Crinetics Pharmaceuticals Inc (CRNX) 2024 Q3 法說會逐字稿

Welcome to the Crinetics Pharmaceuticals third-quarter 2024 financial results conference call.

歡迎參加 Crinetics Pharmaceuticals 2024 年第三季財務業績電話會議。

(Operator Instructions)

（操作員指令）

I would now like to turn the call over to Gayathri Diwakar of Crinetics.

現在我想將電話轉給 Crinetics 的 Gayathri Diwakar。

Please go ahead.

請繼續。

Thank you, operator.

謝謝您，接線生。

Hello, everyone, and welcome to Crinetics earnings call.

大家好，歡迎參加 Crinetics 財報電話會議。

Joining me today are Dr. Scott Struthers, Founder and Chief Executive Officer; and Marc Wilson, Chief Financial Officer.

今天與我一起參加的是創辦人兼執行長 Scott Struthers 博士；以及財務長馬克·威爾遜（Marc Wilson）。

Also joining us for the Q&A portion of the call are Dr. Dana Pizzuti, Chief Medical and Development Officer; and Dr. Alan Krasner, Chief Endocrinologist.

首席醫療和發展官 Dana Pizzuti 博士也參加了本次電話會議的問答部分；以及首席內分泌學家 Alan Krasner 博士。

A press release announcing the third-quarter 2024 financial results was issued today and is also available on our corporate website.

今天發布了一份宣布 2024 年第三季財務業績的新聞稿，也可在我們的公司網站上查閱。

As a reminder, we'll be making forward-looking statements, and I invite you to learn more about the risks and uncertainties associated with these statements as disclosed in our SEC filings.

提醒一下，我們將做出前瞻性陳述，我邀請您了解更多有關我們在美國證券交易委員會文件中披露的與這些陳述相關的風險和不確定性的信息。

Such forward-looking statements are not a guarantee of performance, and the company's actual results could differ materially from those stated or implied in such statements due to risks and uncertainties associated with the company's business.

此類前瞻性陳述並非績效保證，由於與公司業務相關的風險和不確定性，本公司的實際結果可能與此類陳述中明示或暗示的結果有重大差異。

These forward-looking statements are qualified in their entirety by the cautionary statements contained in today's news release, the company's other news releases and Crinetics' SEC filings, including its annual report on Form 10-K and quarterly reports on 10-Q.

這些前瞻性陳述完全符合今天的新聞稿、公司的其他新聞稿和 Crinetics 的 SEC 文件（包括其 10-K 表年度報告和 10-Q 表格季度報告）中包含的警示聲明。

I would also like to specify that the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, November 12, 2024.

我還想指出的是，本次電話會議的內容包含時間敏感信息，這些信息僅截至本次直播之日（2024 年 11 月 12 日）準確。

Crinetics takes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this conference call.

Crinetics 不承擔修改或更新任何前瞻性陳述以反映本次電話會議召開日後發生的事件或情況的義務。

With that, I'll turn the call over to Scott.

說完這些，我會把電話轉給史考特。

Thank you, Gayathri.

謝謝你，Gayathri。

Good afternoon, everyone, and thank you for joining us on our third-quarter 2024 results call.

大家下午好，感謝您參加我們的 2024 年第三季業績電話會議。

We've had yet another incredibly productive quarter with advancements up and down the pipeline, and we continue to strengthen our financial position.

我們又度過了一個非常有成效的季度，各項工作都在不斷推進，我們的財務狀況也持續加強。

For today's call, I will summarize our recent accomplishments shown on slide 3, preview some of our upcoming events, and then hand the call over to Marc Wilson for a review of our financials.

在今天的電話會議上，我將總結幻燈片 3 中顯示的我們最近的成就，預覽我們即將舉行的一些活動，然後將電話交給馬克威爾遜 (Marc Wilson) 審查我們的財務狀況。

We'll end this, as always, by taking your questions.

像往常一樣，我們將以回答您的問題來結束本次會議。

As some of you may know, November 1 was Acromegaly Awareness Day.

有些人可能知道，11 月 1 日是肢端肥大症宣傳日。

We commemorated this day by hosting acromegaly patients at our headquarters to bring life to the impact of our mission of improving patients' lives.

我們在總部接待肢端肥大症患者來紀念這一天，以反映我們改善患者生活的使命的影響。

That was the picture you saw on the first slide of our presentation today.

這就是您在我們今天簡報的第一張投影片上看到的圖片。

It was especially timely for Crinetics as we recently submitted our first NDA for our investigational drug paltusotine for the treatment and long-term maintenance of acromegaly.

對於 Crinetics 來說，這尤其及時，因為我們最近提交了我們的研究藥物 paltusotine 的首份 NDA，用於治療和長期維持肢端肥大症。

We very much look forward to Acromegaly Awareness Day next November.

我們非常期待明年 11 月的肢端肥大症宣傳日。

We believe paltusotine will represent a next-generation therapy for people living with acromegaly.

我們相信，帕妥索汀將成為肢端肥大症患者的下一代治療方法。

We expect to receive the FDA filing notification later in December and expect a standard review period.

我們預計將在 12 月下旬收到 FDA 的申請通知，並預計有一個標準的審查期。

In the meantime, we continue to focus on building our commercial capabilities and preparing for the anticipated launch of our first drug next fall.

同時，我們將繼續專注於建立我們的商業能力，為明年秋季推出我們的第一款藥物做準備。

As part of these preparations, our national accounts team is meeting with payers to discuss formulary placement and product coverage.

作為這些準備工作的一部分，我們的國家帳戶團隊正在與付款人會面，討論處方集的放置和產品覆蓋範圍。

We believe that having these conversations early and often allows us to positively influence formulary placement and coverage decisions with the goal of broad access for patients living with acromegaly.

我們相信，儘早並經常進行這些對話使我們能夠積極影響處方集的放置和覆蓋決策，從而讓肢端肥大症患者能夠廣泛獲得治療。

In addition, our medical science liaisons are in the field speaking with academic KOLs and community endocrinologists to get their feedback from these clinicians on how treatment protocols are established within their practices and to better understand the patient experience.

此外，我們的醫學科學聯絡員正在現場與學術 KOL 和社區內分泌學家進行交談，以獲得這些臨床醫生的回饋，了解如何在實踐中製定治療方案，並更好地了解患者的體驗。

In addition to preparing for the US paltusotine launch, we are also in the early stages of building capabilities for commercialization of paltusotine and to support global clinical development of our other potential future drugs in the pipeline.

除了為帕妥索汀在美國上市做準備之外，我們還處於帕妥索汀商業化能力建設的早期階段，並支持我們正在研發的其他未來潛在藥物的全球臨床開發。

As you are aware, we partnered paltusotine in Japan with SKK, and they are doing an excellent job of advancing our Japanese Phase 3 trial in patients with acromegaly.

如您所知，我們與日本的 SKK 合作開發了 paltusotine，他們在推進我們針對肢端肥大症患者的日本 3 期試驗方面做得非常出色。

Based on the strength of the clinical data for paltusotine and atumelnant, the depth of our evolving pipeline and the capabilities of Crinetics today, we believe that we can retain more of the global value of our pipeline by maintaining closer control of the European market and development activities.

基於 paltusotine 和 atumelnant 臨床數據的強度、我們不斷發展的產品線的深度以及 Crinetics 目前的能力，我們相信，透過對歐洲市場和開發活動保持更緊密的控制，我們可以保留更多產品線的全球價值。

Towards this, we anticipate submitting the MAA in the first half of next year for the use of paltusotine in patients with acromegaly.

為此，我們預計在明年上半年提交使用帕妥索汀治療肢端肥大症患者的 MAA。

We have also recently established operations in Switzerland, hired a General Manager for Europe and are recruiting supporting staff in the areas of regulatory, market access, medical affairs and operations.

我們最近還在瑞士建立了業務機構，聘請了一位歐洲總經理，並正在招聘監管、市場准入、醫療事務和營運方面的支援人員。

We are committed to eventually bringing paltusotine and our other future products to patients in Europe and the rest of the world.

