Corcept Therapeutics Inc (CORT) 2024 Q4 法說會逐字稿

Thank you for standing by and welcome to Corcept Therapeutics conference call. (Operator Instructions)

感謝您的支持，歡迎參加 Corcept Therapeutics 電話會議。（操作員指令）

I would now like to hand the call over to Atabak Mokari, CFO. Please go ahead.

現在我想把電話交給財務長阿塔巴克‧莫卡里 (Atabak Mokari)。請繼續。

Hello, everyone, good afternoon and thank you for joining us. Today we issued a press release announcing our financial results for the fourth quarter and providing a corporate update. The 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 to Investors Past Events tab of our website.

大家好，下午好，感謝大家的參與。今天，我們發布了一份新聞稿，公佈了第四季度的財務業績並提供了公司最新動態。副本可在 corcept.com 上取得。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。我們網站的「投資者過去事件」標籤上將提供重播。

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 be materially different from those such statements expressed or imply.

本次電話會議中的陳述，除歷史事實陳述外，均為基於我們的計劃和預期的前瞻性陳述，這些陳述受風險和不確定性的影響，可能導致實際結果與此類陳述明示或暗示的結果存在重大差異。

The risks and uncertainties that may affect our forward-looking statements are described in our annual report on Form 10-K and our quarterly reports on Form 10-Q, all of which are available at the SEC's website. Please refer to those documents for additional information. We disclaim any intention or duty to update forward-looking statements.

可能影響我們前瞻性陳述的風險和不確定性在我們的 10-K 表年度報告和 10-Q 表季度報告中有所描述，所有這些報告均可在美國證券交易委員會的網站上查閱。請參閱這些文件以獲取更多資訊。我們不承擔更新前瞻性陳述的任何意圖或義務。

Our 2024 revenue was $675 million, an increase of 40% compared to the prior year. We expect our revenue growth to continue and have provided 2025 revenue guidance of $900 million to $950 million. Net income was $141 million for the full-year 2024, an increase of 33% compared to the prior year. Our cash and investments at December 31, 2024, were $603 million compared to $425 million at the end of the prior year.

我們的 2024 年營收為 6.75 億美元，比前一年成長 40%。我們預計營收將持續成長，並已給出 2025 年 9 億至 9.5 億美元收入預期。2024年全年淨收入為1.41億美元，較上年成長33%。截至 2024 年 12 月 31 日，我們的現金和投資為 6.03 億美元，而去年年底為 4.25 億美元。

In 2024, we acquired $38 million of our common stock pursuant to our stock repurchase program, the net exercise of stock options by Corcept employees, and the net vesting of restricted stock grants.

2024 年，我們根據股票回購計畫、Corcept 員工的股票選擇權淨行使以及限制性股票授予的淨歸屬，收購了價值 3,800 萬美元的普通股。

I will now turn the call over to Charlie Robb, our Chief Business Officer. Charlie.

現在我將電話轉給我們的商務長 Charlie Robb。查理。

Thanks, Atabak. I don't have much to report this quarter. As many of you know, in March 2018, we sued Teva to stop it from marketing a version of Korlym in violation of our patents. In December of last year, the trial court ruled against us.

謝謝，阿塔巴克。本季我沒有太多要報告的內容。大家可能都知道，2018 年 3 月，我們起訴了 Teva，阻止其銷售侵犯我們專利的 Korlym 版本。去年12月，初審法院對我們做出了不利的判決。

We have appealed that decision to the Federal Circuit Court of Appeals. Briefing in the matter is complete. Documents are available at the government's PACER website, and the next step is for the Federal Circuit to schedule oral argument, which is still not done. The earliest plausible date, given the Court's scheduling process, is for argument in May or later, the decision issuing three or four months after that.

我們已就該裁決向聯邦巡迴上訴法院提出上訴。有關此事的通報已經完成。相關文件可在政府的 PACER 網站上查閱，下一步是聯邦巡迴法院安排口頭辯論，但目前仍未完成。考慮到法院的日程安排，最早可能的日期是在五月或更晚進行辯論，並在此之後的三到四個月內發布判決。

No matter the [acute] schedule, if we prevail, Teva would lose FDA approval of its product and be required to withdraw it from the market until the expiration of our patents in 2037. As I've said before, we are eager to advance this appeal. We strongly believe that our position is correct, that the Federal Circuit will agree.

無論[急性]時間表如何，如果我們獲勝，Teva 將失去 FDA 對其產品的批准，並被要求將其從市場上撤出，直至 2037 年我們的專利到期。正如我以前所說，我們渴望推進這項呼籲。我們堅信我們的立場是正確的，聯邦巡迴法院也會同意。

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

現在我將把電話轉給我們的執行長喬貝拉諾夫 (Joe Belanoff)。喬。

Thank you, Charlie. And thank you, everyone, for joining us this afternoon.

謝謝你，查理。感謝大家今天下午加入我們。

2024 was a great year for Corcept. Each successive quarter of 2024 brought a record number of new Korlym prescribers and patients receiving Korlym. A rapidly increasing number of physicians now know that hypercortisolism is much more prevalent than was previously assumed. They are screening and treating many more patients than ever before. We are confident that our Cushing's syndrome business will continue to grow for years.

2024 年對 Corcept 來說是偉大的一年。2024 年每個季度，新的 Korlym 處方者和接受 Korlym 治療的患者數量都創下了歷史新高。現在，越來越多的醫生認識到皮質醇增多症比以前認為的更為普遍。他們篩檢和治療的患者比以前多得多。我們相信，我們的庫欣氏症候群業務將在未來幾年持續成長。

On December 30, we submitted a new drug application for our proprietary selective cortisol modulator, relacorilant. Our NDA is based on compelling results from the GRACE, GRADIENT, long-term extension, and Phase 2 relacorilant studies.

12月30日，我們為我們的專有選擇性皮質醇調節劑relacorilant提交了新藥申請。我們的 NDA 是基於 GRACE、GRADIENT、長期擴展和第 2 階段 relacorilant 研究的令人信服的結果。

Our pivotal GRACE Phase 3 study had two parts. In the trial's open-label phase, 152 patients with hypercortisolism and either hypertension, hyperglycemia, or both, proceed relacorilant for 22 weeks. Patients who met pre-specified improvements were given the opportunity to enter the trial's randomized double-blind withdrawal phase in which half of the patients continued to receive relacorilant and half received placebo for 12 weeks.

