Corcept Therapeutics Inc (CORT) 2025 Q2 法說會逐字稿

Thank you for standing by, and welcome to the Corcept Therapeutics second quarter 2025 earnings conference call. (Operator Instructions) I would now like to hand the call over to Atabak Mokari, CFO. Please go ahead.

感謝您的支持，歡迎參加 Corcept Therapeutics 2025 年第二季財報電話會議。（操作員指示）現在我想將電話交給財務長 Atabak Mokari。請繼續。

Thank you. Hello, everyone. Good afternoon, and thank you for joining us. 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. Today's call is being recorded. A replay will be available at the Investors Past Events tab of our website.

謝謝。大家好。下午好，感謝您加入我們。今天，我們發布了一份新聞稿，宣布了第二季的財務表現並提供了公司最新動態。副本可在 corcept.com 取得。完整的財務表現將在我們向美國證券交易委員會 (SEC) 提交 10-Q 表時公佈。今天的通話正在錄音。重播將在我們網站的「投資者過往事件」標籤中提供。

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 be materially different from those such statements expressed or implied. 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.

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，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。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 表季度報告中均有描述，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 revenue in the second quarter of 2025 was $194.4 million, compared to $163.8 million in the prior year period. We have modified our 2025 revenue guidance to $850 million to $900 million. Net income was $35.1 million compared to $35.5 million in the second quarter of last year. Our cash and investments at June 30 were $515 million. Balance reflects our acquisition of $115 million of our common stock in the second quarter, pursuant to our stock repurchase program, the net exercise of stock options by Corcept employees and the net vesting of restricted stock grants.

我們 2025 年第二季的營收為 1.944 億美元，而去年同期的營收為 1.638 億美元。我們已將 2025 年的營收預期修改為 8.5 億至 9 億美元。淨收入為 3,510 萬美元，而去年第二季為 3,550 萬美元。截至 6 月 30 日，我們的現金和投資為 5.15 億美元。餘額反映了我們根據股票回購計劃在第二季度收購的價值 1.15 億美元的普通股、Corcept 員工淨行使股票選擇權以及限制性股票授予的淨歸屬。

I'll now turn the call over to Sean Maduck, President of our Endocrinology division. Sean?

現在我將把電話轉給我們內分泌科總裁 Sean Maduck。肖恩？

Thank you, Atabak. The endocrinology division had an excellent second quarter. For the sixth quarter in a row, we added a record number of new prescribers and new prescriptions, and there are a record number of patients on therapy. We shipped more tablets to patients than ever before, 49% more than the second quarter last year.

謝謝你，阿塔巴克。內分泌科第二季表現優異。連續六個季度，我們新增處方人員和新處方數量均創歷史新高，接受治療的患者數量也創歷史新高。我們向患者運送的藥片數量比以往任何時候都多，比去年第二季度增加了 49%。

Our financial results don't fully reflect the surge in demand. While our quarterly revenue growth was substantial, a $37 million increase over the first quarter, it should have been more. I discussed on the last call the insufficient capacity of our pharmacy vendor. Its capacity has increased in the second quarter but not as much as we expected and not enough to keep pace with our growth. Capacity will increase further in the second half of the year. We dispensed another record number of tablets in July with more increases to follow.

我們的財務表現並未完全反映需求的激增。雖然我們的季度收入成長顯著，比第一季增加了 3700 萬美元，但應該更多。我在上次通話中討論了我們的藥房供應商產能不足的問題。其產能在第二季有所增加，但沒有達到我們的預期，也不足以跟上我們的成長步伐。下半年運力將進一步增加。7 月我們分發的藥片數量再創歷史新高，接下來還會繼續增加。

We are also bringing online a second pharmacy. You will see the financial impact of this addition in the fourth quarter. Increased pharmacy capacity is important because I'm certain our growth is poised to accelerate. For many years, physicians only screened and treated the most physically obvious cases of hypercortisolism. In the last 15 years, many studies have been published supporting the identification and the treatment across a much broader spectrum of disease. The results of the CATALYST study confirm and build on these findings and will lead to much higher rates of screening and treatment of hypercortisolism. The study unequivocally shows that one in four patients with difficult to control diabetes have hypercortisolism and that treatment with a cortisol modulator dramatically improves many of their signs and symptoms. Even when all current medications including Ozempic and Mounjaro have not.

我們也將在網路上開設第二家藥局。您將在第四季度看到這項新增功能的財務影響。提高藥局容量非常重要，因為我確信我們的成長將會加速。多年來，醫生僅篩檢和治療身體症狀最明顯的皮質醇增多症病例。在過去的 15 年裡，已經發表了許多研究來支持​​更廣泛疾病的識別和治療。CATALYST 研究的結果證實並鞏固了這些發現，並將大大提高皮質醇增多症的篩檢和治療率。該研究明確表明，四分之一的難以控制的糖尿病患者患有皮質醇增多症，使用皮質醇調節劑治療可顯著改善他們的許多體徵和症狀。即使目前包括 Ozempic 和 Mounjaro 在內的所有藥物都沒有。

The CATALYST results are now published in Diabetes Care, the field-leading journal. This crucial information is now being absorbed by the broader physician community. We have amplified our efforts to educate physicians about hypercortisolism and we will ramp those activities even further. For example, we have increased the size of our sales force substantially and we'll continue to grow that team. We currently have 145 clinical specialists, up from 60 at the beginning of 2024, and our plan is to have 175 in place before year-end.

CATALYST 研究結果現已發表在該領域領先期刊《糖尿病護理》上。這一重要訊息現在正被更廣泛的醫生群體所吸收。我們已經加強了對醫生進行皮質醇增多症相關知識教育的力度，並且我們將進一步加強這些活動。例如，我們大幅增加了銷售隊伍的規模，並且我們將繼續擴大該團隊。我們目前擁有 145 名臨床專家，比 2024 年初的 60 名有所增加，我們的計劃是到年底前達到 175 名。

In the increasing context of a much better understanding of the prevalence of hypercortisolism, I'm eagerly anticipating relacorilant's approval. While Korlym is a great medication, relacorilant is even better. Relacorilant will be a terrific option for both prescribers and patients. I expect that almost all patients who are receiving Korlym will choose to transition to relacorilant and our growth will accelerate when it becomes available.

隨著人們對皮質醇增多症的流行程度的了解不斷加深，我熱切期待 relacorilant 獲得批准。雖然 Korlym 是一種很好的藥物，但 relacorilant 甚至更好。Relacorilant 對於處方醫生和患者來說都是一個絕佳的選擇。我預計，幾乎所有接受 Korlym 治療的患者都會選擇轉用 relacorilant，當藥物上市後，我們的成長將會加速。

I've never been more confident in both our current and future commercial growth and most important, our potential to help many more patients. I believe that in the next three to five years, relacorilant will generate $3 billion to $5 billion in annual revenue in hypercortisolism alone.

我對我們當前和未來的商業成長以及最重要的是我們幫助更多患者的潛力從未如此有信心。我相信，未來三到五年內，Relacorilant僅在皮質醇增多症領域就能帶來每年30億到50億美元的收入。

I'll now turn the call over to Charlie Robb, our Chief Business Officer. Charlie?

現在我將把電話轉給我們的商務長查理羅布 (Charlie Robb)。查理？

Thanks, Sean. At last, there is something to report regarding our patent litigation with Teva. Recall that in 2018, we sued Teva to keep it from marketing a generic version of Korlym in violation of our patents. Trial took place in September 2023. In December 2023, the District Court ruled against us. We appealed that decision to the Federal Circuit Court of Appeals and completed briefing in May 2024. A few weeks ago on July 7, the court heard oral argument in the case, the last step before issuing an opinion.

