Good morning, everyone, and thank you for joining the 2024 H.C. Wainwright 26th Annual Global Investment Conference. I'm Dr. Jade Montgomery, an associate biotech research analyst at the firm, and I'd like you to please join me in welcoming Dr. Javier Szwarcberg, CEO of Spruce Biosciences, a late-stage biopharmaceutical company developing novel therapeutics for underserved endocrine and neurological disorders. Javier?
Thank you so much, and thank you, everyone here at HCW for hosting Spruce. So, I'll be speaking to you about Spruce. I'll be making through my presentation a few forward-looking statements. This is not clicking forward. So I refer you to our SEC filings to follow on those. There you go. All right, so, you know, at Spruce, we're working to advance science and develop medicines for a couple of disease states, including CAH, which stands for congenital adrenal hyperplasia, PCOS, polycystic ovary syndrome, and MDD, major depressive disorders. Tildacerfont, our lead asset, is an oral second-generation CRF1 receptor antagonist, which has a validated mechanism of action and a, so far, safety profile that's beneficial.
In the future, the next few months, we'll be unveiling data from our 204 study, which is one of the two studies that we've conducted as part of our CAHmelia program in CAH, as well as data from the CAHptain study, which is also studying tildacerfont in pediatric patients with CAH, and we're expecting those data in Q4 of this year. We have a strategic collaboration with a company named Brain Health to develop tildacerfont, along with a companion diagnostic, which they called Cortibon, in patients with major depression. In essence, the companion diagnostic allows for the selection of patients that are likely to respond to a CRF1 receptor antagonist, namely tildacerfont, in this case.
I've also wanted to mention the POWER study is a trial that we've conducted in patients with PCOS, where we saw meaningful, statistically significant reductions in DHEAS. We presented those data at ENDO, which is a large endocrinology meeting this year, and are quite open to embark in strategic collaborations, which we've been having for quite a while now. And around IP for Tilda composition of matter through 2027, with method of use patents that extend through 2038. And just to remind folks that we've got an orphan designation, both in the U.S. and Europe, for CAH. So end of 2024, frankly, quite important for us. We have top-line data from 204 coming up, as well as top-line data from 205.
We'll be unveiling those results at the same time, concurrently. The phase II study, proof of concept in PCOS, was already completed, and as I said, was presented at ENDO. Brain Health, which is a company we had partnered with for major depressive disorders, is due to initiate and enroll their first patient toward the end of the year. To conclude, we have a cash runway close to Q2, actually, with around $70 million, with a cash runway that extends into 2025. Speaking a little bit about Tilda and how Tilda works, Tilda is intended to work in the pituitary, which is the organ that's part of the HPA axis, or hypophyseal, hypothalamic axis.
That binds to a CRF1 receptor and therefore limits the oversecretion of ACTH, which is a hormone that's responsible for adrenal stimulation and resulting in elevated levels of androstenedione, or A4, which is a biomarker that most people use to track disease. It's a 2nd-gen drug. We licensed it from Eli Lilly a while back. And now into CAH for a bit. So CAH is an autosomal recessive disease. The body's unable to make cortisol. It's lacking enzymes, in this case, twenty-one hydroxylase, which is a rate-limiting enzyme in that pathway, due to a single genetic mutation, the CYP21A2 gene, and leads to a number of hormonal imbalances. When patients are lacking cortisol, it's frankly incompatible with life.
So the disease is now part of newborn screening for now a few decades, throughout most of the developed world. Prevalence of CAH, it's a rare disease, but not super small, 20-30 thousand patients in the U.S. All of them are diagnosed. They have an ICD-9 or ICD-10 code for CAH, around 50 thousand in the EU, and 145,000 in China, between 6 and 10 thousand in Japan, so it's a fairly large disease globally. So what's missing is this enzyme called 21-hydroxylase, which is required for the making of cortisol and also aldosterone. Aldosterone regulates salt and water in the body. Cortisol obviously regulates a ton of body functions, and when you're lacking, you just don't live. You die upon being stressed....