我們關鍵的 GRACE 第三階段研究分為兩部分。在試驗的開放標籤階段，152 名患有皮質醇增多症和高血壓、高血糖或兩者兼有的患者接受 22 週的 relacorilant 治療。達到預先指定的改善情況的患者有機會進入試驗的隨機雙盲停藥階段，其中一半患者繼續接受 relacorilant 治療，另一半患者接受安慰劑治療，為期 12 週。

Patients in the open-label phase of GRACE exhibited clinically meaningful and statistically significant improvements in hypertension, hyperglycemia, weight, lean muscle mass, waist circumference, cognition, Cushing's quality-of-life score, and other important clinical measures.

GRACE 開放標籤階段的患者在高血壓、高血糖、體重、肌肉質量、腰圍、認知、庫欣生活品質評分和其他重要臨床指標方面表現出具有臨床意義和統計學意義的改善。

In the randomized withdrawal phase of GRACE, which compared patients taking relacorilant to those taking placebo, relacorilant met its primary endpoint of retaining improved blood pressure control. The odds ratio, which was the study's primary endpoint, was 0.17 with a p-value of 0.02. An odds ratio of 0.17 means that patients taking relacorilant were six times more likely to maintain their blood-pressure response compared to those taking placebo.

在 GRACE 的隨機停藥階段，對服用 relacorilant 的患者和服用安慰劑的患者進行了比較，結果發現 relacorilant 達到了維持改善的血壓控制這一主要終點。作為研究的主要終點，比值比為 0.17，p 值為 0.02。 0.17 的優勢比意味著服用 relacorilant 的患者維持血壓反應的可能性是服用安慰劑的患者維持血壓反應的可能性的六倍。

In addition, patients who continued to take relacorilant in the randomized withdrawal phase of the study maintained or increased the broader range of other improvements in the signs and symptoms of hypercortisolism generated in the open-label phase of the study, while those who received placebo experienced a significant worsening of these signs and symptoms.

此外，在研究的隨機停藥階段繼續服用 relacorilant 的患者維持或增加了研究開放標籤階段產生的皮質醇增多症體徵和症狀的其他更廣泛的改善，而接受安慰劑的患者這些體徵和症狀顯著惡化。

Patients who completed the Phase 2 GRACE and GRADIENT studies were eligible to enter our long-term extension study where they continued to receive relacorilant or for patients in the placebo arm of gradient, receive relacorilant for the first time. Patients in the extension study have now taken relacorilant for up to six years. This group of 116 patients has exhibited additional clinically meaningful and durable cardio metabolic improvements.

完成第 2 期 GRACE 和 GRADIENT 研究的患者有資格參加我們的長期擴展研究，在該研究中他們將繼續接受 relacorilant 治療，或者對於梯度安慰劑組的患者，則首次接受 relacorilant 治療。參與延伸研究的患者目前已服用 relacorilant 長達六年。這群 116 名患者表現出了額外的具有臨床意義和持久的心臟代謝改善。

For instance, at week 24 of the study, I'm sorry, for instance, at month 24 of the study, they experienced a further reduction in their systolic blood pressure of 10 millimeters of mercury, a p-value of 0.012, and their diastolic blood pressure of 7.3 millimeters of mercury, a p-value of 0.016, compared to those measurements at the time they entered the extension study. Again, please remember these improvements were in addition to the improvements already exhibited in the Phase 2 GRACE or GRADIENT parent study.

例如，在研究的第 24 週，對不起，例如在研究的第 24 個月，與進入延伸研究時的測量值相比，他們的收縮壓進一步降低了 10 毫米汞柱，p 值為 0.012，舒張壓進一步降低了 7.3 毫米汞柱，p 值為 0.016。再次提醒，請記住這些改進是在第二階段 GRACE 或 GRADIENT 母研究中已經展現的改進的補充。

Relacorilant efficacy and safety, which I will discuss in a moment, is clearly evident when one follows the clinical course of patients as they enter the Phase 2 GRACE or GRADIENT study, complete that study, then participate in the long-term extension study. As a group, patients exhibit rapid improvement at the start of relacorilant therapy which maintained or continues to improve in the extension study.

我稍後會討論 Relacorilant 的療效和安全性，當人們追蹤患者的臨床病程，包括進入第 2 階段 GRACE 或 GRADIENT 研究、完成研究，然後參與長期擴展研究時，這一點是顯而易見的。作為一個群體，患者在開始 relacorilant 治療時表現出快速改善，並且在延伸研究中維持或繼續改善。

Patients as relacorilant treatment is interrupted, for instance, by being assigned to placebo in the GRACE randomized withdrawal phase, exhibit rapid improvements at the start of relacorilant therapy, then deterioration when switched to placebo, followed by a resumption of improvement when relacorilant is restarted.

例如，當雷拉科瑞林治療中斷時，患者在 GRACE 隨機停藥階段被分配接受安慰劑治療，在開始雷拉科瑞林治療時會迅速改善，但在轉為安慰劑治療時會惡化，隨後在重新開始使用雷拉科瑞林時會恢復改善。

Just as important as relacorilant's efficacy is its safety. Relacorilant has been well tolerated in all of its studies. The most common adverse events have been mild to moderate nausea, edema, pain in the extremities and back, and fatigue. These symptoms are consistent with the cortisol withdrawal that patients with hypercortisolism experience following a rapid reduction in their cortisol activity, whether due to surgery that removes an ACTH or cortisol-secreting tumor, or at the start of medical therapy.

relacorilant 的功效與它的安全性同樣重要。Relacorilant 在所有研究中均表現出良好的耐受性。最常見的不良事件是輕度至中度的噁心、水腫、四肢和背部疼痛以及疲勞。這些症狀與皮質醇增多症患者在皮質醇活性快速降低後出現的皮質醇戒斷症狀一致，無論是因為手術切除促腎上腺皮質激素或皮質醇分泌腫瘤，或是開始藥物治療時。

As expected, there have been no relacorilant-induced instances of hypokalemia, endometrial hypertrophy, or drug-induced vaginal bleeding. No cases of adrenal insufficiency, and no instances of QT prolongation. These adverse events can have serious health consequences. Each of the currently available medications for patients with Cushing's syndrome can cause one or more of them.