謝謝，肖恩。最後，有一些關於我們與 Teva 的專利訴訟的事情需要報告。回想一下，2018 年，我們起訴了 Teva，阻止其銷售侵犯我們專利的 Korlym 仿製藥。審判於2023年9月進行。2023年12月，地方法院對我們做出了不利判決。我們向聯邦巡迴上訴法院對該決定提出上訴，並於 2024 年 5 月完成了簡報。幾週前的7月7日，法院對此案進行了口頭辯論，這是發布意見前的最後一步。

The three-judge panel was led by Chief Judge Kimberly Moore. In 2021, Judge Moore was a member of the panel that rejected Teva's challenge to the validity of one of the patents we asserted a trial and wrote the opinion in our favor. I don't mean to suggest that Judge Moore's favorable decision in 2021 means she is more likely to rule for us now. The issues now are different. Judge Moore's decision in 2021 concerned the validity of our patent. She found it valid. The current argument concerns infringement will Teva infringe our patent an entirely different question.

該審判小組由三名法官組成，由首席法官金伯利摩爾 (Kimberly Moore) 領導。2021 年，摩爾法官作為陪審團成員駁回了 Teva 對我們在審判中主張的其中一項專利的有效性提出的質疑，並撰寫了對我們有利的意見。我並不是說摩爾法官在 2021 年做出的有利判決意味著她現在更有可能為我們做出判決。現在的問題不同了。摩爾法官於 2021 年做出的裁決涉及我們專利的有效性。她認為這是正確的。目前的爭論涉及侵權，Teva 是否會侵犯我們的專利是一個完全不同的問題。

My point is simply that Judge Moore is not new to this dispute. She understands our particular situation, not just the law in the abstract. For a party that believes, as we do, that the law and the facts are on its side, Judge Moore's patent expertise and depth of knowledge is a good thing. It is impossible to say when the Federal Circuit will issue its decision. Sometime in the next two to three months would be a reasonable guess. If we prevail in this case, Teva will lose FDA approval of its product until the expiration of our patents in 2037. As I've said before, we are eager to resolve this appeal. We strongly believe our position is correct and that the Federal Circuit will agree.

我的觀點很簡單，摩爾法官對這爭議並不陌生。她了解我們的具體情況，而不僅僅是抽象的法律。對於像我們一樣相信法律和事實站在自己這邊的一方來說，摩爾法官的專利專業知識和深厚的知識是一件好事。目前還無法確定聯邦巡迴法院何時會做出裁決。未來兩到三個月內某個時間是一個合理的猜測。如果我們在此案中勝訴，Teva 將失去 FDA 對其產品的批准，直到 2037 年我們的專利到期為止。正如我之前所說，我們渴望解決這個上訴問題。我們堅信我們的立場是正確的，聯邦巡迴法院也會同意我們的立場。

I will now turn the call over to Dr. 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博士。喬？

Thank you, Charlie, and thank you, everyone, for joining us this afternoon. After many important years building this point, the next era at Corcept is about to arrive. As we have always known, cortisol enters all organs of the body and modulating its effects has the potential to be useful in many diseases. We now have two new drug applications, NDAs in progress in hypercortisolism and platinum-resistant ovarian cancer. The results of the studies leading to these NDAs were published in major medical journals in the second quarter. We have also generated promising results in our ALS and liver disease programs.

謝謝你，查理，也謝謝大家今天下午加入我們。經過多年的重要努力，Corcept 的下一個時代即將到來。眾所周知，皮質醇會進入身體的所有器官，調節其作用可能對許多疾病有用。我們現在有兩種新藥申請，分別是針對皮質醇增多症和鉑抗藥性卵巢癌的 NDA。這些 NDA 的研究結果於第二季發表在主要醫學期刊上。我們的 ALS 和肝病計畫也取得了可喜的成果。

In short, we have established a new medical platform useful to many patients suffering from serious disorders. The results of our CATALYST trial, the largest and most rigorous trial ever conducted to assess the prevalence and treatment of hypercortisolism in patients with difficult to control type II diabetes will transform medicine. The prevalence phase of CATALYST demonstrated that one in four of these refractory patients has hypercortisolism, a far higher rate than was previously assumed. In April, these results were published in Diabetes Care, a leading peer-reviewed journal of the American Diabetes Association.

簡而言之，我們建立了一個新的醫療平台，對許多患有嚴重疾病的患者有幫助。我們的 CATALYST 試驗是迄今為止規模最大、最嚴格的試驗，旨在評估難以控制的 II 型糖尿病患者中皮質醇增多症的盛行率和治療方法，其結果將改變醫學。CATALYST 的流行階段表明，這些難治性患者中有四分之一患有皮質醇增多症，這一比例遠高於先前的假設。今年4月，這些結果發表在美國糖尿病協會領先的同行評審期刊《糖尿病照護》。

Patients who enrolled in the treatment phase of CATALYST had uncontrolled diabetes despite receiving multiple glucose-lowering therapies, including the most potent GLP-1 agonists. Even so, in only 24 weeks, patients treated with Korlym experienced a 1.47% reduction in hemoglobin A1c compared to just 0.15% for those receiving placebo. The p-value of this result was less than 0.001.

參與 CATALYST 治療階段的患者儘管接受了多種降血糖療法（包括最有效的 GLP-1 激動劑），但糖尿病仍未得到控制。即便如此，僅僅 24 週後，接受 Korlym 治療的患者的糖化血紅蛋白就降低了 1.47%，而接受安慰劑治療的患者僅降低了 0.15%。此結果的p值小於0.001。

In addition, patients saw significant improvements in a range of additional endpoints, including reductions in body weight and waist circumference. Notably, patients CATALYST experienced these improvements even as they decreased or entirely discontinued their other glucose-lowering medications. The results were presented last month during a keynote session at the American Diabetes Association's 85th Scientific session with a simultaneous publication in diabetes care.

此外，患者在一系列其他終點方面也看到了顯著改善，包括體重和腰圍的減少。值得注意的是，即使減少或完全停止服用其他降血糖藥物，CATALYST 患者仍能感受到這些改善。這項研究結果於上個月在美國糖尿病協會第 85 屆科學會議的主題演講中公佈，並同時在《糖尿病護理雜誌》上發表。

CATALYST findings will substantially accelerate the screening and treatment of hypercortisolism. Leading diabetologists are advocating for their quick integration into treatment guidelines. Concurrent with the rapidly increasing physician awareness of hypercortisolism, relacorilant is approaching approval. Its PDUFA date in hypercortisolism is December 30. Relacorilant's NDA is supported by our pivotal Phase III GRACE trial as well as our GRADIENT long-term extension and Phase II trials. In these studies, patients treated with relacorilant experienced clinically meaningful improvements across all of the signs and symptoms of hypercortisolism including hypertension, hyperglycemia, weight, lean muscle mass, waist circumference, cognition, Cushing's quality of life score and other important clinical measures.

CATALYST 的研究結果將大大加速皮質醇增多症的篩檢和治療。領先的糖尿病專家正在倡導將其迅速納入治療指南。隨著醫生對皮質醇增多症的認識迅速提高，relacorilant 也即將獲得批准。其皮質醇增多症的 PDUFA 日期為 12 月 30 日。Relacorilant 的 NDA 得到了我們關鍵的 III 期 GRACE 試驗以及 GRADIENT 長期擴展和 II 期試驗的支持。在這些研究中，接受 relacorilant 治療的患者在皮質醇增多症的所有體徵和症狀方面均獲得了具有臨床意義的改善，包括高血壓、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的臨床指標。

These benefits were observed consistently and durably with improvements emerging early and continuing or deepening over time. Equally noteworthy are relacorilant safety characteristics. Relacorilant has been well tolerated in all of its studies. Importantly, no instances of drug-induced hypokalemia, endometrial hypertrophy, vaginal bleeding, adrenaline efficiency or QT prolongation have been observed. These adverse events can have serious health consequences and are associated with one or more of the currently available therapies. We expect that relacorilant's efficacy and safety will make it a new standard of care for hypercortisolism. As awareness of the disease and its ability to be treated grows, many more patients with hypercortisolism will be identified and Corcept is well positioned to help them.

