Corcept Therapeutics Inc (CORT) 2022 Q4 法說會逐字稿

Greetings, and welcome to the Corcept Therapeutics conference call. (Operator Instructions) As a reminder, this conference is being recorded.

問候，歡迎來到 Corcept Therapeutics 電話會議。 （操作員說明）提醒一下，正在錄製此會議。

I would now like to turn the conference over to your host, Atabak Mokari, CFO. Thank you. You may now begin.

我現在想把會議轉交給你的主持人，首席財務官 Atabak Mokari。謝謝。你現在可以開始了。

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 fourth 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-K with the SEC. Today's call is being recorded. A replay will be available at the Investors Past Events tab of our website.

下午好，感謝您加入我們。我是 Corcept 的首席財務官 Atabak Mokari。今天，我們發布了一份新聞稿，宣布了我們第四季度的財務業績並提供了公司更新。可在 corcept.com 獲取副本。當我們向美國證券交易委員會提交 10-K 表格時，我們將提供完整的財務結果。今天的通話正在錄音中。重播將在我們網站的“投資者過去的事件”選項卡上提供。

Statements during this call, other than statements of historical fact, 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 in 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.

本次電話會議中的陳述，除歷史事實陳述外，都是基於我們的計劃和預期的前瞻性陳述，存在風險和不確定性，可能導致實際結果與此類明示或暗示的陳述存在重大差異。這些前瞻性陳述在今天的新聞稿中進行了描述，可能影響它們的風險和不確定性在新聞稿和我們的 10-K 表格年度報告以及我們的 10-Q 表格季度報告中進行了描述。請參閱這些文檔以獲取更多信息。我們不承擔更新前瞻性陳述的任何意圖或義務。

Our revenue in the fourth quarter of 2022 was $103.1 million compared to $98.8 million in the fourth quarter of 2021. We expect our revenue growth to continue and have provided 2023 revenue guidance of $430 million to $450 million compared to 2022 revenue of $401.9 million. Net income was $16.6 million in the fourth quarter and $101.4 million for the full year 2022. Our cash and investments at December 31 was $436.6 million compared to $335.8 million at the end of the prior year.

我們在 2022 年第四季度的收入為 1.031 億美元，而 2021 年第四季度為 9880 萬美元。我們預計我們的收入將繼續增長，並提供了 2023 年 4.3 億美元至 4.5 億美元的收入指導，而 2022 年的收入為 4.019 億美元。第四季度淨收入為 1660 萬美元，2022 年全年淨收入為 1.014 億美元。截至 12 月 31 日，我們的現金和投資為 4.366 億美元，而去年年底為 3.358 億美元。

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布，以提供法律更新。查理？

Thanks, Atabak. Since we last spoke, we have successfully terminated 2 lawsuits. On February 13, we announced that we had reached an agreement in principle settling all claims to the reported securities class action known as Melucci versus Corcept Therapeutics Incorporated. This lawsuit was brought by Plaintiff's attorneys in March 2019. Since then, our position has not wavered. We said in March 2019 that we were confident in the strength of our legal position, having spent 4 years litigating. We are even more confident. I, and I know I speak for my colleagues as well, am proud of Corcept in the way we do business. Allegations such as those asserted in the Melucci lawsuit are repugnant. We have looked forward. We have looked forward to our named court where we can explain publicly the reasons for our pride in what we do and the way we do it.

謝謝，阿塔巴克。自上次通話以來，我們已經成功終止了 2 起訴訟。 2 月 13 日，我們宣布已原則上達成協議，解決所有對已報告的證券集體訴訟（稱為 Melucci 訴 Corcept Therapeutics Incorporated）的索賠。這起訴訟由原告律師於2019年3月提起。從那時起，我們的立場就沒有動搖過。我們在 2019 年 3 月表示，經過 4 年的訴訟，我們對自己的法律地位充滿信心。我們更有信心。我，我知道我也代表我的同事們，我為 Corcept 做生意的方式感到自豪。 Melucci 訴訟中的指控令人反感。我們期待著。我們期待著我們命名的法庭，在那裡我們可以公開解釋我們對我們所做的事情和我們做事的方式感到自豪的原因。

That being said, litigation is a distraction for more important matters. Simply put, time spent preparing for trial is time not spent developing medications or helping patients. We present with the chance to put the Melucci distraction behind us for an amount covered by our insurance we felt compel to accept. The second terminated case concerns Hikma Pharmaceuticals. In March 2021, we sued Hikma to prevent it from marketing generic KORLYM in violation of our patents. As we announced in December, we have settled this case. Hikma then begin selling a generic version of KORLYM in the United States beginning October 1, 2034, more than 11 years from now or earlier under circumstances customary for settlement agreements of this type.

話雖如此，訴訟會分散人們對更重要事情的注意力。簡而言之，花在準備試驗上的時間是沒有花在開發藥物或幫助患者上的時間。我們提供了一個機會，將 Melucci 的分心拋在腦後，以獲得我們感到不得不接受的保險所涵蓋的金額。第二個終止的案例涉及 Hikma Pharmaceuticals。 2021 年 3 月，我們起訴 Hikma 以阻止其銷售仿製藥 KORLYM 侵犯我們的專利。正如我們在 12 月宣布的那樣，我們已經解決了此案。 Hikma 然後從 2034 年 10 月 1 日開始在美國銷售 KORLYM 的仿製藥，從現在起超過 11 年或更早，在此類和解協議的慣例情況下。

This is the same entry date as our previous settlement with Sun Pharmaceuticals. Finally, there was a development yesterday in our lawsuit against Teva. In March 2018, we sued Teva to prevent it from marketing a generic version of KORLYM in violation of our patents. In April 2021, we filed for summary judgment based on Teva's infringement of our 214 for patent. Teva is expected to respond it by filing its own motion for summary judgment. Summary judgment is a procedure whereby courts decide a case without holding a trial. Yesterday, the court denied both our motion and Teva's motion without prejudice and ordered the parties to begin negotiating a schedule for pretrial activities. No trial date has been set. It is important to note that this change in the procedural posture of our action against Teva has not changed our point of view. We remain confident in the strength of our legal position and are very comfortable proceeding to trial, if necessary.