如預期的那樣，沒有出現由雷科瑞蘭引起的低血鉀、子宮內膜肥大或藥物引起的陰道出血的病例。沒有腎上腺功能不全的病例，也沒有出現 QT 延長的病例。這些不良事件可能會造成嚴重的健康後果。目前用於治療庫欣氏症候群的每一種藥物都可能導致一種或多種症狀。

As we advance relacorilant, we continue to work at increasing physician awareness and understanding of hypercortisolism. The prevalence phase of our catalyst study showed that one in four patients with difficult to control type 2 diabetes has hypercortisolism, a far higher rate than was assumed.

隨著我們推進 relacorilant 的發展，我們將繼續致力於提高醫生對皮質醇增多症的認識和理解。我們的催化研究的流行階段表明，四分之一的難以控制的 2 型糖尿病患者患有皮質醇增多症，這一比例遠高於假設。

In December, we completed CATALYST treatment phase, a double-blind placebo-controlled study in which 136 patients identified in CATALYST first phase as having hypercortisolism were randomized to receive either Korlym or placebo. The results were striking.

12 月，我們完成了 CATALYST 治療階段，這是一項雙盲安慰劑對照研究，其中 CATALYST 第一階段確定為患有皮質醇增多症的 136 名患者被隨機分配接受 Korlym 或安慰劑治療。結果是驚人的。

Patients who received Korlym exhibited a large reduction, 1.47%, in hemoglobin A1c, a key measure of glucose control, compared to a 0.15% decrease in patients who receive placebo, a p-value of less than 0.0001. The magnitude of reductions seen in the treatment arm is especially striking given that these patients were already receiving the best diabetes treatments available, including Ozempic and Mounjaro.

接受 Korlym 治療的患者的糖化血紅蛋白（血糖控制的關鍵指標）大幅下降了 1.47%，而接受安慰劑治療的患者則下降了 0.15%，p 值小於 0.0001。考慮到這些患者已經在接受最好的糖尿病治療，包括 Ozempic 和 Mounjaro，治療組中看到的減少幅度尤其驚人。

Another CATALYST finding is that hypercortisolism is even more common in patients who have cardiovascular disease in addition to diabetes. In a substantial group of patients in the catalyst study taking three or more medications to manage their hypertension, more than a third were found to have hypercortisolism.

CATALYST 的另一個發現是，除糖尿病外，患有心血管疾病的患者中皮質醇增多症更為常見。在催化劑研究中，有相當一部分患者服用三種或三種以上的藥物來控制高血壓，其中超過三分之一的患者被發現患有皮質醇增多症。

Later this quarter, we will start our newest study, MOMENTUM, which will help establish the prevalence of hypercortisolism in patients with resistant hypertension. We are confident that increased physician awareness and understanding of hypercortisolism combined with the advancement of relacorilant, a safe and effective therapy, will improve the lives of patients who struggle with the devastating impact of this disease. We are already seeing it.

本季度晚些時候，我們將啟動最新的研究 MOMENTUM，這將有助於確定難治性高血壓患者中皮質醇增多症的盛行率。我們相信，隨著醫生對皮質醇增多症的認識和理解不斷提高，加上安全有效的治療方法雷科瑞蘭的進步，將改善那些與這種疾病的毀滅性影響作鬥爭的患者的生活。我們已經看到了它。

As you know, we are also studying relacorilant as a treatment for types of cancer where cortisol plays a role. We expect data soon from our pivotal ROSELLA study. In the study, 381 women with platinum-resistant ovarian cancer have been randomized on a one-to-one basis to receive either nab-paclitaxel, probably the most effective chemotherapy currently prescribed to women with platinum-resistant disease or nab-paclitaxel plus relacorilant.

如您所知，我們也正在研究 relacorilant 作為治療皮質醇發揮作用的癌症類型的藥物。我們期待很快獲得關鍵的 ROSELLA 研究的數據。在研究中，381 名患有鉑耐藥性卵巢癌的女性被一對一隨機分配接受白蛋白結合型紫杉醇治療（這可能是目前針對鉑耐藥性卵巢癌女性最有效的化療方案）或白蛋白結合型紫杉醇加雷科瑞林治療。

For many of these patients, nab-paclitaxel or any chemotherapy has become much less useful than earlier in the course of treatment. Our expectation is that relacorilant will re-sensitize ovarian tumors to the effects of nab-paclitaxel by blunting the anti-apoptotic effects of cortisol activity.

對於許多此類患者來說，白蛋白結合型紫杉醇或任何化療的效果都已遠不如治療早期那麼明顯。我們期望 relacorilant 能夠透過減弱皮質醇活性的抗凋亡作用，重新使卵巢腫瘤對白蛋白紫杉醇的作用敏感。

ROSELLA's design tracks the design of our successful controlled Phase 2 trial. In that study, women 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.

ROSELLA 的設計遵循了我們成功的第 2 階段對照試驗的設計。在該研究中，與接受白蛋白結合型紫杉醇單藥治療的組別相比，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 治療的女性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。

Women in the relacorilant group also lived longer than those in the comparator arm. 29% of the patients who took intermittent relacorilant were alive two years after study start, compared to only 14% who took nab-paclitaxel alone. Importantly, the women who received relacorilant plus nab-paclitaxel experienced no additional side effect burden compared to those who received nab-paclitaxel monotherapy. We expect relacorilant to replicate these results.

接受 relacorilant 治療的女性的壽命也比對照組更長。間歇性服用 relacorilant 的患者在研究開始後兩年內存活率為 29%，而單獨服用白蛋白紫杉醇的患者存活率僅為 14%。重要的是，與接受白蛋白結合型紫杉醇單藥治療的女性相比，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。我們期望 relacorilant 能夠複製這些結果。

Enrollment in ROSELLA is complete. We anticipate having progression-free survival results by the end of this quarter. We are conducting ROSELLA in collaboration with leading clinicians from the Gynecologic Oncology Group, or GOG, in the United States and the European Network of Gynecologic Oncology Trials or NGOT Group in Europe and deeply appreciate their enthusiasm and support.