這些好處是持續且持久的，改善很早就出現了，並且隨著時間的推移而持續或深化。同樣值得注意的是 relacorilant 安全特性。Relacorilant 在所有研究中均表現出良好的耐受性。重要的是，沒有觀察到藥物引起的低血鉀、子宮內膜肥大、陰道出血、腎上腺素效率或 QT 延長的情況。這些不良事件可能會造成嚴重的健康後果，並與目前可用的一種或多種療法有關。我們期望 relacorilant 的有效性和安全性將使其成為治療皮質醇增多症的新標準。隨著人們對該疾病及其治療能力的認識不斷提高，將會有更多的皮質醇增多症患者被發現，而 Corcept 可以很好地幫助他們。

As Sean said earlier, we are confident that our Cushing's syndrome business will continue to grow for years. Since the founding of Corcept, our research and development has been built on the hypothesis that cortisol modulation can be a powerful therapeutic mechanism in many serious disorders. The success of our pivotal ROSELLA trial in platinum-resistant ovarian cancer provides clear evidence that cortisol receptor antagonism has substantial potential in oncology. In ROSELLA, 381 women with platinum-resistant ovarian cancer were randomized 1:1 to receive either nab-paclitaxel, the most potent chemotherapy currently available for these patients, or nab-paclitaxel plus relacorilant.

正如肖恩之前所說，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。自 Corcept 成立以來，我們的研究和開發一直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。我們在鉑類抗藥性卵巢癌中的關鍵 ROSELLA 試驗的成功提供了明確的證據，證明皮質醇受體拮抗劑在腫瘤學中具有巨大的潛力。在 ROSELLA 研究中，381 名患有鉑類抗藥性卵巢癌的女性以 1:1 的比例隨機分配接受白蛋白結合型紫杉醇治療（這是目前針對此類患者最有效的化療方案）或白蛋白結合型紫杉醇合併雷科瑞林治療。

In these patients, the efficacy of nab-paclitaxel and chemotherapy in general, had diminished markedly. Our expectation was that relacorilant would blunt the anti-apoptotic effect of cortisol activity, thereby resensitizing ovarian tumors to the effective nab-paclitaxel. This expectation was resoundingly confirmed. ROSELLA trial met its primary endpoint of improved progression-free survival. Patients treated with relacorilant plus nab-paclitaxel experienced a 30% reduction in the risk of disease progression compared to patients treated with nab-paclitaxel alone, the hazard ratio of 0.7 and a p-value of 0.008.

對於這些患者來說，白蛋白結合型紫杉醇和化療的療效總體上已經明顯降低。我們的預期是，relacorilant 會減弱皮質醇活性的抗凋亡作用，使卵巢腫瘤對有效的白蛋白結合型紫杉醇重新敏感。這一預期得到了有力的證實。ROSELLA 試驗達到了改善無惡化存活期的主要終點。與單獨使用白蛋白結合型紫杉醇治療的患者相比，使用 relacorilant 合併白蛋白結合型紫杉醇治療的患者病情進展風險降低了 30%，風險比為 0.7，p 值為 0.008。

At 12 months, 25% of patients in the relacorilant arm remained progression-free almost twice as many as in the control arm. In the interim evaluation of overall survival, patients treated with relacorilant plus nab-paclitaxel had a median overall survival of 16 months compared to 11.5 months for those receiving nab-paclitaxel alone. The hazard ratio was 0.69, with a p-value of 0.01. These results were obtained without the need for a biomarker diagnostic test, a prerequisite of many currently available treatments and were even observed in patients with particularly poor prognosis such as patients who had received multiple lines of prior therapy and patients who have progressed while on standard of care therapy.

12 個月後，relacorilant 組有 25% 的患者保持無惡化狀態，幾乎是對照組的兩倍。在總存活期的中期評估中，接受 relacorilant 合併白蛋白結合型紫杉醇治療的患者的中位總存活期為 16 個月，而單獨接受白蛋白結合型紫杉醇治療的患者的中位總存活期為 11.5 個月。風險比為0.69，p值為0.01。這些結果無需生物標記診斷測試（這是許多現有治療方法的先決條件）即可獲得，甚至在預後特別差的患者中也觀察到了這一點，例如接受過多線治療的患者和在接受標準治療期間病情進展的患者。

Relacorilant plus nab-paclitaxel was well tolerated. The adverse events observed were consistent with the known safety profile of nab-paclitaxel. Because patients in the relacorilant plus nab-paclitaxel arm fared better than those in the nab-paclitaxel monotherapy arm, they had an approximately 30% longer duration of nab-paclitaxel therapy. When adjusted for treatment duration, the safety profile of relacorilant plus nab-paclitaxel was very similar to that of nab-paclitaxel alone.

Relacorilant 加白蛋白結合型紫杉醇的耐受性良好。觀察到的不良事件與已知的白蛋白結合型紫杉醇的安全性一致。由於 relacorilant 合併白蛋白結合型紫杉醇治療組患者的療效優於白蛋白結合型紫杉醇單一治療組患者，因此他們的白蛋白結合型紫杉醇治療時間延長了約 30%。當調整治療持續時間時，relacorilant 加白蛋白紫杉醇的安全性與單獨使用白蛋白紫杉醇的安全性非常相似。

The results of the ROSELLA study were presented last month in an oral late-breaker session at the American Society of Clinical Oncology's Annual Meeting and simultaneously published in the Lancet, the general medical journal with the world's highest impact factor. Physicians have responded with great enthusiasm to these results, improving progression-free survival and overall survival without an added safety burden positions relacorilant to become the new standard of care for patients with platinum-resistant ovarian cancer.

ROSELLA 研究結果於上個月在美國臨床腫瘤學會年會的口頭最新進展會議上公佈，並同時發表在全球影響因子最高的綜合醫學雜誌《柳葉刀》上。醫生們對這些結果反應非常積極，在沒有增加安全負擔的情況下改善無進展生存期和總體生存期使 relacorilant 成為鉑耐藥卵巢癌患者的新治療標準。

We submitted relacorilant's NDA in platinum-resistant ovarian cancer earlier this month and will submit a marketing authorization application in Europe soon. In anticipation of a successful regulatory outcome, we have made substantial progress in establishing a dedicated oncology division. We are prepared to move swiftly to bring relacorilant plus nab-paclitaxel to the women who can benefit from it once it is approved.

我們本月初提交了 relacorilant 在鉑類抗藥性卵巢癌治療中的 NDA，並將很快在歐洲提交上市許可申請。為了獲得成功的監管結果，我們在建立專門的腫瘤科方面取得了實質進展。一旦獲得批准，我們準備迅速採取行動，將 relacorilant 和白蛋白結合型紫杉醇帶給女性，讓她們從中受益。

ROSELLA established relacorilant's therapeutic value in a highly challenging stage of ovarian cancer. These results support relacorilant's potentially broader utility, including in earlier stages of ovarian cancer and in other solid tumors. The first step in advancing this strategy is with our BELLA trial, which is enrolling briskly and will test whether combining relacorilant plus nab-paclitaxel with bevacizumab offers an additional effective option for patients with platinum-resistant ovarian cancer. We will soon begin additional studies.

