Good afternoon, everyone. My name is Javier Szwarcberg. I'm the CEO of Spruce. A real pleasure to be here, and thanks so much for the invite and for listening in. I'll be making some forward-looking statements as I present and speak today about the company, about the drug. I'll refer you to our SEC filings, 8-Ks, 10-Ks, and all those to evaluate the risks and forthcoming statements that I'll make as I move forward. So, as you know, Spruce is a rare endocrine disease company. We're operating and advancing drugs in multiple spaces, one of which is CAH, which is our primary target. CAH stands for Congenital Adrenal Hyperplasia. It's a fairly large market opportunity. We estimate that the market will be around $3 billion.
PCOS is another area where we're advancing our molecule, tildacerfont, with a very large market opportunity there. And lastly, we yesterday announced a deal with a German company that works developing a companion diagnostic for major depressive disorders. And as you know, major depression is an underserved market with a fairly large opportunity there as well. Our drug, tildacerfont, is a CRF1 receptor antagonist, blocks the CRF1 receptor at the level of the pituitary. It's a second-generation molecule that we licensed from Eli Lilly back in 2016, and we've been developing it for our CAH, PCOS, and, as announced yesterday, will be developed by Brain Health for major depressive disorders. In terms of milestones, we're very excited about our upcoming data readouts from the 204 and 205 studies.
204 is in adult CAH, 205 is in pediatric CAH, and we expect results in Q3 of this year. As I've mentioned before, Brain Health is the collaboration that we have most recently established. I'll be talking to you later about more details of that collaboration, but Brain Health has developed a companion diagnostic based on a prior dataset of a CRF1 receptor antagonist in major depression, and we'll be studying tildacerfont using that companion diagnostic to select patients that are likely to respond to a CRF1 receptor blockade, and the target is to start that study in Q4. We've reported POWER, the POWER study, which is a study that we've conducted in PCOS, where we've noticed significant reductions in DHEAS, which stands for Dehydroepiandrosterone, in patients with PCOS.
It was just reported final results at the ENDO meeting this past weekend in Boston. Lastly, at the moment, seeking partnership opportunities, we... This is not an indication that Spruce can actually take on and tackle by itself. PCOS is a large indication, difficult, will require substantial investment and not the core focus of the company at the moment. From an IP perspective, we have exclusivity through 2038 through method of use patents. We have also gotten orphan drug designation for CAH in the U.S. and Europe. Moving forward, this is our schedule of events as well as our cash runway. As I mentioned earlier, we presented two or three results in March. I'll be highlighting to you some of those findings momentarily.
We plan to get data readout from 204 and 205 in Q3, and initiate the major depressive disorder study in Q4. From our cash runway point of view, we have cash that would to. Currently, we closed the quarter actually with $81 million in cash, and which will provide enough cash to run the company until through the end of 2025. So talking about the molecule, tildacerfont is a CRF1 receptor antagonist. It blocks the CRF1 receptor at the level of the pituitary. It's a second-generation molecule by virtue of its PK features. You know, it's more potent against the CRF1 receptor, binds to the receptor for longer, has better lipophilicity, better absorption than the first-generation CRF1 receptors, and a few other PK features that distinguish it.
Jumping into CAH, it's a autosomal recessive disease. It's a pinpoint mutation in the CYP21A2 gene. It's a disease that's diagnosed through newborn screening in most developed countries, and its prevalence is not small at all, actually. It's 30,000 patients in the U.S., 50,000 patients in Europe, and 150,000 patients in China. About 12,000 patients in Japan, 2,000 patients in Korea. What happens in this disease is that the rate-limiting enzyme, 21-hydroxylase, is missing or highly ineffective, highly mutated, which leads to a deficiency in aldosterone and cortisol.