ROSELLA 的註冊已完成。我們預計本季末將獲得無惡化存活期的結果。我們正在與美國婦科腫瘤組（GOG）和歐洲婦科腫瘤試驗網絡（NGOT）組的領先臨床醫生合作 ROSELLA，並深深感謝他們的熱情和支持。

In anticipation of a successful outcome, we have established a stand-alone oncology division so we can move swiftly after the conclusion of ROSELLA to bring relacorilant to the women who can benefit from it. Positive results will also prompt us to explore relacorilant as a treatment for earlier stages of ovarian cancer and other solid tumors that express the glucocorticoid receptor.

為了取得成功的結果，我們建立了一個獨立的腫瘤科，以便我們能夠在 ROSELLA 試驗結束後迅速採取行動，為能夠從中受益的女性提供 relacorilant。正面的結果也將促使我們探索使用 relacorilant 來治療早期卵巢癌和其他表達糖皮質激素受體的實體腫瘤。

In addition to exploring cortisol's potential to re-sensitize tumors to chemotherapy, we are evaluating its potential to use in combination with androgen-deprivation therapy. 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 tumors switched to cortisol activity to stimulate growth.

除了探索皮質醇使腫瘤對化療重新敏感的潛力之外，我們還在評估其與雄性激素剝奪療法合併使用的潛力。皮質醇刺激是使用廣泛使用的雄性激素受體拮抗劑恩雜魯胺治療的前列腺癌患者最終出現疾病復發的主要原因。由於缺乏雄性激素刺激，他們的腫瘤轉而利用皮質醇活性來刺激生長。

Leading academic researchers and clinicians hypothesized that cortisol modulation can block this tumor escape route. Our collaborators at the University of Chicago are currently enrolling a randomized placebo-controlled Phase 2 trial of relacorilant plus enzalutamide in patients with early-stage prostate cancer before these patients have had an initial prostatectomy.

領先的學術研究人員和臨床醫生推測皮質醇調節可以阻斷這種腫瘤逃脫路徑。我們在芝加哥大學的合作者目前正在對早期前列腺癌患者進行一項隨機安慰劑對照的 2 期試驗，研究 relacorilant 合併恩雜魯胺的療效，這些患者尚未接受初次前列腺切除術。

Another possible role of cortisol receptor antagonists is in combination with immunotherapy. Because cortisol suppresses the immune system, it may blunt the effectiveness of cancer therapies intended to stimulate an immune response.

皮質醇受體拮抗劑的另一個可能的作用是與免疫療法結合。由於皮質醇會抑制免疫系統，它可能會削弱旨在刺激免疫反應的癌症療法的有效性。

Adding a cortisol modulator to immunotherapies, such as checkpoint inhibitors, may enhance their effectiveness. Following our Phase 1b trial in advanced adrenal cancer, we're deciding how best to investigate the utility of our compounds in combination with immunotherapies and other tumor types and earlier stages of cancer.

在免疫療法中添加皮質醇調節劑（如檢查點抑制劑）可能會增強其有效性。在對晚期腎上腺癌進行 1b 期試驗之後，我們正在決定如何最好地研究我們的化合物與免疫療法以及其他腫瘤類型和早期癌症階段相結合的效用。

One of our proprietary compounds, dazucorilant, readily crosses the blood-brain barrier and is a candidate for the treatment of neurologic disorders. Based on compelling data showing improved motor performance and reduced neural inflammation and muscular atrophy in a commonly used mouse model of ALS, we conducted a 249-patient randomized double-blind placebo-controlled Phase 2 trial of dazucorilant in that dire disease.

我們的專有化合物之一達祖科里蘭 (dazucorilant) 能夠輕易穿過血腦屏障，是治療神經系統疾病的候選藥物。基於令人信服的數據，該數據表明常用的 ALS 小鼠模型的運動能力得到改善、神經發炎和肌肉萎縮得到減少，我們對 249 名患者進行了一項隨機雙盲安慰劑對照的 2 期臨床試驗，以評估達珠可瑞蘭對這種可怕疾病的療效。

Unfortunately, patients who received dazucorilant did not show improvement in the ALS Functional Rating Scale, the study's primary endpoint. However, we did observe a statistically significant improvement in patient survival at week 24 of the study. No deaths occurred in the 83 patients who received 300 milligrams of dazucorilant, while 5 deaths occurred in the 82-patient placebo group, a p-value of 0.02.

不幸的是，接受達珠可瑞蘭治療的患者在 ALS 功能評估量表（研究的主要終點）中沒有表現出改善。然而，我們確實觀察到研究第 24 週患者存活率有統計學上顯著改善。在接受 300 毫克達珠可瑞林的 83 名患者中，無人死亡，而在接受安慰劑的 82 名患者中，有 5 人死亡，p 值為 0.02。

The open-label, long-term extension study is ongoing, and we expect to receive one-year overall survival results early in the second quarter. MASH, Metabolic Dysfunction-Associated Steatohepatitis, is a serious liver disorder that afflicts millions of patients in the United States alone. Cortisol activity plays a role in both the initial development and progression of the disease, and cortisol modulation may serve as a treatment.

開放標籤、長期擴展研究正在進行中，我們預計將在第二季初獲得一年總體生存率的結果。MASH，即代謝功能障礙相關脂肪性肝炎，是一種嚴重的肝臟疾病，光在美國就有數百萬患者患有此病。皮質醇活性在疾病的初始發展和進展中都發揮作用，皮質醇調節可以作為一種治療方法。

One of our proprietary molecules, miricorilant, has very potent activity in the liver. Our Phase 1b dose finding study of miricorilant found that patients who received 100 milligrams orally, just twice a week for 12 weeks, experienced a 30% reduction in liver fat and improvements in liver enzymes, markers of fibrosis, and key metabolic and lipid measures such as insulin resistance, serum triglycerides, and LDL. The compound was also very well tolerated, with none of the GI side effects which commonly arise in patients being treated for MASH.