我們致力於最終將 paltusotine 和我們未來的其他產品帶給歐洲和世界其他地區的患者。

But as with all our investments, we will do so in a fiscally prudent way and consider the continuously evolving reimbursement landscape in making final decisions about where and when to launch.

但與我們所有的投資一樣，我們將以財政審慎的方式進行投資，並在最終決定何時何地推出時考慮不斷變化的報銷狀況。

Carcinoid syndrome is the second indication in development with paltusotine.

類癌症候群是 paltusotine 正在開發的第二個適應症。

We reported positive results from our Phase 2 study earlier this year and we remain on track to start the Phase 3 trial on our anticipated timeline.

我們在今年稍早報告了第二階段研究的積極成果，並且我們仍將按照預期的時間表開始第三階段試驗。

We've had productive interactions with the FDA regarding the Phase 3 protocol and received feedback on details of endpoints, inclusion criteria, rescue criteria, et cetera.

我們與 FDA 就第 3 階段方案進行了富有成效的互動，並收到了有關終點、納入標準、救援標準等細節的回饋。

We are finalizing the protocol and expect to begin site activation activities shortly.

我們正在最終確定協議並期望很快開始站點激活活動。

Paltusotine is just the first of many therapeutic candidates that we have been purposely designed in-house to transform the treatment of endocrine conditions.

帕妥索汀只是我們專門內部設計的眾多候選治療藥物中的第一個，旨在改變內分泌疾病的治療方法。

Beyond paltusotine, our investigational drug, atumelnant, is in Phase 2 development for both congenital adrenal hyperplasia, or CAH, and Cushing's disease.

除 paltusotine 外，我們的試驗藥物 atumelnant 也正處於針對先天性腎上腺增生症（CAH）和庫欣氏症的 2 期開發階段。

We previously shared exciting initial data from both of atumelnant's Phase 2 studies earlier this year at the Endocrine Society's annual meeting in June.

我們先前曾在今年 6 月的內分泌學會年會上分享了 atumelnant 兩項第 2 階段研究的令人興奮的初步數據。

As a reminder, we previously showed partial data from a small subset of patients at ENDO.

提醒一下，我們之前展示了來自 ENDO 一小部分患者的部分數據。

By early next year, we plan to share the complete 12 weeks of data from all the 28 patients recruited across three doses -- 40, 80 and 120 milligrams.

到明年年初，我們計劃分享所有 28 名患者在三種劑量（40、80 和 120 毫克）下的完整 12 週數據。

We expect to initiate a Phase 3 study in adults with CAH in the first half of 2025.

我們預計在 2025 年上半年針對 CAH 成人患者啟動 3 期研究。

There's also a very high level of unmet need in children with CAH due to the irreversible effects of early hyperandrogenism and the consequences of supraphysiologic glucocorticoid use.

由於早期雄性激素過多症的不可逆影響以及超生理性糖皮質激素使用的後果，先天性腎上腺皮質增生症 (CAH) 兒童的未滿足需求水平也非常高。

We plan to initiate a pediatric CAH program with atumelnant in 2025.

我們計劃於 2025 年與 atumelnant 合作啟動一項兒科 CAH 計畫。

We also shared remarkable initial data at the endocrine meeting about the use of atumelnant in patients with Cushing's disease.

我們也在內分泌會議上分享了關於使用 atumelnant 治療庫欣氏症患者的重要的初步數據。

Encouraged by the positive emergent data, we are also planning to initiate a full development program in Cushing's in 2025 pending regulatory feedback on program design.

受到新興正面數據的鼓舞，我們也計劃於 2025 年在庫欣啟動一項全面的開發計劃，等待監管機構對計劃設計的回饋。

We've also continued to make great progress on our early stage pipeline as shown on slide 4, with four new candidates currently the subject of first-in-human enabling activities with INDs anticipated next year if these studies are positive.

如幻燈片 4 所示，我們在早期研發管線方面也繼續取得了巨大進展，目前有四種新的候選藥物正在進行首次人體試驗，如果這些研究取得積極成果，預計明年將獲得 IND 批准。

As we mentioned previously, IND-enabling studies of our PTH receptor antagonist in development for hyperparathyroidism are ongoing.

正如我們之前提到的，我們用於治療副甲狀腺功能亢進的 PTH 受體拮抗劑的 IND 支持研究正在進行中。

Assuming positive results, we expect to file an IND for this candidate in 2025.

假設取得正面成果，我們預計將在 2025 年為該候選藥物提交 IND。

We've also initiated IND-enabling studies of our SST3 agonist for autosomal dominant polycystic kidney disease.

我們也啟動了針對常染色體顯性多囊性腎病變的 SST3 激動劑的 IND 支持研究。

Assuming positive results, we expect to file an IND in 2025.

假設取得正面成果，我們預計將在 2025 年提交 IND。

Today, we are excited to announce that we recently nominated a development candidate for our TSH antagonist program.

今天，我們很高興地宣布，我們最近為我們的 TSH 拮抗劑計畫提名了一位開發候選人。

As you may recall, a TSH antagonist could be developed for both Graves' hyperthyroidism and Graves' ophthalmopathy, often referred to as thyroid eye disease or TED.

您可能還記得，可以開發一種 TSH 拮抗劑來治療格雷夫斯甲狀腺亢進和格雷夫斯眼病（通常稱為甲狀腺眼病或 TED）。

We are initiating IND-enabling studies for this compound.

我們正在啟動針對該化合物的 IND 支持研究。

Assuming positive results, we expect to file an IND in 2025.

假設取得正面成果，我們預計將在 2025 年提交 IND。

As you can see from our progress in these programs, our commitment to GPCR drug discovery continues to unlock scientific and medical innovations that have the potential to bring transformative therapies to patients and significant value to our co-owners.

從這些計畫的進展可以看出，我們對 GPCR 藥物發現的承諾將繼續釋放科學和醫學創新，這些創新有可能為患者帶來變革性的治療方法，並為我們的共同所有者帶來重大價值。

We believe we have a unique, deep pipeline of drug candidates.

我們相信我們擁有獨特、深入的候選藥物管道。

These were all developed by our in-house R&D team and driven by a passion for the pursuit of science and medicine to help patients.

這些都是由我們的內部研發團隊開發的，其動力來自於對科學和醫學的追求，以幫助病人。

Our goal is to relieve the burden of disease so that patients can focus on living their lives.

我們的目標是減輕疾病負擔，使患者能夠專注於自己的生活。

To-date, our drug discovery and development efforts have been focused on novel therapies to manage endocrine disorders, including those caused by the secretory activity of endocrine tumors.

迄今為止，我們的藥物發現和開發工作一直集中在治療內分泌疾病的新療法，包括由內分泌腫瘤的分泌活動引起的療法。

Today, I'd like to introduce you to non-peptide drug conjugates or NDCs.

今天，我想向大家介紹非勝肽藥物偶聯物或NDC。

NDCs are a new technology that we've developed in-house, enabled by our premier in-house drug discovery capabilities in the area of GPCRs.

NDC 是我們內部開發的一項新技術，得益於我們在 GPCR 領域一流的內部藥物發現能力。

This novel platform leverages endocrine receptors for highly selective targeting of antitumor agents with the goal of treating the underlying tumors themselves.

此新平台利用內分泌受體高度選擇性地標靶抗腫瘤藥物，目的是治療潛在的腫瘤本身。

If successful, we anticipate our NDC platform may be applicable to a wide range of different cancers.

如果成功，我們預計我們的 NDC 平台可能適用於多種不同的癌症。

We're extremely excited about the long-term potential of this approach.

我們對這種方法的長期潛力感到非常興奮。

By way of background, we've all heard a lot about the success of antibody drug conjugates or ADCs in cancers.

從背景上講，我們都聽說過很多關於抗體藥物偶聯物或 ADC 在癌症治療中的成功案例。

These combine a targeting antibody that recognizes tumor cell surface markers and delivers a cytotoxic payload to the constituent tumor cells.

它們結合了一種靶向抗體，可以識別腫瘤細胞表面標誌，並向組成腫瘤細胞提供細胞毒性有效載荷。

ADCs are now a well validated platform and contribute to the therapeutic armamentarium for a wide range of different cancers.

