Corcept Therapeutics Inc (CORT) 2023 Q2 法說會逐字稿

Good day, and welcome to the Corcept Therapeutics Conference Call. (Operator Instructions) Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Atabak Mokari, CFO. Please go ahead.

美好的一天，歡迎參加 Corcept Therapeutics 電話會議。 （操作員指示）請注意，今天的會議正在錄製中。現在我想將會議交給今天的發言人、首席財務官阿塔巴克·莫卡里 (Atabak Mokari)。請繼續。

Hello, everyone. Good afternoon, and thank you for joining us. I'm Atabak Mokari, Corcept's Chief Financial Officer. Today, we issued a press release announcing our financial results for the second quarter and providing a corporate update. A copy is available at corcept.com. Our complete financial results will be available when we file our Form 10-Q with the SEC.

大家好。下午好，感謝您加入我們。我是 Atabak Mokari，Corcept 的首席財務官。今天，我們發布新聞稿，宣布第二季度的財務業績並提供公司最新情況。可以在 corcept.com 上獲取副本。當我們向 SEC 提交 10-Q 表格時，即可獲得完整的財務結果。

Today's call is being recorded. A replay will be available at the Investors Past Events tab of our website. Statements during this call, other than statements of historical facts, are forward-looking statements based on our plans and expectations that are subject to risks and uncertainties, which might cause actual results to differ materially from those such statements expressed or implied. These forward-looking statements are described in today's press release and the risks and uncertainties that may affect them are described in the press release and in our annual report on Form 10-K and our quarterly reports on Form 10-Q. Please refer to those documents for additional information. We disclaim any intention or duty to update forward-looking statements.

今天的通話正在錄音。我們網站的“投資者過去的活動”選項卡上將提供重播。除歷史事實陳述外，本次電話會議期間的陳述均為基於我們的計劃和預期的前瞻性陳述，這些陳述存在風險和不確定性，可能導致實際結果與明示或暗示的此類陳述存在重大差異。這些前瞻性陳述在今天的新聞稿中進行了描述，可能影響這些前瞻性陳述的風險和不確定性在新聞稿以及我們的 10-K 表年度報告和 10-Q 表季度報告中進行了描述。請參閱這些文檔以獲取更多信息。我們不承擔任何更新前瞻性陳述的意圖或義務。

Our revenue in the second quarter of 2023 was $117.7 million, an increase of 14% compared to the second quarter of last year. To reflect that growth, we are raising our 2023 revenue guidance again to a range of $455 million to $470 million, up from $435 million to $455 million. Net income was $27.5 million or $0.25 per share in the second quarter compared to $27.4 million or $0.24 per share in the same period last year. Our cash and investments of $363.3 million at June 30 reflects the purchase of 6.6 million Corcept shares for $145.4 million during the quarter.

我們2023年第二季度的收入為1.177億美元，比去年第二季度增長14%。為了反映這一增長，我們再次將 2023 年收入指導從 4.35 億美元至 4.55 億美元上調至 4.55 億美元至 4.7 億美元。第二季度淨利潤為 2750 萬美元，即每股 0.25 美元，而去年同期為 2740 萬美元，即每股 0.24 美元。截至 6 月 30 日，我們的現金和投資為 3.633 億美元，反映了本季度以 1.454 億美元的價格購買了 660 萬股 Corcept 股票。

I will now turn the call over to Charlie Robb, our Chief Business Officer, to provide a legal update. Charlie?

我現在將把電話轉給我們的首席商務官查理·羅伯 (Charlie Robb)，以提供最新的法律信息。查理？

Thanks, Atabak. In March 2018, we sued Teva Pharmaceuticals in the Federal District Court to prevent it from marketing a generic version of Korlym in violation of our patents. Trial is set to begin next month on the 27th of September. As a reminder, Teva cannot dispute the validity of 2 patents we are serving against it, 214 patent and the 800 patent, which concerned the safe coadministration of Korlym, the commonly prescribed class of drugs known as strong CYP3A inhibitors.

謝謝，阿塔巴克。 2018 年 3 月，我們在聯邦地方法院起訴 Teva Pharmaceuticals，阻止其銷售 Korlym 的仿製藥，侵犯了我們的專利。審判定於下個月 9 月 27 日開始。需要提醒的是，Teva 不能對我們正在向其提起訴訟的2 項專利的有效性提出異議，即214 號專利和800 號專利，這些專利涉及Korlym 的安全聯合用藥，Korlym 是一種常用的處方藥，被稱為強效CYP3A 抑製劑。

Issues determinative of these patents' validity were decided in our favor, and Teva lost the post-grant review challenge initiated at the Patent Office. Teva's only defense with respect to these 2 patents is that its proposed product would not infringe them, position, we believe, has no legal or factual support. 214 and 800 patents are 2 of the 4 patents we are asserting against Teva. As I said last quarter and then all of the calls we've held since this litigation began, we are supremely confident in the strength of our case. We are happy that our trial date is approaching. We look forward to our day in court. Why? Because the law and the facts are on our side.

決定這些專利有效性的問題得到了對我們有利的裁決，Teva 在專利局發起的授權後審查挑戰中敗訴。梯瓦公司對這兩項專利的唯一辯護是其提出的產品不會侵犯這些專利，我們認為這一立場沒有法律或事實支持。 214 和 800 專利是我們針對 Teva 主張的 4 項專利中的 2 項。正如我上個季度所說，以及自訴訟開始以來我們接到的所有電話，我們對我們案件的實力非常有信心。我們很高興審判日期即將到來。我們期待著出庭的那一天。為什麼？因為法律和事實都站在我們這邊。

I'll now turn the call over to Dr. Joseph Belanoff, our Chief Executive Officer. Joe?

現在我將把電話轉給我們的首席執行官 Joseph Belanoff 博士。喬？

Thank you, Charlie. The strong results of our commercial business in the second quarter reflect the early return on our substantial investment to stimulate physicians to both better recognize to treat hypercortisolism. In the second quarter, we saw a continued increase in the number of patients receiving Korlym and the number of physicians prescribing the medication. The business translation of more panicked patients benefiting from Korlym treatment is a new record high in our quarterly revenue. We expect our growth to continue.

謝謝你，查理。我們第二季度商業業務的強勁業績反映了我們大量投資的早期回報，以刺激醫生更好地認識到治療皮質醇增多症。第二季度，我們看到接受 Korlym 治療的患者數量和開藥的醫生數量持續增加。更多恐慌患者受益於 Korlym 治療的業務轉化創下了我們季度收入的新紀錄。我們預計我們的增長將持續下去。

Korlym is an excellent treatment for patients with Cushing's syndrome, and there are many eligible patients who have yet to receive it. Leading endocrinologists increasingly believe that there are considerably more patients with Cushing's syndrome than was once assumed. Results of our ongoing CATALYST study will likely provide further evidence to bolster this belief and equally likely to lead physicians to begin to identify and provide effective treatment for a large group of patients with hypercortisolism whose disease currently goes undiagnosed. We are confident in the growth potential of our Cushing's syndrome business and are raising our 2023 revenue guidance range again, this time to $455 million to $470 million.

Korlym 對於庫欣綜合徵患者來說是一種極好的治療方法，並且有許多符合條件的患者尚未接受該治療。領先的內分泌學家越來越相信庫欣綜合徵患者的數量比以前想像的要多得多。我們正在進行的 CATALYST 研究的結果可能會提供進一步的證據來支持這一信念，並且同樣有可能引導醫生開始識別一大群目前尚未確診的皮質醇增多症患者並提供有效的治療。我們對庫欣綜合徵業務的增長潛力充滿信心，並再次提高 2023 年收入指導範圍，這次達到 4.55 億美元至 4.7 億美元。

We are also very excited by the potential of our clinical development programs. Since inception, our research and development efforts have built on the hypothesis that cortisol modulation can be a powerful therapeutic mechanism in many serious disorders. Our proprietary compounds modulate cortisol's effects by binding to the glucocorticoid receptor or GR, the receptor, which is activated when cortisol levels are high.

我們也對我們的臨床開發項目的潛力感到非常興奮。自成立以來，我們的研究和開發工作就建立在這樣的假設之上：皮質醇調節可以成為許多嚴重疾病的強大治療機制。我們的專有化合物通過與糖皮質激素受體或 GR（當皮質醇水平較高時被激活的受體）結合來調節皮質醇的作用。

They do not bind to the progesterone receptor and don't cause some of Korlym's, our approved products with serious off-target effects. Interestingly, while our compounds modulate cortisol activity without modulating progesterone's activity, they are not identical. Some cross the blood-brain barrier. Others do not. Some perform best in models of solid tumors. Others are more potent in models of metabolic disease. Some appear to be tissue specific. Others have more global effects. These diverse qualities allow us to study a wide variety of disorders.