Surgery, infections, heat stroke, any type of stressor will actually have an effect on cortisol levels and make the body to go into adrenal crisis. So cortisol also supplies kind of a negative loop in other parts of that HPA axis that I mentioned, normally hypothalamus and the pituitary. And when cortisol is missing, you have elevated levels of CRF and elevated levels of ACTH. So the management of patients with CAH is a delicate one, right? Where you need to supply cortisol levels at baseline levels to supply physiologic needs. But if you really want to control the androgens and suppress the HPA axis, you have to provide supraphysiologic levels. And that excess steroids is what leads to one element of the comorbidity piece.
And I'm not gonna go through the list that you see on the right-hand side of the slide, but there are a lot of issues related to supraphysiologic doses of steroids. On the left-hand side of the slide is when you don't treat the disease effectively, and you're using less than what's actually needed, you end up with hyperandrogenemia. And there are a lot of complications related to hyperandrogenemia, which patients with CAH have actually learned to cope with and live with. But, you know, ranging from short stature, which usually happens when they're young, infertility, psychological effects, attention deficit disorders, abnormal puberty, and also how they look. I mean, they gain weight, they have male pattern of baldness, hirsutism. They don't menstruate.
It's impossible or nearly impossible for them, unless they're well managed, to bear a child, or become pregnant. So all of that led us to develop this program, which we call the CAHmelia program. It's composed of two studies, 203 and 204. On the left-hand side of the slide, the first column, you have a summary of baseline characteristics for the 203 study, which we unveiled in March, 204 in the center, and a reference study conducted by a competitor who's also developing a CRF1, is on the far right. Comparable in age across the three groups. The 203 study used meaningfully less steroids than the 204 study, and the competitor trial filled in between.
But of importance, the amount of A4 accumulation in the 203 study on the far left was around five times the upper limit of normal. The center study, 204 , has A4 value, which is the one, two, three, four, fourth row from the top, and 204 was 224 , so that's very close to normal. Normal is around 200-220 . And then you can see the other hormones listed there. But just to acknowledge one of the comorbidities that are typically afflicting patients with CAH, that's related to both androgens but also steroids, is overweight and obesity, right? With nearly 50% or more patients being on the obese range, with BMIs above 30mg/m² .
The design of 203 was a dose-ranging study, where we tested 50, 100, and 200 milligrams of tildacerfont relative to placebo. We enrolled 96 patients in this trial, where patients were not allowed to titrate steroids for the first 12 weeks. The primary was measured at 12 weeks, which was change from baseline A4. Patients came in with, as I said earlier, very high levels of A4s, fivefold above the upper limit of normal. Upon completing week 12, patients were escalated up to the tildacerfont full dose, and then maintained on tildacerfont full dose. We unveiled results from the 203 study in March. The study failed to achieve its primary, as well as demonstrate dose response. The drug was deemed to be safe.
I mean, and there were a number of reasons as to why this study failed, or at least that we attributed to the failure of the trial. This was a very difficult patient population to address, given their highly dysregulated adrenal glands, as well as the compliance rate in this study was actually below what we expected. 50% of patients were reported compliance that was greater than 80%. And that's a very low value in reference. Most of the studies that you see conducted have compliance rates above 80% or 90%, 90% of patients. And that's frankly the compliance rate that we are seeing in our 204 trial. So the studies are being conducted, frankly, at the same clinical sites, applying the same clinical development standards.
We think that the low compliance rates in two or three relate to just the disease state and who those patients are, right? To be a two or three patient, you tend to be less compliant with steroids. You tend to take less steroids. And that's measured or affected by the levels of A4 that these patients had at baseline, which were very high. Very different than the two or four study, which I present here in this slide, where we compared tildacerfont 200 milligrams, so the highest dose tested in two or three relative to placebo. In two or four, patients are coming in more controlled, with A4 values that are generally within the upper limit of normal.