我們的專有分子之一 miricorilant 在肝臟中具有非常強的活性。我們對米利可蘭進行的 1b 期劑量探索研究發現，患者每週口服兩次，每次 100 毫克，持續 12 週，肝臟脂肪減少了 30%，肝臟酶、纖維化標誌物以及胰島素抗性、血清三酸甘油酯和 LDL 等關鍵代謝和脂質指標均有所改善。該化合物的耐受性也非常好，沒有出現接受 MASH 治療的患者常見的胃腸道副作用。

Our randomized double-blind, placebo-controlled Phase 2b MONARCH study aims to expand on our encouraging Phase 1b results. MONARCH is enrolling two cohorts. In the first, 120 patients with biopsy-confirmed MASH, are randomized two to one to receive either 100 milligrams of miricorilant twice weekly or placebo for 48 weeks. The primary endpoint for this cohort is reduction in liver fat, with biopsy-confirmed MASH resolution and fibrosis improvement as key secondary endpoints. The second cohort has a planned enrollment of 75 patients with presumed MASH.

我們的隨機雙盲、安慰劑對照的 2b 期 MONARCH 研究旨在擴展我們令人鼓舞的 1b 期結果。MONARCH 正在招收兩批學生。首先，120 名經活檢確診為 MASH 的患者以二比一的比例隨機分配接受每週兩次 100 毫克米利可蘭或安慰劑治療，持續 48 週。此族群的主要終點是減少肝臟脂肪，以活檢確認的 MASH 消退和纖維化改善為關鍵次要終點。第二組計劃招募 75 名疑似 MASH 患者。

Patients in this cohort will be randomized two to one to receive either 100 milligrams miricorilant twice weekly for 6 weeks, followed by 200 milligrams of miricorilant twice weekly for 18 weeks, or placebo for the whole 24 weeks. In this cohort, the primary endpoint is also reduction in liver fat.

該組患者將以二比一的比例隨機分配接受以下治療：每週兩次服用 100 毫克的 Miricorilant，共 6 週；然後每週兩次服用 200 毫克的 Miricorilant，共 18 週；或整整 24 週服用安慰劑。在這個族群中，主要終點也是肝臟脂肪的減少。

As I said earlier, 2024 was a great year for Corcept. We expect even greater success for years to come. Physicians are becoming increasingly aware of hypercortisolism and its clinical consequences. We have seen that understanding translates to a long string of record quarters for new prescribers and patients receiving cortisol modulation therapy.

正如我之前所說，2024 年對 Corcept 來說是偉大的一年。我們期望在未來幾年取得更大的成功。醫生對皮質醇增多症及其臨床後果的認知越來越高。我們已經看到，這種理解轉化為新開處方人員和接受皮質醇調節療法的患者的一系列創紀錄的季度數據。

The catalyst results provide potent evidence to further advance the field by demonstrating that hypercortisolism is clearly much more common than previously assumed, and the treatment with a cortisol modulator is highly effective. Relacorilant's strong efficacy and safety profile positions it to become the new standard-of-care for patients with hypercortisolism. The positive results from our GRACE, GRADIENT, long-term extension and Phase 2 studies provide powerful support for successful relacorilant NDA and hypercortisolism.

催化劑結果透過證明皮質醇增多症顯然比以前假設的更為常見，並且使用皮質醇調節劑治療非常有效，為進一步推動該領域的發展提供了有力的證據。Relacorilant 的強大功效和安全性使其成為皮質醇增多症患者的新治療標準。我們的 GRACE、GRADIENT、長期擴展和第 2 階段研究的積極結果為成功治療 relacorilant NDA 和皮質醇增多症提供了有力的支持。

Meanwhile, our development programs continue to advance. We expect results from our pivotal ROSELLA study in ovarian cancer in just a few weeks. Our prostate cancer, ALS and MASH studies are ongoing, and we plan to initiate our momentum study this quarter.

同時，我們的發展計畫也持續進行。我們預計卵巢癌關鍵性 ROSELLA 研究的結果將在幾週內公佈。我們的前列腺癌、ALS 和 MASH 研究正在進行中，我們計劃本季啟動我們的動量研究。

We don't spend much time on these calls discussing the topic, but you should also know that we have a broad and active research portfolio, many proprietary selective cortisol modulators with potential, very distinctive clinical attributes. We are comprehensively evaluating these attributes and their therapeutic applications and will advance the most promising compounds to the clinic.

我們不會花太多時間在這些討論該主題的電話會議上，但您也應該知道，我們擁有廣泛而活躍的研究組合，許多專有的選擇性皮質醇調節劑具有潛在的、非常獨特的臨床屬性。我們正在全面評估這些屬性及其治療應用，並將最有前景的化合物推向臨床。

The problems caused by excess cortisol activity often have profoundly negative effects on patients. We are dedicated to finding new, more effective and safer treatments to help them.

皮質醇活動過多所引起的問題往往會對患者產生嚴重的負面影響。我們致力於尋找新的、更有效、更安全的治療方法來幫助他們。

Operator, let's proceed now to questions.

接線員，現在我們開始提問。

(Operator Instructions) David Amsellem, Piper Sandler.

（操作員指示）David Amsellem，Piper Sandler。

Thanks. So I just had a few on relacorilant. First, can you talk to when we should hear about NDA acceptance and what are your thoughts on the potential for an ad com here and is that something you're preparing for? So that's number one.

謝謝。所以我剛服用了一些 relacorilant。首先，您能否談談我們什麼時候應該聽到有關 NDA 接受的消息，以及您對這裡出現廣告委員會的可能性有何看法，以及您正在為此做準備嗎？這是第一點。

And then on the ROSELLA trial regarding the change and the endpoints or I guess elevating overall survival to a co-primary, I guess what I'm wondering is, how unusual is something like that at this sort of advanced stage of the trial, and what should we make of that, number one. And then number two, can you talk to statistical penalties associated with now having a co-primary endpoint instead of a single progression-free survival endpoint. Thank you.