ROSELLA 確立了 relacorilant 在卵巢癌高度挑戰階段的治療價值。這些結果支持了 relacorilant 潛在的更廣泛的用途，包括在卵巢癌早期階段和其他實體腫瘤中。推動這項策略的第一步是我們的 BELLA 試驗，該試驗正在快速招募患者，並將測試將 relacorilant 加白蛋白結合型紫杉醇與貝伐單抗相結合是否為鉑耐藥性卵巢癌患者提供了額外的有效選擇。我們很快將開始進一步的研究。

In addition to exploring cortisol receptors antagonisms potential to resensitize tumors to chemotherapy, we are evaluating its use in combination with androgen deprivation therapy in prostate cancer. Cortisol stimulation is a major reason why patients with prostate cancer treated with the widely prescribed androgen receptor antagonist enzalutamide, eventually experience resurgent disease. Deprived of androgen stimulation, their tumor switched to cortisol activity to stimulate growth. Our collaborators at the University of Chicago are currently enrolling a randomized placebo-controlled Phase II trial of relacorilant plus enzalutamide in patients with early-stage prostate cancer to determine if cortisol receptor antagonism can block this tumor escape route.

除了探討皮質醇受體拮抗劑使腫瘤對化療重新敏感的潛力外，我們還在評估其與前列腺癌雄激素剝奪療法的聯合使用。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病情復發的主要原因。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。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雷拉科林特聯合恩雜魯胺的隨機安慰劑對照 II 期試驗，以確定皮質醇受體拮抗劑是否可以阻斷這種腫瘤逃脫途徑。

Another possible role of cortisol receptor antagonism is in combination with immunotherapy. Because cortisol suppresses the immune system, it may blunt the effectiveness of cancer therapies intended to stimulate an immune response. Adding a cortisol receptor antagonist to immunotherapies such as checkpoint inhibitors, may enhance their effectiveness. Following our Phase Ib trial in advanced adrenal cancer, we are deciding how best to investigate the utility of our compounds in combination with immunotherapies in other tumor types and earlier stages of cancer.

皮質醇受體拮抗劑的另一個可能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。在檢查點抑制劑等免疫療法中添加皮質醇受體拮抗劑可能會增強其有效性。在對晚期腎上腺腺癌進行 Ib 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聯合治療其他腫瘤類型和早期癌症的效用。

Our proprietary compound, dazucorilant, is an excellent candidate for the treatment of neurologic disorders. While our DAZALS trial, a 249 patient randomized double-blind placebo-controlled Phase II trial of dazucorilant in patients with ALS did not meet its primary endpoint of improvement in the ALS functional rating scale. The data did suggest a powerful benefit, prevention of early death. One year after entering DAZALS, patients who received 300 milligrams of dazucorilant daily exhibited an 84% reduction in death -- the risk of death compared to patients who only received placebo.

我們的專有化合物達珠可瑞蘭 (dazucorilant) 是治療神經系統疾病的絕佳候選藥物。而我們的 DAZALS 試驗（一項針對 249 名 ALS 患者進行的隨機雙盲安慰劑對照的 dazucorilant II 期試驗）並未達到其 ALS 功能評定量表改善的主要終點。數據確實顯示了其強大的益處，即預防早逝。參加 DAZALS 治療一年後，每天服用 300 毫克達珠可利特的患者的死亡風險與僅接受安慰劑治療的患者相比降低了 84%。

The p-value for this finding was 0.0009. The benefit emerged in the first 24 weeks of the study during which time five patients randomized to placebo had died compared to no deaths in the group that received 300 milligrams of dazucorilant.

此結果的p值為0.0009。益處在研究的前24週顯現出來，在此期間，隨機分配到安慰劑組的患者中有5人死亡，而接受300毫克達珠可利特的組則無人死亡。

An important point to know about the survival benefit is that it emerges from the start of treatment when patients still retain considerable function and quality of life. The common understanding of ALS is that it progresses by degrading motor function until patients are completely paralyzed with death following. While this is true in some cases, many more patients die long before then from conditions such as pneumonia that they would have survived had it not been for their ALS. It is these early deaths that patients receiving dazucorilant experience less frequently. We presented these notable findings last month at the European Network to Cure ALS Annual Meeting. We are engaged with regulatory authorities to determine the fastest path for advancing dazucorilant.

關於生存益處，需要了解的一點是，它從治療開始時就已出現，此時患者仍然保留著相當多的功能和生活品質。對 ALS 的普遍理解是，它會逐漸降低運動功能，直到患者完全癱瘓並死亡。雖然在某些情況下確實如此，但更多的患者早在那時就死於肺炎等疾病，如果沒有患上 ALS，他們本可以活下來。接受達珠可利特治療的患者較少出現過早死亡的情況。我們上個月在歐洲治療 ALS 網路年會上公佈了這些顯著的發現。我們正在與監管機構合作，以確定推進 dazucorilant 的最快途徑。

NASH metabolic dysfunction associated steatohepatitis is a serious liver disorder that afflicts millions of patients in the United States and globally. Cortisol activity plays a role in both the initial development and progression of the disease, and cortisol modulation may serve as a treatment. Our proprietary molecules, miricorilant has very potent activity in the liver.

NASH 代謝功能障礙相關脂肪性肝炎是一種嚴重的肝臟疾病，困擾著美國和全球數百萬名患者。皮質醇活動在疾病的初始發展和進展中都起著作用，皮質醇調節可以作為一種治療方法。我們的專有分子 miricorilant 在肝臟中具有非常強的活性。

Our phase Ib study showed that miricorilant rapidly reduced liver fat and improved other markers of liver health, fibrosis and metabolism. Miricorilant was also very well tolerated without the GI side effects commonly seen in patients being treated for MASH. Our randomized double-blind, placebo-controlled Phase IIb MONARCH study aims to expand on our encouraging Phase Ib results. MONARCH has two cohorts. The first cohort of patients has biopsy-confirmed MASH. The second cohort consists of patients with presumed MASH. Enrollment in MONARCH will be completed in the next few weeks and results will be available late next year.

我們的 Ib 期研究表明，miricorilant 可快速減少肝臟脂肪並改善肝臟健康、纖維化和代謝的其他標記。Miricorilant 的耐受性也很好，沒有接受 MASH 治療的患者常見的胃腸道副作用。我們的隨機雙盲、安慰劑對照 IIb 期 MONARCH 研究旨在擴展我們令人鼓舞的 Ib 期結果。MONARCH 有兩個隊伍。第一批患者經切片確診為 MASH。第二組由疑似患有 MASH 的患者組成。MONARCH 的註冊將在未來幾週內完成，結果將於明年稍後公佈。

As I said earlier, this is the dawn of a new era at Corcept. Let me reiterate our important developments. The CATALYST trial, the largest and most rigorous of its kind proves that there are far more patients with hypercortisolism than was previously believed, and that cortisol modulation is very beneficial for these patients. With results from both phases of CATALYST now published, leading physicians are recognizing the significance of the findings and joining us in raising awareness. We are certain that this will lead to many more patients being screened, identified and properly treated.

正如我之前所說，這是 Corcept 新時代的曙光。讓我重申我們的重要進展。CATALYST 試驗是同類試驗中規模最大、最嚴格的，它證明患有皮質醇增多症的患者數量遠遠超過先前的認識，且皮質醇調節對這些患者非常有益。隨著 CATALYST 兩個階段結果的公佈，領先的醫生認識到了這些發現的重要性並加入我們，提高人們的認識。我們確信這將使更多的患者得到篩檢、識別和適當治療。

While Korlym's effectiveness in treating hypercortisolism is well established, relacorilant is a substantial advance. Its strong efficacy and safety positions it to become a new standard of care. We expect its approval on hypercortisolism by the end of this year, and are eager to make it available immediately thereafter. The ROSELLA trial validated cortisol receptors antagonisms utility in oncology. Relacorilant delivered a clear clinical benefit with no added side effect safety burden in patients with platinum-resistant ovarian cancer treated with nab-paclitaxel.

