discovered from the catalog trial, but overall, I would say the people represented in the Catalyst trial were not, All that different from the majority of the people in the catalog trial because a lot of people were taking high doses of glucocorticoids. There are a lot of people in these groups that are in poor control and taking super physiologic glucocorticoid doses either singly or in combination, and There is a need for better treatments because we really want people in that quadrant of good control and physiologic dosing. Very few people are there, and most of the people are suffering from one of the two problems or both. In fact, I would say the largest group is the people who are on high dose glucocorticoids and in poor control.
