Crinetics Pharmaceuticals Inc (CRNX) 2024 Q2 法說會逐字稿

Good day everyone, and welcome to the Crinetics Pharmaceuticals second quarter 2024 Earnings Conference Call.

大家好，歡迎參加 Crinetics Pharmaceuticals 2024 年第二季財報電話會議。

Please note this call may be recorded.

請注意，此通話可能會被錄音。

(Operator Instructions).

（操作員說明）。

It is now my pleasure to turn the program over to Gayathri Diwakar.

現在我很高興將該計劃移交給 Gayathri Diwakar。

Thank you, operator.

謝謝你，接線生。

Hello everyone and welcome to Crinetics earning call.

大家好，歡迎來到 Crinetics 賺錢電話。

Joining me today are Dr. Scott Struthers, Founder and Chief Executive Officer; Dr. Dana Pizzuti, Chief Medical and Development Officer; Jim Hassard, Chief Commercial Officer; and Marc Wilson, Chief Financial Officer; also joining us for the Q&A portion of the call is Dr. Alan Krasner, Chief Endocrinologist.

今天加入我的是創辦人兼執行長 Scott Struthers 博士； Dana Pizzuti 博士，首席醫療和發展長；吉姆‧哈薩克，首席商務官；財務長馬克‧威爾遜 (Marc Wilson)；首席內分泌學家艾倫·克拉斯納 (Alan Krasner) 博士也參加了電話會議的問答部分。

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

今天發布了宣布 2024 年第一季財務業績的新聞稿，也可在我們的公司網站上查看。

We'll be using slides for today's presentation, which can be viewed on the Investor Relations section of the Crinetics’ website.

我們將在今天的簡報中使用幻燈片，您可以在 Crinetics™ 網站的投資者關係部分查看幻燈片。

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

提醒一下，我們將做出前瞻性聲明，我邀請您了解我們在 SEC 文件中揭露的與這些聲明相關的風險和不確定性。

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 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 filing, including its annual report on Form 10-K.

這些前瞻性陳述完全符合今天的新聞稿、該公司的其他新聞稿和 Crinetics SEC 文件（包括其 10-K 表格年度報告）中包含的警示性陳述。

I would also like to specify that the content of this conference call contains time sensitive information that's accurate only as of the date of this live broadcast August 8th, 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，僅截至 2024 年 8 月 8 日直播之日準確。

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

Crinetics 沒有義務修改或更新任何前瞻性聲明以反映本次電話會議之後發生的事件或情況。

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

這樣，我就把電話轉給史考特。

Thank you, Gayathri.

謝謝你，加亞瑟裡。

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

大家下午好，感謝您參加我們的 2024 年第二季業績電話會議。

I'll begin by spending a few moments summarizing our recent accomplishments.

首先，我將花一些時間總結我們最近的成就。

Then I'll hand the call over to Dr. Dana Pizzuti, our Chief Medical and Development Officer who’ll provide a regulatory update.

然後我會將電話轉交給我們的首席醫療和開發官 Dana Pizzuti 博士，他將提供監管最新資訊。

Jim Hassard, our Chief Commercial Officer will share our plans to bring our lead candidate paltusitine to patients.

我們的首席商務官 Jim Hassard 將分享我們將主要候選藥物帕圖西汀帶給患者的計劃。

And Marc Wilson, our Chief Financial Officer, will wrap up with a thrilling financial update.

我們的財務長馬克威爾遜 (Marc Wilson) 將以令人興奮的財務最新動態作為總結。

The second quarter of 2024 with extremely productive for Crinetics.

2024 年第二季 Crinetics 的生產力極高。

The Endocrine Society annual meeting in June proved to be an impactful meeting for us.

六月的內分泌學會年會對我們來說是個有影響力的會議。

We were thrilled to share highly encouraging initial results from the ongoing Phase 2 studies of our second development candidate Atumelnant in both Congenital Adrenal Hyperplasia and Cushing's disease.

我們很高興與大家分享我們的第二個候選藥物 Atumelnant 在先天性腎上腺增生和庫欣氏症方面正在進行的 2 期研究的非常令人鼓舞的初步結果。

These unprecedented data were very well received by the endocrinology community.

這些前所未有的數據受到內分泌學界的熱烈歡迎。

This reinforced already strong confidence in the potential of Atumelnant to be a best-in-class and first-in-class agent in both indications.

這增強了人們對 Atumelnant 在這兩個適應症上成為同類最佳和一流藥物的潛力的強烈信心。

Patients need better therapeutic options and we are committed to realizing Atumelnant's full potential as a revolutionary new treatment paradigm for people suffering from CAH and Cushing's disease.