它們不會與黃體酮受體結合，也不會導致我們批准的產品 Korlym 產生嚴重的脫靶效應。有趣的是，雖然我們的化合物調節皮質醇活性而不調節黃體酮活性，但它們並不相同。有些可以穿過血腦屏障。其他人則不然。有些在實體瘤模型中表現最好。其他的在代謝疾病模型中更有效。有些似乎是組織特異性的。其他一些則具有更大的全球影響。這些不同的特性使我們能夠研究各種各樣的疾病。

Currently, we are conducting programs with 3 of our proprietary selective cortisol modulators: relacorilant, dazucorilant and miricorilant in ovarian, adrenal and prostate cancer, ALS, NASH and, of course, Cushing's syndrome. We have additional compounds in clinical and preclinical development.

目前，我們正在使用 3 種專有的選擇性皮質醇調節劑開展項目：relacorilant、dazucorilant 和 miricorilant，用於治療卵巢癌、腎上腺癌和前列腺癌、ALS、NASH，當然還有庫欣綜合徵。我們還有其他化合物處於臨床和臨床前開發階段。

In the next 12 months, we expect data from our GRACE, Gradient and CATALYST studies, submission of an NDA for relacorilant in Cushing's Syndrome, completion of enrollment of our ROSELLA and DAZALS studies and initiation of a Phase IIb trial of miricorilant in patients with NASH.

在接下來的12 個月內，我們預計將獲得GRACE、Gradient 和CATALYST 研究的數據，提交relacorilant 治療庫欣綜合徵的NDA，完成ROSELLA 和DAZALS 研究的入組，以及啟動miricorilant 在NASH 患者中的IIb期試驗。

This is a very exciting time for Corcept. We are evaluating relacorilant for the treatment of hypercortisolism in 2 Phase III trials: GRACE and GRADIENT. Relacorilant is a selective cortisol modulator. Like Korlym, it achieves its effect by competing with cortisol at the glucocorticoid receptor. Unlike Korlym, it does not bind to the progesterone receptor, PR for short, and so does not cause PR-related side effects, including termination of pregnancy, endometrial thickening and vaginal bleeding. By a different mechanism, relacorilant also does not cause hypokalemia, low potassium, a serious side effect experienced by 44% of patients in Korlym's pivotal trial. Korlym-induced hypokalemia is a leading cause of Korlym discontinuation.

對於 Corcept 來說，這是一個非常激動人心的時刻。我們正在兩項 III 期試驗中評估 relacorilant 治療皮質醇增多症的效果：GRACE 和 GRADIENT。 Relacorilant 是一種選擇性皮質醇調節劑。與 Korlym 一樣，它通過與皮質醇競爭糖皮質激素受體來實現其效果。與Korlym不同的是，它不與孕激素受體（簡稱PR）結合，因此不會引起PR相關的副作用，包括終止妊娠、子宮內膜增厚和陰道出血。通過不同的機制，relacorilant 也不會引起低鉀血症，低鉀血症是 Korlym 關鍵試驗中 44% 的患者經歷過的嚴重副作用。 Korlym 引起的低鉀血症是 Korlym 停藥的主要原因。

Relacorilant's Phase II efficacy and safety data were compelling. Patients experienced meaningful improvements in hypertension and glucose control as well as in a variety of other signs and symptoms of Cushing's syndrome. There were no relacorilant-induced instances of endometrial thickening or vaginal bleeding and no drug-induced hypokalemia. The trial results were published in Frontiers in Endocrinology in July 2021.

Relacorilant 的 II 期療效和安全性數據令人信服。患者的高血壓和血糖控制以及庫欣綜合徵的各種其他體徵和症狀都得到了有意義的改善。沒有出現因緩和劑引起的子宮內膜增厚或陰道出血的情況，也沒有藥物引起的低鉀血症。試驗結果於 2021 年 7 月發表在《內分泌學前沿》上。

With enrollment in GRACE complete, we are focused on finishing the trial and preparing our NDA, which we plan to submit in the second quarter of 2024. Relacorilant has tremendous promise as a treatment for patients with all etiologies of endogenous Cushing's syndrome, and we are eager to make it available.

隨著GRACE 的入組完成，我們的重點是完成試驗並準備NDA，我們計劃在2024 年第二季度提交NDA。Relacorilant 作為治療患有內源性庫欣綜合徵所有病因的患者俱有巨大的前景，我們正在渴望使其可用。

Our second Phase III trial in hypercortisolism, GRADIENT, is studying relacorilant effects to patients whose Cushing's syndrome is caused by an adrenal adenoma or adrenal hyperplasia. Patients with this etiology of Cushing's syndrome often experience a less rapid decline, but their health outcomes are poor including a higher risk of premature death. While we do not expect our NDA in Cushing's syndrome to depend on data from GRADIENT, we do expect the study to produce valuable data about an etiology of Cushing's syndrome that affects many patients whose hypercortisolism frequently goes undiagnosed and untreated.

我們的第二項皮質醇增多症 III 期試驗 GRADIENT 正在研究對由腎上腺腺瘤或腎上腺增生引起的庫欣綜合徵患者的相關影響。患有這種庫欣綜合徵病因的患者通常病情衰退速度較慢，但​​他們的健康結果很差，包括過早死亡的風險較高。雖然我們並不期望庫欣綜合徵的NDA 依賴於GRADIENT 的數據，但我們確實期望該研究能夠產生有關庫欣綜合徵病因學的有價值的數據，庫欣綜合徵影響許多皮質醇增多症經常未被診斷和治療的患者。

I'm pleased to announce that our CATALYST study is progressing ahead of schedule. CATALYST is a 1,000-patient Phase IV trial examining the prevalence of hypercortisolism in patients with difficult-to-control type 2 diabetes.

我很高興地宣布，我們的 CATALYST 研究正在提前取得進展。 CATALYST 是一項包含 1,000 名患者的 IV 期試驗，旨在檢查難以控制的 2 型糖尿病患者皮質醇增多症的患病率。

Patients diagnosed with hypercortisolism in the CATALYST study we choose to enter a randomized, double-blind, placebo-controlled study of Korlym. Many independent studies conducted over the last 15 years have found that the prevalence of hypercortisolism in patients with type 2 diabetes is substantially higher than in general population. The most prominent diabetologists in the United States help us design and are participating in CATALYST, which will be the largest study of its kind. We have received very positive feedback from leading endocrinologists regarding this study and expect to complete enrollment in the fourth quarter, a bit ahead of our previous estimate.

在 CATALYST 研究中診斷為皮質醇增多症的患者，我們選擇參加 Korlym 的一項隨機、雙盲、安慰劑對照研究。過去 15 年進行的許多獨立研究發現，2 型糖尿病患者皮質醇增多症的患病率明顯高於普通人群。美國最著名的糖尿病專家幫助我們設計並參與了 CATALYST，這將是同類研究中規模最大的一項。我們收到了領先內分泌學家對這項研究的非常積極的反饋，並預計在第四季度完成入組，比我們之前的估計稍早一些。

Our oncology program is testing 3 anticancer mechanisms first postulated by investigators at the University of Chicago and later confirmed by other prominent researchers. One mechanism is increasing apoptosis, a programmed cell death that chemotherapy is meant to induce in solid tumors. Cortisol works against the beneficial effect of chemotherapy by suppressing apoptosis. And our successful controlled Phase II trial in women with platinum-resistant ovarian cancer, the addition of our selective cortisol modulator relacorilant enhanced the effect of chemotherapy, likely by blending cortisol's anti-apoptotic effect. Relacorilant provided meaningful benefit to many of the women in our study.

我們的腫瘤學項目正在測試 3 種抗癌機制，這些機制首先由芝加哥大學的研究人員提出，後來得到其他著名研究人員的證實。一種機制是增加細胞凋亡，這是化療在實體瘤中誘導的一種程序性細胞死亡。皮質醇通過抑制細胞凋亡來對抗化療的有益作用。我們在患有鉑耐藥性卵巢癌的女性中成功進行了 II 期對照試驗，添加我們的選擇性皮質醇調節劑 relacorilant 增強了化療的效果，可能是通過混合皮質醇的抗細胞凋亡作用。 Relacorilant 為我們研究中的許多女性帶來了有意義的益處。

While these women's disease have progressed on 2 or more previous lines of treatment, including previous taxanes, relacorilant appeared to resensitize the disease to chemotherapy's beneficial effects on some women. Those who received relacorilant intermittently, the day before, the day of and the day after they received nab-paclitaxel, exhibited a statistically significant improvement in progression-free survival and duration of response compared to the group who received nab-paclitaxel monotherapy. Women in the intermittent relacorilant group also lived longer than those in the comparator arm with a p-value that approached statistical significance. Our analysis to date indicates that 29% of the patients who took intermittent relacorilant were alive 2 years after study start versus only 14% who took nab-paclitaxel alone.