雖然 Korlym 在治療皮質醇增多症方面的有效性已得到充分證實，但 relacorilant 是一項重大進步。其強大的功效和安全性使其成為新的護理標準。我們預計該藥物將在今年年底前獲準用於治療皮質醇增多症，並渴望在獲準後立即投入使用。ROSELLA 試驗驗證了皮質醇受體拮抗劑在腫瘤學中的效用。對於接受白蛋白結合型紫杉醇治療的鉑金抗藥性卵巢癌患者，Relacorilant 具有明顯的臨床益處，且沒有增加副作用安全負擔。

We expect relacorilant approval in oncology next year. We are working to unlock its potential in earlier stages of cancer, other tumor types and in combination with other anticancer agents. In addition, we are actively exploring the potential of cortisol modulation to treat a broad range of additional severe diseases, including neurologic and hepatic diseases. We continue to discover and develop proprietary selective cortisol modulators with likely very distinctive clinical attributes and are advancing the most promising to the clinic. Cortisol modulation's vast potential to help many patients is just beginning to unfold. It is a very exciting time at Corcept.

我們預計 relacorilant 將於明年獲準用於腫瘤學領域。我們正在努力釋放其在癌症早期階段、其他腫瘤類型以及與其他抗癌藥物聯合治療中的潛力。此外，我們正在積極探索皮質醇調節治療多種其他嚴重疾病（包括神經系統疾病和肝臟疾病）的潛力。我們繼續發現和開發具有非常獨特臨床屬性的專有選擇性皮質醇調節劑，並將最有前景的藥物推向臨床。皮質醇調節對幫助眾多患者的巨大潛力才剛開始顯現。這是 Corcept 非常令人興奮的時刻。

Operator, let's proceed to questions.

接線員，我們繼續提問。

(Operator Instructions)

（操作員指示）

David Amsellem, Piper Sandler.

大衛·阿姆塞勒姆、派珀·桑德勒。

I have a few Korlym specific questions. First, actually, I want to ask you about the authorized generic, what portion of your business came from the authorized generic during the quarter relative to 1Q? And can you talk about the pricing headwind in percentage terms year-over-year? So that's number one.

我有幾個關於 Korlym 的具體問題。首先，實際上，我想問您有關授權仿製藥的問題，相對於第一季度，本季度您的業務有多少部分來自授權仿製藥？您能否談談與去年同期相比定價逆風的百分比？這是第一點。

Number two is just with the supply chain issues and fulfillment issues, can you talk about the disconnect between prescriptions that are actually written and prescriptions that are actually filled. In other words, what portion of prescriptions that were actually written were pull-through to actually -- to actual filled prescriptions. And did that gap narrow in the second quarter? In other words, were the fulfillment issues for lack of a better term, less bad in 2Q versus 1Q? So I'll stop there on that.

第二，僅就供應鏈問題和履行問題而言，您能否談談實際開出的處方和實際填寫的處方之間的脫節。換句話說，實際開出的處方中有多少部分實際上是實際填寫的處方。那麼第二季差距縮小了嗎？換句話說，缺乏更好的術語來描述履行問題，第二季度的履行問題是否比第一季的履行問題更嚴重？我就講到這裡。

All right. Thank you, David. I think we understand exactly what you're asking. And I just want to pass it over to Sean Maduck. Sean as you know, is the President of our Endocrinology division, and these are things that are on display every day.

好的。謝謝你，大衛。我想我們完全明白您的要求。我只想把它交給 Sean Maduck。如你所知，肖恩是我們內分泌科的總裁，這些都是每天都會展示的東西。

David, thanks for the question. I'm going to touch on the AG question first. So if you recall on the last call, we had stated that just over 50% of our business had transitioned over to the AG. Over the course of the second quarter, we're now at about two-third of our business. So we've seen sort of that transition slow. We expect over the next six months, maybe a little bit more movement but we have seen some stabilization. So a percentage point here or there. But I think we'll settle at the end of the year around two-third of our business.

大衛，謝謝你的提問。我將首先談一下 AG 問題。因此，如果您還記得上次電話會議，我們曾表示，超過 50% 的業務已轉移給 AG。在第二季度，我們的業務已完成約三分之二。因此，我們看到這種轉變進展緩慢。我們預計未來六個月可能會出現更多變動，但我們已經看到了一些穩定性。所以這裡或那裡有一個百分點。但我認為我們將在今年年底完成約三分之二的業務。

In terms of the pricing question you asked, I mean, when we launched our AG in June of last year, we launched it at a 12% discount to Korlym's list price but you know that's a starting point with payers, right? Payers negotiate. And so it varies by payer contract. But when you look on average across all of our contracts, it's about a 30% discount to Korlym's list price.

關於您詢問的定價問題，我的意思是，當我們在去年 6 月推出 AG 時，我們以比 Korlym 標價低 12% 的價格推出它，但您知道這是付款人的起點，對嗎？付款人協商。因此它因付款人合約而異。但如果你平均看一下我們所有的合同，你會發現它比 Korlym 的標價低了 30% 左右。

Okay. So now in terms of your question, before I talk about the supply chain specifics, I do want to spend a couple of minutes talking about the health of our business, and then I'll talk specifically about the pharmacy. So we had an excellent quarter. I mean, we grew our volume by 49% year-over-year, and it could have been more. And I'll talk about that in a minute when I talk about the pharmacy. So why is our business growing and why is it so strong?

好的。所以現在就您的問題而言，在我談論供應鏈細節之前，我確實想花幾分鐘談談我們業務的健康狀況，然後我將具體談論藥房。因此，我們度過了一個出色的季度。我的意思是，我們的銷量比去年同期成長了 49%，而且本來還可以更多。當我談論藥房時，我會談論這一點。那麼，為什麼我們的業務正在成長並且如此強勁？

Well, the first point is the market is expanding. There has been a significant amount of data over the last couple of years, most notably CATALYST, and Joe referenced this in his comments. But it has made a real splash. Physicians are way more interested today than they were a couple of years ago. It's expanding the conversation. We're getting in front of them. And a real-life example of this, we monitor this, of course. A real-life example is at the Endo conference about three weeks ago here in San Francisco, the Endo Society Conference, we had a presentation on the CATALYST data in a room that had seats for about 225 people. 500 people attended that session. There were more people standing than sitting. And that would have been absolutely unheard of two years ago.

嗯，第一點是市場正在擴大。過去幾年出現了大量數據，其中最引人注目的是 CATALYST，Joe 在他的評論中提到了這一點。但它確實引起了轟動。如今，醫生對此的興趣比幾年前大得多。它正在擴大對話範圍。我們正在趕在他們前面。這是一個現實生活中的例子，我們當然會監控它。一個現實生活中的例子是大約三週前在舊金山舉行的 Endo 會議，即 Endo 學會會議，我們在一個可容納約 225 人的房間裡就 CATALYST 數據進行了演示。有 500 人參加了那次會議。站著的人比坐著的人多。這在兩年前是絕對是聞所未聞的。

And here we are today. That's driving, again, more conversation, more outreach with Corcept, and we're working hard to make sure that information is disseminated broadly so that physicians are actively looking for these patients, which is exactly what they're doing. There's more screening going on and more patients are being diagnosed. And because of that, our Korlym prescriptions have increased significantly over the last few months. And that's just going to continue. We expect -- we're just really at the start of that.

今天我們就在這裡。這再次推動了與 Corcept 的更多對話和更多推廣，我們正在努力確保訊息廣泛傳播，以便醫生積極尋找這些患者，這正是他們正在做的事情。正在進行的篩檢越來越多，越來越多的患者得到診斷。正因為如此，我們的 Korlym 處方量在過去幾個月大幅增加。而這種情況還會持續下去。我們預計——我們才剛開始這項工作。

And to put that in perspective, I mean we now have days that we get more Korlym new patient prescriptions than we used to get in a month. And again, it's just the start of that. We're just at the start of CATALYST. We think that's going to accelerate through the rest of the year and really lay a very strong foundation for relacorilant, which, of course, we're very excited for, which is going to come at the beginning of next year.