ADC 現在是一個經過充分驗證的平台，並為多種不同癌症的治療手段做出了貢獻。

NDCs leverage Crinetics' deep expertise in small molecule ligand design for GPCR targets to replace the antibody of ADCs with a fit-for-purpose novel small molecule, and this is non-peptide.

NDC 利用 Crinetics 在 GPCR 標靶小分子配體設計方面的深厚專業知識，以適合用途的新型小分子取代 ADC 的抗體，而且這是非勝肽類的。

Our first NDC candidate from this platform is CRN09682, and its overall design is shown on slide 5.

我們基於該平台的第一個 NDC 候選產品是 CRN09682，其整體設計如幻燈片 5 所示。

The NDC approach is intended to enhance tumor penetration, selectively target specific GPCR expressing tumor cells, induce internalization and selectively release a potent antitumor agent intracellularly, all while minimizing systemic exposure and toxicities.

NDC 方法旨在增強腫瘤滲透，選擇性地靶向表達特定 GPCR 的腫瘤細胞，誘導內化並選擇性地在細胞內釋放強效的抗腫瘤藥物，同時最大限度地減少全身暴露和毒性。

Additionally, NDCs are manufactured by traditional chemical synthesis methods, avoiding the limitations of complex and heterogeneous manufacturing methods required by most ADCs.

此外，NDC 採用傳統的化學合成方法製造，避免了大多數 ADC 所需的複雜和異構製造方法的限制。

9682 is made up of small molecule SST2 agonist optimized to selectively bind with high affinity and potently induce internalization, then trafficking to specific intracellular targets.

9682 由小分子 SST2 激動劑組成，經過最佳化，可選擇性地以高親和力結合併有效誘導內化，然後運輸至特定的細胞內靶點。

This is in contrast to paltusotine, which was designed to minimize internalization in order to maximize G protein signaling at the plasma membrane to inhibit growth hormone and serotonin secretion.

這與帕妥索汀形成了對比，帕妥索汀的設計目的是盡量減少內化，從而最大限度地增強質膜上的 G 蛋白信號傳導，以抑制生長激素和血清素的分泌。

The small molecule agonist in 9682 is linked to a monomethyl auristatin E or MMAE, which is a well-established cytotoxic payload in approved ADCs.

9682 中的小分子激動劑與單甲基金瑞他汀 E 或 MMAE 相連，後者是已批准的 ADC 中已證實的細胞毒性有效載荷。

The linker was designed to be selectively cleaved by enzymes only present in specific intracellular compartments and not present in the general circulation.

此接頭被設計為僅被存在於特定細胞內區室而非一般循環中的酵素選擇性切割。

When intact, 9682 has little cytotoxicity.

當 9682 完整時，其細胞毒性很小。

But when the MMAE portion is released inside the cell, it causes cell cycle arrest and subsequent apoptosis or cell death.

但當 MMAE 部分在細胞內釋放時，它會導致細胞週期停滯，隨後導致細胞凋亡或細胞死亡。

The net result of all this craftsmanship is a low molecular weight compound that readily penetrates solid tumors, and as shown on slide 6, selectively delivers its payload to the inside of tumor cells, where it accumulates and kills these cells with little circulating free payload and associated toxicities.

所有這些製程的最終結果是，生產出一種能夠輕鬆穿透實體腫瘤的低分子量化合物，並且如幻燈片 6 所示，它能夠選擇性地將有效載荷運送到腫瘤細胞內部，在那裡積聚並殺死這些細胞，而循環中幾乎沒有遊離有效載荷和相關毒性。

In preclinical in vivo tumor models, 9682 is very effective at shrinking and often eliminating well established tumors in mice.

在臨床前體內腫瘤模型中，9682 能非常有效地縮小甚至消除小鼠體內已形成的腫瘤。

The IND-enabling toxicology studies so far suggest a more than adequate preclinical safety margin to begin clinical evaluation.

到目前為止，IND 支持的毒理學研究表明，開始臨床評估的臨床前安全邊際已經足夠了。

The IND-enabling studies are nearly complete and we anticipate filing an IND to support the clinical development of 9682 in early 2025.

IND 支持研究已接近完成，我們預計將在 2025 年初提交 IND 來支持 9682 的臨床開發。

Details of the design and preclinical results for 9682 are expected to be presented at the North American Neuroendocrine Tumor Society meeting in Chicago later this month.

9682 的設計細節和臨床前結果預計將於本月稍後在芝加哥舉行的北美神經內分泌腫瘤學會會議上公佈。

The clinical development -- the 9682 clinical development plan will begin with a dose range finding study in patients with SST2 expressing tumors, including NETs.

臨床開發－9682 臨床開發計畫將從對錶達 SST2 的腫瘤（包括 NET）患者進行劑量範圍探索研究開始。

This leverages the routine use of SST2 targeted PET imaging agents in patients to precisely identify patients whose tumors express SST2 and are therefore good candidates for 9682.

這利用患者常規使用 SST2 靶向 PET 造影劑來精確識別腫瘤表達 SST2 並因此成為 9682 的良好候選人的患者。

Strategically, we believe the development of 9682 in patients with non-functional NETs is complementary to the use of paltusotine in patients with the functional NETs who develop carcinoid syndrome.

從策略上講，我們相信，在非功能性 NET 患者中開發 9682 與在患有類癌綜合徵的功能性 NET 患者中使用 paltusotine 是互補的。

We'll be working with many of the same centers and investigators for the development of both compounds.

我們將與許多相同的中心和研究人員合作開發這兩種化合物。

When metastatic, NETs are typically incurable with surgery or current therapies regardless of tumor grade.

當發生轉移時，無論腫瘤水平如何，NET 通常都無法透過手術或當前療法治癒。

We believe this is a large population with high unmet need, and we are excited to be developing 9682 for these patients.

我們相信這是一個龐大的群體，有著巨大的未滿足醫療需求，我們很高興能夠為這些患者開發 9682。

As you can probably tell, we're very excited about the potential of this first-in-class NDC that may provide an important new treatment option for patients with NETs and potentially multiple other SST2 expressing tumor types.

您可能已經看出來了，我們對這種一流的 NDC 的潛力感到非常興奮，它可能為 NET 患者以及潛在多種其他 SST2 表達腫瘤類型的患者提供重要的新治療選擇。

Beyond SST2, we'll use our experience with 9682 to learn how to best optimize and develop future NDCs for other GPCR targets and cancer types.

除了 SST2 之外，我們還將利用 9682 的經驗來學習如何最好地優化和開發針對其他 GPCR 標靶和癌症類型的未來 NDC。

As you can see from this update, we have a robust pipeline shown on slide 7 spanning registration, late stage development and discovery.

從本次更新中您可以看到，我們擁有幻燈片 7 上展示的強大管道，涵蓋註冊、後期開發和發現。

Our recent $575 million equity offering positions us to continue delivering important innovative medicines well beyond the paltusotine launch in acromegaly next year -- anticipated paltusotine launch.

我們最近發行了 5.75 億美元的股票，這使我們能夠在明年推出用於治療肢端肥大症的帕妥索汀之後繼續提供重要的創新藥物——預計帕妥索汀將於明年推出。

Our existing pipeline is filled with possibilities to bring new hope to patients struggling with many different endocrine conditions and endocrine-related tumors.

我們現有的產品線充滿了可能性，可以為患有多種不同內分泌疾病和內分泌相關腫瘤的患者帶來新的希望。

Those who have followed the history of Crinetics know that we have always been judicious with our spending and thoughtful about deploying capital in a way that creates both hope for our patients and value for our co-owners.

關注 Crinetics 歷史的人都知道，我們在支出方面始終十分謹慎，並深思熟慮地部署資本，以便為我們的患者創造希望，並為我們的共同所有者創造價值。

We will continue to carefully steward the resources with which we have been entrusted as we continue the exciting trajectory of growth and transformation at Crinetics.

我們將繼續謹慎管理我們所委託的資源，繼續推動 Crinetics 令人興奮的成長和轉型軌跡。

With that, I'll now hand it over to Marc to review the financials.

說完這些，我現在將把財務狀況交給馬克來審查。

Marc?

馬克？

Thank you, Scott.

謝謝你，斯科特。

Turning to slide 8, Crinetics continues to be in a strong financial position, having ended the third quarter with approximately $863 million in cash and investments.