雖然這些女性的疾病在之前的 2 種或多種治療方案（包括之前的紫杉烷類藥物）中有所進展，但 relacorilant 似乎使這些女性的疾病對化療的有益作用重新敏感。與接受白蛋白結合型紫杉醇單一療法的組相比，那些在接受白蛋白結合型紫杉醇治療前一天、當天和後一天間歇性接受relacorilant 治療的患者，在無進展生存期和反應持續時間方面表現出統計學上顯著的改善。間歇性抵抗組中的女性也比對照組中的女性壽命更長，p 值接近統計顯著性。我們迄今為止的分析表明，在研究開始後 2 年內，服用間歇性 relacorilant 的患者中有 29% 仍存活，而單獨服用白蛋白結合型紫杉醇的患者中只有 14% 存活。

Just as important, the women who received relacorilant plus nab-paclitaxel experienced no additional side effect burden compared to those who received nab-paclitaxel alone. The results from this study were recently published in the prestigious Journal of Clinical Oncology. Results have also been featured in podium presentations at the 2021 and 2022 European Society for Medical Oncology, ESMO, meeting and at the 2022 American Society of Clinical Oncology, ASCO, annual meeting.

同樣重要的是，與單獨接受白蛋白結合型紫杉醇治療的女性相比，接受 relacorilant 加白蛋白結合型紫杉醇治療的女性沒有經歷額外的副作用負擔。這項研究的結果最近發表在著名的臨床腫瘤學雜誌上。研究結果還出現在 2021 年和 2022 年歐洲腫瘤內科學會 (ESMO) 會議以及 2022 年美國臨床腫瘤學會 (ASCO) 年會上的講台演講中。

ROSELLA, our confirmatory pivotal Phase III trial in platinum-resistant ovarian cancer is enrolling patients. ROSELLA's design closely tracks our Phase II study, and its goal is simply to replicate our positive Phase II results in a larger group. Planned enrollment is 360 women randomized 1:1 to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone. The primary end point is progression-free survival with overall survival a key secondary end point. We are conducting this study in collaboration with leading clinicians from the Gynecological Oncology Group in the United States and the European Network of Gynaecological Oncology Trials group in Europe. We are on track to complete enrollment by the end of the year.

ROSELLA 是我們針對鉑類耐藥卵巢癌的驗證性關鍵 III 期試驗，正在招募患者。 ROSELLA 的設計密切跟踪我們的 II 期研究，其目標只是在更大的群體中復制我們積極的 II 期結果。計劃招募 360 名女性，按 1:1 的比例隨機分配接受 relacorilant 加白蛋白結合型紫杉醇或單獨接受白蛋白結合型紫杉醇治療。主要終點是無進展生存期，總生存期是關鍵的次要終點。我們正在與美國婦科腫瘤學組和歐洲婦科腫瘤試驗組歐洲網絡的領先臨床醫生合作進行這項研究。我們有望在今年年底前完成註冊。

Leading gynecological oncologists have told us that, in their view, relacorilant's potential benefit, improved progression-free and overall survival without increased side effect burden would constitute an important medical advance and that relacorilant plus nab-paclitaxel has the potential to become a new standard of care in women with platinum-resistant ovarian cancer.

領先的婦科腫瘤學家告訴我們，在他們看來，relacorilant 的潛在益處、改善無進展生存期和總體生存率而不增加副作用負擔將構成一項重要的醫學進步，並且relacorilant 聯合白蛋白結合型紫杉醇有可能成為治療的新標準。患有鉑耐藥性卵巢癌的女性的護理。

Second mechanism by which cortisol modulation may prove useful is by blocking an important tumor growth pathway. Cortisol stimulation is a major reason why patients with prostate cancer treated with a widely prescribed androgen receptor antagonist, enzalutamide, eventually experience resurgent disease. Deprived of androgen stimulation, their tumor switched to cortisol activity to stimulate growth.

皮質醇調節可能被證明有用的第二種機制是阻斷重要的腫瘤生長途徑。皮質醇刺激是前列腺癌患者接受廣泛使用的雄激素受體拮抗劑恩雜魯胺治療後最終病情復發的主要原因。失去雄激素刺激後，他們的腫瘤轉而利用皮質醇活性來刺激生長。

Our hypothesis is that adding a cortisol modulator to androgen depravation therapy can close this tumor escape route. Our collaborators at the University of Chicago plan to begin a randomized placebo-controlled Phase II trial of relacorilant plus enzalutamide in patients with prostate cancer before these patients have had an initial prostatectomy this quarter.

我們的假設是，在雄激素破壞療法中添加皮質醇調節劑可以關閉這種腫瘤逃逸途徑。我們在芝加哥大學的合作者計劃在本季度對前列腺癌患者進行初次前列腺切除術之前，開始對 relacorilant 加 enzalutamide 進行隨機安慰劑對照 II 期試驗。

Third therapeutic mechanism seeks to treat tumors by enhancing the body's immune response. Cortisol suppresses the immune system, which may blunt the effectiveness of cancer therapies intended to stimulate the immune system. Our hypothesis is that adding a cortisol modulator to immunotherapies such as checkpoint inhibitors, may enhance the effectiveness of these therapies. We are conducting a Phase Ib trial of relacorilant plus the PD-1 checkpoint inhibitor, pembrolizumab, in patients with advanced adrenal cancer as tumors produce excess cortisol. Pembrolizumab is rarely effective as monotherapy in treating this form of adrenal cancer.

第三種治療機制旨在通過增強人體的免疫反應來治療腫瘤。皮質醇會抑制免疫系統，這可能會削弱旨在刺激免疫系統的癌症療法的有效性。我們的假設是，在免疫療法（例如檢查點抑製劑）中添加皮質醇調節劑可能會增強這些療法的有效性。我們正在對晚期腎上腺癌患者進行 relacorilant 聯合 PD-1 檢查點抑製劑 pembrolizumab 的 Ib 期試驗，因為腫瘤會產生過量的皮質醇。派姆單抗作為單一療法治療這種形式的腎上腺癌很少有效。

ALS, commonly known as Lou Gehrig's disease, is a devastating illness with an urgent need for better treatment. DAZALS, our 19-patient randomized double-blind placebo-controlled Phase II trial of dazucorilant in patients with ALS, is briskly enrolling patients. Dazucorilant is a selective cortisol modulator that has shown great promise in animal models of ALS, improving motor performance and reducing neuroinflammation and muscular atrophy. We are conducting this important study in collaboration with TRICALS, the leading ALS academic consortium in Europe. We recently added clinical trial sites in the United States and are on track to complete enrollment in DAZALS by early next year.

ALS，俗稱盧伽雷氏病，是一種毀滅性的疾病，迫切需要更好的治療。 DAZALS 是我們針對 ALS 患者進行的 19 名患者隨機雙盲安慰劑對照 II 期試驗，目前正在迅速招募患者。 Dazucorilant 是一種選擇性皮質醇調節劑，在 ALS 動物模型中顯示出巨大的前景，可改善運動表現並減少神經炎症和肌肉萎縮。我們正在與歐洲領先的 ALS 學術聯盟 TRICALS 合作開展這項重要研究。我們最近在美國增加了臨床試驗地點，並有望在明年初完成 DAZALS 的註冊。

Finally, I'll turn to our program in NASH, a serious liver disorder that afflicts millions of patients in the United States. Miricorilant, an oral medication, continues to demonstrate great promise as a treatment for NASH. In our prior NASH studies, patients who received 600 milligrams or 900 milligrams of miricorilant daily exhibited large rapid reductions in liver fat but also substantial, albeit transient, elevations of the liver enzymes ALT and AST. The improvements in liver fat in these patients was greater and occurred much more rapidly than we had expected and is rarely seen over any period of treatment.

最後，我將談談我們在 NASH 方面的項目，NASH 是一種嚴重的肝臟疾病，困擾著美國數百萬患者。 Miricorilant 是一種口服藥物，在治療 NASH 方面繼續展現出巨大的前景。在我們之前的 NASH 研究中，每天接受 600 毫克或 900 毫克 miricorilant 的患者表現出肝臟脂肪大幅快速減少，但肝酶 ALT 和 AST 也顯著升高（儘管是短暫的）。這些患者的肝臟脂肪改善程度比我們預期的要大得多且發生得快得多，並且在任何治療期間都很少見。

Our ongoing Phase Ib dose-finding study, which evaluated a range of doses and dosing schedules of miricorilant, found that patients who received just 100 milligrams of miricorilant orally twice a week for 12 weeks experienced an approximately 30% reduction in liver fat and showed improvements in liver enzymes and markers of liver disease. These patients also experienced improvements in key metabolic and lipid measures such as HOMA-IR, serum triglycerides and LDL. Importantly, miricorilant was very well tolerated. We plan to submit these results for presentation at a scientific conference and will initiate a Phase IIb trial in the fourth quarter.