這與我們之前與 Sun Pharmaceuticals 達成和解的日期相同。最後，昨天我們對 Teva 的訴訟有了進展。 2018 年 3 月，我們起訴 Teva 以阻止其銷售侵犯我們專利的 KORLYM 仿製藥。 2021 年 4 月，我們以 Teva 侵犯我們的 214 專利為由提出簡易判決。預計 Teva 將通過提交自己的簡易判決動議來回應。簡易判決是法院在不進行審判的情況下決定案件的程序。昨天，法院無偏見地駁回了我們的動議和 Teva 的動議，並命令雙方開始協商預審活動的時間表。尚未確定試用日期。重要的是要注意，我們對 Teva 採取行動的程序姿態的這種變化並沒有改變我們的觀點。我們仍然對我們的法律地位充滿信心，並且在必要時非常樂意進行審判。

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

我現在將電話轉給我們的首席執行官 Joseph Belanoff 博士。喬？

Thank you, Charlie. Our Cushing's syndrome business is built on a solid foundation, a life-saving medication promoted by a commercial team that puts the interest of patients first. Leading endocrinologists increasingly believe there are considerably more patients with Cushing's syndrome than was once assumed. KORLYM is an excellent treatment for patients with Cushing's syndrome and there are many eligible patients who have yet to receive it. We are extremely optimistic about the growth potential of our Cushing's syndrome business and are making substantial investments to improve the screening and treatment of this disease.

謝謝你，查理。我們的庫欣綜合徵業務建立在堅實的基礎之上，這是一種由將患者利益放在首位的商業團隊推廣的救命藥物。領先的內分泌學家越來越相信，患有庫欣綜合徵的患者比以前認為的要多得多。 KORLYM 是庫欣綜合徵患者的一種極好的治療方法，還有許多符合條件的患者尚未接受它。我們對庫欣綜合徵業務的增長潛力極為樂觀，並正在進行大量投資以改善對該病的篩查和治療。

We are providing 2023 revenue guidance of $430 million to $450 million. In addition to generating substantial cash in 2022, we significantly advanced the clinical development programs of our proprietary selective cortisol modulators, relacorilant, dazucorilant and miricorilant. We expect to make further progress in the next 12 months with the submission of relacorilant's NDA in Cushing's syndrome and enrollment of our confirmatory Phase III trial of relacorilant in platinum-resistant ovarian cancer and Phase II trial of dazucorilant in ALS and Phase II trial of miricorilant in NASH. Since inception, our research and development efforts have built upon the hypothesis that cortisol modulation can be a powerful therapeutic mechanism in many serious disorders.

我們提供 4.3 億至 4.5 億美元的 2023 年收入指導。除了在 2022 年產生大量現金外，我們還顯著推進了我們專有的選擇性皮質醇調節劑 relacorilant、dazucorilant 和 miricorilant 的臨床開發計劃。我們希望在未來 12 個月內取得進一步進展，提交 relacorilant 治療庫欣綜合徵的 NDA 並註冊我們的 relacorilant 治療鉑耐藥卵巢癌的確認性 III 期試驗和 dazucorilant 治療 ALS 的 II 期試驗以及 miricorilant 的 II 期試驗在納什。自成立以來，我們的研發工作就建立在皮質醇調節可以成為許多嚴重疾病的強大治療機制的假設之上。

Our proprietary compounds modulate cortisol effects by binding to the glucocorticoid receptor, or GR. They do not bind to the progesterone receptor, so it don't cause some of KORLYM's our approved products, with serious off-target effects. Interestingly, while our compounds modulate cortisol's activity without modulating progesterones activity, they're not identical. Some cross the blood brain barrier, others do not. Some perform best in models of solid tumors, others in more potent in models with 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. Currently, we are conducting programs in ovarian, adrenal and prostate cancer, ALS, NASH and, of course, Cushing's syndrome.

我們專有的化合物通過與糖皮質激素受體 (GR) 結合來調節皮質醇的作用。它們不與孕激素受體結合，因此不會導致我們批准的某些 KORLYM 產品出現嚴重的脫靶效應。有趣的是，雖然我們的化合物在不調節孕酮活性的情況下調節皮質醇的活性，但它們並不相同。有些能穿過血腦屏障，有些則不能。有些在實體瘤模型中表現最好，有些在代謝性疾病模型中表現更佳。有些似乎是組織特異性的，有些則具有更全面的影響。這些不同的品質使我們能夠研究各種各樣的疾病。目前，我們正在開展卵巢癌、腎上腺癌和前列腺癌、ALS、NASH，當然還有庫欣綜合徵的項目。

We are investigating cortisol modulation's role in other diseases and have additional compounds in clinical and pre-clinical development. Our Cushing's syndrome business has funded all of these activities and will continue to do so. As most of you know, we are evaluating relacorilant with the treatment of hypercortisolism in 2 Phase III trials, GRACE and GRADIENT. Relacorilant is a selective cortisol modulator. Like KORLYM, achieves its effects by competing with cortisol at the glucocorticoid receptor. Unlike KORLYM, it does not bind to the progesterone receptor, PR for short, and so it does not cause PR-related side effects, including termination of pregnancy, endometrial thickening and vaginal bleeding.

我們正在研究皮質醇調節在其他疾病中的作用，並在臨床和臨床前開發中有其他化合物。我們的庫欣綜合徵業務已經資助了所有這些活動，並將繼續這樣做。正如你們大多數人所知，我們正在 2 項 III 期試驗 GRACE 和 GRADIENT 中評估 relacorilant 與皮質醇增多症的治療。 Relacorilant 是一種選擇性皮質醇調節劑。與 KORLYM 一樣，通過與糖皮質激素受體上的皮質醇競爭來實現其效果。與 KORLYM 不同，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。

By a different mechanism, relacorilant also does not appear to 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. 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.

通過不同的機制，relacorilant 似乎也不會引起低鉀血症，低鉀是 KORLYM 關鍵試驗中 44% 的患者經歷的嚴重副作用。 KORLYM 誘發的低鉀血症是 KORLYM 停藥的主要原因。 Relacorilant 的 II 期療效和安全性數據令人信服。患者在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方面均有顯著改善。沒有因藥物引起的子宮內膜增厚或陰道出血的不良反應，也沒有藥物引起的低鉀血症。試驗結果於 2021 年 7 月發表在 Frontiers in Endocrinology 上。

We are pleased to announce that we believe that we have enough patients in screening in our GRACE trial to complete enrollment in the coming weeks. We expect rates to serve as the basis for our NDA submission in Cushing's syndrome, which we plan to submit in the first quarter of 2024. Our second Phase III trial in hypercortisolism, GRADIENT, is studying relacorilant effects in patients whose Cushing's syndrome is caused by 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. While we do not expect our NDA in Cushing's syndrome to depend on data from GRADIENT, we do expect that its findings will improve care of these patients.