第 8 頁，Crinetics 繼續保持強勁的財務狀況，第三季結束時其現金和投資約為 8.63 億美元。

As Scott mentioned, we completed a $575 million public offering that closed after the end of the third quarter.

正如斯科特所提到的，我們完成了 5.75 億美元的公開發行，並在第三季結束後結束。

This further strengthened our financial position and our cash, cash equivalents and investment securities following the equity offering, totaled approximately $1.4 billion on a pro forma basis.

這進一步增強了我們的財務狀況，股票發行後的現金、現金等價物和投資證券按備考基礎總計約為 14 億美元。

We project that with the proceeds from the recent offering, we will be able to fund our current operating plan into 2029.

我們預計，利用最近發行的收益，我們將能夠資助我們到 2029 年的當前營運計劃。

That operating plan includes the commercialization of paltusotine for acromegaly, if approved, as well as the initiation of multiple later stage clinical trials in carcinoid syndrome, in CAH and in Cushing's disease.

此運作計畫包括將用於治療肢端肥大症的帕妥索汀商業化（如果獲得批准），以及啟動針對類癌症候群、先天性腎上腺皮質增生症和庫欣氏症的多個後期臨床試驗。

In addition, we plan to continue investing in the product candidates that are emerging from our discovery pipeline, including the four development candidates that have been nominated this year.

此外，我們計劃繼續投資於我們發現的候選產品，包括今年已提名的四個開發候選產品。

With respect to the financial results, there were no revenues for the quarter ended September 30, 2024, compared to $0.3 million for the same period in 2023.

就財務結果而言，截至 2024 年 9 月 30 日的季度沒有收入，而 2023 年同期為 30 萬美元。

The third-quarter 2023 revenues were derived from the paltusotine licensing arrangement with our Japanese partner, SKK.

2023 年第三季的收入來自與日本合作夥伴 SKK 達成的 paltusotine 授權協議。

Research and development expenses were $61.9 million for the quarter ended September 30, 2024, compared to $43.8 million for the same period in 2023.

截至 2024 年 9 月 30 日的季度研發費用為 6,190 萬美元，而 2023 年同期為 4,380 萬美元。

The increase was primarily driven by higher personnel costs, outside services and manufacturing activities, the majority of which were attributable to the advancement of the paltusotine and atumelnant development programs and the expansion of our preclinical portfolio.

成長的主要原因是人員成本、外部服務和製造活動增加，其中大部分歸因於 paltusotine 和 atumelnant 開發項目的進展以及我們臨床前產品組合的擴展。

For the quarter ended September 30, 2024, general and administrative expenses were $25.9 million compared to $15.5 million for the same period in 2023.

截至 2024 年 9 月 30 日的季度，一般及行政費用為 2,590 萬美元，而 2023 年同期為 1,550 萬美元。

These increases were primarily due to higher personnel costs and commercial planning activities.

這些增長主要是由於人員成本和商業規劃活動增加所致。

Net loss for the quarter ended September 30, 2024, was $76.8 million compared to a net loss of $57.5 million for the same period in 2023.

截至 2024 年 9 月 30 日的季度淨虧損為 7,680 萬美元，而 2023 年同期的淨虧損為 5,750 萬美元。

Net cash used for operating activities for the quarter ended September 30, 2024, was $62.8 million.

截至 2024 年 9 月 30 日的季度，用於經營活動的淨現金為 6,280 萬美元。

We plan to provide updated financial guidance during our year-end earnings call in the first quarter of 2025.

我們計劃在 2025 年第一季的年終收益電話會議上提供更新的財務指引。

It is worth highlighting that in the next year we plan to initiate multiple Phase 3 studies in carcinoid syndrome and in adults with CAH.

值得強調的是，我們計劃在明年啟動多項針對類癌症候群和成人 CAH 的多項 3 期研究。

In addition, we are planning to initiate later stage development in pediatrics with CAH and in Cushing's disease.

此外，我們還計劃啟動兒科先天性腎上腺皮質激素 (CAH) 和庫欣氏症的後期開發。

As such, we expect our quarterly R&D spend will increase as we initiate and advance paltusotine and atumelnant into these clinical trials over the remainder of this year and throughout 2025.

因此，我們預計，隨著我們在今年剩餘時間和整個 2025 年啟動和推進 paltusotine 和 atumelnant 進入這些臨床試驗，我們的季度研發支出將會增加。

We also anticipate increases in SG&A expenses as we prepare for the potential launch of paltusotine for acromegaly.

在為治療肢端肥大症的 paltusotine 藥物的潛在上市做準備時，我們也預期銷售、一般及行政費用 (SG&A) 增加。

Crinetics has practiced disciplined expense management, and that continues to be our goal as we continue to grow the organization and invest in our deep pipeline, and we are well financed to do so.

Crinetics 一直實行嚴格的費用管理，這仍然是我們的目標，因為我們將繼續發展組織並投資於我們的深度管道，我們有充足的資金來做到這一點。

I will now hand it back to Scott for closing remarks before we begin Q&A.

在我們開始問答環節之前，我現在將發言權交還給斯科特，請他作結束語。

Thank you, Marc.

謝謝你，馬克。

I'm incredibly excited about the future of Crinetics.

我對 Crinetics 的未來感到無比興奮。

As we look to the end of 2024 and the start of 2025, we will continue to build on our strong progress.

展望 2024 年末和 2025 年初，我們將繼續鞏固強勁進步。

We've consistently delivered on our plans and we're committed to maintaining this level of execution.

我們始終如一地執行我們的計劃，並致力於保持這一執行水平。

We look forward to sharing upcoming clinical and regulatory milestones from paltusotine and atumelnant and updates on the continued advancement of our deep pipeline of emerging candidates.

我們期待分享 paltusotine 和 atumelnant 即將到來的臨床和監管里程碑，以及我們新興候選藥物深度管道的持續進展更新。

Crinetics continues to be well positioned to become the premier fully integrated endocrine-focused global pharmaceutical company.

Crinetics 將繼續保持有利地位，成為首屈一指的、完全一體化的、專注於內分泌領域的全球製藥公司。

Thank you, all, for your attention.

謝謝大家的關注。

Operator, we're ready to take your questions.

接線員，我們已準備好回答您的問題。

(Operator Instructions) Cory Jubinville, LifeSci Capital.

(操作員指示) Cory Jubinville，LifeSci Capital。

Congrats on the news.

恭喜這個消息。

The NDCs in CRN09682 is pretty exciting.

CRN09682 中的 NDC 非常令人興奮。

Anything more you could tell us about this program and kind of where you see it best fitting within the existing paradigm?

您能否告訴我們有關該計劃的更多資訊？

And I guess what else are some of the key challenges that needed to be overcome to develop an NDC?

我想問一下，開發 NDC 還需要克服哪些關鍵挑戰？

And what are some of the specific advantages you could point to of an NDC approach over, say, ADCs or radiotherapies?

您能指出 NDC 方法與 ADC 或放射療法相比具有哪些具體優勢嗎？

So for more details, I'd encourage folks to come to Chicago for the NANETS meeting, where we'll be presenting some of the preclinical data on 9682 and data on paltusotine in carcinoid syndrome and can talk at some more length with data in hand.

因此，為了了解更多詳細信息，我鼓勵大家來芝加哥參加 NANETS 會議，我們將在會議上展示一些有關 9682 的臨床前數據和有關類癌綜合徵中 paltusotine 的數據，並可以根據手中的數據進行更詳細的討論。

But broadly, the NDC platform is an extension of the types of ideas that led to the formation of Radionetics a few years ago.

但從廣義上講，NDC 平台是幾年前促成 Radionetics 成立的理念類型的延伸。

We believe that these non-peptides, small molecules provide a variety of different advantages when targeting GPCRs over antibodies in the typical NDC formats.

我們相信，這些非肽小分子在針對 GPCR 時比典型的 NDC 格式的抗體具有多種不同的優勢。

For one thing, GPCRs are very difficult to make antibodies against, yet there are a whole class of selectively expressed cell surface targets.