我們正在進行的 Ib 期劑量探索研究評估了 miricorilant 的一系列劑量和給藥方案，發現每週兩次口服 100 毫克 miricorilant 持續 12 週的患者的肝臟脂肪減少了約 30%，並且表現出改善肝酶和肝病標誌物。這些患者的關鍵代謝和血脂指標（例如 HOMA-IR、血清甘油三酯和低密度脂蛋白）也得到改善。重要的是，mirorilant 的耐受性非常好。我們計劃提交這些結果以在科學會議上展示，並將在第四季度啟動 IIb 期試驗。

In conclusion, we are extremely optimistic about the future of Corcept. Our Cushing's syndrome business has tremendous growth potential and generates substantial profits even as we invest in our advancing development programs. We are again raising our revenue guidance for this year and anticipate growth for years to come.

總而言之，我們對 Corcept 的未來非常樂觀。我們的庫欣綜合徵業務具有巨大的增長潛力，即使我們投資於先進的開發項目，也能產生可觀的利潤。我們再次提高了今年的收入指引，並預計未來幾年的增長。

Our CATALYST study holds great promise as the data generated will help physicians to improve the screening and treatment of patients whose difficult-to-control diabetes is caused by hypercortisolism, a population whose Cushing's syndrome frequently goes undiagnosed. For these patients, hypercortisolism is their disease, and diabetes is a symptom of their hypercortisolism.

我們的 CATALYST 研究前景廣闊，因為生成的數據將幫助醫生改進對由皮質醇增多症引起的難以控制的糖尿病患者的篩查和治療，而庫欣綜合徵經常未被診斷出來。對於這些患者來說，皮質醇增多症是他們的疾病，而糖尿病是他們皮質醇增多症的症狀。

Our development programs are generating increasing evidence that validates our long-held belief that cortisol modulation has the potential to treat a wide range of diseases. Reducing cortisol activity is a straightforward and effective way to treat Cushing's syndrome and can offer substantial benefits to patients with other serious disorders. Ovarian cancer, ALS and NASH are current examples, but there will be others.

我們的開發計劃正在產生越來越多的證據，證實了我們長期以來的信念，即皮質醇調節具有治療多種疾病的潛力。減少皮質醇活性是治療庫欣綜合徵的一種簡單而有效的方法，並且可以為患有其他嚴重疾病的患者帶來巨大的好處。卵巢癌、ALS 和 NASH 是當前的例子，但還會有其他例子。

In addition to relacorilant, dazucorilant and miricorilant, we have many other proprietary selective cortisol modulators in our portfolio with potentially very different clinical attributes. In the next 12 months, we will see data from our GRACE, GRADIENT and CATALYST studies in Cushing's syndrome. We'll submit relacorilant's NDA in Cushing's syndrome, and we'll complete enrollment in large controlled studies of platinum-resistant ovarian cancer and ALS. We will also begin a Phase IIb study in patients with NASH.

除了 relacorilant、dazucorilant 和 miricorilant 之外，我們的產品組合中還有許多其他專有的選擇性皮質醇調節劑，它們具有潛在的非常不同的臨床屬性。在接下來的 12 個月中，我們將看到來自庫欣綜合徵 GRACE、GRADIENT 和 CATALYST 研究的數據。我們將提交 relacorilant 治療庫欣綜合徵的 NDA，並將完成鉑類耐藥卵巢癌和 ALS 大型對照研究的入組。我們還將開始針對 NASH 患者的 IIb 期研究。

As I said, this is an exciting time for Corcept. I thank our dedicated, creative employees and loyal investors for making that possible. I'll stop here for questions.

正如我所說，這對 Corcept 來說是一個激動人心的時刻。我感謝我們敬業、富有創造力的員工和忠誠的投資者使這一切成為可能。我會在這裡停下來提問。

(Operator Instructions) Our first question comes from the line of Matt Kaplan with Ladenburg.

（操作員說明）我們的第一個問題來自馬特·卡普蘭（Matt Kaplan）與拉登堡（Ladenburg）的對話。

Congrats on the strong quarter.

祝賀季度表現強勁。

Thanks, Matt.

謝謝，馬特。

You're welcome. Can you give us some sense in terms of what drove the revenues in the second quarter and your confidence in increasing your guidance for this year as well?

不客氣。您能否告訴我們一些關於第二季度收入增長的因素以及您對提高今年指導的信心？

Sure, Matt. I'm just going to reintroduce to the group Sean Maduck, who is the President of our endocrinology division and runs our Cushing's syndrome business.

當然，馬特。我要向團隊重新介紹肖恩·馬杜克 (Sean Maduck)，他是我們內分泌部門的總裁，負責我們的庫欣綜合徵業務。

Matt, thanks for the question, and I'll just start by saying we're very pleased with the results. Your question was what drove it. It was driven by improved access and improved field execution. And we're starting to see some early returns from our investments. Many of our investments have been on sort of expanding the field and working to get our field more productive and efficient.

馬特，謝謝你的提問，我首先要說的是我們對結果非常滿意。你的問題是什麼推動了它。這是由改進的訪問和改進的現場執行驅動的。我們開始看到一些早期投資回報。我們的許多投資都是為了擴大該領域並努力提高我們的領域的生產力和效率。

So through that process this quarter, we've added both new patients and new prescribers, and we have more patients taking Korlym than ever before. Disease awareness continues to increase, and really, we're more confident than ever about the potential size of the Cushing's syndrome market. For the remainder of the year. I mean, at this point, our belief is just a fraction of hypercortisolism patients have been identified and treated. And over the coming months and quarters, there's going to be many more.

因此，通過本季度的流程，我們增加了新患者和新處方者，並且服用 Korlym 的患者比以往任何時候都多。人們對疾病的認識不斷提高，實際上，我們對庫欣綜合徵市場的潛在規模比以往任何時候都更有信心。今年剩餘時間。我的意思是，在這一點上，我們的信念是只有一小部分皮質醇增多症患者已被識別和治療。在接下來的幾個月和幾個季度裡，還會有更多這樣的事情發生。

Got it. That's helpful. And just looking at your pipeline with GRACE and GRADIENT, GRACE completing enrollment and GRADIENT to complete in the near term. Can you help us set expectations in terms of what we're -- what to expect for GRACE and GRADIENT as they read out perhaps next year.

知道了。這很有幫助。只需查看您的 GRACE 和 GRADIENT 管道，GRACE 完成註冊，GRADIENT 近期完成。您能否幫助我們設定對我們的期望——對 GRACE 和 GRADIENT 的期望，因為他們可能會在明年宣讀。

Yes. Let me introduce you again to Bill Guyer who runs all of our development areas, Chief Development Officer. Bill, comment.

是的。讓我再次向您介紹 Bill Guyer，他負責管理我們所有的開發領域，也是首席開發官。比爾，發表評論。

Great. Thank you, Matt, for that question. So as we have now completed enrollment for the GRACE trial, the investigators, and we are very excited because of that. And now we're in the plans of submitting that NDA, and we've actually been working on that NDA since last year. And as we collaboratively work with the FDA, we're going to be working on developing and submitting all of our studies.

偉大的。謝謝你，馬特，提出這個問題。我們現在已經完成了 GRACE 試驗的招募，研究人員和我們因此感到非常興奮。現在我們正在計劃提交該 NDA，實際上自去年以來我們一直在致力於該 NDA。當我們與 FDA 合作時，我們將致力於開發和提交我們的所有研究。

So the NDA will include many different studies. It will include the full Phase II data from a safety and efficacy perspective, the GRACE study from a safety and efficacy perspective, the GRADIENT trial from an integrated safety perspective as well as our long-term extension study, which has been ongoing for over 5 years, and we have patients on relacorilant for doing well over 5 years. And then we're also going to include many other new recently presented and published data that I think we're going to be excited to include in the NDA.

因此 NDA 將包括許多不同的研究。它將包括從安全性和有效性角度來看的完整II 期數據、從安全性和有效性角度來看的GRACE 研究、從綜合安全性角度來看的GRADIENT 試驗以及我們已經進行了超過5 年的長期擴展研究。多年，我們的患者服用 relacorilant 已經有 5 年以上的良好表現。然後我們還將納入許多其他最近提出和發布的新數據，我認為我們會很高興將這些數據納入 NDA 中。

One of those being we just completed a thorough QT study, where we evaluated the heart's QT interval and looked at relacorilant, and it saw no effects on the QT interval. And that would make this the only drug in Cushing's syndrome that does not affect the QT interval. So that's exciting news as we have completed that study.

其中之一是我們剛剛完成了一項徹底的 QT 研究，我們評估了心臟的 QT 間期並觀察了 relacorilant，結果發現它對 QT 間期沒有影響。這將使其成為治療庫欣綜合徵的唯一不影響 QT 間期的藥物。這是令人興奮的消息，因為我們已經完成了這項研究。

We've also seen published preclinical research citing how relacorilant can uniquely shrink pituitary tumors in tissue cultures. And with those tumors, we've also seen 2 published case reports highlighting similar clinical benefit of relacorilant in patients. This is a differentiating factor because mifepristone was also used in those preclinical studies and saw no change in pituitary tumors.