患者需要更好的治療選擇，我們致力於充分發揮 Atumelnant 作為 CAH 和庫欣氏症患者革命性新治療範例的潛力。

Crinetics team is working hard to move development of Atumelnant in both indications and bring this potential therapy to people around the world.

Crinetics 團隊正在努力推動 Atumelnant 在這兩種適應症上的開發，並將這種潛在的療法帶給世界各地的人們。

We also presented data from paltusitine’s PATHFINDER Phase 3 acromegaly program at Endo.

我們也提供了來自 paltusitine 在 Endo 的 PATHFINDER 第 3 期肢端肥大症計畫的數據。

A new analysis from PATHFINDER-1 highlighted results from an exploratory analysis using patient-reported outcomes captured in the Acromegaly Symptom Diary or ASD.

PATHFINDER-1 的一項新分析強調了使用肢端肥大症症狀日記 (ASD) 中捕獲的患者報告結果進行探索性分析的結果。

These data showed that patients on monthly standard-of-care injections who are defined as biochemically controlled actually experience variability in symptom control.

這些數據表明，被定義為生化控制的每月標準護理注射的患者實際上在症狀控制方面存在差異。

In contrast, once daily Paltusitine’s treatment was associated with stable biochemical control and low rates of breakthrough symptoms.

相較之下，每天一次帕圖西汀治療與穩定的生化控制和較低的突破性症狀發生率有關。

Dana and Jim will speak on more on our progress of bringing Paltusitine to patients.

達納和吉姆將更多地談論我們將帕圖西汀帶給患者的進展。

But I'm incredibly excited about its potential to transform the future of acromegaly treatment and define a new standard of care.

但我對它改變肢端肥大症治療的未來並定義新的護理標準的潛力感到非常興奮。

Overall, our 2024 plans remain on track.

總體而言，我們的 2024 年計劃仍在按計劃進行。

Our next steps this year include filing the Paltusitine NDA for acromegaly, engaging with regulators to align on the initiation of a Phase 3 program in carcinoid syndrome.

我們今年的下一步包括提交帕圖西汀治療肢端肥大症的 NDA，與監管機構合作以啟動類癌症候群 3 期計畫。

Completing the Phase 2 studies of Atumelnant and CAH and Cushing’s, and transitioning multiple new drug candidates from our discovery efforts into preclinical and IND enabling development.

完成 Atumelnant 、 CAH 和 Cushing 的 2 期研究，並將多種新藥候選物從我們的發現工作過渡到臨床前和 IND 開發。

Along these lines, we've continued to make meaningful progress on our early-stage pipeline.

沿著這些思路，我們繼續在早期管道上取得有意義的進展。

First, we've identified a Parathyroid Hormone or PTH receptor antagonist development candidate for our hyperparathyroidism program.

首先，我們已經為我們的副甲狀腺功能亢進計畫確定了副甲狀腺素或 PTH 受體拮抗劑開發候選藥物。

Preclinical data demonstrates that this candidate reduces both PTH and PTH-related protein-induced hypercalcemia in rodent models and it possesses a favorable drug-like profound.

臨床前數據表明，該候選藥物可降低囓齒動物模型中 PTH 和 PTH 相關蛋白誘導的高鈣血症，並具有良好的藥物樣作用。

This profile is likely consistent with once-per-day dosing in humans.

此曲線可能與人類每天一次的給藥劑量一致。

We began IND-enabling studies and anticipate filing an IND in 2025.

我們開始了 IND 支持研究，並預計於 2025 年提交 IND。

We've also selected an SST3 agonist development candidate to explore a completely new mechanism for the treatment of autosomal dominant polycystic kidney disease, or ADPKD.

我們也選擇了一種 SST3 激動劑開發候選藥物，以探索治療常染色體顯性多囊性腎病變 (ADPKD) 的全新機制。

ADPKD is one of the most common genetic diseases and affects over 140,000 people in the US.

ADPKD 是最常見的遺傳疾病之一，影響美國超過 14 萬人。

Preclinical data for this candidate are very promising, and we are pursuing options to advance this program to clinical studies, either with a partner or independently.

該候選藥物的臨床前數據非常有希望，我們正在尋求與合作夥伴或獨立合作將該計畫推進臨床研究的選擇。

Our discovery programs for Graves' discovery program for Graves’ disease, including thyroid eye disease and obesity, continue to make great progress, and we look forward to announcing optimized candidates for these programs in the near future.

我們針對格雷夫斯疾病（包括甲狀腺眼疾和肥胖症）的格雷夫斯發現計劃的發現計劃繼續取得巨大進展，我們期待在不久的將來宣布這些計劃的優化候選者。

As a reminder, our pipeline also includes novel molecules and technologies that are being developed by our partners.