首先，GPCR 很難製造抗體，但有一類選擇性表現的細胞表面標靶。

And unlike many of the targets of ADCs, binding of ligands to GPCRs can be tuned to selectively optimize internalization of these conjugates into the inside of the cell, which is something you want to do for selective intracellular cleavage.

與 ADC 的許多標靶不同，配體與 GPCR 的結合可以進行調整，以選擇性地優化這些結合物進入細胞內部的內化，這是選擇性細胞內裂解所要做的事情。

So I think it opens up new targets.

所以我認為它開闢了新的目標。

It opens up simpler chemical synthesis.

它開闢了更簡單的化學合成。

It opens up the ability to tune things in ways that you can't with antibodies.

它能夠以抗體無法實現的方式調節事物。

Some as simple as most antibodies will stick around for weeks, whereas we can clear small molecules in a day or two.

大多數簡單的抗體會持續存在數週，而我們可以在一兩天內清除小分子。

So I think it offers a number of different potential advantages.

所以我認為它提供了許多不同的潛在優勢。

But with 9682, we're going to go learn about what these are in a real world setting and in the type of patients that we're already working with, with neuroendocrine tumors for those who have carcinoid syndrome.

但透過 9682，我們將了解這些在現實世界中的情況，以及我們已經在治療的患者類型，患有類癌症候群的神經內分泌腫瘤患者。

So it's highly synergistic with our ongoing efforts for paltusotine, the internal relationships we've developed with the investigators and the patient community, and it's pioneering this new idea about how we might branch out and use our core platform to expand into antitumor agents.

因此，它與我們在 paltusotine 方面的持續努力、我們與研究人員和患者群體建立的內部關係具有高度的協同作用，並且它開創了關於我們如何擴展並利用我們的核心平台擴展到抗腫瘤藥物領域的新想法。

Jessica Fye, JPMorgan.

摩根大通的傑西卡·菲伊 (Jessica Fye)。

So with several products entering the clinic next year, what's the soonest that we can expect Phase 1 data from any of those?

那麼，明年將有幾種產品進入臨床階段，我們最快什麼時候可以獲得其中任何一種產品的第一階段資料？

And which will it be from?

它會來自哪一個？

And then if I could sneak a couple in on 9682.

然後如果我能偷偷地把幾個放在 9682 上。

Can you talk about how you chose the MMAE toxin for that product and how different or similar the ligand is to paltusotine?

您能談談如何為該產品選擇 MMAE 毒素以及該配體與 paltusotine 有何不同或相似之處嗎？

Okay.

好的。

There's a good batch -- thanks, Jess, and look forward to seeing you later this week.

這是一批好貨 — — 謝謝，傑西，期待本週晚些時候見到你。

In terms of the time line on the different programs, I think we'll probably stick away from providing precise guidelines on each of those.

關於不同計劃的時間表，我認為我們可能不會為每個計劃提供精確的指導。

Just have to stay tuned throughout the year and see how they come.

只需全年保持關注，看看它們如何發展。

In part, it's because you also don't know how far you need to go up in dose response curves to know when you're starting to get meaningful results.

部分原因是因為您也不知道需要在劑量反應曲線上上升多少才能知道何時開始獲得有意義的結果。

So it's a little difficult to predict when they'll each complete.

因此，預測它們何時能完成有點困難。

But I think you can expect a nice flow of new information from those and some other compounds that are getting close over the next year and a little into 2026.

但我認為，你可以期待從這些化合物和一些其他化合物中得到大量新的信息，這些信息將在明年和 2026 年前後陸續面世。

And then in terms of 9682, it's not paltusotine, it's not a direct homolog of paltusotine.

就 9682 而言，它不是 paltusotine，它不是 paltusotine 的直接同源物。

It's another SST2 agonist that was selectively optimized to be the best ligand we could get for the purpose at hand, which is to bind selectively and internalize receptors and get the right biodistribution so it spends very little time in the periphery.

這是另一種 SST2 激動劑，經過選擇性優化成為我們可以獲得的最佳配體，以實現當前的目的，即選擇性結合和內化受體並獲得正確的生物分佈，因此它在外圍停留的時間很短。

And all those various factors were considered as we built that conjugate, both the ligand and the linker group.

當我們建構這個結合物時，我們考慮了所有這些不同的因素，包括配體和連接基團。

And MMAE was chosen simply because it's a very well-established payload in the ADC world.

選擇 MMAE 只是因為它是 ADC 領域非常成熟的有效載荷。

But we have ongoing activities to explore alternative payloads as well, and that may be seen in some of our backup or follow-on compounds.

但我們也在持續探索替代有效載荷，這可能會在我們的一些備用或後續化合物中看到。

Jeff Hung, Morgan Stanley.

摩根士丹利的 Jeff Hung。

From your early stage pipeline, how are you thinking about the obesity indications for candidate selection in 2025?

從您早期的研發管線來看，您如何考慮 2025 年肥胖症適應症的候選選擇？

What would you need to see with your GLP-1 or GIP programs in order to have confidence advancing those given the increasingly competitive landscape?

在日益激烈的競爭環境下，您需要對 GLP-1 或 GIP 計劃抱持怎樣的信心才能有信心推進這些計劃？

And what I think we're seeing in the competitive landscape is some of the limitations that arise if you're not super careful about how you select candidates.

我認為我們在競爭環境中看到的是，如果你在選擇候選人時不特別謹慎，就會出現一些限制。

These are things as simple as getting to easily manufacture dose levels.

這些事情就像輕鬆製造劑量水平一樣簡單。

Clearly, there's questions around tolerability in some molecules and the doses needed for good weight loss versus good tolerability.

顯然，對於某些分子的耐受性以及達到良好減肥效果所需的劑量和良好的耐受性存在疑問。

And we have a variety of different hypotheses we're testing as we tune these molecules to be what we think can be the best-in-class profile for an easy to synthesize small molecule GLP-1 agonist.

我們在調整這些分子時測試了多種不同的假設，以使其成為我們認為可以成為易於合成的小分子 GLP-1 激動劑的最佳配置。

And basically, the course limiting step is we want a really, really good molecule and we're not going to settle for anything less than what we think is as close as reasonably expected to perfection.

基本上，當然限制步驟是我們想要一個真正好的分子，我們不會滿足於任何低於我們認為盡可能接近完美的分子。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

This is Charlie on for Brian.

這是 Charlie 為 Brian 表演的。

Just kind of piggybacking off the last question, noting that your GLP-1 and GIP assets are non-peptides, how are you guys thinking about the potential advantage of a non-peptide compound here relative to other assets in the space?

只是順便問一下最後一個問題，注意到您的 GLP-1 和 GIP 資產是非肽類，您如何看待非肽類化合物相對於該領域其他資產的潛在優勢？

Well, I think the whole field in the obesity space is moving towards alternative modes for delivery of the activity.

嗯，我認為整個肥胖領域正在朝著替代模式發展。

And the main challenge on the peptides is twofold.

肽面臨的主要挑戰有兩個面向。

One is manufacturing that I think everybody and their brother has been hearing about.

一個是製造業，我想每個人，包括他們的兄弟都聽過。

But also peptides just limit you in the physical chemical space that you can explore and the delivery methods that you can utilize.

但是勝肽也限制了您可以探索的物理化學空間和您可以利用的傳遞方法。

And with small molecules, you don't have those limitations.

而對於小分子來說，就不會有這些限制。

You can tune every dimension of chemical space to get the types of physiologic or pharmacologic activities, pharmacokinetic activities and test different types of hypothesis to get the right clinical profile.

您可以調整化學空間的每個維度來獲得生理或藥理活動的類型、藥物動力學活動，並測試不同類型的假設以獲得正確的臨床特徵。

And so I think what this -- today's talk about 9682 and paltusotine gives you a sense of some of the depth of types of things we try and optimize when we're making small molecule drugs.

所以我認為，今天關於 9682 和 paltusotine 的討論讓您深入了解我們在製造小分子藥物時嘗試和優化的一些類型的事物。

And you'll see us employ all these different type of techniques as we're applying it to the obesity space and in molecules that can be made at scale, because this is one of the biggest public health problems in the world or at least in most Western societies.