我們還看到已發表的臨床前研究，其中引用了 relacorilant 如何獨特地縮小組織培養中的垂體腫瘤。對於這些腫瘤，我們還看到了 2 份已發表的病例報告，強調了 relacorilant 對患者的類似臨床益處。這是一個區分因素，因為米非司酮也用於這些臨床前研究，並且沒有發現垂體瘤發生變化。

And then finally, we just presented new data from our Phase II trial looking at coagulopathy parameters, which was important because Cushing's syndrome patients are high risk for developing hypercoagulopathy events, and relacorilant showed no effects on those coagulopathy patterns. And that would be, again, the only drug in the Cushing's syndrome space to have no effect on hypercoagulopathy patterns. All of this data makes me confident in the benefit relacorilant can bring to patients and confident as we proceed towards our NDA in the next coming year.

最後，我們剛剛提供了關於凝血病參數的 II 期試驗的新數據，這很重要，因為庫欣綜合徵患者發生高凝血病事件的風險很高，而 relacorilant 對這些凝血病模式沒有影響。這將是庫欣綜合徵領域中唯一對高凝狀態沒有影響的藥物。所有這些數據讓我對 relacorilant 可以給患者帶來的好處充滿信心，並對我們明年的 NDA 進展充滿信心。

Great. And just a quick follow-up on that. Where are you with the manufacturing? And is manufacturing at all a rate-limiting step?

偉大的。對此進行快速跟進。你在哪裡從事製造業？製造到底是一個限速步驟嗎？

Manufacturing is not a rate-limiting step, Matt. And we'll certainly be ready to have commercial supply when and if our NDA is approved.

馬特，製造並不是一個限速步驟。如果我們的 NDA 獲得批准，我們肯定會做好商業供應的準備。

And one last question for me, and then I'll jump back in the queue. The CATALYST study, moving ahead of plans. Do you have a sense in terms of -- based on the design of the study, what percentage of patients that you're screening have hypercortisolism over in this difficult-to-treat type 2 diabetes patients?

還有最後一個問題要問我，然後我會跳回到隊列中。 CATALYST 研究正在按計劃進行。根據這項研究的設計，您是否知道，在這種難以治療的 2 型糖尿病患者中，您所篩查的患者中患有皮質醇增多症的患者比例是多少？

Yes, Matt. I understand the question. I'm going to hand you back to Bill.

是的，馬特。我明白這個問題。我會把你交還給比爾。

So CATALYST is building on a tremendous amount of research already generated with multiple different studies, and I can cite all the studies and send you all the references. Many of those studies are in hundreds of patients. And in those independent studies over the past 15 to 20 years, we found that hypercortisolism is higher than the normal general population. And I would guesstimate it to be around -- when you look at the average for those studies, it's about 10% to 20% for those patients who have difficult-to-control diabetes.

因此，CATALYST 是建立在通過多項不同的研究已經產生的大量研究的基礎上的，我可以引用所有的研究並向您發送所有的參考文獻。其中許多研究是針對數百名患者進行的。在過去 15 到 20 年的獨立研究中，我們發現皮質醇增多症的發病率高於正常人群。我猜想，當你查看這些研究的平均值時，你會發現對於那些患有難以控制的糖尿病的患者來說，這一比例約為 10% 到 20%。

And with CATALYST, this would be then that landmark study because it is the largest study of its kind evaluating 1,000 patients to evaluate those with type 2 diabetes who are difficult to control. And we're doing a simple test of just 1 DST. All of our investigators who are part of this are highly motivated by this, and that's why screening is ahead of schedule. And thus far, in the CATALYST study, even though it's early, I would say that the results so far are mirroring what we've seen in past published studies.

對於 CATALYST，這將是一項具有里程碑意義的研究，因為這是同類研究中規模最大的研究，評估了 1,000 名患者，以評估那些難以控制的 2 型糖尿病患者。我們正在對 1 個 DST 進行簡單測試。我們所有參與其中的研究人員都對此充滿動力，這就是篩查提前的原因。到目前為止，在 CATALYST 研究中，儘管還為時過早，但我想說，迄今為止的結果反映了我們在過去發表的研究中看到的結果。

Our next question comes from the line of Edward Nash with Canaccord.

我們的下一個問題來自愛德華·納什與 Canaccord 的對話。

Yes, congrats guys on such a strong quarter, really great. Want to ask you, and I guess this goes in the same vein of it being a really strong quarter and just the additional input in the sales efforts really kind of is what you attribute that to, but I see that the European Society of Endocrinology has updated their practice guidelines on the treatment of adrenal incidentalomas. And I just wanted to find out what the implications are there. I think it's been a while since we've been updated. So just want to kind of better understand what the implications could be there for usage of Korlym.

是的，恭喜大家，季度表現如此強勁，真的很棒。我想問你，我想這與一個非常強勁的季度是同樣的，只是銷售工作中的額外投入確實是你所歸因的，但我看到歐洲內分泌學會已經更新了腎上腺偶發瘤治療的實踐指南。我只是想知道其中的含義。我想我們已經有一段時間沒有更新了。所以只是想更好地了解 Korlym 的使用可能會產生什麼影響。

Good, Edward. Thank you for the question, and I'm going to direct it to Sean again.

好，愛德華。謝謝你提出這個問題，我將再次將其轉給肖恩。

Yes. Ed, thanks for the question. And just adding on Bill just spoke about. There's study after study after study. There's been mounting evidence over time that this illness is more prevalent. And these European guidelines that were just updated are just another example of the evolution of the mindset around hypercortisolism. Endocrinologists recognize that hypercortisolism is more prevalent than once thought. And what these guidelines do is that they encourage physicians to look harder for the disease, which is great.

是的。艾德，謝謝你的提問。剛剛補充一下比爾剛剛談到的內容。有一個又一個的研究。隨著時間的推移，越來越多的證據表明這種疾病更加普遍。這些剛剛更新的歐洲指南只是皮質醇增多症心態演變的另一個例子。內分泌學家認識到皮質醇增多症比以前想像的更為普遍。這些指南的作用是鼓勵醫生更加努力地尋找這種疾病，這很好。

The guidelines also highlight the use of the relatively simple dexamethasone suppression test, or the DST, as a testing standard, which is going to support increased screening. So these guidelines will influence and increase both screening and diagnosis of hypercortisolism patients.

該指南還強調使用相對簡單的地塞米松抑制試驗（DST）作為檢測標準，這將支持增加篩查。因此，這些指南將影響並增加皮質醇增多症患者的篩查和診斷。

Our next question comes from the line of David Amsellem with Piper Sandler.

我們的下一個問題來自大衛·阿姆塞勒姆和派珀·桑德勒的對話。

So just have a few. First, I wanted to ask a couple on miricorilant in NASH. I know you're going to have data at an upcoming medical meeting. But just thinking about the Phase IIb, can you just talk about the contours of the design of that trial? Is it -- I'm assuming we're going to have liver biopsies in this trial? And is this something where you're thinking about as more of a Phase II/III and -- or is this something where we should think about it as you're still going to have to do a full Phase III program beyond this Phase IIb? That's number one.

所以只要有幾個就可以了。首先，我想詢問一些關於 NASH 治療中的 miricorilant 的問題。我知道您將在即將召開的醫學會議上獲得數據。但想想 IIb 期，您能談談該試驗的設計輪廓嗎？是嗎——我假設我們將在這次試驗中進行肝臟活檢？這是您更多地考慮的第二/第三階段的事情嗎？或者這是我們應該考慮的事情，因為您仍然需要在第二階段b之後進行完整的第三階段計劃？這是第一。

Number two is as you think about miricorilant, strategically, is this something that you're going to look to partner down the road? Is this something that you're going to look to keep and commercialize? And where does it fit in the broader business, particularly given the comments of that other cortisol modulators that you're looking at that you haven't disclosed?

第二個問題是，從戰略上講，您對 miricorilant 的看法是，您會在未來尋求合作嗎？這是您想要保留並商業化的東西嗎？它在更廣泛的業務中適合什麼，特別是考慮到您正在考慮但尚未披露的其他皮質醇調節劑的評論？

Yes. Thanks, David. And then 2 questions, I think I understand. Bill, would you first describe the Phase IIb miricorilant study, and then I'll describe -- I'll discuss the business possibilities.

是的。謝謝，大衛。然後還有2個問題，我想我明白了。 Bill，您可以先描述一下 IIb 期 miricorilant 研究，然後我將描述——我將討論商業可能性。

Absolutely. Thank you for that question. So as we progress towards our Phase IIb program, let me back up a little bit. One, we just completed a great advisory board at the EASL conference, which is the European conference for the study of liver disease. And we met with the top hepatologists in the world who have done research for every molecule in the NASH space for the past decades, and I've known them for many decades as well.