The primary endpoint in 204 is the absolute change in glucocorticoids, as opposed to the change from baseline A4, because patients are coming in mostly controlled. At the end of a 24-week period, patients that are on placebo are allowed to actually take tildacerfont, 200 milligrams. And we are hopeful about the 204 study and expecting results in the Q4 of this year, along with results from the CAHptain study, which I'll describe next. So in CAHptain , we've conducted. CAHptain has, in essence, two parts, cohorts one through three, which I present on this slide. Tested tildacerfont 50 milligrams and 200 milligrams once daily in children and adolescent patients. We saw, frankly, favorable results.
I mean, we saw meaningful improvements in A4 values, which was the endpoint that we were assessing for efficacy, whereby 70% of participants at the very bottom of the slide with elevated levels of A4 achieve A4 reductions. We also demonstrated that 73% of patients had either A4 or GC reduction through the initial 12 weeks of treatment. We saw some variability in response, which is what resulted in an amendment in the study and our desire to dose patients with tildacerfont at 200 BID and 400 BID, which is twice and four times the dose we've used in cohorts one through three, and frankly, in our CAHmelia adult study. So in order to enable pediatric dosing, we have adult patients that are kind of sentinel patients, leading patients.
We are dosing adults at 200 BID and then adults at 400 BID, and that ungates the dosing of younger patients. Currently, the study is ongoing. We hope to report data in Q4, and as I said, will be reported concurrently with 204. Hopefully, 204 and 205 inform the path forward, about what we do. Will inform the timing of a meeting with regulators. This will probably be an end of phase II meeting, where we'll discuss with the FDA the path forward and the design if there's a need to conduct a phase III study, of that phase III study. Jumping indications now, shifting from CAH into PCOS. Again, polycystic ovary syndrome, it's a very heterogeneous disease, is polygenic.
Patients suffer from elevated androgens, ovulation dysfunction, which leads to infertility and cysts in the ovaries. You know, overt cysts in the ovaries are not necessarily key to diagnosis, but the first two criteria are. Metabolic dysfunction is very, very common with type two diabetes, NASH syndrome, hyperinsulinemia, and there are a number of hereditary and environmental factors that contribute to PCOS. It's the number one reason of infertility in women of childbearing potential. There's no approved therapy for PCOS. A lot of drugs are being used off-label for it. A very profound disease that leads to a lot of comorbidities in female patients, so we designed this study as a dose escalation trial, not parallel group design, where we tested 50, 100, and 200 milligrams of tildacerfont sequentially over four-week intervals against placebo.
The primary endpoint was DHEAS, which stands for dehydroepiandrosterone, a hormone that's solely made in the adrenals, a hormone that itself is not very pathogenic, and it doesn't result in PCOS symptoms. But upon absorption into selective tissues like hair, ovaries, adrenals, it actually has, gets converted to a lot of the ketotestosterones and keto hormones and results in pathogenesis. The results were highly statistically significant, to the extent that I present on the slide. I think that, you know, the next phase of PCOS development will likely involve a parallel group design with doses that are probably higher than 200 milligrams QD, so that we can have more of an effect size here, a larger effect size, not just one that denotes statistical significance.
Yeah, so we are currently in discussions with interested parties to potentially partner out the PCOS indication, if there is interest. It's a massive disease state and one that will require an investment that we're not ready to take on ourselves. And now, to pretty much close my presentation, major depressive disorder. This is a disease state that we partner with a company called Brain Health, using this companion diagnostic, which they have named Cortibon, using SNPs of the genome to define responders versus non-responders. The study is due to start as a phase two study, proof of concept trial, slated to start in Q4.
Upon completion of that trial and upon assessment of the data, Spruce will have the option to in-license exclusively worldwide rights for Cortibon, and we're frankly very excited about this opportunity, which will diversify our pipeline and allow us to venture into the precision psychiatry space. So with that, I'll close my presentation and open it up to questions, if there are any.