When that enzyme is deficient, you know, the body tries to make more CRF and make more ACTH to overcome the deficiency, and that leads to a buildup of precursors, and you see that on the far right on this cartoon slide. Those precursors are then shifted into androgens, and patients have high degrees of hyperandrogenemia, in addition to deficiencies in cortisol and aldosterone. The fact is that cortisol cannot provide a negative feedback on the pituitary and on the hypothalamus. And that's the culprit of the disease, right? So what doctors tend to do is to provide physiologic doses of cortisol to overcome the deficiency, as well as providing the negative feedback on the HPA axis. The problem is that you can never really achieve proper balance, right?
So patients end up being hyperandrogenic and hypercortisolemic, and the hypercortisolemia is a big deal. I mean, you, in essence, end up over-treating patients with hypercortisolemia for life. The hyperandrogenemia is also very complicated, and as you can appreciate on the slide, there are a number of abnormalities that are associated with hyperandrogenemia that patients try to avoid. These are results from our phase IIa study, one of which we dosed at 400 milligrams QD. On the far left side of the slide, you can see changes from baseline in ACTH, which were profound, where we've seen a maximum decline from baseline in ACTH of 84% at week 10. We also saw comparable reductions in A4 through the initial 12 weeks of the study, with the most profound reduction at week 10.
With 60% of patients achieving normalcy in ACTH levels, and 40% of patients achieving normalcy on A4 levels at the conclusion of the 12 weeks of the study. This study prompted the origination of the CAHmelia program, which is our phase IIb registrational program, which includes two studies in adult patients, II/III and II/IV. The II/III study baseline characteristics are presented on the far left, and the center is the II/IV. On the far right, we present the phase III study conducted by Neurocrine as a reference. You can see baseline characteristics from all three studies on this slide. We enrolled 96 patients in II/III, 100 patients in II/IV, and Neurocrine enrolled 182 patients in a 2:1 ratio.
Major differences that are worth highlighting are the glucocorticoid dose. You can see that in II/III, the dose of steroids on average was lower than in II/IV of 27 and 37, respectively. Neurocrine falls kind of in the middle with 32 milligrams of hydrocortisone equivalent a day. The A4 levels are very different across the studies, with II/III being about fivefold above the A4 levels in II/IV, of 1,151 in II/III, 224 in II/IV, and Neurocrine about in the middle, with 620 nanograms per deciliter. Importantly, all three at the very bottom of this slide, all three studies enrolled patients with severe comorbidities. The one that we're highlighting here is the weight, is the BMI for the patients.
II/III patients, despite taking meaningfully lower doses of steroids relative to II/IV and the Neurocrine trial, have very high rates of obesity. We also looked at high, you know, rates of severe obesity or morbid obesity with BMIs above 40, and the numbers are staggeringly high. So this patient population is not, frankly, free of problems, even though their androgens might be controlled, and their steroids may not be that high. So unmet need is highly unrealized, and I think that disease education and market shaping is gonna be required to educate patients about the severity of this disease and what this disease really means long term for them. So, as you probably know, the II/III study was negative, did not meet its primary endpoint of A4 change through week 12.
Post-hoc work that we've conducted shows directional benefit in ACTH, with meaningful reductions through the totality of the study, with most profound changes at week 64 of about 45% change in ACTH. We've also looked at markers that will likely predict response in the II/III study. So glucocorticoid usage was associated with a better A4 change. So the higher the glucocorticoid use, the bigger the A4 change at week 12, as well as compliance with therapy. I mean, this study was unfortunately doomed by poor patient compliance, with less than 50% of patients complying to more than 80% of study drug, which we believe highly explains the findings of the trial, the negative findings of the trial.
We show that patients with the most compliance had the biggest effect size relative to patients with only 55% compliance to study drug. So now jumping into the II/III study, which is one of our upcoming data readouts, we're comparing tildacerfont to placebo, 200 milligrams QD of tildacerfont against placebo. Patients are allowed to dose-modify the steroids so long as the A4 is within the upper limit of normal. We're enrolling patients taking between 30 and 60 milligrams of hydrocortisone equivalent per day. We sample-sized the study at 90 but ended up enrolling 100 patients. The study is fully enrolled and targeted to a data readout in Q3. And the other study that we'll read out in Q3 is the CAHptain studies, our pediatrics program, additional cohort.