然後關於 ROSELLA 試驗的變化和終點，或者我猜是將總體生存率提升為共同主要因素，我想知道的是，在試驗的這種後期階段出現這樣的情況有多麼不尋常，我們應該如何看待這一點，這是第一點。然後第二點，您能否談談現在擁有共同主要終點而不是單一無進展生存終點相關的統計懲罰。謝謝。

Hey David, thank you for the questions and I will turn them over to the best people to answer in the in the company, but let me just clarify one small thing before we start, which is that we don't have co-primary endpoints. We have dual primary endpoints. And that's a very big difference. And Bill Guyer, when he gets to it, will actually answer that question. But the first question about the relacorilant for Cushing syndrome NDA is, I think, best answered by Charlie Robb, our Chief Business Officer and Head of Regulatory.

嘿，戴維，謝謝你的提問，我會把這些問題交給公司裡最優秀的人來回答，但在開始之前，讓我先澄清一件小事，那就是我們沒有共同的主要終點。我們有雙重主要終點。這是一個很大的區別。當比爾蓋耶 (Bill Guyer) 談到這個問題時，他將會回答這個問題。但關於雷可瑞特治療庫欣氏症候群的 NDA 的第一個問題，我認為，最好由我們的商務長兼監管主管查理羅布來回答。

Sure, so yeah, thanks for the question. We submitted our NDA on December 30, as we put out in our press release, and the FDA has 60 days to sort of review it for acceptance, and that review is typically not a sort of a preview of their substantive review for drug approval. But it's -- I'm sure all the parts of the application are there that there's sufficient data for them to review and then they can go ahead and proceed.

當然，謝謝你的提問。正如我們在新聞稿中所說，我們於 12 月 30 日提交了 NDA，FDA 有 60 天的時間對其進行審核和接受，而且該審核通常不是對藥品批准實質審核的預覽。但是 - 我確信申請的所有部分都已存在，有足夠的數據供他們審查，然後他們就可以繼續進行。

And it's typical to receive during that 60-day period your various information requests from the agency for this data or that data where could they find this or that piece of information. And we've been receiving that very ordinary course routine correspondence and responding to it over the past 60 days. So the process has been moving exactly as we understood it to move and by statute or regulation, the FDA is due to give us a response within 60 days, so soon.

在這 60 天期間，通常會收到機構針對這些數據或那個數據的各種資訊請求，他們可以在哪裡找到這條或那條資訊。在過去的 60 天裡，我們一直在接收這些非常普通的例行信件並做出回應。所以整個流程完全按照我們的理解進行，根據法規，FDA 將在 60 天內盡快回覆我們。

Okay. And the second question, Charlie, about an ad com.

好的。第二個問題，查理，關於廣告公司。

We're not expecting an ad com. I mean, the past couple of medications for Cushing's syndrome were approved without them. Korlym was approved without one, and there's nothing about relacorilant's efficacy or safety that we think would require one. So we would be ready for one, of course. Recurred, it would not bother us, but we don't expect it.

我們不期待廣告。我的意思是，過去幾種治療庫欣氏症候群的藥物都是在沒有他們的情況下獲得批准的。Korlym 在沒有批准的情況下就獲得了批准，而且我們認為 relacorilant 的功效和安全性也不需要得到批准。因此我們當然會做好準備。再次發生，它不會打擾我們，但我們也不指望它。

Thank you, Charlie. And now I'd like to reintroduce you to Bill Guyer. Bill's our Chief Development Officer and in charge of everything related to relacorilant's development. Alright.

謝謝你，查理。現在我想再次向你們介紹比爾·蓋耶。Bill 是我們的首席開發官，負責與 relacorilant 開發相關的一切事務。好吧。

Thank you for that question related to ROSELLA. So first, before I answer that question, I'm really proud to share that we just reached the number of events for PFS by BICR. And that allows us to now work with every one of the 120 investigators to ensure that all the data for the 381 patients are entered into the database so we can then do our analysis and that's why we believe we will have our analysis done by the end of this quarter. So it's a very good positive thing for the ROSELLA study.

感謝您提出有關 ROSELLA 的問題。因此，首先，在我回答這個問題之前，我很自豪地告訴大家，我們剛剛達到了 BICR 的 PFS 活動數量。這樣，我們現在就可以與 120 名研究人員中的每一位合作，確保所有 381 名患者的數據都輸入資料庫，以便我們進行分析，這就是為什麼我們相信我們將在本季度末完成分析。所以這對 ROSELLA 研究來說是一件非常正面的事情。

Now specific to your question about the endpoints, we, how common is this? I'd say very common because we've been actively working with regulators, both the FDA and EMA related to the ROSELLA study. And based upon their comments, we came to an agreement to have a dual primary endpoint of PFS by BICR and OS to give us two shots on goal, so two chances for a positive study where we only need to meet one of them to have this be defined as a positive study.

現在具體到您關於端點的問題，我們，這種情況有多普遍？我認為這是十分常見的，因為我們一直在積極與 FDA 和 EMA 等監管機構合作參與 ROSELLA 研究。根據他們的意見，我們一致同意透過 BICR 和 OS 設定 PFS 雙重主要終點，從而給我們兩次機會，也就是進行一次陽性研究的兩次機會，我們只需滿足其中之一即可將其定義為陽性研究。

Now, with that change from a statistical point of view, the p-value for PFS by BICR is now 0.04 and for OS is 0.01 and we are adequately powered to detect the difference for both PFS and OS.

現在，從統計學的角度來看，有了這個變化，BICR 的 PFS p 值現在為 0.04，OS 的 p 值是 0.01，我們有足夠的能力來檢測 PFS 和 OS 的差異。

But let me come back to, dual primary endpoint. What does that mean? Basically for us to have a positive study, all we need is for one of them to be successful in order to declare the ROSELLA study a positive study. And once we meet that PFS by BICR endpoint, we really don't have to wait for OS even though we expect to meet that OS endpoint.

但讓我回到雙重主要終點的話題。這意味著什麼？基本上，為了進行積極的研究，我們只需要其中一個研究取得成功，即可宣布 ROSELLA 研究是一項積極的研究。一旦我們透過 BICR 端點滿足了 PFS，我們就實際上不必等待 OS，儘管我們希望滿足 OS 端點。

Of note also from a statistical point of view, once we meet our PFS endpoint, statistically we can recycle that alpha, where now for OS it no longer becomes 0.01, we can now elevate that to be a value of 0.05. Now, once we hit that PFS endpoint by the end of this quarter, we then plan to proceed with an NDA and MAA. So I see this change as a very positive for the program and very positive for women with platinum-resistant ovarian cancer.