我們很高興地宣布，我們相信我們有足夠的患者在我們的 GRACE 試驗中進行篩查，可以在未來幾週內完成入組。我們預計率將作為我們提交庫欣綜合徵 NDA 的基礎，我們計劃在 2024 年第一季度提交。我們在皮質醇增多症的第二個 III 期試驗 GRADIENT 正在研究庫欣綜合徵由以下原因引起的患者的相關效應腎上腺腺瘤或腎上腺增生。患有這種庫欣綜合徵病因的患者通常會經歷較慢的衰退，但他們的健康結果很差。雖然我們不希望庫欣綜合徵的 NDA 依賴於 GRADIENT 的數據，但我們確實希望其發現將改善對這些患者的護理。

Finally, we plan to initiate a randomized double-blind placebo-controlled Phase IV study in KORLYM this quarter. We have named the study CATALYST. CATALYST will examine the prevalence of hypercortisolism in patients with difficult to control type 2 diabetes and treat the patients to determine to have hypercortisolism with KORLYM. Planned enrollment is 1,000 patients, which we expect to complete by the end of this year. The most prominent diabetologists in the country helped design and are participating in this study. Our oncology program is testing 3 anticancer mechanisms first postulated by investigators at the University of Chicago and later confirmed by other prominent researchers.

最後，我們計劃本季度在 KORLYM 啟動一項隨機雙盲安慰劑對照的 IV 期研究。我們將這項研究命名為 CATALYST。 CATALYST 將檢查難以控制的 2 型糖尿病患者皮質醇增多症的患病率，並用 KORLYM 治療患者以確定是否患有皮質醇增多症。計劃招募 1,000 名患者，我們預計在今年年底完成。該國最著名的糖尿病學家幫助設計並參與了這項研究。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，後來由其他著名研究人員證實。

One mechanism is increasing apoptosis, a program cell that the 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, enhance the effect of chemotherapy, likely by blending cortisol's anti-apoptotic effect. Relacorilant provided meaningful benefit to many of the women in our study. While these women's disease have progressed on 2 or more previous lines of treatment, including previous taxanes, relacorilant appear to resensitize the disease to chemotherapy's beneficial effects in some women.

一種機制是增加細胞凋亡，這是化學療法旨在在實體瘤中誘導的一種程序細胞。皮質醇通過抑制細胞凋亡來對抗化學療法的有益作用。我們在鉑類耐藥卵巢癌女性中成功進行了 II 期對照試驗，添加了我們的選擇性皮質醇調節劑 relacorilant，可能通過混合皮質醇的抗細胞凋亡作用來增強化療的效果。 Relacorilant 為我們研究中的許多女性提供了有意義的益處。雖然這些女性的疾病在之前的 2 條或更多條治療線（包括之前的紫杉烷類藥物）中取得了進展，但 relacorilant 似乎使某些女性的疾病對化療的有益效果重新敏感。

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 live longer than those comparator one with a p-value that approached statistical significance. Our analysis to date indicates that 29% of the patients who took intermittent relacorilant were live 2 years after study start, which is only 14% who took nab-paclitaxel alone. 13% of patients who took intermittent relacorilant are live 3 years after study start compared to none who took nab-paclitaxel alone.

與接受白蛋白結合型紫杉醇單一療法的組相比，在接受白蛋白結合型紫杉醇治療的前一天、當天和後一天間歇性接受 relacorilant 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的顯著改善。間歇性 relacorilant 組中的女性也比那些 p 值接近統計顯著性的比較組的女性活得更長。我們迄今為止的分析表明，29% 服用間歇性 relacorilant 的患者在研究開始後存活了 2 年，而僅服用白蛋白結合型紫杉醇的患者只有 14%。 13% 服用間歇性 relacorilant 的患者在研究開始後存活了 3 年，而單獨服用白蛋白結合型紫杉醇的患者則沒有。

Perhaps even more important, the women who receive relacorilant plus nab-paclitaxel experienced no additional side effect burden compared to those who received nab-paclitaxel alone. The results from the study were featured in podium presentations at the 2021 and 2022 European Society for Medical Oncology, ESMO, meetings and in the 2022 American Society of Clinical Oncology, ASCO Annual Meeting. ROSELLA, our pivotal Phase III trial in platinum-resistant ovarian cancer is active in enrolling patients. ROSELLA's design closely tracks our Phase II study with planned enrollment of 360 women randomized 1:1 to receive either relacorilant plus nab-paclitaxel or nab-paclitaxel alone. The primary endpoint will be progression-free survival with overall survival a key secondary endpoint.

也許更重要的是，與單獨接受 nab-紫杉醇的女性相比，接受 relacorilant 和 nab-paclitaxel 的女性沒有經歷額外的副作用負擔。該研究的結果在 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 年會的講台上發表。 ROSELLA 是我們針對鉑類耐藥卵巢癌的關鍵 III 期試驗，目前正在積極招募患者。 ROSELLA 的設計密切跟踪我們的 II 期研究，計劃招募 360 名女性，按 1:1 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。主要終點將是無進展生存期，總生存期是關鍵的次要終點。

We are conducting the study in collaboration with leading clinicians from the Gynecological Oncology Group in the United States and the European Network of Gynecological Oncology Trial Group in Europe. Our goal in Phase III is simply to replicate our positive Phase II results. Leading gynecological oncologists have told this that in their view, relacorilant's potential benefit, improved survival without increased side effect burden, would begin to constitute an important medical advance and relacorilant plus nab-paclitaxel has the potential to become a new standard of care in women with platinum-resistant ovarian cancer.

我們正在與美國婦科腫瘤組和歐洲婦科腫瘤試驗組歐洲網絡的主要臨床醫生合作開展這項研究。我們在第三階段的目標只是複制我們在第二階段的積極成果。領先的婦科腫瘤學家告訴我們，在他們看來，relacorilant 的潛在益處，即在不增加副作用負擔的情況下提高生存率，將開始構成一項重要的醫學進步，並且 relacorilant 加白蛋白結合型紫杉醇有可能成為女性的新護理標準鉑耐藥卵巢癌。

A 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 the widely prescribed androgen receptor antagonist enzalutamide eventually experience resurgent disease. The product of androgen stimulation mean their tumor switch to cortisol activity to stimulate growth. Our hypothesis is that adding a cortisol modulator to androgen deprivation therapy will close this tumor escape route. By midyear, 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.

皮質醇調節可能證明有用的第二種機制是阻斷重要的腫瘤生長途徑。皮質醇刺激是使用廣泛處方的雄激素受體拮抗劑恩雜魯胺治療的前列腺癌患者最終會復發的主要原因。雄激素刺激的產物意味著它們的腫瘤轉變為皮質醇活性以刺激生長。我們的假設是，在雄激素剝奪療法中加入皮質醇調節劑將關閉這種腫瘤逃逸途徑。到年中，我們在芝加哥大學的合作者計劃在前列腺癌患者進行初始前列腺切除術之前，開始一項隨機安慰劑對照的 II 期試驗，在這些患者中使用 relacorilant 加恩雜魯胺。

A 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 cortisol -- 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 PD-1 checkpoint inhibitor, pembrolizumab, Merck's drug, KEYTRUDA, in patients with advanced adrenal cancer whose tumors produce excess cortisol. These patients suffer the effects of adrenal cancer and Cushing's syndrome, a usually quickly lethal combination. Pembrolizumab is rarely effective in treating this form of adrenal cancer.