絕對地。謝謝你提出這個問題。因此，當我們的 IIb 期計劃取得進展時，讓我稍微回顧一下。第一，我們剛剛在 EASL 會議（歐洲肝病研究會議）上組建了一個出色的顧問委員會。我們會見了世界上頂尖的肝病專家，他們在過去幾十年裡對 NASH 領域的每一個分子進行了研究，我也認識他們幾十年了。

And as we reviewed all the Phase IIa data from our original study and all the Phase IIb -- or our Phase Ib data, they were really impressed with that. And they helped guide us in designing our Phase IIb trial. And so that was really encouraging as we move forward. And so that Phase IIb trial right now as our study is a biopsy-confirmed NASH study in patients with NASH. This study will be a double-blind, placebo-controlled trial, evaluating 150 patients randomized to miricorilant 100 milligrams twice weekly or placebo for 48 weeks. This is intended to be a Phase IIb study, and based upon those results, we will then progress and design a Phase III trial.

當我們審查原始研究中的所有 IIa 期數據和所有 IIb 期數據（或 Ib 期數據）時，他們對此印象深刻。他們幫助指導我們設計 IIb 期試驗。因此，當我們前進時，這確實令人鼓舞。因此，我們現在的 IIb 期試驗是一項針對 NASH 患者進行的經活檢證實的 NASH 研究。這項研究將是一項雙盲、安慰劑對照試驗，評估 150 名患者隨機接受每週兩次 100 毫克的 miricorilant 或安慰劑，為期 48 週。這是一項 IIb 期研究，然後根據這些結果，我們將進展並設計 III 期試驗。

And David, the second question is an interesting one, and I just -- for a variety of reasons, particularly for those who have followed Corcept for a long time. I mean, as you know, most of the things, starting with Cushing's syndrome, that we've worked on have been orphan diseases, niche markets, very obvious clinical need but to a relatively small group of patients. NASH is, of course, a different story.

大衛，第二個問題很有趣，我只是——出於多種原因，特別是對於那些長期關注 Corcept 的人來說。我的意思是，正如你所知，從庫欣綜合徵開始，我們研究的大多數事情都是孤兒疾病、利基市場、非常明顯的臨床需求，但針對的是相對較小的患者群體。當然，NASH 是一個不同的故事。

The number of people in the United States with fatty liver disease is very large and a sizable percentage of them have NASH and progresses to worse things than that. So it's a big market. I don't know if sort of the older term primary care market is the right way to describe it, but there's certainly a market with many, many patients in it.

在美國，患有脂肪肝疾病的人數非常多，其中相當大一部分患有 NASH，並且會發展為更糟糕的情況。所以這是一個很大的市場。我不知道舊術語初級保健市場是否是描述它的正確方式，但肯定有一個擁有很多很多患者的市場。

Now good question and one that we thought about a lot. Is this something that we can do on our own as we have with the other diseases we've looked at? Or is this a disease space where we will need to partner? I don't really know the answer to that at this point in time, but what I will tell you is that we are not in need of anyone else's money to support the development plan.

現在是個好問題，也是我們思考了很多的問題。這是否是我們可以像對待我們研究過的其他疾病一樣自己做的事情？或者這是一個我們需要合作的疾病領域？目前我真的不知道這個問題的答案，但我要告訴你的是，我們不需要其他人的錢來支持開發計劃。

So if we decide that commercialization is better with a partner, we'll go in that direction. But I think we're really in the lucky space because of our profitable business and our long-term profitable business that we can take this as far as we want. And should we partner, we'll be in a place where it's clearly advantageous for us to do so. And I'll end it with a simple answer. That decision has not yet been made.

因此，如果我們認為與合作夥伴合作商業化效果更好，我們就會朝這個方向前進。但我認為我們真的很幸運，因為我們的盈利業務和長期盈利業務使我們可以隨心所欲地發展。如果我們合作，我們將處於一個顯然對我們有利的位置。我將用一個簡單的答案來結束它。該決定尚未做出。

Okay. That's helpful. If I might sneak in an additional question, just on Catalyst, as you get learnings from the study and particularly the answers that you're looking for, which is the Cushing's syndrome and hypercortisolism is more prevalent and raising awareness among diabetologists, do you think about calling on a sizable group of diabetologists in your rollout and broader commercialization of relacorilant? In other words, is this going to be a bigger, splashier, more expensive, wider launch into a wider group of physicians?

好的。這很有幫助。如果我可以在Catalyst 上偷偷提一個額外的問題，當您從研究中獲得經驗教訓，特別是您正在尋找的答案時，即庫欣綜合徵和皮質醇增多症更為普遍並提高了糖尿病學家的認識，您認為關於在 relacorilant 的推廣和更廣泛的商業化中召集相當多的糖尿病專家？換句話說，這是否會是一次規模更大、更引人注目、更昂貴、更廣泛的面向更廣泛的醫生群體的推廣？

Sean?

肖恩？

Yes. No, thank you for the question. And look, we're in the process of really working through that now to understand what the most effective way will be for us to launch relacorilant. We do recognize that these patients are in more than just endocrinology practices. Diabetologists, in general, are endocrinologists, but there's cardiologists showing up in some primary care offices sort of throughout the country. So we are right now are working on trying to figure out scalable ways that we can get this message to physicians that they can be educated for.

是的。不，謝謝你的提問。看，我們現在正在真正解決這個問題，以了解我們推出 relacorilant 的最有效方法是什麼。我們確實認識到這些患者不僅僅從事內分泌治療。一般來說，糖尿病專家是內分泌專家，但全國各地的一些初級保健辦公室都有心髒病專家。因此，我們現在正在努力尋找可擴展的方法，以便我們可以向醫生傳達這一信息，讓他們接受教育。

Yes. And then -- but just -- I appreciate the question, David, particularly because we have been thinking about that. I think at some point, maybe a decade ago, we thought that the patients with Cushing's syndrome were likely to be treated by really a very, very small number of endocrinologists. We do not think that is true anymore. We think it's -- they are distributed to a much larger group and making sure that these patients get to optimum treatment is really -- that's our ethos. That's what we really want to get to. So how it translates to a practical matter is absolutely on our mind.

是的。然後——但只是——我很欣賞這個問題，大衛，特別是因為我們一直在思考這個問題。我認為在某個時候，也許十年前，我們認為庫欣綜合徵患者可能會由非常非常少數的內分泌科醫生進行治療。我們認為這不再是真的。我們認為，他們被分配到更大的群體，並確保這些患者得到最佳治療，這就是我們的精神。這就是我們真正想要達到的目標。因此，如何將其轉化為實際問題絕對取決於我們。

Our next question comes from the line of Roanna Ruiz with Leerink.

我們的下一個問題來自 Roanna Ruiz 和 Leerink 的對話。

So a couple for me maybe on tagging on a question about your revenue guidance for a second. I was curious, what are some of the pushes and pulls that could get Korlym revenues closer to the higher end or the lower end of this range in your view.

因此，我可能會暫時標記一個有關您的收入指導的問題。我很好奇，在您看來，有哪些推動和拉動可以使 Korlym 的收入更接近該範圍的高端或低端。

Sean, please take that.

肖恩，請收下這個。

Yes. Thank you for the question. Look, our guidance, it's pretty simple, is driven by the number of patients on medicine. We have more patients taking Korlym than ever before, and we expect that there will be more in the future. We have a number of initiatives underway, and we're expecting them to impact the second half of the year. So the more patients that are prescribed Korlym, the higher the end of the range it will be. If it's a little bit fewer, it will be on the lower end.

是的。感謝你的提問。看，我們的指導非常簡單，是由接受藥物治療的患者數量驅動的。我們服用 Korlym 的患者比以往任何時候都多，我們預計未來還會有更多。我們正在進行多項舉措，預計它們將在今年下半年產生影響。因此，服用 Korlym 處方的患者越多，範圍的上限就越高。如果少一點，就會處於低端。

It's really as simple as that. There aren't other factors besides the number of patients that are really very appreciable.

真的就是這麼簡單。除了患者數量之外，沒有其他因素是非常可觀的。

Got it. Okay. And wanted to ask a bit about your field force. So I know you've reached a target of 60%. Are you thinking of possibly expanding that later this year or maybe into next year? And what type of launch metrics are you looking forward to help you make that kind of decision?

知道了。好的。並想詢問一些有關您的現場人員的情況。所以我知道您已經達到了 60% 的目標。您是否考慮可能在今年晚些時候或明年擴大這一範圍？您希望什麼類型的發布指標來幫助您做出此類決定？

Sean, please.

肖恩，請。

Yes, it's a great question. I'll start by saying we're always evaluating the effectiveness of the team and looking to see what is the appropriate size. I think stepping back in time a little bit. Through the pandemic, we felt that it was very important for us to maintain the stability of that team, but over the last year, we've taken a very hard look and that's where we've made changes. We've strengthened and streamlined our training program, the goal of making our current clinical specialists more productive and our new clinical specialists more productive more quickly. And we've also, and as you just alluded to, added top talent to the team.