值得注意的是，從統計學的角度來看，一旦我們達到 PFS 端點，從統計上講我們就可以回收該 alpha，現在對於 OS 它不再是 0.01，我們現在可以將其提升為 0.05 的值。現在，一旦我們在本季結束時達到 PFS 終點，我們就計劃繼續進行 NDA 和 MAA。所以我認為這個變化對於該計畫以及患有鉑耐藥性卵巢癌的女性來說都非常積極。

Thank you, Joe. Thank you, David.

謝謝你，喬。謝謝你，大衛。

Ramakanth Swayampakula, H.C. Wainwright.

拉瑪坎特·斯瓦亞姆帕庫拉，H.C.溫賴特。

Really appreciate taking questions. So couple of questions, one on ROSELLA and the other is CATALYST. So on ROSELLA, on this dual endpoints. So how does that work? So Bill just said that if we hit the PFS endpoint at the end of March we can file and go forward.

非常感謝您的提問。所以有幾個問題，一個關於 ROSELLA，一個關於 CATALYST。因此在 ROSELLA 上，有這個雙端點。那麼它是如何運作的呢？所以比爾剛才說，如果我們在三月底達到 PFS 終點，我們就可以提交申請並繼續前進。

However, if it turns negative, so what happens, and how long do you think we need to wait for the OS data to come through for filing. So that's question number one. And question number two on CATALYST, it's great to see continued increase. Of patients on Korlym and Korlym screening -- or screening patients for Cushing's syndrome, that's what I meant.

然而，如果結果變成負數，那麼會發生什麼情況呢？您認為我們需要等待多長時間才能獲得 OS 資料以供歸檔。這是第一個問題。關於 CATALYST 的第二個問題，很高興看到持續的成長。對於接受 Korlym 和 Korlym 篩檢的患者 - 或篩檢庫欣氏症候群的患者，這就是我的意思。

In in terms of utilization of the CATALYST data and the benefit of the CATALYST study, are you folks already seeing some of that, either in terms of screening patients, or also getting patients on the drug and, how would you start talking more about the entire CATALYST data, both the prevalence and the treatment.

就 CATALYST 數據的利用和 CATALYST 研究的益處而言，您是否已經看到了其中的一些，無論是在篩檢患者方面，還是在讓患者服用藥物方面，您如何開始更多地談論整個 CATALYST 數據，包括患病率和治療方法。

Thank you, RK. I think I caught your question. The first one is best answered by Bill Geyer again. Bill on the ROSELLA study.

謝謝你，RK。我想我已經理解你的問題了。第一個問題最好還是由 Bill Geyer 來回答。關於 ROSELLA 研究的法案。

So thanks for the question, RK. So one related to our endpoints, we don't plan to miss our PFS endpoints, so we do plan to hit that PFS endpoint and not have to wait for OS, as I stated before. But if we happen to miss that PFS endpoint, we do then have that second chance for a positive study with OS, and we would hit OS approximately one year from now.

感謝 RK 的提問。因此，與我們的端點相關的是，我們不打算錯過我們的 PFS 端點，所以我們確實計劃達到那個 PFS 端點，而不必等待 OS，正如我之前所說的那樣。但如果我們恰好錯過了 PFS 終點，那麼我們確實有第二次機會對 OS 進行積極的研究，並且我們將在大約一年後達到 OS。

Thank you, Bill. And Sean, you, in fact -- let me reintroduce Sean. Sean is the President of our Endocrinology Division, and was really responsible for all (inaudible). So Sean, why don't you take the crack at the CATALYST question?

謝謝你，比爾。肖恩，事實上，你——讓我重新介紹肖恩。Sean 是我們內分泌科的主任，負責所有（聽不清楚）。那麼肖恩，為什麼不嘗試回答 CATALYST 問題呢？

Okay, thanks for the question. So in terms of CATALYST, the question of are we starting to see an impact, I would say that we started to see a small impact. Recognize that there's always a delay between data generation, publication, guideline inclusion, and then medical practice changes. So when we really expect to see more of an impact in the second half of this year and in the years to come, and why do we expect to see that? And that's because more data is going to be released as the year goes on.

好的，謝謝你的提問。因此就 CATALYST 而言，我們是否開始看到影響，我想說我們開始看到一點影響。認識到數據生成、發布、指南納入以及醫療實踐改變之間總是存在延遲。那麼，我們是否真的預計會在今年下半年以及未來幾年看到更大的影響？我們為什麼預計會看到這種影響？這是因為隨著時間的推移，將會有更多數據被發布。

And so your question about how are we utilizing that data now we are we can speak to and when the data is published, we'll be able to more broadly communicate the complete story of both the prevalence as well as the treatment findings to physicians.

所以你的問題是我們現在如何利用這些數據，我們可以談論這些數據，當數據公佈時，我們將能夠更廣泛地向醫生傳達患病率和治療結果的完整情況。

Yeah, thank you.

是的，謝謝。

Joon Lee, Truist.

Joon Lee，Truist。

We're out in the quarter and thanks for taking the questions. This is Asim Rana on for Joon. Just back on the ROSELLA study, just want to understand a little bit better, like, was there something specifically that prompted the change in the endpoint? And did you have buy in from the FDA on the change? And then just on the 2025 revenue guidance, what was baked into that. Revenue was flat quarter to quarter, just wondering about that. Thank you.

本季我們已經結束，感謝您回答這些問題。我是 Asim Rana，為 Joon 主持節目。回顧 ROSELLA 研究，只是想更深入地了解一下，例如，是否有某些具體因素促使終點發生了變化？您是否已經獲得 FDA 的認可？那麼關於 2025 年的收入指引，其中包含了什麼呢？營收與上一季持平，對此我感到好奇。謝謝。

The first question, please, Bill, go ahead and why don't you answer that.

第一個問題，比爾，請你繼續說，為什麼不回答呢？

That. So again, for ROSELLA, what prompted the change is just again we've been actively discussing ROSELLA with the FDA and EMA and just through those collaborative conversations we came in an agreement in a very positive way to elevate OS as a dual primary endpoint to give us two chances for positive trial. And that really is what prompted it, just having a collaborative conversation with the FDA. So yes, they are in agreement with this change.