提醒一下，我們的產品線還包括我們的合作夥伴正在開發的新穎分子和技術。

For example, several years ago, we developed a novel non-peptide radiotherapy agnostic program that could be used in multiple oncology indications.

例如，幾年前，我們開發了一種新型非勝肽放射治療不可知程序，可用於多種腫瘤適應症。

With this, we created a company around the technology called Radionetics Oncology, and entered into a collaboration and license agreement with the company.

由此，我們圍繞著該技術創建了一家名為 Radionetics Oncology 的公司，並與該公司簽訂了合作和授權協議。

Radionetics announced on July 1st that it entered into a strategic relationship with Eli Lilly and Company.

Radionetics於7月1日宣布與禮來公司建立策略合作關係。

Under the terms of the agreement, Radionetics received $140 million upfront, and Lilly obtained a warrant for the exclusive right to purchase Radionetics for $1 billion.

根據協議條款，Radionetics 獲得了 1.4 億美元預付款，禮來公司獲得了以 10 億美元購買 Radionetics 的獨家權認股權證。

Crinetics currently owns approximately 25% of Radionetics.

Crinetics 目前擁有 Radionetics 約 25% 的股份。

If Lilly were to exercise its right to purchase Radionetics, Crinetics would receive its pro rata share of the $1 billion purchase price.

如果禮來公司行使收購 Radionetics 的權利，Crinetics 將按比例獲得 10 億美元收購價中的份額。

Crinetics is also entitled to single-digit royalties and commercialization milestones for the three programs currently in development at Radionetics.

Crinetics 也有權獲得 Radionetics 目前正在開發的三個專案的個位數特許權使用費和商業化里程碑。

We believe this transaction is a great validation of the strength of our discovery platform and has the potential to generate non-dilutive funding for Crinetics in the future.

我們相信，這筆交易是對我們發現平台實力的有力驗證，並有可能在未來為 Crinetics 帶來非稀釋性資金。

We also have a partnership with Lloyd in which we license another one of our targeted somatostatin molecules to extend the lifespan and health span of dogs.

我們還與 Lloyd 建立了合作夥伴關係，我們授權另一種目標生長抑素分子來延長狗的壽命和健康壽命。

The entire company, is hard at work executing our strategy to help more patients with endocrine-related diseases and to build long-term value for kinetic shareholders.

整個公司正在努力執行我們的策略，以幫助更多患有內分泌相關疾病的患者，並為動力股東創造長期價值。

Lastly, as you may have seen in our press release, Marc, our Chief Financial Officer will be leaving the company for personal reasons.

最後，正如您在我們的新聞稿中看到的那樣，我們的財務長馬克將因個人原因離開公司。

The Crinetics executive team and board are grateful for Marc's contributions to the company as he has been an invaluable member of the Crinetics team since before the IPO.

Crinetics 執行團隊和董事會感謝 Marc 對公司的貢獻，因為他自 IPO 以來一直是 Crinetics 團隊的寶貴成員。

His leadership was instrumental in the success of all our public market activities, which have put Crinetics on a strong financial footing.

他的領導對於我們所有公開市場活動的成功發揮了重要作用，這使 Crinetics 擁有了強大的財務基礎。

We've initiated a Thank you, Scott. I'll start with our lead candidate paltusitine. As Scott just mentioned, we remain on track to submit our NDA for paltusitine in its first indication, acromegaly this year. As we have discussed, the Phase 3 PATHFINDER program was designed to evaluate the safety and efficacy of paltusitine for the treatment of a broad spectrum of patients with acromegaly.

我們發起了感謝活動，斯科特。我將從我們的主要候選人帕圖西汀開始。正如史考特剛才提到的，我們仍有望在今年提交帕圖西汀的第一個適應症——肢端肥大症的新藥申請。正如我們所討論的，3 期 PATHFINDER 計劃旨在評估帕圖西汀治療廣泛肢端肥大症患者的安全性和有效性。

Based on the success of both Phase 3 PATHFINDER studies, we intend to seek approval for all patients, including those switching from the standard of care injected SRLs to paltusitine as studied in PATHFINDER-1 and those who are not currently treated as studied in PATHFINDER-2.