第三種治療機制旨在通過增強身體的免疫反應來治療腫瘤。皮質醇抑制免疫系統，這可能會削弱皮質醇的有效性——旨在刺激免疫系統的癌症療法。我們的假設是，在檢查點抑製劑等免疫療法中加入皮質醇調節劑可能會增強這些療法的有效性。我們正在對腫瘤產生過量皮質醇的晚期腎上腺癌患者進行 relacorilant 加 PD-1 檢查點抑製劑 pembrolizumab、Merck 的藥物 KEYTRUDA 的 Ib 期試驗。這些患者患有腎上腺癌和庫欣綜合症，這是一種通常迅速致死的綜合症。派姆單抗很少能有效治療這種形式的腎上腺癌。

Our trial is evaluating whether relacorilant can treat these patients' Cushing's syndrome by reducing excess cortisol and by reversing cortisol-induced immune suppression, allow pembrolizumab to achieve its full cancer killing effect. The primary endpoint of the study is objective response rate, with secondary endpoints including progression-free survival, duration of response and overall survival. ALS, commonly known as Lou Gehrig's disease, is a devastating illness with an urgent need for better treatment. DAZALS, our 198-patient randomized double-blind placebo-controlled Phase II trial of dazucorilant in patients with ALS, has begun enrolling patients. Dazucorilant is selective cortisol modulator and 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.

我們的試驗正在評估 relacorilant 是否可以通過減少過量皮質醇和逆轉皮質醇誘導的免疫抑制來治療這些患者的庫欣綜合徵，從而使 pembrolizumab 達到其完全的癌症殺傷效果。該研究的主要終點是客觀反應率，次要終點包括無進展生存期、反應持續時間和總生存期。 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 198 名隨機雙盲安慰劑對照 II 期試驗，該試驗已開始招募患者。 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潛力，可改善運動性能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。

Finally, I'll turn to our program in NASH, a serious liver disorder that affects 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 study, patients who received miricorilant exhibited large, rapid reductions in liver fat, but also substantial, albeit transient, elevations in the liver enzymes ALT and AST. The improvement 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. Our Phase Ib dose-finding study has identified a range of doses, all substantially lower than our originally-tested doses that appear to cause substantial reductions in liver fat without causing excessive liver irritation. We expect to share results from this study by midyear and plan to start a Phase II trial later this year.

最後，我將談談我們在 NASH 中的項目，NASH 是一種影響美國數百萬患者的嚴重肝病。 Miricorilant 是一種口服藥物，繼續顯示出治療 NASH 的巨大希望。在我們之前的 NASH 研究中，接受微克利蘭的患者表現出肝臟脂肪大量快速減少，但肝酶 ALT 和 AST 也顯著升高，儘管是短暫的。這些患者肝臟脂肪的改善比我們預期的要大得多，發生得也快得多，而且在任何治療期間都很少見到。我們的 Ib 期劑量探索研究確定了一系列劑量，所有這些劑量都大大低於我們最初測試的劑量，這些劑量似乎可以顯著減少肝臟脂肪，而不會引起過度的肝臟刺激。我們希望在年中之前分享這項研究的結果，併計劃在今年晚些時候開始 II 期試驗。

In conclusion, we are extremely optimistic about the growth potential of our Cushing's syndrome business and are making significant investments to improve the screening and treatment of these patients. In the meantime, the business continues to generate substantial profits even after funding all of our development programs. Our development programs continue to generate evidence validating 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. It is also clear that cortisol modulation can offer substantial benefits for many other serious disorders.

總之，我們對庫欣綜合徵業務的增長潛力極為樂觀，並正在投入大量資金來改善對這些患者的篩查和治療。與此同時，即使在為我們所有的開發項目提供資金後，該業務仍繼續產生可觀的利潤。我們的開發計劃不斷產生證據，證實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。降低皮質醇活性是治療庫欣綜合徵的一種直接有效的方法。同樣清楚的是，皮質醇調節可以為許多其他嚴重疾病提供實質性益處。

Ovarian cancer, ALS and NASH are prime examples, but there will be others. And in addition to relacorilant, dazucorilant and miricorilant, we have many other cortisol modulators in our portfolio with potential -- potentially different and valuable clinical attributes. Corcept continues to advance across multiple fronts. I thank our dedicated creative employees and loyal investors for making this possible.

卵巢癌、ALS 和 NASH 是主要的例子，但還會有其他例子。除了 relacorilant、dazucorilant 和 miricorilant，我們的產品組合中還有許多其他皮質醇調節劑，它們具有潛在的——可能不同且有價值的臨床屬性。 Corcept 繼續在多個領域取得進展。我感謝我們敬業的創意員工和忠實的投資者讓這一切成為可能。

I'll stop here for questions.

我會在這裡停下來提問。

(Operator Instructions) And our first question is from the line of Matt Kaplan with Ladenburg Thalmann.

（操作員說明）我們的第一個問題來自 Matt Kaplan 和 Ladenburg Thalmann。

This is Raymond in for Matt. Congrats on all the progress. I just wanted to ask perhaps on the ALS program. Specifically, kind of what endpoints are you kind of looking for in the study? Is it ALSFRS? And do you have any specific guidance from the FDA if the study could serve as the basis for an NDA pilot? And I have 1 more question.

這是馬特的雷蒙德。祝賀所有的進步。我只是想問一下關於 ALS 計劃的問題。具體來說，您在研究中尋找什麼樣的終點？是ALSFRS嗎？如果該研究可以作為 NDA 試點的基礎，您是否有來自 FDA 的任何具體指導？我還有 1 個問題。

Yes, Matt (sic) [Raymond]. I wanted to reintroduce you to Bill Guyer, who is our Chief Development Officer. Bill will address that question.

是的，馬特（原文如此）[雷蒙德]。我想再次向您介紹我們的首席開發官 Bill Guyer。比爾將解決這個問題。

Appreciate the question. So, again, DAZALS is like Phase II (inaudible) randomized, double-blind, placebo-controlled trial, evaluating the safety and efficacy of dazucorilant in patients with ALS. In this Phase II trial, we're going to look at 198 patients. The primary endpoint is a 24-week endpoint where we're going to be evaluating those patients related to placebo. And we're going to look at the efficacy and change from baseline for the ALS functional rating scale and that is a validated FDA endpoint, as well as other primary endpoints of safety to assess the safety and efficacy or the safety of dazucorilant patients with ALS. And these are all validated endpoints with the FDA. And if we complete this trial and we see positive results, this could end up with an NDA.