那。因此，對於 ROSELLA 而言，促使這一變化的原因是，我們一直在積極地與 FDA 和 EMA 討論 ROSELLA，並且透過這些協作對話，我們以非常積極的方式達成協議，將 OS 提升為雙重主要終點，從而給我們兩次進行陽性試驗的機會。這確實是促使我們這麼做的原因，只是與 FDA 進行合作對話。所以是的，他們同意這個改變。

Okay, and Sean, the second question please about guidance and overall strength of the business and in endocrinology.

好的，肖恩，第二個問題請問關於業務和內分泌學的指導和整體實力。

And I believe the question was around sort of the flat quarter. So we had a fantastic fourth quarter with a record number of patients and prescribers, and in fact, as Joe mentioned in his opening remarks, it was the best quarter we've ever had. However, our pharmacy partner had some operational challenges that impacted our Q4 revenues.

我相信問題在於季度持平的問題。因此，我們度過了一個非常棒的第四季度，患者和處方數量創下了歷史新高，事實上，正如喬在開場白中提到的，這是我們有史以來最好的一個季度。然而，我們的藥房合作夥伴在營運方面遇到了一些挑戰，影響了我們第四季度的收入。

So why did that happen? Well, more and more healthcare providers are recognizing that hypercortisolism is more prevalent than they once thought, and they're aggressively screened for it in their practices. And because of that, we experienced significant prescription growth in 2024, and the majority of that growth came in the second half of the year.

那為什麼會發生這種情況呢？越來越多的醫療保健提供者認識到皮質醇增多症比他們曾經認為的更為普遍，並且他們在實踐中積極地對其進行篩檢。正因為如此，我們在 2024 年經歷了處方藥數量的大幅增長，其中大部分增長發生在下半年。

Although growth is obviously fantastic, it temporarily overwhelmed the operational capabilities of our pharmacy vendor, and it took longer than expected to start patients on Korlym. Now we're confident that these issues have been identified and are being resolved, and we expect that the pharmacy will handle the demand of our business growth going forward. Things are moving in the right direction, and we have incorporated all of that into our guidance.

儘管成長顯然非常驚人，但它暫時壓倒了我們的藥房供應商的營運能力，並且患者開始使用 Korlym 的時間比預期的要長。現在我們相信這些問題已經被發現並正在解決，我們預計藥房將滿足我們未來業務成長的需求。事情正在朝著正確的方向發展，我們已將所有這些都納入我們的指導中。

So now in terms of the guidance, what's baked into that, and we take all factors into account. One thing that's emerged this year through CATALYST and through all the other studies that preceded it is that this patient population is understated. And the old historical epidata would say that there were 10,000 of these patients, and we now know that that number is larger and the FDA agrees with us on that.

因此，現在就指導而言，我們已經考慮到了所有因素。今年透過 CATALYST 以及之前所有其他研究發現的一件事是，這群患者被低估了。舊的歷史數據表明，這類患者有 10,000 名，但現在我們知道，這個數字要大得多，FDA 也同意我們的觀點。

So we're focused on unlocking the full potential of the market and see continued growth through the rest of this year. And I think more importantly, we see ourselves more confident than ever that we're on track to grow our hypercortisolism in business from $3 billion to $5 billion in annual revenues in three to 1 years. This market is expanding and it's expanding rapidly.

因此，我們專注於充分釋放市場的潛力，並實現今年剩餘時間的持續成長。我認為更重要的是，我們比以往任何時候都更有信心，我們預計在三到一年內將業務年收入從 30 億美元成長到 50 億美元。這個市場正在擴大，而且擴張得很快。

And I just like to underscore just a very important thing. It's now clear that there are many more patients with hypercortisol than were once presumed. And they are in many practices throughout the country, all large practices. And even more important, what CATALYST showed was that treating these patients with cortisol antagonists like Korlym or upcoming corolla is very effective in treating patients who often have not gotten any relief from other treatments.

我只是想強調一件很重要的事。現已清楚，患有皮質醇增多症的患者數量比曾經估計的要多得多。他們在全國各地的許多診所工作，都是大型診所。更重要的是，CATALYST 表明，使用 Korlym 或即將推出的 Corolla 等皮質醇拮抗劑治療這些患者非常有效，因為其他治療方法通常無法緩解患者的病情。

And so that's really a very beneficial thing. Now we've really taken this one step at a time. You saw the CATALYST treatment results at the end of last year. We are going to appear in major conferences throughout this year. These findings will be in substantial publications starting soon and then going through the rest of the year. But there's many data points that will actually get out there now.

這確實是一件非常有益的事情。現在我們確實已經一步步邁出了這一步。您在去年年底就看到了CATALYST的治療效果。我們今年將會出席各種大型會議。這些研究結果將很快在大量出版物中發表，並持續到今年年底。但現在其實已經有很多數據點可以被取得。

Medicine changes slowly over time. Sometimes to the detriment of patients, but as Sean has pointed out, we've really seen that change pick up in the second half of last year, and we think that is going to continue through this year, accelerating as the year goes along. So I think medicine's really changed by this work, and I think patient benefit will really be substantial as we go forward, and that's going to go on for an extended period of time.

醫學隨著時間的推移而緩慢改變。有時這會損害患者的利益，但正如肖恩所指出的，我們確實看到這種變化在去年下半年有所加速，而且我們認為這種變化將持續到今年，並且隨著時間的推移而加速。所以我認為這項研究確實改變了醫學，我認為隨著我們不斷前進，患者將受益匪淺，而且這種情況將會持續很長一段時間。

Okay, thank you.

好的，謝謝。

I don't see any more questions out there, so I'm going to call it up now. Thank you very much for all listening in. As you've heard on this call, this, probably will, you will be getting other important information from Corcept in the upcoming weeks and months, so please stay tuned. Thank you very much.

我沒有看到還有其他問題，所以我現在就開始提問。非常感謝大家的收聽。正如您在本次電話會議中聽到的那樣，您可能會在未來幾週和幾個月內從 Corcept 獲得其他重要信息，因此請繼續關注。非常感謝。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。