是的，這是一個很好的問題。首先我要說的是，我們一直在評估團隊的有效性，並尋找合適的規模。我想時間倒退一點。通過這次大流行，我們覺得保持團隊的穩定性對我們來說非常重要，但在過去的一年裡，我們進行了非常認真的審視，這就是我們做出改變的地方。我們加強並簡化了我們的培訓計劃，目標是使我們現有的臨床專家和新的臨床專家更快地提高工作效率。正如您剛才提到的，我們還為團隊增添了頂尖人才。

So in terms of the current size of the team, we're actually currently in the mid-50s, and we are continuing to add clinical specialists throughout the country. Right now, our target is 60, but we're unlikely to stop there. If we can continue to find top talent, we will be adding it to the team. And as we continue to evaluate what the future looks like, we'll determine if we need to go beyond that.

所以就目前的團隊規模而言，我們目前實際上是50多歲，並且我們正在繼續在全國范圍內增加臨床專家。目前，我們的目標是 60，但我們不太可能就此止步。如果我們能夠繼續找到頂尖人才，我們會將其添加到團隊中。當我們繼續評估未來時，我們將決定是否需要超越這一目標。

Our next question comes from the line of Joon Lee with Truist.

我們的下一個問題來自李俊 (Joon Lee) 與 Truist 的對話。

Congrats on the strong quarter. I'm particularly intrigued by your Phase IV CATALYST study of Korlym in difficult-to-treat diabetics. How are you making the determination of hypercortisolism and advancing them to the randomized portion of the trial? And how deployable is that screening for hypercortisolism by generalists and endocrinologists who treat diabetics? And lastly, what is the end point in the randomized portion? And is the positive result there sufficient to get a labeled indication for diabetics? And I have a follow-up.

祝賀季度表現強勁。我對 Korlym 在難以治療的糖尿病患者中進行的 IV 期 CATALYST 研究特別感興趣。您如何確定皮質醇增多症並將其推進到試驗的隨機部分？治療糖尿病患者的全科醫生和內分泌科醫生對皮質醇增多症的篩查是否可行？最後，隨機部分的終點是什麼？那裡的陽性結果是否足以獲得糖尿病患者的標籤適應症？我有一個後續行動。

Yes. Look, Joon, first, welcome or welcome back. Nice to hear from you. And I think that Bill has sort of best got his arms around, I think, all of that information, so I'm going to turn it over to him.

是的。瞧，俊，首先，歡迎或歡迎回來。很高興聽到你的消息。我認為比爾已經最好地掌握了所有這些信息，所以我將把它交給他。

So thanks for the question. So when we look at CATALYST, we designed it specifically again and collaboratively with top diabetologists, endocrinologists to make this as simple and easy as possible. And it's now aligned with the guidelines, as we spoke about earlier. We have just deployed a simple test of 1 DST, a dexamethasone suppression test and looking for those patients with a DST greater than 1.8. Those are the patients who are then positive, who then can qualify and be screened for -- or enrolled into the randomized double-blind placebo-controlled trial of Korlym.

謝謝你的提問。因此，當我們看到 CATALYST 時，我們再次專門設計了它，並與頂級糖尿病學家、內分泌學家合作，使之盡可能簡單和容易。正如我們之前談到的，它現在與指導方針保持一致。我們剛剛部署了 1 DST 的簡單測試，即地塞米松抑制測試，並尋找 DST 大於 1.8 的患者。這些患者隨後呈陽性，然後就可以符合資格並接受篩查，或者參加 Korlym 的隨機雙盲安慰劑對照試驗。

In that trial, the primary end point is just to look at the difference between glucose control between Korlym and that of placebo. And that will be our primary end point.

在那次試驗中，主要終點只是觀察 Korlym 和安慰劑的血糖控制之間的差異。這將是我們的主要終點。

And related to will it change the label of Korlym, it's already consistent with the label of Korlym because when you look at the Korlym indication, Korlym has indicated to control hyperglycemia secondary to hypercortisolism in adult patients with endogenous Cushing's syndrome who have type 2 diabetes.

與它是否會改變Korlym的標籤有關，它已經與Korlym的標籤一致，因為當你看Korlym的適應症時，Korlym表明它可以控制患有2型糖尿病的內源性庫欣綜合徵成年患者繼發於皮質醇增多症的高血糖。

And I think you asked just another small question, which was is that -- is the dexamethasone suppression test something that doctors in usual practice can undertake. The answer is yes. It's not a hard test to run.

我認為你只是問了另一個小問題，那就是——地塞米松抑制試驗是醫生在通常實踐中可以進行的嗎？答案是肯定的。這不是一個很難運行的測試。

Great. So if CATALYST is positive, then would you need to run a trial using relacorilant in difficult-to-treat diabetics to get the similar use commercially? And if not -- either way actually, would dosing be different or some aspect of the drug be different between the Cushing's patients and diabetics to maybe get different pricing given the different opportunities?

偉大的。因此，如果 CATALYST 呈陽性，那麼您是否需要在難以治療的糖尿病患者中進行使用 relacorilant 的試驗才能在商業上獲得類似的用途？如果不是——實際上，無論哪種方式，庫欣患者和糖尿病患者之間的劑量或藥物的某些方面是否會有所不同，從而在不同的機會下獲得不同的定價？

I just want to make sure to clarify this. All of these patients' disease is hypercortisolism, and diabetes or glucose intolerance is secondary to their hypercortisolism. It is what is causing their hypercortisolism. So in some sense, there's no difference, except for degree of illness between these patients. And some of them actually can be quite ill.

我只是想確保澄清這一點。所有這些患者的疾病都是皮質醇增多症，而糖尿病或葡萄糖不耐症是繼發於皮質醇增多症的。這就是導致他們皮質醇增多症的原因。因此，從某種意義上說，除了這些患者之間的病情程度之外，沒有任何區別。其中一些人實際上可能病得很重。

So I just want to make that distinction. This is not diabetes in general. These medicines, whether it's Korlym or relacorilant, are not for diabetes in general. They're for the treatment of hypercortisolism where diabetes appears as a prominent manifestation of hypercortisolism.

所以我只想做出區分。這不是一般的糖尿病。這些藥物，無論是 Korlym 還是 Relacorilant，一般不適用於治療糖尿病。它們用於治療皮質醇增多症，其中糖尿病是皮質醇增多症的突出表現。

And then to answer the question about would we use relacorilant, I see no reason to repeat this study. I see this, CATALYST, as a landmark study that would easily apply to relacorilant. And I'll remind you, relacorilant, we're looking for an indication -- a full indication for hypertension and diabetes, not just diabetes.

然後，為了回答我們是否會使用 relacorilant 的問題，我認為沒有理由重複這項研究。我認為 CATALYST 是一項具有里程碑意義的研究，可以輕鬆應用於 relacorilant。我要提醒你，儘管如此，我們正在尋找一種適應症——高血壓和糖尿病的完整適應症，而不僅僅是糖尿病。

Our next question comes from the line of Swayampakula Ramakanth with H.C. Wainwright.

我們的下一個問題來自 Swayampakula Ramakanth 和 H.C.溫賴特。

This is RK from H.C. Wainwright. Most of my questions have been answered, but I have a quick question on clinical data expectations for the rest of this year.

我是 H.C. 的 RK。溫賴特。我的大部分問題都已得到解答，但我有一個關於今年剩餘時間臨床數據預期的快速問題。

I'm sorry, I didn't quite understand your question, RK. I apologize.

抱歉，我不太明白你的問題，RK。我道歉。

So I'm just trying to understand what sort of clinical data could we expect in this year from here till the end of the year.

所以我只是想了解今年從現在到年底我們可以期待什麼樣的臨床數據。

Yes, I'm going to turn you -- now I understand your question. Bill, would you please answer that?

是的，我要轉向你——現在我明白你的問題了。比爾，請你回答一下好嗎？

So as I look at all the studies that are ongoing, the one study that I could see that we are planning to submit to a conference in the fourth quarter of this year would be the NASH Phase Ib data. And so that is our plan to present that data, hopefully, at that conference.

因此，當我查看所有正在進行的研究時，我發現我們計劃在今年第四季度向會議提交的一項研究將是 NASH Ib 期數據。這就是我們希望在該會議上展示這些數據的計劃。

CATALYST will be close. We're ahead of schedule. I would say it's probably first quarter of next year, but it could -- we could see results from the screening and prevalence study later this year in December.

CATALYST 將接近。我們比計劃提前了。我想說可能是明年第一季度，但也有可能——我們可以在今年 12 月晚些時候看到篩查和患病率研究的結果。

Yes, I'm just going to underscore that. I think what you can count on is the Phase Ib results in NASH. We will have that. But everything else falls into the next year, off in the early part of next year, but in 2024.

是的，我只是想強調這一點。我認為您可以信賴的是 NASH 的 Ib 期結果。我們會有的。但其他一切都在明年，在明年初，但在 2024 年。

Our next question comes from the line of Alan Leong with BioWatch.