感謝這個問題。因此，DAZALS 再次類似於 II 期（聽不清）隨機、雙盲、安慰劑對照試驗，評估 dazucorilant 在 ALS 患者中的安全性和有效性。在這個 II 期試驗中，我們將研究 198 名患者。主要終點是一個 24 週的終點，我們將在其中評估那些與安慰劑相關的患者。我們將研究 ALS 功能評分量表的療效和相對於基線的變化，這是經過驗證的 FDA 終點，以及其他安全性主要終點，以評估 dazucorilant 肌萎縮性側索硬化患者的安全性和有效性或安全性.這些都是經過 FDA 驗證的終點。如果我們完成了這個試驗並且我們看到了積極的結果，這可能會以保密協議告終。

And I guess, maybe just for the NASH program, what would you like to see from the Phase Ib that is kind of increasing your confidence as you enter the Phase II study? And is it possible you would try multiple dosing regimens?

我想，也許僅對於 NASH 計劃，您希望從 Ib 階段看到什麼可以在您進入 II 階段研究時增強您的信心？您是否有可能嘗試多種給藥方案？

Yes, that is the goal. That's a great question. Since this is an open label trial, we're evaluating all the various different doses. And our goal has been to find the right dose or dosing regimen where we get a progressive fat loss over time with then no ALT rises. And hopefully, we see ALT improvements. We believe we've identified multiple doses or dosing regimens to move into Phase II where we've seen that progressive fat loss over time and no ALT rises. And so yes, our plan is to move to Phase II in the fourth quarter of this year.

是的，這就是目標。這是一個很好的問題。由於這是一項開放標籤試驗，我們正在評估所有不同的劑量。我們的目標是找到合適的劑量或給藥方案，隨著時間的推移，我們會逐漸減少脂肪，然後 ALT 不會升高。希望我們能看到 ALT 的改進。我們相信我們已經確定了多個劑量或給藥方案以進入第二階段，我們已經看到隨著時間的推移脂肪逐漸減少並且 ALT 沒有升高。所以是的，我們的計劃是在今年第四季度進入第二階段。

Our next question is from the line of Dennis Ding with Jefferies.

我們的下一個問題來自 Jefferies 的 Dennis Ding。

I just have one around the base business. Maybe talk about the pushes and pulls on 2023 revenue in terms of what can get you towards the high end versus the low end of your guidance? And perhaps what are some of the different assumptions for you to get there? And as a follow-up, maybe remind us of the seasonality issue for Q1? And when might we get better visibility towards growth acceleration in 2023?

我只有一個圍繞基礎業務。也許就什麼可以使您走向指導的高端與低端而言，談談對 2023 年收入的推動和拉動？也許您要達到目標有哪些不同的假設？作為後續行動，也許提醒我們第一季度的季節性問題？我們什麼時候可以更好地了解 2023 年的增長加速？

Good, Dennis. I want to again reintroduce you to Sean Maduck, who is the President of our Endocrinology division. And Sean is responsible for all of our business in Cushing's syndrome. He'll be glad to answer that question.

很好，丹尼斯。我想再次向您介紹 Sean Maduck，他是我們內分泌科的總裁。肖恩負責我們在庫欣綜合症方面的所有業務。他會很樂意回答這個問題。

Hello, Dennis. I think your question was directly in regards to sort of the range. Our range is driven by the number of patients that we add to our active patient base. Our pricing is known and our average dose and patient retention rates have been stable for many years. So where we fall within the range is really driven by the number of patients that we add to our base. And that's the -- the pushes and pulls are constant. It's really about patient pulls.

你好，丹尼斯。我認為您的問題直接與範圍有關。我們的範圍取決於我們添加到活躍患者群中的患者數量。我們的定價眾所周知，我們的平均劑量和患者保留率多年來一直穩定。因此，我們在這個範圍內的位置實際上是由我們添加到我們的基礎中的患者數量驅動的。這就是 - 推拉是恆定的。這真的是關於耐心的拉動。

Right. But as a follow-up maybe talk about what can you do or what are you guys doing in terms of initiatives that are ongoing that could drive more patient adds versus driving less patient adds, appreciating that there is competition out there?

正確的。但作為後續行動，也許可以談談你能做什麼，或者你們正在做什麼，這些正在進行的計劃可以推動更多的病人增加，而不是減少病人的增加，意識到那裡存在競爭？

Yes. No, great question. So look, I'll start by just saying the evidence is clear that there are more hypercortisolism patients out there than we once thought. Physicians as they become more educated about screening and about treatment options that are available to them, more patients are going to be diagnosed and treated. And our job as an organization is to maximize our physician touch points, continue to raise disease awareness, educate on screening and then educate on the benefits of KORLYM. And the evolving market and our execution will really drive that growth into 2023 and beyond.

是的。不，很好的問題。所以看，我首先要說的是證據很清楚，那裡的皮質醇增多症患者比我們曾經想像的要多。隨著醫生對篩查和他們可用的治療方案的了解越來越多，更多的患者將得到診斷和治療。作為一個組織，我們的工作是最大化我們的醫生接觸點，繼續提高疾病意識，進行篩查教育，然後教育 KORLYM 的好處。不斷發展的市場和我們的執行力將真正推動這種增長持續到 2023 年及以後。

In terms of initiatives, obviously, we have many going on. But there's a couple I want to touch on that I think are very important for the organization. The first is the growth of our sales force. Last year, we had 45 clinical specialists. We currently have 55, going to 60 in the next couple of months. Physician awareness of the potential for Cushing's syndrome in their patient population has increased substantially. And we think that, that disease awareness and our streamlined training efforts will make our clinical specialist more productive and for our newest clinical specialist more productive more rapidly.

顯然，就倡議而言，我們正在進行許多活動。但是我想談談我認為對組織非常重要的幾個問題。首先是我們銷售隊伍的增長。去年，我們有 45 名臨床專家。我們目前有 55 個，在接下來的幾個月內將增加到 60 個。醫生對庫欣綜合徵在其患者群體中的潛在可能性的認識已大大提高。我們認為，這種疾病意識和我們簡化的培訓工作將使我們的臨床專家更有效率，並使我們最新的臨床專家更快地提高效率。

In terms of the second initiative, which is more long-term, is what was just discussed and that's the CATALYST study, the Phase IV KORLYM study that we announced on the call today. It's not going to have an impact in 2023. But it's the largest prospective study that's ever been done in this patient population. As Joe stated, the investigators are a very prominent group of diabetologists and they are representative of a group of physicians that we have not historically called on. So we believe that patients with difficult to control diabetes and -- is a very rich patient population for hypercortisolism, I mean I believe that this study will provide the definitive prevalence and treatment data needed to encourage increased screening and ultimately treatment for this patient group.