從這個角度來看，我的意思是，我們現在每天收到的 Korlym 新患者處方比過去一個月收到的還要多。再說一遍，這只是一個開始。我們才剛開始 CATALYST。我們認為，這一增長將在今年剩餘時間內加速，並為 relacorilant 奠定堅實的基礎，當然，我們對此感到非常興奮，該產品將於明年年初上市。

So in terms of your specific question around the pharmacy, I mean, in short, the pharmacy just did not meet our expectations. They improved in Q2. They got closer to where we were but not all the way. And the best way that I think I can explain this is to use a bit of an analogy. And bear with me for a second, I'm going to talk about cars for a second here. But assume that a few months ago, Optime was operating in a car that was driving about 60 miles per hour. Of course, that was in a car that was driving 70 miles per hour, and we needed them to catch up, not just catch up but sustain their speed to support our business.

因此，關於您關於藥房的具體問題，簡而言之，藥房沒有達到我們的期望。他們在第二季度有所進步。他們離我們越來越近了，但還沒有完全到達。我認為解釋這一點的最好方法就是使用一個比喻。請稍等片刻，我將在這裡談論一下汽車。但假設幾個月前，Optime 正在一輛時速約 60 英里的汽車上運行。當然，那是在一輛時速 70 英里的汽車裡，我們需要他們趕上來，不僅要趕上，還要保持速度來支持我們的業務。

They improved. They got closer to where we were but that's the operative word. Where we were is not where we are today. This is not a static business. Our business continues to grow and to accelerate. And we're now driving at 80, 85 miles per hour. So you asked specifically, as the gap narrowed, I mean, there's been such a flood of volume has continued to create a problem. And when you look to quantify that, that probably had about a $15 million impact on our second quarter results.

他們進步了。他們離我們的位置越來越近了，但這就是關鍵字。我們過去的情況與現在的情況不同。這不是一成不變的業務。我們的業務持續成長並加速。我們現在的行駛速度是每小時 80 到 85 英里。所以你具體問到，隨著差距縮小，我的意思是，如此大量的湧入持續造成了問題。當你量化這一點時，這可能對我們第二季的業績產生了約 1500 萬美元的影響。

So heading into the second half of the year, where are we? Well, we saw improvement. We expect that we're going to continue to see improvement in the third quarter, and we expect that we're going to continue to see even more improvement with our current pharmacy vendors or through the end of the year. But as we said in our opening statements, we're also onboarding a second pharmacy, which we're very excited about that will support our business both today and in the future with relacorilant, and we expect them to start contributing in the fourth quarter.

那麼，進入下半年，我們的處境如何？嗯，我們看到了進步。我們預計第三季的情況將繼續改善，並且我們預計到今年年底，我們現有的藥房供應商的情況將繼續改善。但正如我們在開場白中所說的那樣，我們還將引入第二家藥局，我們對此感到非常興奮，它將透過 relacorilant 支持我們現在和未來的業務，我們預計他們將在第四季度開始做出貢獻。

Joon Lee, Truist Securities.

Joon Lee，Truist Securities。

Regarding the $3 billion to $5 billion in peak sales opportunity for your hypercortisolism franchise that mentioned on the call, how much of that is coming from Korlym. And given the pending approval of relacorilant, how important is it to you that you win the -- on the ongoing appeals process with Teva? And I have a follow-up.

關於您在電話中提到的皮質醇增多症特許經營權的 30 億至 50 億美元的高峰銷售機會，其中有多少來自 Korlym。鑑於 relacorilant 即將獲得批准，在與 Teva 的上訴過程中獲勝對您來說有多重要？我還有一個後續問題。

I'll be glad to take that question. I want to reiterate a few of the points we've made already, but they're important, which is that relacorilant is a better medication. Korlym works extremely well, but relacorilant has very, very tangible advantages. And we think that relacorilant ultimately will entirely replace Korlym. There's also another point, which is that we think that we have penetrated a very small percentage of the overall potential market. There are many more patients with hypercortisolism to be treated that have ever been treated.

我很樂意回答這個問題。我想重申我們已經提出過的幾點，但它們很重要，那就是 relacorilant 是一種更好的藥物。Korlym 效果非常好，但 relacorilant 具有非常非常明顯的優勢。我們認為 relacorilant 最終將完全取代 Korlym。還有一點，我們認為我們已經滲透到整體潛在市場的一小部分。有待治療的皮質醇增多症患者比已經接受治療的患者多得多。

So our longer-term estimates when you referenced $3 billion to $5 billion certainly takes into account relacorilant, really has, in some sense, very little impact from at that point. But maybe just another important point to make, which we don't often say out loud is we don't think $3 billion to $5 billion are peak sales. I mean, $3 billion to $5 billion is what we think we can do in three to five years. But we think that this market is substantially larger than that, and we will have a substantial piece of that substantial mark.

因此，當您提到 30 億至 50 億美元時，我們的長期估計肯定考慮到了 relacorilant，從某種意義上說，從那時起，它的影響確實很小。但也許還有另一個重要的觀點，我們不常大聲說出來，那就是我們不認​​為 30 億到 50 億美元是銷售額的高峰。我的意思是，我們認為我們可以在三到五年內實現 30 億到 50 億美元的目標。但我們認為這個市場比這大得多，而且我們將佔據相當大的份額。

The other part of the question was around the patent.

問題的另一部分涉及專利。

Please repeat the other part of the question.

請重複問題的另一部分。

The other part of this question was winning the patent case impact of $3 billion to $5 billion.

這個問題的另一部分是贏得專利案的影響為 30 億至 50 億美元。

Winning the case does not impact the $3 billion to $5 billion, what impacts the pie because that's a Korlym patent case. We think that, of course, maybe everyone in our situation, we think we have a very good reason to win the patent case. But in some sense, that's looking through the rearview mirror. This is really about the advancement of relacorilant and its future growth.

贏得這場官司並不會影響 30 億到 50 億美元的收入，但這會影響整體收入，因為這是 Korlym 專利案。我們認為，當然，也許處於我們這種情況的每個人都認為我們有充分的理由贏得這場專利案。但從某種意義上來說，這就像透過後視鏡看東西一樣。這實際上與 relacorilant 的進步及其未來發展有關。

Understood. I had a quick follow-up. When will the second pharmacy come online? And at what point would you consider activating more distributors because isn't that sort of the plan for relacorilant, which you think and we think will have a broader adoption?

明白了。我進行了快速跟進。第二家藥局什麼時候上線？在什麼時候您會考慮啟動更多的經銷商，因為這不正是 relacorilant 的計劃嗎？您和我們都認為它會得到更廣泛的採用？

Yes. I'm going to pass you back to Sean for that answer.

是的。我將把答案轉交給肖恩。

Yes. So thanks for the question. So the onboarding of that pharmacy is in process, and we expect them to attribute sort of value and have an impact in the fourth quarter. We -- to your second question and comment, we had always planned to expand this network for relacorilant. And it really was the surge of demand that we saw with Korlym that caused us to sort of pull that back a quarter, and that's why we're accelerating this.

是的。感謝您的提問。因此，該藥局的入職工作正在進行中，我們預計它們將在第四季度產生一定價值並產生影響。對於您的第二個問題和評論，我們一直計劃擴展 relacorilant 的網絡。正是我們看到的 Korlym 需求的激增，導致我們將其推遲了一個季度，這就是我們加快這一進程的原因。

But to your question about will we expand further, it's something that we're looking into. I mean, we're being very thoughtful as we set up our current structure with the addition of the second pharmacy, so that we have the ability to add to that should we see fit. So something we're always looking at, and we will do that if we see fit into the future.