So, what you see on the slide here are the results from the first three cohorts, where we show clear benefit and clear target engagement. The drug was safe and well-tolerated. Most patients achieve A4 control at week four, and also, most patients demonstrated an A4 or GC reduction during the initial 12 weeks of treatment. We're fairly confident that we'll be able to show more benefit upon exposing patients to a higher dose of tildacerfont. This is the schedule of treatment. We have six additional cohorts added into the trial, five patients targeted, and we hope to go a bit over in terms of sample size for each of the cohorts. Cohort four and cohort five actually check whether the compound reduces A4 at four weeks, when dosed at 200 BID and 400 BID.
So we're shifting from 200 QD to 200 BID and 400 BID, so twofold increase and fourfold increase in dosing given twice daily. The study is properly monitored by DMC. So far, we haven't seen any toxicities worth mentioning, and we're very excited about this upcoming interim data from the 205 study. So I'll move forward and describe quickly our polycystic ovary syndrome program. PCOS, again, a very common disease, affects 12% of women of childbearing potential, is the most common cause of anovulatory infertility of women of childbearing potential, and is characterized by elevated androgens, ovulatory dysfunction, and polycystic ovaries. Patients have both androgenic excess and also metabolic syndrome with usually insulin resistance.
It's really not a monogenic disease, but rather an interplay between genes and the environment that causes the disease. We named the study the POWER study, and enrolled patients in a 2-to-1 fashion. We enrolled 27 patients with increasing doses of tildacerfont of 50, 100, and 200. Patients were increased into, you know, to the higher dose, if tolerated, at 4-week intervals, and we assess efficacy and safety at week 12. We showed, t hese are the baseline characteristics of the patients. Their BMIs were fairly elevated, their DHEAS's were elevated for the most part. Although we targeted patients with DHEAS, all patients with DHEAS elevations, there were a few patients that were entered violating the entry protocol.
But among the patients that came into the trial with DHEAS elevations, we noticed a significant improvement and reduction in DHEAS. The magnitude and effect size in DHEAS wasn't crazy impressive, but we believe that on a follow-on study with a higher dose of tildacerfont, more profound effects on DHEAS might be achieved. DHEAS is an androgen that originates almost primarily from the adrenals. And the intent here is to, although PCOS seems to be an ovarian disease, for about a third of the patients, there is a mixed etiology of androgens, where androgens also come from the adrenals. So by controlling adrenal androgens, the hope was to be able to control symptoms. And although this study didn't study symptoms because of its duration, a follow-on study could do that.
We also noticed improvements in sex hormone-binding globulin. This is a protein that circulates, that binds to sex hormones. And the concept here is that if you have elevated levels, you have more binding of free bioactive sex hormones and hopefully leading to improved symptoms. Again, another important biomarker to measure in this disease. So by the way, open to partnering in polycystic ovary, we've had numerous discussions and with a multitude of partners, a space that's heating up and and that where there's substantial research going on. So jumping into our third program in major depressive disorders, as I said before, we've collaborated with HMNC Brain Health to develop tildacerfont coupled with their companion diagnostic called Cortibon in major depressive disorder patients.
Frankly, the whole class of CRF1 inhibitors were developed to treat depression, anxiety, and other type of drug withdrawal symptoms. They were shelved in around, you know, I would say early 2000s, primarily because these drugs were no better than the serotonin reuptake inhibitors among the totality of the patient population studied. When patients were sub-selected using this companion diagnostic tool, which looks at SNPs in those patients using blood samples, the efficacy was fairly profound and much better than the serotonin reuptake inhibitors. So we're fairly excited about this partnership. HMNC will conduct a phase II study starting in Q4 of this year, using tildacerfont and their companion diagnostic.
And at the end of the study is positive, Spruce has the option to in-license the companion diagnostic and take on the development of tildacerfont in major depressive disorders. In exchange, HMNC will be entitled to milestone payments and royalties according to our contract. So we're fairly excited about this new opportunity for tildacerfont in addition to our development program in CAH and PCOS. With that, I'll end my presentation and open it up to questions, if any?