就第二項計劃而言，這是更長期的，就是剛才討論的內容，那就是 CATALYST 研究，即我們今天在電話會議上宣布的 IV 期 KORLYM 研究。它不會在 2023 年產生影響。但這是迄今為止針對該患者群體進行的最大規模的前瞻性研究。正如 Joe 所說，研究人員是一群非常傑出的糖尿病學家，他們代表了我們過去從未拜訪過的一群醫生。因此，我們相信患有難以控制的糖尿病的患者是非常豐富的皮質醇增多症患者群體，我的意思是我相信這項研究將提供明確的患病率和治療數據，以鼓勵增加對這一患者群體的篩查和最終治療。

And then, on the seasonality question for Q1 and growth reacceleration towards the back half of the year?

然後，關於第一季度的季節性問題和下半年的增長再加速？

Yes. So we always see a hit in the first quarter, because of insurance reauthorizations and the doughnut hole this year has been no different than any other. But yes, I guess that's all I would add there. I don't know if there's anything else, Joe, you'd like to add?

是的。所以我們總是在第一季度看到成功，因為保險重新授權和今年的甜甜圈洞與其他任何時候都沒有什麼不同。但是，是的，我想這就是我要添加的全部內容。不知道Joe還有什麼要補充的嗎？

Dennis, I really do understand what you're asking about. Yes, as Sean said that one of the issues, not just for KORLYM, but for all medications, particularly orphan medications is that insurance companies make decisions get a reauthorization at the beginning of the year. And that's obviously our job to see if we can turn those -- help those get turned around as quickly as possible. One of the things I'll just point out is that it's been our philosophy from the beginning of the company, but anytime a patient gets a prescription for Cushing's syndrome, they get the medication regardless of whether or not they have insurance. So they continue to get that medication. We never leave a patient off of that medication. But getting them back on paid insurance as they have before is, in some sense, a maneuver that occurs every year. And the quicker we do that, the more it adds back to first quarter revenues. And then, once that's in place, we're on our ark for the rest of the year.

丹尼斯，我真的明白你在問什麼。是的，正如肖恩所說，其中一個問題，不僅是 KORLYM，而且對於所有藥物，特別是孤兒藥物，是保險公司做出的決定在年初獲得重新授權。這顯然是我們的工作，看看我們是否可以扭轉這些局面——幫助那些人盡快扭轉局面。我要指出的一件事是，這從公司成立之初就是我們的理念，但只要患者獲得庫欣綜合徵的處方，他們就會得到藥物，無論他們是否有保險。所以他們繼續服用這種藥物。我們永遠不會讓病人停止服用那種藥物。但從某種意義上說，讓他們像以前一樣重新獲得付費保險是一種每年都會發生的策略。我們做得越快，第一季度的收入就越多。然後，一旦就緒，我們將在今年餘下的時間裡繼續前進。

Our next question is from the line of Greg Fraser with Truist.

我們的下一個問題來自 Greg Fraser with Truist。

I got on a little late, I apologize if you covered this already. But I was hoping you could comment on the protocol for the CATALYST study and talk about the enrollment criteria, the types of patients that will be enrolled? And I'm curious about it, it seems like it's a study that -- obviously, it's quite large and it's unprecedented. It seems like a study that could potentially capture patients that would otherwise be started on KORLYM. I know you're -- the study will be run by docs that you're not calling on, it sounds like. But could this create a headwind for new starts on KORLYM? Or am I thinking about that the wrong way?

我來晚了一點，如果你已經報導了，我很抱歉。但我希望您能對 CATALYST 研究的方案發表評論，並談談入組標準、將入組的患者類型？我很好奇，這似乎是一項研究——顯然，它規模很大，而且是前所未有的。這似乎是一項有可能捕獲患者的研究，否則這些患者將在 KORLYM 上開始。我知道你 - 這項研究將由你沒有拜訪的文檔進行，聽起來像是。但這是否會對 KORLYM 的新起點造成不利影響？還是我想錯了？

Hey, Greg, just sort of sorting this out, I want to give the first part to Bill, who is conducting the study. So Bill, can you answer the questions about protocol.

嘿，格雷格，只是整理一下，我想把第一部分交給主持這項研究的比爾。那麼 Bill，你能回答關於禮儀的問題嗎？

Yes. So CATALYST is an example that I think we are showing our continued investment in our compounds whether approved or investigational. And the CATALYST, as Sean had mentioned, is the largest study of its kind. We're going to be testing 2 really rigorous important points. One is to understand the prevalence of hypercortisolism in patients with difficult to control type 2 diabetes. And the second is to understand the efficacy and safety of KORLYM in these patients. And in that patient population, we're going to be looking at 1,000 patients and where we're going to be simply testing them for hypercortisolism with a simple DST.

是的。所以 CATALYST 是一個例子，我認為我們正在展示我們對我們的化合物的持續投資，無論是批准的還是研究的。正如肖恩提到的那樣，CATALYST 是同類研究中規模最大的。我們將測試 2 個非常嚴格的重要點。一是了解難以控制的2型糖尿病患者皮質醇增多症的患病率。其次是了解 KORLYM 在這些患者中的療效和安全性。在那個患者群體中，我們將觀察 1,000 名患者，我們將使用簡單的 DST 簡單地測試他們的皮質醇增多症。

And from there, we're going to be then evaluating them. And for those who are positive will then be selected to and have a choice to go into the second part of the study, which is that treatment part of the study. As Sean had also previously mentioned, we're working with the top diabetologists. And while this is a large study, these diabetologists have thousands of patients in their practice. And I have already identified many of them who could meet the inclusion and exclusion criteria of this study.

從那裡開始，我們將對它們進行評估。對於那些呈陽性的人，然後將被選中並可以選擇進入研究的第二部分，即研究的治療部分。正如 Sean 之前也提到的，我們正在與頂級糖尿病專家合作。雖然這是一項大型研究，但這些糖尿病專家在他們的實踐中有數千名患者。我已經確定了其中許多人可以滿足這項研究的納入和排除標準。

And when you look at that inclusion and exclusion criteria, I'll give you a few points there. It's for adult patients who are aged 18 to 80; those who are difficult to control diabetes, and that's defined simply by having a hemoglobin A1C of greater than 7.5, but less than 11.5 and are taking multiple anti-hyperglycemic drugs plus many other things. But that's the simple design of the trial of how to get in. We believe by working with these top diabetologists that we've designed a trial that's easy to enroll and we're on track to start the trial this -- next month in March and complete enrollment of this trial by the end of this year.