但對於您問到的我們是否會進一步擴張的問題，我們正在研究。我的意思是，我們在建立現有結構並增加第二家藥局時非常謹慎，這樣我們就有能力在適當的情況下進行擴建。因此，我們一直在關注某些事情，如果我們認為未來合適，我們就會去做。

Swayampakula Ramakanth, HCW.

Swayampakula Ramakanth，HCW。

A couple of quick questions. So you have initiated the CATALYST today a couple of years ago. So you were -- even before study, you kind of confident that the way the data was going to come from CATALYST because you are always aware that the patients are not being identified as much as they should be. Having -- where I'm leading to that question is, what kind of -- what steps were missed in not having a second pharmacy onboard earlier in time because you knew that there was going to be an upsurge of this demand from the market, especially once the data comes out.

幾個簡單的問題。所以你們幾年前的今天就啟動了 CATALYST。所以，甚至在研究之前，您就很有信心數據將來自 CATALYST，因為您始終意識到患者的識別並不充分。我想問的是，為什麼沒有儘早開設第二家藥局，因為你知道市場需求會激增，尤其是在數據公佈之後。

And the other question is, with the expectation that the second pharmacy is going to come on board in the fourth quarter, why are we still pulling down the guidance? Does that mean there is something else that we are not understanding?

另一個問題是，既然預計第二家藥局將在第四季開業，為什麼我們還要下調預期？這是否意味著還有其他一些我們尚未理解的事情？

Okay. Let me see if I can order those questions. I think I'll try the first question, and I'll give Sean, the second question. First question is, why didn't we get it a second pharmacy sooner? And I'll be honest, hindsight 2020, good question. And I think that part of it was that sort of a combination of things to build from the CATALYST information has gone much more rapidly than we thought. And frankly, we thought that our original pharmacy would be able to keep up and live and learn. The demand has been even greater than we thought it was, and our current pharmacy wasn't able to stay with it. So Sean, the second question?

好的。讓我看看是否可以整理這些問題。我想我會嘗試回答第一個問題，然後我會把第二個問題交給肖恩。第一個問題是，為什麼我們沒有早點去第二家藥局？說實話，回想起來，2020 年，這是一個好問題。我認為，部分原因是，從 CATALYST 資訊中建構的各種事物的組合比我們想像的要快得多。坦白說，我們認為我們原來的藥房能夠跟上並生存和學習。需求比我們想像的還要大，我們目前的藥局無法滿足需求。那麼肖恩，第二個問題是什麼？

Yes. So the second question was, given the second pharmacy coming on and adding value in the fourth quarter, why did we change? So look, we take all factors into account when we look at our range. And one of the challenges is as I mentioned earlier, the impact of the patient delays, and that's what's happening here. It's taking longer for patients to a medication. It was a $15 million impact in the second quarter but that doesn't just go away. I mean, that sort of flows through the model. It takes longer to start patients, it takes longer to titrate up. And when you do sort of the math throughout the course of the year, it has the potential to be a larger impact than that $15 million. So that was the main driver.

是的。所以第二個問題是，鑑於第二家藥局在第四季開業並增加價值，我們為什麼要改變？所以，當我們考慮我們的範圍時，我們會考慮所有因素。正如我之前提到的，其中一個挑戰是患者延誤的影響，而這就是這裡發生的情況。患者接受藥物治療的時間較長。第二季的影響為 1500 萬美元，但這種影響不會就此消失。我的意思是，這種流程貫穿整個模型。開始治療患者需要更長的時間，滴定治療也需要更長的時間。如果你對全年的情況進行計算，你會發現它的影響可能會比 1500 萬美元更大。這就是主要驅動因素。

On the BELLA study, what's the time line for that? And also in terms of evaluating relacorilant in other solid tumors, is that basically the prostate cancer that you're talking about? Or is there any additional solid tumors that you would be looking at?

關於 BELLA 研究，其時間表是什麼？另外，在評估 relacorilant 在其他實體瘤中的作用方面，您所說的基本上就是前列腺癌嗎？還是您正在研究其他實體腫瘤？

Thank you very much for asking that, RK and that gives me an opportunity to reintroduce you to Bill Guyer, who is our Chief Development Officer. This is all his domain, and I'll let him get started.

非常感謝您提出這個問題，RK，這讓我有機會再次向您介紹我們的首席開發長 Bill Guyer。這都是他的領域，我會讓他開始的。

Great. Thanks, RK, for that question. So for the BELLA trial, enrollment has gone better than expected. I mean, our Phase II and a Phase III study is using relacorilant plus nab-paclitaxel enrolled also very quickly. This is going even faster than that. And so we will have this study enrolled by the end of this year, and therefore, we'll see results about a year after that. And when it comes to other solid tumors, I'll comment on there. Yes, prostate cancer is one of those but we're thinking much bigger than that because our vision for is to establish its role as an agent capable of synergizing with many other agents to enhance efficacy with no added toxicity in many different tumor types.

偉大的。謝謝 RK 提出這個問題。因此，對於 BELLA 試驗而言，入組情況比預期的要好。我的意思是，我們的 II 期和 III 期研究正在使用 relacorilant 加 nab-paclitaxel，招募工作也進展得非常快。這比那還要快。因此，我們將在今年年底前完成這項研究，大約一年後我們就能看到結果。當談到其他實體腫瘤時，我會對此發表評論。是的，前列腺癌就是其中之一，但我們的設想遠不止於此，因為我們的願景是確立其作為一種能夠與許多其他藥物協同作用的藥物的作用，以增強療效，並且不會在許多不同類型的腫瘤中增加毒性。

Now in the near term, we're going to study and move forward in looking at moving up in the treatment paradigm in ovarian cancer, and we'll be expanding in across gynecological oncology spaces like endometrial cancer and cervical cancer. And when we look at other solid tumors, I'll give you more details in the coming weeks by the end of this year but we're going to be also looking at other selective glucocorticoid receptor antagonist in combination with other agents like immunotherapy. So finalizing our oncology development plans is ongoing. We've got a great plan, and we will give you the details very soon.

現在，在短期內，我們將研究並推動卵巢癌治療模式的改進，並將擴展到子宮內膜癌和子宮頸癌等婦科腫瘤領域。當我們研究其他實體瘤時，我將在今年年底的未來幾週內向您提供更多細節，但我們還將研究其他選擇性糖皮質激素受體拮抗劑與其他藥物（如免疫療法）的聯合應用。因此，我們正在最終確定腫瘤學發展計劃。我們有一個很棒的計劃，我們很快就會向你們公佈詳細資訊。

And the last question from me, Joe, is, yes, on the conversation with the FDA on the ALS front. Did you already have that conversation with the FDA? And if not, what's the strategy there? Do you think as soon as you get the for another study, would you be doing another study? Or would you want to utilize whatever data you have to file?

喬，我的最後一個問題是關於與 FDA 就 ALS 問題的對話。你已經和 FDA 進行過對話了嗎？如果不是，那麼策略是什麼？您是否認為，一旦您獲得另一項研究的資格，您就會進行另一項研究？或者您想利用您必須歸檔的任何資料？

I think we heard and understand your question. And I'm going to pass you back to Charlie Robb. Charlie is our Chief Business Officer, and he oversees all of our regulatory interactions.

我想我們聽到並理解了您的問題。我要把你交還給查理羅伯。查理是我們的首席商務官，他負責監督我們所有的監管互動。

So we've not yet had the meeting. We said in the last call that we were going to contact the regulators immediately, which we did. And so we have a meeting scheduled later in August to discuss the path forward. And one of the options is certainly an approval based on the data we have now, that would be an unusual thing no one should count on but that's one we're putting that forward as a very serious possibility and subject to a conversation with the regulators.