你會看到我們採用各種不同類型的技術，將其應用於肥胖領域和可以大規模生產的分子，因為這是世界上最大的公共衛生問題之一，或者至少在大多數西方社會中是如此。

(technical difficulty) And Dennis, your line is open.

（技術故障）丹尼斯，你的線路已經接通。

I had one on the non-peptide drug conjugate.

我有一個非勝肽類藥物偶聯物。

Can you remind us of the common toxicities associated with MMAE ADCs like Polivy, PADCEV and TIVDAK?

您能提醒我們與 Polivy、PADCEV 和 TIVDAK 等 MMAE ADC 相關的常見毒性嗎？

And just curious around your confidence in your ability to thread the needle on efficacy and tolerability?

我只是好奇您對於療效和耐受性方面的能力有信心嗎？

It's a great question and certainly something we explored carefully in our preclinical program.

這是一個很好的問題，我們在臨床前專案中也仔細探討過這個問題。

Now we need to see it in the clinical setting.

現在我們需要在臨床環境中觀察它。

But we obviously were aware of the types of common toxicities for MMAE and looked carefully for that in the preclinical packages.

但我們顯然知道 MMAE 的常見毒性類型，並在臨床前包中仔細尋找。

And we think we've got very, very good margins.

我們認為我們的利潤率非常非常好。

And in part, that's because we tuned the molecule.

部分原因是我們調整了分子。

So there's very little circulating free MMAE.

因此流通的免費 MMAE 非常少。

The conjugates are cleared rapidly from systemic accumulation, but cleaved MMAE is accumulated both rapidly and persistently in tumor cells.

結合物會從系統性累積中迅速清除，但裂解的 MMAE 會在腫瘤細胞中迅速且持續地累積。

And we'll show this data at NANETS.

我們將在 NANETS 上展示這些數據。

Joe Schwartz, Leerink Partners.

Leerink Partners 的 Joe Schwartz。

It's great to see you select the TSH antagonist development candidate.

很高興看到您選擇 TSH 拮抗劑開發候選藥物。

So I was wondering if you could talk about what your criteria has been for the characteristics you need to reach in order to be satisfied that the candidate meets your criteria.

所以我想知道您是否可以談談您的標準是什麼，即候選人需要達到哪些特徵才能滿足您的標準。

And how high is the hurdle here compared to what you needed to clear for other programs such as paltusotine and atumelnant?

與您需要清除的其他項目（例如 paltusotine 和 atumelnant）相比，這裡的障礙有多高？

And then from a biological standpoint, how should we think about the relative degree of efficacy which an IGF-1 or a TSH antagonist can inherently offer, all else equal, based on crosstalk or any other factors?

然後從生物學的角度來看，在其他所有條件相同的情況下，基於串擾或任何其他因素，我們應該如何看待 IGF-1 或 TSH 拮抗劑本身能夠提供的相對療效程度？

So just the chemistry and the biology, if you could address those, that would be great.

因此，如果您能解決化學和生物學問題，那就太好了。

Yes.

是的。

A great question, Joe. Philosophically, we try and make every molecule as high a quality of a drug candidate as we can.

這個問題問得好，喬。從哲學上講，我們盡力嘗試使每個分子都具有盡可能高品質的候選藥物。

Frankly, I'll tell you that when we advanced paltusotine into the clinic, we took a couple of risks.

坦白說，我告訴你，當我們將帕妥索汀推廣到臨床時，我們承擔了一些風險。

One is there was a slight risk of drug-drug interactions, which we disproved later in the clinic.

一是存在輕微的藥物交互作用的風險，我們後來在臨床上證實了這一點。

And there is a slight risk of lower than hoped oral bioavailability, which we disproved later in the clinic.

並且存在口服生物利用度低於預期的輕微風險，我們後來在臨床上證明了這一點。

So we did very well with paltusotine.

因此，我們在使用 paltusotine 方面做得很好。

I think you'll agree.

我想你會同意的。

But as we get into some of these more prevalent indications like Graves' disease or obesity, we're adding extra layers of carefulness, including broad testing against any other potential liability, making sure the physical, chemical properties are good, making sure it's scalable at high levels of production, because you're going to have a lot more patients in Graves' disease than you would in acromegaly, for example.

但當我們遇到一些更為普遍的病症，如格雷夫斯病或肥胖症時，我們會更加謹慎，包括對任何其他潛在責任進行廣泛的測試，確保物理和化學性質良好，確保其在高水平生產下可擴展，因為格雷夫斯病患者的數量會比肢端肥大症患者多得多。

So I don't think we've changed our goals that much, but we're just looking with an even closer eye at the quality of these candidates as you get into the very, very large indications.

因此，我認為我們並沒有改變太多的目標，但隨著病情越來越嚴重，我們只會更密切地關注這些候選人的品質。

And then I'm sorry, I missed the -- what was the second part about that?

然後很抱歉，我錯過了——第二部分是什麼？

It just seems like your TSH antagonist has a different approach than IGF --

看起來 TSH 拮抗劑的作用方式與 IGF 不同——

Yes.

是的。

So remember in Graves' disease, the root cause of the disease is autoantibodies which bind to the TSH receptor and activate cell signaling.

所以請記住，格雷夫茲病的根本原因是與 TSH 受體結合並激活細胞信號傳導的自身抗體。

And our candidates that are TSH receptor antagonists block the activity of those antibodies at the level of the receptor.

我們的候選藥物是 TSH 受體拮抗劑，可在受體層面阻斷這些抗體的活性。

Now in Graves' eye disease what happens in the cells at the back of the eye is those antibodies bind to the TSH receptor that activates the TSH receptor, which then signals down its main pathway of cyclic AMP, but it also cross activates the IGF-1 receptor.

現在，在格雷夫斯眼疾中，眼球後部細胞中發生的情況是，那些抗體與 TSH 受體結合，從而激活 TSH 受體，然後 TSH 受體向其主要環磷酸腺苷通路發出信號，但也會交叉激活 IGF-1 受體。

And that IGF receptor also starts signaling into the back of the eye.

且 IGF 受體也開始向眼球後部發出訊號。

And TEPEZZA and the other drugs are aimed at IGF signaling or acting downstream of TSH.

TEPEZZA 和其他藥物針對的是 IGF 訊號傳導或作用於 TSH 的下游。

So if you block the activity of the TSH receptor, and we've shown this in preclinical studies that I believe we published at end of last year, you also block the signaling of IGF and the cells from the back of the eye.

因此，如果你阻斷 TSH 受體的活動，我們已經在臨床前研究中證明了這一點，我相信我們是在去年年底發表的，你也會阻斷 IGF 和眼後部細胞的信號傳導。

So generally, we expect this to be more efficacious or at least equally efficacious as the IGF approaches, and it can be used to treat the underlying Graves' at the level of the thyroid.

因此一般來說，我們預計這會比 IGF 更有效，或至少同樣有效，並且它可以用於治療甲狀腺水平的潛在格雷夫茲病。

And if we had the right drug for the treatment of Graves' disease itself, we wouldn't be having thyroid eye disease.

如果我們有正確的藥物來治療格雷夫茲病本身，我們就不會患上甲狀腺眼疾。

So one of the challenges for this program is to figure out the sequence of indications that we address in later stage trials.

因此，該計劃面臨的挑戰之一是找出我們在後期試驗中處理的適應症的順序。

Douglas Tsao, H.C. Wainwright.

曹國偉，H.C.溫賴特。

Congrats on the progress.

祝賀你取得進展。

I guess, Scott, maybe as a follow-up to that, I mean, historically, you as a company have been very innovative in terms of using sort of Phase 1 study to provide very compelling proof of mechanism data that has really sort of given confidence in derisked programs as they enter Phase 2 and ultimately Phase 3.

我想，斯科特，也許作為對此的後續行動，我的意思是，從歷史上看，你們作為一家公司在使用第 1 階段研究方面非常具有創新性，以提供非常令人信服的機制數據證明，這確實在進入第 2 階段和最終第 3 階段時為去風險項目帶來了信心。

When you think about the TSH program and Graves' as well as TED, from your sort of initial sense, will you be able to accomplish that in sort of a Phase 1, Phase 1b study?