當您查看納入和排除標準時，我會給您幾點意見。適用於18-80歲的成年患者；那些難以控製糖尿病的人，簡單地定義為血紅蛋白 A1C 大於 7.5 但小於 11.5，並且正在服用多種抗高血糖藥物以及許多其他藥物。但這就是如何進入試驗的簡單設計。我們相信，通過與這些頂級糖尿病專家合作，我們設計了一個易於註冊的試驗，我們有望在下個月 3 月開始試驗並在今年年底前完成該試驗的招募。

Second part of the question, Greg, I'm going to give you to Sean.

問題的第二部分，格雷格，我要把你交給肖恩。

And the question was whether or not this study will impact potentially KORLYM patients that would have been on KORLYM previously. The answer to that is no. Remember, this is a group of physicians not only are they not prescribing KORLYM today, they're not even aware that these hypercortisolism patients exist in their practice. They are treating these patients for their diabetes and aren't aware. So again, let me go back to what I said a moment ago is just that the hope of this study is that, that will provide definitive prevalence in treatment data that will help, I'll say, sway and motivate this group of physicians who currently aren't treating or diagnosing.

問題是這項研究是否會影響以前使用 KORLYM 的潛在 KORLYM 患者。答案是否定的。請記住，這是一群醫生，他們今天不僅沒有開 KORLYM 處方，他們甚至不知道這些皮質醇增多症患者存在於他們的實踐中。他們正在治療這些患者的糖尿病，但他們並不知道。所以，讓我再次回到我剛才所說的，這項研究的希望在於，這將提供治療數據的明確流行率，這將有助於，我會說，影響和激勵這群醫生目前沒有治療或診斷。

That's very helpful. Can you help with how to think about the growth for SG&A and R&D this year given the investments that you're making on the commercial side and also on the clinical side with the CATALYST study?

這很有幫助。考慮到您在商業方面以及 CATALYST 研究的臨床方面所做的投資，您能否幫助考慮今年 SG&A 和 R&D 的增長？

Sure. Greg, it's Atabak. I'll take that one. We have -- as you know, we've historically been profitable and fund to remain profitable. Our R&D expenses will increase as we invest in our development programs and invest in programs to advance. And on the SG&A side, Sean discussed the continued investments we're making on the commercial side there. So you'll see some increases on both sides there.

當然。格雷格，是阿塔巴克。我會拿那個。我們有——如你所知，我們在歷史上一直盈利，並為保持盈利提供資金。我們的研發費用將隨著我們投資於我們的發展計劃和投資於推進計劃而增加。在 SG&A 方面，Sean 討論了我們在商業方面的持續投資。所以你會看到雙方都有一些增長。

Last question, I just wanted to ask about the reason. You recently had the class action settlement. Curious about what you think that might mean if anything for the other several cases that are pending and also for the DOJ investigation?

最後一個問題，我只是想問一下原因。您最近達成了集體訴訟和解。想知道您認為這對其他幾個懸而未決的案件以及美國司法部的調查可能意味著什麼嗎？

Charlie?

查理？

Yes, sure. So, just a brief background for those who haven't followed the story. We've been in this -- defending the class action or purported class action lawsuit since 2018, so quite some time. And we -- over time, as we prepared for trial some day in the distant future, we started off confident in our position and confident the way we were doing business and we really only got more so as things developed and as we got over (inaudible) around and really reviewed all of the possible evidence, we just felt better and better, but had the opportunity recently to settle it. Because when I said that litigation is a distraction for more important matters, I really hope that everyone will really take that on board.

是的，當然。所以，對於那些沒有關注這個故事的人來說，只是一個簡短的背景。自 2018 年以來，我們一直在為集體訴訟或據稱的集體訴訟辯護，所以已經有一段時間了。而且我們——隨著時間的推移，當我們準備在遙遠的未來某天進行審判時，我們開始對自己的立場充滿信心，並對我們開展業務的方式充滿信心，隨著事情的發展和我們的結束，我們真的只會得到更多（聽不清）並真正審查了所有可能的證據，我們感覺越來越好，但最近有機會解決它。因為當我說訴訟是為了更重要的事情而分心時，我真的希望每個人都能真正接受這一點。

And imagine you had a day where you could spend your time helping to move a drug -- promising drug candidate through, say, the regulatory process or the development process or you can review a giant stack of emails from 3 years ago. And that's really the difference between settling and not settling. So we chose to settle when we had an opportunity to do so on advantageous terms. Now what you're referring to are there are a handful of sort of associated civil cases brought by plaintiff's law firms sort of around the country.

想像一下，有一天您可以花時間幫助推動一種藥物——有前途的候選藥物通過監管流程或開發流程，或者您可以查看 3 年前的一大堆電子郵件。這就是解決和不解決之間的真正區別。因此，當我們有機會以有利的條件這樣做時，我們選擇了和解。現在你指的是全國各地的原告律師事務所提起的一些相關民事案件。

They think of these as sort of like the pilot fish that attack -- attach themselves to sharks as they move through the ocean and try to survive off the food that escapes from the shark's mouth, that's what these lawsuits are like. And there are a handful of them. We will dispose of those, one way or the other, shortly following. This is my expectation, but you never -- one never can tell. But one thing I can say for sure is that we're very, very confident in our legal position with respect to them.

他們認為這些有點像攻擊的領航魚——當鯊魚在海洋中移動時，它們會依附在鯊魚身上，並試圖依靠從鯊魚嘴裡逃脫的食物生存，這就是這些訴訟的樣子。其中有少數。我們將在不久之後以一種或另一種方式處理這些。這是我的期望，但你永遠——永遠也說不准。但我可以肯定地說的一件事是，我們對我們對他們的法律立場非常、非常有信心。

So that's what Melucci securities class action portends for those ancillary cases. I think with respect to the Department of Justice, of course, I have no idea what the attorneys at the Department of Justice are thinking. However, my understanding is that generally speaking, the Department of Justice does pay attention to what happens as you would imagine and sort of not loosely related, but sort of parallel civil case. There's no actual legal connection between the Department of Justice action, our inquiry and the Melucci class action, but they probably have their eye on it.

這就是 Melucci 證券集體訴訟對這些附屬案件的預示。我認為關於司法部，當然，我不知道司法部的律師在想什麼。然而，我的理解是，一般來說，司法部確實會關注發生的事情，就像你想像的那樣，並且不是鬆散相關的，而是平行的民事案件。司法部的行動、我們的調查和 Melucci 集體訴訟之間沒有實際的法律聯繫，但他們可能會關注它。

And I don't know what they're thinking because they don't and wouldn't tell me obviously. But I hope what they see is what we see, which is a settlement on very advantageous terms for the company, which reflects the sort of the confidence that we have in the way we do business. So I hope that's the impression they take away from it and that colors their thinking, but of course, I cannot be sure. And that inquiry proceeds and we'll just have to see how that plays out. We are very comfortable with respect to that inquiry also.