所以我們還沒有舉行會議。我們在上次電話會議上表示，我們將立即聯繫監管機構，我們也確實這麼做了。因此，我們計劃在八月下旬舉行一次會議，討論未來的道路。其中一個選擇當然是根據我們目前掌握的數據進行批准，這將是一件不尋常的事情，沒有人應該指望它，但這是我們提出的一個非常嚴肅的可能性，並且需要與監管機構進行對話。

The other, of course, would be the optimum design of a confirmatory trial, which we would expect to conduct in any event, whatever the use of the Phase II data we have now turns out to be. So when we have that meeting and settle on our plans, we will let folks know about it but that's sort of the state of play right now.

當然，另一個是確認性試驗的最佳設計，無論我們現在擁有的第二階段數據的用途如何，我們都希望進行該試驗。因此，當我們召開會議並確定計劃時，我們會讓人們知道，但這就是目前的狀況。

Edward Nash, Canaccord Genuity.

愛德華‧納許 (Edward Nash)，Canaccord Genuity。

This is Xinwei An for Edwards. My questions are -- my questions are focused on the BELLA for platinum resistance ovarian cancer side of things. So the first part of my question is maybe -- could you help us understand BELLA positioning in the current treatment paradigm? Because you mentioned that it is the expectation that BELLA can help treat earlier stages of ovarian cancer. So does this also include patients that are not platinum-resistant?

我是愛德華茲的 Xinwei An。我的問題是——我的問題集中在 BELLA 治療鉑類抗藥性卵巢癌。所以我的問題的第一部分可能是——您能幫助我們了解 BELLA 在當前治療模式中的定位嗎？因為您提到，BELLA 有望幫助治療早期卵巢癌。那麼這是否也包括對鉑類無抗藥性的患者？

Yes. I think I caught most of your questions. And if we've missed anything, ask us and we'll clarify. But I'd like to introduce everyone to Roberto Vieira, who is President of our Oncology division, and he is all over this material. So please Roberto start. And if we've missed something, let us know.

是的。我想我回答了你的大部分問題。如果我們遺漏了任何內容，請詢問我們，我們會澄清。但我想向大家介紹我們腫瘤科的總裁羅伯托·維埃拉 (Roberto Vieira)，他對此非常了解。那麼請羅伯托開始。如果我們遺漏了什麼，請告訴我們。

Thank you for the question. So let me just start by saying that since we have presented our bid at ASCO, we have had the opportunity to speak. We've got a wide range of key opinion leaders in the field. We have also ran a comprehensive market research getting input from a large number of treating physicians across all major US regions. And the feedback on the ROSELLA result has been very, very encouraging to us. It speaks really to the strength of the data we have. So we are very confident about our path to market leadership, specifically in platinum-resistant ovarian cancer, and we believe relacorilant has the potential to deliver over $1 billion in long-term revenues.

謝謝你的提問。首先我要說的是，自從我們在 ASCO 上提出我們的競標以來，我們就有機會發言。我們在該領域擁有眾多關鍵意見領袖。我們也進行了全面的市場調查，並獲得了美國各主要地區的大量主治醫生的意見。ROSELLA 結果的回饋對我們來說非常令人鼓舞。這確實證明了我們擁有的數據的可靠性。因此，我們對成為市場領導者的道路充滿信心，特別是在鉑類抗藥性卵巢癌領域，我們相信 relacorilant 有潛力帶來超過 10 億美元的長期收入。

Now specifically to your question about positioning, the ROSELLA trial data supports relacorilant as a flexible option that can be used in multiple lines of therapy both before and after biomarker specific agent by ELAHERE, for example, which was very much corroborated by the market research I alluded to before.

現在具體回答您關於定位的問題，ROSELLA 試驗數據支持 relacorilant 作為一種靈活的選擇，例如，它可以在 ELAHERE 的生物標誌物特異性藥物之前和之後用於多種治療，這與我之前提到的市場研究非常吻合。

Okay. Yes. That's very helpful. So I guess, since you already mentioned maybe squeezing in a follow-up over here that your discussion with physicians, are you finding that they will tend to use relacorilant in the earlier stage patients were rather to preserve or sort of preserve the drug for late-stage patients because of its safety profile, which is positive? And for late-stage patients, usually, there's not that many options out there?

好的。是的。這非常有幫助。所以我想，既然您已經提到也許會在這裡擠出時間進行後續討論，那麼您是否發現他們傾向於在早期患者中使用 Relacorilant，而不是為了保留或某種程度上保留該藥物用於晚期患者，因為它的安全性，這是積極的嗎？對於晚期患者來說，通常沒有那麼多選擇嗎？

Please, Roberto.

請吧，羅伯托。

Yes. So our data, as you know, looks into patients with multiple lines of therapy early and late. So it supports flexible utilization, as I mentioned before. But as we speak to physicians about this, it's not just the efficacy. They're actually look into the safety as a very strong attribute of this regimen and the as well, it's also something that really appeals to them. So we see significant utilization getting earlier lines of platinum resistance ovarian cancer and potential for utilization even earlier as the data evolves.

是的。因此，如您所知，我們的數據調查了早期和晚期接受多種治療的患者。因此，正如我之前提到的，它支援靈活利用。但當我們與醫生談論此事時，我們關注的不僅僅是療效。他們實際上將安全性視為該療法的一個非常重要的屬性，而且它也確實對他們有吸引力。因此，我們看到鉑類抗藥性卵巢癌的早期治療利用率顯著提高，隨著數據的發展，利用率甚至有可能更早。

And I would just like to add to that one point that Bill alluded to. I think that our trial in platinum-resistant ovarian cancer ROSELLA enrolled twice as fast as any other study, which has ever been completed in that disease. And I think that the current study, the BELLA study, we really have to keep up. I mean, the enrollment is really so brisk there.

我只想補充一下比爾提到的一點。我認為，我們針對鉑類抗藥性卵巢癌 ROSELLA 的試驗的招募速度是該疾病領域中任何其他研究的兩倍。我認為我們必須跟上目前的研究，即 BELLA 研究。我的意思是，那裡的入學情況確實很活躍。

And I think it speaks to the ease of use of this drug in combination. So look, we're -- we've done our research, and we're only speculating until we actually get to the market, but it seems as if physicians kind of all along the spectrum of disease severity are interested.

我認為這說明了這種藥物聯合使用的便利性。所以你看，我們已經做了研究，在真正進入市場之前我們只是在進行推測，但似乎各種疾病嚴重程度的醫生都對此感興趣。

Okay. Great. And very last part of my question, is regarding rela with the potential of being used in combination with other therapies like immunotherapy, as you mentioned before, or ADCs in the future, any specific concerns on overlapping toxicities over here?

好的。偉大的。我的問題的最後一部分是關於 rela 與其他療法（如您之前提到的免疫療法或 ADC）聯合使用的可能性，這裡對重疊毒性有什麼具體擔憂嗎？

I'm going to give you to Bill Guyer.

我要把你交給比爾·蓋爾。

Yes. Thank you for that question. No, there are absolutely no concerns of overlapping toxicities. We look to see, again, to be the agent of choice in combination with any immunotherapy or chemotherapy. And we will do that in many future studies to come to prove that.

是的。謝謝你的提問。不，完全不用擔心毒性重疊。我們再次期待看到它成為與任何免疫療法或化學療法聯合使用的首選藥物。我們將在未來的許多研究中證明這一點。

And there really is no mechanistic reason to think that there would be that problem. It looks like we're out of questions. Thank you very much for everybody who has called in. We look forward to really what's next. It is -- I really do view this personally. It's an exceptionally exciting time. We really have an opportunity to help many, many people, and you'll be a part of it. So thank you very much, and we'll talk to you next quarter.

並且確實沒有任何機械原因可以認為有該問題。看起來我們已經沒有什麼問題了。非常感謝每一位來電的人。我們真正期待接下來會發生什麼。是的——我個人確實這麼認為。這是一個異常令人興奮的時刻。我們確實有機會幫助很多人，而您將成為其中的一員。非常感謝您，我們下個季度再與您聯繫。

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。