當您考慮 TSH 計劃、Graves 計劃以及 TED 計劃時，從您最初的感覺來看，您是否能夠在第 1 階段、第 1b 階段的研究中實現這一目標？

And will that necessarily inform the initial direction you take with that program in terms of the sort of time at which you sort of intervene with Graves' and if patients are already starting to show manifestations of eye disease?

這是否必然會為您在該計畫上採取的初步方向提供參考，即何時對格雷夫斯病進行幹預，以及患者是否已經開始出現眼疾症狀？

Why don't I let Alan answer that question?

我為什麼不讓艾倫回答這個問題？

Yes, I think actually a TSH antagonist is very, very -- it would be a nice model in Phase 1 to evaluate in the sense that we do have biomarkers that we can evaluate in real time as we've done in our previous Phase 1 studies before.

是的，我認為 TSH 拮抗劑實際上非常非常——它將是第 1 階段評估的一個很好的模型，因為我們確實有可以即時評估的生物標誌物，就像我們之前在第 1 階段研究中所做的那樣。

In particular, thyroid hormone levels, TSH and T4 responses to a TSH antagonist could tell us, I think in theory at least, very quickly whether we're hitting the intended pharmacologic target as we've done in other studies before.

具體來說，甲狀腺激素水平、TSH 和 T4 對 TSH 拮抗劑的反應可以告訴我們，我認為至少在理論上，我們是否達到了預期的藥理目標，就像我們之前在其他研究中所做的那樣。

So -- now it's a typical Phase 1 study.

所以——現在這是一個典型的第一階段研究。

That time course is a little short to measure efficacy in thyroid eye disease.

這個時間段對於衡量甲狀腺眼疾的療效來說有點短。

But certainly, this is still, I think, a good candidate for pharmacologic proof of concept even in Phase 1.

但可以肯定的是，我認為，即使在第一階段，這仍然是一個很好的藥理學概念驗證候選方案。

Jon Wolleben, Citizens JMP.

喬恩‧沃勒本 (Jon Wolleben)，公民 JMP。

This is Catherine on for Jon.

這是凱瑟琳，代替喬恩。

I have a question about the carcinoid syndrome program.

我對類癌綜合症計劃有一個疑問。

And if you can give any additional color on kind of the feedback from the FDA and how you kind of foresee the Phase 3 program looking relative to kind of what's been guided before?

您能否進一步說明 FDA 的回饋，以及您如何預見第三階段計畫相對於先前的指導？

Anything that the FDA has kind of required that's sort of been unexpected?

FDA 有什麼要求是出乎意料的嗎？

Yes.

是的。

Why don't I let Dana answer that question?

我為什麼不讓達娜回答這個問題呢？

Yes, the interaction with the FDA on carcinoid went very well.

是的，與 FDA 在類癌方面的互動進展順利。

I think that there were many areas that we had agreement on, and then needed their perspective on issues like the endpoints and duration of the trial.

我認為我們在許多方面已經達成了一致，並且需要他們對試驗終點和持續時間等問題的看法。

But we had anticipated a lot of those potential perspectives.

但我們已經預見了許多潛在的觀點。

And it wasn't very challenging to be able to accommodate those changes into our proposed plan.

將這些變更納入我們提議的計劃並不是很困難。

So we're just finalizing that right now, and we are continuing to be on track to get that started in the same timeframe that we've always been saying.

因此，我們現在正在最終確定這一點，並且我們將繼續按照我們一直所說的時間範圍開始這項工作。

Leland Gershell, Oppenheimer.

利蘭‧格謝爾 (Leland Gershell)、奧本海默。

Thanks for unveiling this new program in NDC.

感謝您在 NDC 中推出這個新計劃。

Scott, I just wanted to ask sort of a forward-looking question with respect to the opportunities here with this new approach as we think about ways in which you can tune ligands to successfully cause the internalization of GPCRs versus not having them be internalized, i.e., with paltusotine.

史考特，我只是想問一個關於這種新方法的機會的前瞻性問題，因為我們在思考如何調整配體以成功引起 GPCR 的內化，而不是讓它們被內化，例如使用 paltusotine。

Are you able to identify others that you could approach following the first compound for perhaps other tumor types with GPCRs?

您能否確定繼第一種化合物之後可以用於治療其他具有 GPCR 的腫瘤類型的其他化合物？

I think there's lots of other opportunities.

我認為還有很多其他機會。

But at this point, we really want to learn from 9682 about what it's really going to take to be successful in the clinic.

但此時，我們真正想從 9682 身上學到的是，在臨床上取得成功真正需要什麼。

And I think those lessons that we'll learn there, both in pharmacokinetics and tumor responses and lines of therapy and things like that, will be very informative for us.

我認為我們在那裡學到的關於藥物動力學、腫瘤反應、治療方法等方面的經驗對我們來說都非常有益。

So in the meantime, the discovery group is exploring new ideas, new payloads, new targets, things like that.

因此與此同時，探索小組正在探索新想法、新有效載荷、新目標等等。

But before we advance the next one, we really want to see how this does.

但在我們推進下一個之前，我們真的想看看這個的效果如何。

Got it.

知道了。

And then just a question on the TSH antagonist.

然後只是一個關於 TSH 拮抗劑的問題。

Good to see that be nominated.

很高興看到被提名。

So will you be planning to study that in Graves' and TED as separate kind of campaigns?

那麼，您是否計劃在 Graves 和 TED 中以單獨的活動形式來研究這一點？

Or will you be looking at kind of an overarching Graves' development program with TED as constituting a sort of a subset of those patients?

或者您會將 TED 與 Graves 的整體發展計劃結合起來，作為這些患者的子集？

Well, I think it's maybe a little early to discuss the overall strategy there.

嗯，我認為現在討論整體戰略可能還為時過早。

You might imagine there's both some questions we need to ask ourselves around the economics of the two different indications and the feasibility of recruiting in the different indications and the competitive environment.

您可能會想像，我們需要問自己一些問題，圍繞著兩種不同適應症的經濟性以及在不同適應症和競爭環境中招募的可行性。

But honestly, I think this is the absolutely best approach for both Graves' hyperthyroidism and Graves' associated ophthalmopathy or TED.

但老實說，我認為這對格雷夫斯甲狀腺功能亢進症以及格雷夫斯相關眼疾或 TED 來說絕對是最好的治療方法。

We just have to figure out how to stage those investments.

我們只是要弄清楚如何分階段進行這些投資。

Catherine Novack, JonesTrading.

凱瑟琳·諾瓦克（Catherine Novack），瓊斯貿易公司（JonesTrading）。

Just one on CAH, given that this is an area that has not really seen any new approvals in recent years, I guess what learnings were you able to take from Neurocrine's pivotal programs when you go to design your own, maybe you can learn from anything or have better designs?

關於 CAH 只有一個問題，鑑於這個領域近年來實際上沒有看到任何新的批准，我想當您去設計自己的程序時，您能從 Neurocrine 的關鍵程序中學到什麼，也許您可以從任何東西中學到東西或者有更好的設計？

And then what do you anticipate the standard of care would be following potential crinecerfont approval next year?

那麼，您預計明年 Crinecerfont 獲得批准後，護理標準會是什麼？

Well, I think crinecerfont is -- if it's approved, it will be the first drug specifically for CAH ever.

嗯，我認為 crinecerfont —— 如果獲得批准，它將成為有史以來第一個專門治療 CAH 的藥物。

We've used glucocorticoids to treat these patients.

我們使用糖皮質激素來治療這些患者。

But I'm excited to see the potential approval there and the type of labeling that is awarded by the FDA assuming all goes well.

但我很高興看到那裡的潛在批准以及 FDA 授予的標籤類型（假設一切順利）。

And I think it will be incorporated into the standard of care for some patients.

我認為它將被納入一些患者的護理標準中。

What we've learned is about the role of different hormones in this pathway.

我們了解的是不同荷爾蒙在此途徑中的作用。

And we've speculated for years about how much of the HPA axis is controlled by CRF or vasopressin or ACTH.

多年來我們一直在推測 HPA 軸有多少是由 CRF 或加壓素或 ACTH 控制的。

And I think it's pretty clear now with our early data and Neurocrine's Phase 3 data that CRF contributes to the activation of the adrenal.

