Joseph K. Belanoff
Thank you, Charlie, and thank you, everyone, for joining us this afternoon. After many important years building this point, the next era at Corcept is about to arrive. As we have always known, cortisol enters all organs of the body and modulating its effects has the potential to be useful in many diseases. We now have 2 new drug applications, NDAs in progress in hypercortisolism and platinum- resistant ovarian cancer. The results of the studies leading to these NDAs were published in major medical journals in the second quarter. We have also generated promising results in our ALS and liver disease programs. In short, we have established a new medical platform useful to many patients suffering from serious disorders. The results of our CATALYST trial, the largest and most rigorous trial ever conducted to assess the prevalence and treatment of hypercortisolism in patients with difficult to control type II diabetes will transform medicine. The prevalence phase of CATALYST demonstrated that 1 in 4 of these refractory patients has hypercortisolism, a far higher rate than was previously assumed. In April, these results were published in Diabetes Care, a leading peer-reviewed journal of the American Diabetes Association. Patients who enrolled in the treatment phase of CATALYST had uncontrolled diabetes despite receiving multiple glucose-lowering therapies, including the most potent GLP-1 agonists. Even so, in only 24 weeks, patients treated with Korlym experienced a 1.47% reduction in hemoglobin A1c compared to just 0.15% for those receiving placebo. The p-value of this result was less than 0.001. In addition, patients saw significant improvements in a range of additional endpoints, including reductions in body weight and waist circumference. Notably, patients CATALYST experienced these improvements even as they decreased or entirely discontinued their other glucose-lowering medications. The results were presented last month during a keynote session at the American Diabetes Association's 85th Scientific session with a simultaneous publication in diabetes care. CATALYST findings will substantially accelerate the screening and treatment of hypercortisolism. Leading diabetologists are advocating for their quick integration into treatment guidelines. Concurrent with the rapidly increasing physician awareness of hypercortisolism, relacorilant is approaching approval. Its PDUFA date in hypercortisolism is December 30. Relacorilant's NDA is supported by our pivotal Phase III GRACE trial as well as our GRADIENT long-term extension and Phase II trials. In these studies, patients treated with relacorilant experienced clinically meaningful improvements across all of the signs and symptoms of hypercortisolism including hypertension, hyperglycemia, weight, lean muscle mass, waist circumference, cognition, Cushing's quality of life score and other important clinical measures. These benefits were observed consistently and durably with improvements emerging early and continuing or deepening over time. Equally noteworthy are relacorilant safety characteristics. Relacorilant has been well tolerated in all of its studies. Importantly, no instances of drug-induced hypokalemia, endometrial hypertrophy, vaginal bleeding, adrenaline efficiency or QT prolongation have been observed. These adverse events can have serious health consequences and are associated with 1 or more of the currently available therapies. We expect that relacorilant's efficacy and safety will make it a new standard of care for hypercortisolism. As awareness of the disease and its ability to be treated grows, many more patients with hypercortisolism will be identified and Corcept is well positioned to help them. As Sean said earlier, we are confident that our Cushing's syndrome business will continue to grow for years. Since the founding of Corcept, our research and development has been built on the hypothesis that cortisol modulation can be a powerful therapeutic mechanism in many serious disorders. The success of our pivotal ROSELLA trial in platinum-resistant ovarian cancer provides clear evidence that cortisol receptor antagonism has substantial potential in oncology. In ROSELLA, 381 women with platinum-resistant ovarian cancer were randomized 1:1 to receive either nab-paclitaxel, the most potent chemotherapy currently available for these patients, or nab-paclitaxel plus relacorilant. In these patients, the efficacy of nab-paclitaxel and chemotherapy in general, had diminished markedly. Our expectation was that relacorilant would blunt the anti-apoptotic effect of cortisol activity, thereby resensitizing ovarian tumors to the effective nab- paclitaxel. This expectation was resoundingly confirmed. ROSELLA trial met its primary endpoint of improved progression-free survival. Patients treated with relacorilant plus nab-paclitaxel experienced a 30% reduction in the risk of disease progression compared to patients treated with nab-paclitaxel alone, the hazard ratio of 0.7 and a p-value of 0.008. At 12 months, 25% of patients in the relacorilant arm remained progression-free almost twice as many as in the control arm. In the interim evaluation of overall survival, patients treated with relacorilant plus nab-paclitaxel had a median overall survival of 16 months compared to 11.5 months for those receiving nab-paclitaxel alone. The hazard ratio was 0.69, with a p-value of 0.01. These results were obtained without the need for a biomarker diagnostic test, a prerequisite of many currently available treatments and were even observed in patients with particularly poor prognosis such as patients who had received multiple lines of prior therapy and patients who have progressed while on standard of care therapy. Relacorilant plus nab-paclitaxel was well tolerated. The adverse events observed were consistent with the known safety profile of nab- paclitaxel. Because patients in the relacorilant plus nab-paclitaxel arm fared better than those in the nab-paclitaxel monotherapy arm, they had an approximately 30% longer duration of nab-paclitaxel therapy. When adjusted for treatment duration, the safety profile of relacorilant plus nab-paclitaxel was very similar to that of nab-paclitaxel alone. The results of the ROSELLA study were presented last month in an oral late-breaker session at the American Society of Clinical Oncology's Annual Meeting and simultaneously published in the Lancet, the general medical journal with the world's highest impact factor. Physicians have responded with great enthusiasm to these results, improving progression-free survival and overall survival without an added safety burden positions relacorilant to become the new standard of care for patients with platinum-resistant ovarian cancer. We submitted relacorilant's NDA in platinum-resistant ovarian cancer earlier this month and will submit a marketing authorization application in Europe soon. In anticipation of a successful regulatory outcome, we have made substantial progress in establishing a dedicated oncology division. We are prepared to move swiftly to bring relacorilant plus nab-paclitaxel to the women who can benefit from it once it is approved. ROSELLA established relacorilant's therapeutic value in a highly challenging stage of ovarian cancer. These results support relacorilant's potentially broader utility, including in earlier stages of ovarian cancer and in other solid tumors. The first step in advancing this strategy is with our BELLA trial, which is enrolling briskly and will test whether combining relacorilant plus nab- paclitaxel with bevacizumab offers an additional effective option for patients with platinum-resistant ovarian cancer. We will soon begin additional studies. In addition to exploring cortisol receptors antagonisms potential to resensitize tumors to chemotherapy, we are evaluating its use in combination with androgen deprivation therapy in prostate cancer. Cortisol stimulation is a major reason why patients with prostate cancer treated with the widely prescribed androgen receptor antagonist enzalutamide, eventually experience resurgent disease. Deprived of androgen stimulation, their tumor switched to cortisol activity to stimulate growth. Our collaborators at the University of Chicago are currently enrolling a randomized placebo-controlled Phase II trial of relacorilant plus enzalutamide in patients with early- stage prostate cancer to determine if cortisol receptor antagonism can block this tumor escape route. Another possible role of cortisol receptor antagonism is in combination with immunotherapy. Because cortisol suppresses the immune system, it may blunt the effectiveness of cancer therapies intended to stimulate an immune response. Adding a cortisol receptor antagonist to immunotherapies such as checkpoint inhibitors, may enhance their effectiveness. Following our Phase Ib trial in advanced adrenal cancer, we are deciding how best to investigate the utility of our compounds in combination with immunotherapies in other tumor types and earlier stages of cancer. Our proprietary compound, dazucorilant, is an excellent candidate for the treatment of neurologic disorders. While our DA