我不知道他們在想什麼，因為他們不會也不會明顯地告訴我。但我希望他們看到的是我們所看到的，這是對公司非常有利的條款的解決方案，這反映了我們對我們開展業務的方式的信心。所以我希望這是他們從中帶走的印象，並影響他們的想法，但當然，我不能確定。調查繼續進行，我們只需要看看結果如何。我們對那個詢問也很滿意。

Our next question is from the line of Arthur He with H.C. Wainwright.

我們的下一個問題來自 Arthur He 和 H.C.溫賴特。

This is Arthur on for [RK]. So first one is regarding the Cushing business. Could you give us some color from your perspective there about the in-person clinical interactions in the second -- in fourth quarter and also what you see in the first quarter this year?

這是 [RK] 的亞瑟。所以第一個是關於庫欣業務。你能從你的角度給我們一些關於第二季度 - 第四季度以及你在今年第一季度看到的面對面臨床互動的顏色嗎？

Yes. No, thanks for the question. The question was what are the in-person interactions in the fourth quarter of last year and into this year. And in the past, we've discussed some of the obstacles that we faced because of COVID restrictions. And I'll tell you that through the fourth quarter and today, our in-person interactions are at about 80% to 90% of pre-COVID levels. And we expect that to be our new baseline. Some previously accessible physicians closed their doors to industry during the pandemic. And I believe that some of those will keep restrictions in place permanently. So, we're utilizing alternative means as a company to get in front of these physicians, whether it be virtual meetings, digital marketing and educational programs to try to make up some of that gap and we've seen some success on that.

是的。不，謝謝你的提問。問題是去年第四季度和今年的面對面互動是什麼。過去，我們討論過因 COVID 限製而面臨的一些障礙。我會告訴你，從第四季度到今天，我們的面對面互動大約是 COVID 前水平的 80% 到 90%。我們希望這成為我們的新基線。在大流行期間，一些以前可以接觸到的醫生對行業關閉了大門。我相信其中一些將永久保持限制。因此，作為一家公司，我們正在利用替代方式來吸引這些醫生，無論是虛擬會議、數字營銷和教育計劃，以試圖彌補部分差距，我們已經看到了一些成功。

And so regarding the ovarian cancer study, could you give us more color on enrollment status? And so far, how many sites are active for now?

那麼關於卵巢癌研究，你能給我們更多關於入學狀態的顏色嗎？到目前為止，有多少網站處於活躍狀態？

Bill?

賬單？

I'll give you some color around there. Well, I won't give you exact metrics on it because we don't really talk about metrics but I'll give you more color. Momentum has continued and is tracking to expectations for our ovarian cancer Phase III trial. We expect to fully enroll this trial by the end of this year. And we believe that because we've got great collaborators like the GOG, which is the Gynecological Oncology Group here in the United States and ENGOT, which is the European Network of Gynecological Oncology Trial group. Those groups are helping us get enrolled in a number of sites that we need and we determine we need about 125 sites globally.

我會給你一些顏色。好吧，我不會給你確切的指標，因為我們並沒有真正談論指標，但我會給你更多的顏色。勢頭一直在持續，並且正在追踪我們對卵巢癌 III 期試驗的預期。我們預計將在今年年底之前完全納入該試驗。我們相信，因為我們有很好的合作者，比如 GOG，它是美國的婦科腫瘤組和 ENGOT，它是歐洲婦科腫瘤試驗組網絡。這些團體正在幫助我們註冊我們需要的一些網站，我們確定我們在全球需要大約 125 個網站。

And of those sites, we've had an investigator meeting in the United States and it was probably the most positive investigator meeting we've ever had where we talked about all of the data and the investigators in the U.S. came away with the excitement and the benefit that they saw for relacorilant that could be used in combination with nab-paclitaxel. Next week, we're having an investigator meeting in Europe with all of the top investigators. I think there's about 50 investigators attending that investigator meeting and we expect to see the same result of them seeing the same -- and having the same excitement of relacorilant plus nab-paclitaxel for women in their practice. So we expect very positive things now and moving forward to this trial.

在這些網站中，我們在美國召開了一次調查員會議，這可能是我們舉行過的最積極的調查員會議，我們討論了所有數據，美國的調查員興奮地離開了，他們看到 relacorilant 可以與 nab-paclitaxel 聯合使用的好處。下週，我們將在歐洲與所有頂級調查員召開調查員會議。我認為大約有 50 名研究人員參加了那次研究人員會議，我們希望看到他們看到相同的結果 - 並且在他們的實踐中對 relacorilant 和 nab-paclitaxel 的女性有同樣的興奮。因此，我們現在期待非常積極的事情並繼續進行這項試驗。

My last question is again regarding your capital allocation strategy. With decent amount of cash, do you guys have any idea on the capital allocation?

我的最後一個問題還是關於你的資本配置策略。有了可觀的現金，你們對資金配置有什麼想法嗎？

Yes. Arthur, thank you and thank you, everyone, for all of your questions. Look, we have a cash producing business as we have for many, many years. And so the exciting thing is we have very good things in Corcept in which to invest it. Our clinical programs are advancing. And as you know it, as they succeed and go into later-stage studies, the programs become more expensive to do. Of course, success is a good thing. We're very glad to spend money in that way. And so we're really always taking a careful look at what -- where our money goes. It's not a secret we get solicited all the time from earnest investment bankers who have things that they would like us to invest in. We, of course, take a careful look at that. But at this point, we really believe that the best thing for us to invest in is the business that we're doing in Corcept. And so we will proceed in that way. Anything changes, I will let you know, of course. Thank you.

是的。亞瑟，謝謝你，謝謝大家提出的所有問題。看，我們有很多很多年的現金生產業務。所以令人興奮的是，我們在 Corcept 擁有非常好的東西可以投資。我們的臨床項目正在推進。正如你所知，隨著他們成功並進入後期研究，這些項目變得更加昂貴。當然，成功是好事。我們很高興以這種方式花錢。因此，我們真的一直在仔細研究我們的錢花在哪裡。這不是什麼秘密，我們總是從認真的投資銀行家那裡得到他們希望我們投資的東西。當然，我們會仔細研究。但在這一點上，我們真的相信對我們來說最好的投資是我們在 Corcept 所做的業務。因此，我們將以這種方式進行。如果有任何變化，我當然會通知您。謝謝。

And so I want to thank all of you for tuning in this quarter. Hopefully, big progress in the next 3 months and look forward to seeing you at that point in time. So good rest of the week. Thank you.

因此，我要感謝大家在本季度進行的調整。希望在接下來的 3 個月內取得重大進展，並期待在那個時候見到你。本週休息得很好。謝謝。

This will conclude today's conference. You may disconnect your lines at this time. Thank you for your participation.

今天的會議到此結束。此時您可以斷開線路。感謝您的參與。