我認為現在透過我們的早期數據和 Neurocrine 的 3 期數據可以很清楚地看出，CRF 有助於腎上腺的活化。

But it's not -- the stimulation of the adrenal is not completely dependent on CRF, whereas it does appear to be nearly completely dependent upon ACTH, as we expect.

但事實並非如此——腎上腺的刺激並不完全依賴 CRF，而正如我們所預料的那樣，它似乎幾乎完全依賴 ACTH。

So I think we've chosen ideal target in the pathway and be looking forward to talking more about the rest of the data we have in the not too very distant future.

因此，我認為我們已經選擇了路徑中的理想目標，並期待在不久的將來更多地討論我們擁有的其餘數據。

And at that time, we should be able to clarify more about our Phase 3 plans, too.

到那時，我們也應該能夠更清楚地說明我們的第三階段計劃。

Yasmeen Rahimi, Piper Sandler.

亞斯明·拉希米，派珀·桑德勒。

Thank you so much for the really nice surprise.

非常感謝您給我如此美好的驚喜。

I -- definitely caught many of us for this really wonderful update.

我——確實吸引了我們中的許多人的注意力，並觀看這個非常精彩的更新。

And I'm sure a ton of work went into this.

我確信這需要大量的工作。

So I guess the question to ask is, in terms of development for NETs, like what would a path look like?

所以我想問的問題是，就 NET 的發展而言，路徑是什麼樣的？

I mean, I think many of us may think of these tumors more slow growing, takes a long time to show a separation.

我的意思是，我想我們很多人可能認為這些腫瘤生長得較慢，需要很長時間才能分離。

Could you maybe educate us what a path would look like in NETs if you decided to pursue that?

如果您決定追求這個目標，您能否告訴我們 NET 中的路徑是什麼樣的？

That would be really important.

這確實非常重要。

And how big that market would be if you've done any work in that regard?

如果您在這方面做過任何工作，那麼這個市場會有多大？

I hope we're able to provide a few surprises every now and then.

我希望我們能夠不時地帶給我們一些驚喜。

And we've got a very active discovery group that is working really hard.

我們有一個非常活躍的探索小組，正在努力工作。

We just want to make sure we got things ready for prime time before we start talking about them.

我們只是想確保在開始談論它們之前我們已經為黃金時段做好了準備。

But Alan, maybe you want to comment on some of our ideas on development for this.

但是艾倫，也許你想對我們在這方面的發展的一些想法發表評論。

Yes, so we would -- we are planning on starting with an oncology style Phase 1 study, which is a little bit different than our Phase 1 endocrine trials.

是的，我們計劃開始腫瘤學類型的第 1 期研究，這與我們的第 1 階段內分泌試驗略有不同。

The first step, of course, is to escalate doses from a safe starting dose in volunteers with tumors and increasing that dose in subsequent cohorts till we get close to a maximally tolerated dose.

當然，第一步是針對患有腫瘤的志願者，從安全的起始劑量開始逐步增加劑量，並在後續的志願者中增加該劑量，直到接近最大耐受劑量。

The kinds of tumors we're talking about that would be included in such a trial would be patients who have SST2 receptor expressing tumors.

我們所討論的將納入此類試驗的腫瘤類型是患有 SST2 受體表達腫瘤的患者。

Those are largely patients with neuroendocrine tumors, although I will point out that there are variants of neuroendocrine tumors and even tumors which are not technically neuroendocrine tumors which can express these receptors.

這些人大多是神經內分泌腫瘤患者，但我想指出的是，神經內分泌腫瘤也有變異體，甚至技術上不是神經內分泌腫瘤的腫瘤也能表現這些受體。

And we're going to be pretty agnostic as to which patients we study because these are patients often who have a great deal of medical need and these are patients who would have progressing disease.

而且，我們對研究的患者持相當懷疑的態度，因為這些患者通常有大量的醫療需求，而且他們的病情會不斷惡化。

And we'll first define the right dose and then proceed to dose expansion cohorts, where once we have sort of a dose which we expect to be well tolerated and potentially therapeutic, we would explore a variety of different kinds of tumor types based on the origin of the neuroendocrine tumor.

我們首先會確定正確的劑量，然後進行劑量擴展組，一旦我們確定了預期耐受性良好且具有潛在治療作用的劑量，我們就會根據神經內分泌腫瘤的起源探索各種不同類型的腫瘤類型。

Assuming that's all successful, then we would look at this kind of novel therapeutic -- potentially therapeutic compound in patients who have progressive disease and need adjunctive therapy to improve outcomes in Phase 2 and potentially Phase 3 as well.

假設一切都成功，那麼我們將研究這種新型治療方法——對患有進行性疾病並需要輔助治療的患者進行潛在的治療化合物，以改善第 2 階段和第 3 階段的結果。

So this is a very novel approach.

這是一種非常新穎的方法。

It's a very exciting approach.

這是一個非常令人興奮的方法。

And this is, I would say, a fairly underserved patient population.

我想說，這是一個相當缺乏醫療服務的病患群體。

There's a lot of research going on in neuroendocrine tumor and related tumors now, but not a lot of great options, particularly beyond PRRT, which is a radioactive therapy.

目前，人們對神經內分泌腫瘤和相關腫瘤進行了大量研究，但並沒有太多好的選擇，尤其是除了 PRRT（一種放射性療法）之外。

This is a non-radioactive therapy which we hope would be similarly effective or better.

這是一種非放射性療法，我們希望它具有相同的效果甚至更好。

And you could imagine a lot of advantages to using a small molecule as opposed to a very discrete treatment with a radioactive therapy in the long run.

你可以想像，從長遠來看，使用小分子療法相對於放射性療法這種非常離散的治療有很多優點。

So we're very excited.

所以我們非常興奮。

We would follow this kind of oncology path to approval hopefully some day.

希望有一天我們能夠沿著這種腫瘤學道路獲得批准。

And just to follow-up on your population size, we're still working on some of that.

為了追蹤你們的人口規模，我們仍在努力解決其中的一些問題。

But you'll recall we've said that the carcinoid syndrome patients are roughly 20% of the total population of the neuroendocrine tumor patients.

但您會記得我們曾說過類癌症候群患者約佔神經內分泌腫瘤患者總數的 20%。

And the vast majority of neuroendocrine tumors do express SST2.

絕大多數神經內分泌腫瘤確實表達SST2。

So we expect this just in the NET space to be quite a bit larger population than just the carcinoid.

因此，我們預計，僅在 NET 領域中，其數量就會比類癌的數量大得多。

And then you'll see if you look in the radiopharmaceutical space, where there's a lot of entrants in the SST2 targeted radiopharmaceuticals, that they're starting to expand out into some of the other tumor types.

然後你會發現，如果你關注放射性藥物領域，有很多參與者進入 SST2 靶向放射性藥物領域，他們開始擴展到其他一些腫瘤類型。

In particular, there are certain types of breast cancer that express SST2, many head and neck cancers express SST2 and some of the pheochromocytoma, other types of more rare cancers.

具體來說，某些類型的乳癌會表達 SST2，許多頭頸癌和一些嗜鉻細胞瘤以及其他類型的更罕見的癌症也會表達 SST2。

So that's something we're working on, making sure we understand the full potential, but it's not small.

所以這是我們正在努力的事情，確保我們了解其全部潛力，但其潛力並不小。

Congrats again.

再次恭喜。

A great surprise.

一個大驚喜。

Thank you.

謝謝。

I now like to turn the call back over to Scott Struthers for any closing or additional remarks.

現在，我想將電話轉回給斯科特·斯特拉瑟斯 (Scott Struthers)，請他做結束語或做補充評論。

No.

不。

Thank you, everybody.

謝謝大家。

Thank you for your attention to our story and your support in our financing and participating with the success and growth of the company.

感謝您對我們故事的關注以及對我們融資的支持和參與公司的成功和成長。

We appreciate it and look forward to talking to many of you in the coming days and weeks.

我們對此表示感謝，並期待在未來幾天和幾週內與你們進行交流。

Thank you.

謝謝。

And this does conclude today's program.

今天的節目到此結束。

Thank you for your participation.

感謝您的參與。

You may disconnect at any time.

您可以隨時斷開連線。