我們的下一個問題來自 BioWatch 的 Alan Leong。

Congratulations on the ongoing work.

祝賀正在進行的工作。

Well, Alan, it's wonderful [that you joined]. How -- what might we help you with today?

嗯，艾倫，[你加入]真是太棒了。今天我們可以為您提供什麼幫助？

Well, I have a few questions. Can you talk about the dynamics of safety and efficacy in liver fat with miricorilant, what you learned? What sense -- do you speculate like liver [impairment] level is a significant [covariance]?

嗯，我有幾個問題。您能談談您了解到的 miricorilant 對肝臟脂肪的安全性和有效性的動態變化嗎？什麼意義——您推測肝臟[損傷]水平是一個顯著的[協方差]？

I apologize. It's a poor connection. Could somebody just repeat Alan's question? I'm sorry. I really apologize, Alan. We really just couldn't hear you.

我道歉。這是一個糟糕的連接。有人可以重複一下艾倫的問題嗎？對不起。我真的很抱歉，艾倫。我們真的聽不到你的聲音。

Sorry about that. Yes, I'm using ear buds. Is this better?

對於那個很抱歉。是的，我正在使用耳塞。這是否更好？

Yes.

是的。

Okay. What can you tell us about what you've learned about the dynamics of miricorilant with safety and efficacy in liver fat?

好的。您能告訴我們什麼關於您對 miricorilant 在肝臟脂肪中的安全性和有效性的動態了解嗎？

I'm going to repeat this question. What do we -- the question was what have we learned about the dynamics of miricorilant in terms of efficacy and safety? Bill, could you please talk to that?

我要重複這個問題。我們該做什麼——問題是我們對 micororilant 在功效和安全性方面的動態了解了哪些？比爾，你能談談嗎？

Key pieces there. We've reviewed the Phase IIa data, again, using 600 to 900 milligrams. We saw those dramatic liver fat reductions in a month, corresponding with rises in liver enzymes. And that's what allowed us to then explore various lower doses and different dosing regimens in Phase Ib. And as we have studied various different dosing regimens, we really have determined its -- the rapidity of the liver fat reductions.

關鍵部分在那裡。我們再次審查了 IIa 期數據，使用了 600 至 900 毫克。我們看到一個月內肝臟脂肪急劇減少，與肝酶的上升相對應。這就是我們能夠在 Ib 期探索各種較低劑量和不同給藥方案的原因。當我們研究了各種不同的劑量方案時，我們確實確定了肝臟脂肪減少的速度。

And we confirm that when we reviewed all of the data with our top advisers just about a month ago, and we've determined that, that rapid reduction in liver fat is tied to that rise in increasing free fatty acids, which then causes mitochondrial dysfunction, which then in turn causes that liver enzyme irritation and elevation. And that's key because what we also saw is as it's -- the liver's trying to metabolize all those free fatty acids, it actually can metabolize those because we're not seeing any dumping of fat into the bloodstream, so -- because in our study, we're seeing lowering effects on triglycerides, LDL and VLDL.

我們確認，大約一個月前，當我們與我們的高級顧問審查所有數據時，我們確定，肝臟脂肪的快速減少與游離脂肪酸的增加有關，從而導致線粒體功能障礙，進而導致肝酶刺激和升高。這是關鍵，因為我們也看到了 - 肝臟試圖代謝所有這些游離脂肪酸，它實際上可以代謝這些脂肪酸，因為我們沒有看到任何脂肪傾倒到血液中，所以 - 因為在我們的研究中，我們看到甘油三酯、低密度脂蛋白和極低密度脂蛋白的降低效果。

But importantly, we also saw that if we can slow that down, and we saw that with the 100-milligram twice a week dose, that when we slow that down, we see a steady decline up to 12 weeks and we saw that 30% reduction in liver fat with no rises in ALT or AST. We actually saw decreases in those liver enzymes. And so that's really what we have learned.

但重要的是，我們還看到，如果我們能夠放慢速度，我們發現每週兩次100 毫克的劑量，當我們放慢速度時，我們會看到在長達12 週的時間內穩步下降，我們看到了30%肝臟脂肪減少，但 ALT 或 AST 不增加。我們實際上看到了這些肝酶的減少。這就是我們真正學到的東西。

And we've done many analyses looking at the slope of decline, percentage of decline. It all matches up that it really is tied to the rapidity of liver fat reduction. And we believe we've solved that problem, which is why we're going to Phase IIb.

我們對下降斜率、下降百分比進行了許多分析。這一切都表明它確實與肝臟脂肪減少的速度有關。我們相信我們已經解決了這個問題，這就是我們進入 IIb 階段的原因。

The next set of questions, of the following 3 programs, which do you think has the greatest gap in understanding from your audiences that you kind of go there and you go, wow, we have a little [chasm] on education to do? Feel free to split the investor community versus the life science specialists, ovarian cancer versus -- go ahead.

下一組問題，在以下 3 個節目中，您認為哪個節目與觀眾的理解差距最大，您會說，哇，我們在教育方面還有一點[差距]要做？請隨意分裂投資者群體與生命科學專家、卵巢癌與——繼續吧。

Yes. No, I just want to repeat your question as I understand it, which is, of our programs, which do we think is sort of least recognized by the investor community. And if that's essentially a distillation of your question, I get it because I think one of the things that's surprising, I think, to people until they really dig into the science and as you know, sort of a recovering academic, so I'm really all about the science, is how broad a platform cortisol modulation is.

是的。不，我只是想按照我的理解重複你的問題，即我們認為投資者群體最不認可的項目。如果這本質上是你的問題的昇華，我明白了，因為我認為，在人們真正深入研究科學之前，我認為這是令人驚訝的事情之一，正如你所知，這是一個正在恢復的學術，所以我是真正與科學有關的是皮質醇調節平台的廣泛性。

Cortisol goes into every tissue of the body, so it really has the potential to affect many disease states. Some sense, obvious why a drug like Korlym or relacorilant would be effective in Cushing's syndrome. I think it's initially a little less obvious why it might be effective in a neurologic disease like ALS or a disease like cancer or a variety of cancers.

皮質醇進入身體的每個組織，因此它確實有可能影響許多疾病狀態。從某種意義上講，為什麼像 Korlym 或 relacorilant 這樣的藥物對庫欣綜合徵有效，這是顯而易見的。我認為最初不太明顯的是為什麼它可能對 ALS 等神經系統疾病或癌症或多種癌症等疾病有效。

But I think that the interesting thing for us is that there are individual investors who seem to appreciate kind of individually parts of the story. But I think that there are a few, and I think this is going to change over time, who really understand the global application of cortisol modulation to the whole platform.

但我認為對我們來說有趣的是，有些個人投資者似乎很欣賞故事的各個部分。但我認為，有一些人真正了解皮質醇調製在整個平台上的全球應用，而且我認為這種情況會隨著時間的推移而改變。

So I don't think it's a question of any individual program particularly being unrecognized. I think that it's just that some people recognize one program. Some people recognize another program. And I'm really hoping to see over time is that people can actually connect all of those things because they really are connected. And I'll give you just one sort of personal example from that, is that, every 4 years, we conduct the conference with all of our collaborators.

所以我不認為這是任何個別項目未被認可的問題。我想這只是有些人認可一個程序而已。有些人認識另一個程序。我真的希望隨著時間的推移，人們可以真正連接所有這些東西，因為它們確實是相互聯繫的。我將舉一個個人例子，每四年，我們都會與所有合作者一起召開一次會議。

As you know, we have many academic collaborations at any given time, 35 or 40 of them. So they're all over the world. They're preclinical, and they're clinical. And we bring those people together, I think you said, one time, and many times, they're unaware of the other work that people are doing, even though they're all working in cortisol modulation. It's our mission to make sure that people really understand this entire platform. And I hope that, as I said, even investors, who I know are busy people, really take the time to appreciate the global potential of these programs.

如您所知，我們在任何特定時間都有許多學術合作，其中有 35 或 40 個。所以他們遍布世界各地。它們是臨床前的，也是臨床的。我想你說過，我們把這些人聚集在一起，一次又一次，他們不知道人們正在做的其他工作，即使他們都在皮質醇調節方面工作。我們的使命是確保人們真正了解整個平台。正如我所說，我希望即使是我知道很忙碌的投資者也能真正花時間欣賞這些項目的全球潛力。

The future is bright for both of us.

我們倆的未來都是光明的。

Okay. Thank you very much, Alan. And I think with that, we're out of questions. So I look forward to talking to everybody 3 months from now, and hope you enjoy the rest of your summer.

好的。非常感謝你，艾倫。我認為有了這個，我們就沒有問題了。因此，我期待著 3 個月後與大家交談，並希望你們度過愉快的暑假。

Thank you for your participation in today's conference. This does conclude the program. You may now disconnect.

感謝您參加今天的會議。這確實結束了該程序。您現在可以斷開連接。