基於兩項3 期PATHFINDER 研究的成功，我們打算為所有患者尋求批准，包括那些從標準護理注射SRL 轉為PATHFINDER-1 中研究的帕圖西汀的患者，以及目前未接受PATHFINDER-1 中研究的治療的患者。

In parallel with our Phase 3 program, we have laid the foundation to streamline and accelerate the NDA filing. We have held two productive pre-NDA interactions with the FDA to align on clinical, non-clinical, CMC and quality topics. The FDA confirmed that our proposed package support submission for both the treatment and maintenance of acromegaly. This robust package includes data from our two PATHFINDER Phase 3 studies as well as dose response analysis, data from our long-term safety studies and patient outcomes from the acromegaly symptom diary, which showed significant improvements in patient-reported symptoms in both of our studies. We look forward to updating you as we continue towards the NDA final.

在進行第三階段計畫的同時，我們也為簡化和加速 NDA 申請奠定了基礎。我們與 FDA 進行了兩次富有成效的 NDA 前互動，以就臨床、非臨床、CMC 和品質主題進行協調。 FDA 確認我們提議的一攬子計劃支持提交肢端肥大症的治療和維持。這個強大的資料包包括來自我們兩項PATHFINDER 3 期研究的數據以及劑量反應分析、來自我們長期安全性研究的數據以及來自肢端肥大症症狀日記的患者結果，這表明我們的兩項研究中患者報告的症狀有顯著改善。隨著 NDA 決賽的臨近，我們期待向您通報最新情況。

In addition, we are diligently conducting health economics and outcome studies to further demonstrate the value proposition of paltusitine and acromegaly. This work supports the commercial team's efforts as they engage with payers, physicians, and patients. We are also making progress in paltusitine's second indication carcinoid syndrome. As previously reported, our Phase 2 study showed highly statistically significant results demonstrating the potential of paltusitine to treat people living with carcinoid syndrome.

此外，我們正在努力進行健康經濟學和結果研究，以進一步證明帕圖西汀和肢端肥大症的價值主張。這項工作支持商業團隊在與付款人、醫生和患者互動時的努力。我們在帕圖西汀的第二個適應症類癌症候群方面也取得了進展。如同先前所報導的，我們的 2 期研究顯示了高度統計顯著的結果，證明了帕圖西汀治療類癌症候群患者的潛力。

Importantly, the patients who elected to participate in the ongoing open-label extension continue to benefit from paltusitine. Building on this success, we are preparing to discuss the Phase 2 results with the FDA and align on the design of a Phase 3 protocol. We expect to initiate the Phase 3 trial by the end of 2024.

重要的是，選擇參與正在進行的開放標籤擴展的患者繼續受益於帕圖西汀。在此成功的基礎上，我們正​​準備與 FDA 討論第二階段的結果，並調整第三階段方案的設計。我們預計在 2024 年底前啟動第 3 階段試驗。

Turning now to Atumelnant. We are excited about the progress and potential of Atumelnant in both CAH and Cushing's disease. As Scott mentioned, the initial results from the open-label Phase 2 studies, which were featured at Endo, have exceeded our expectations. The three cohorts evaluating different doses of Atumelnant in the CAH Phase 2 study are now fully enrolled. We anticipate additional data will be available this year, and we are excited to advance this program. We also expect to share additional data from the ongoing study in ACTH dependent Cushing syndrome later this year.

現在轉向阿圖曼南特。我們對 Atumelnant 在 CAH 和庫欣氏症方面的進展和潛力感到興奮。正如斯科特所提到的，Endo 展示的開放標籤第 2 期研究的初步結果超出了我們的預期。在 CAH 2 期研究中評估不同劑量 Atumelnant 的三個隊列現已全部入組。我們預計今年將提供更多數據，我們很高興能推進該計劃。我們還希望在今年稍後分享更多正在進行的 ACTH 依賴性庫欣氏症候群研究的數據。

Crinetics is fundamentally committed to placing patients at the forefront of everything we do. This patient-centric approach is deeply ingrained in the development activities for each of the programs in our pipeline. We actively seek patient input throughout the drug development process. We've gained valuable insights by sharing data with patients, particularly from our acromegaly program. These insights validate our commitment to developing treatments that improve patient's quality of life, such as offering convenient dosing regimens.

Crinetics 從根本上致力於將患者置於我們所做的一切的最前沿。這種以患者為中心的方法深深植根於我們管道中每個項目的開發活動中。我們在整個藥物開發過程中積極尋求患者的意見。透過與患者分享數據，特別是我們的肢端肥大症計畫的數據，我們獲得了寶貴的見解。這些見解證實了我們對開發改善患者生活品質的治療方法的承諾，例如提供方便的給藥方案。

We have also routinely partnered with patient advocacy groups to obtain patient input on clinical trial design. Patients are enthusiastic about the potential of paltusitine, recognizing that it not only delivers the desired biochemical control, but can also improve the symptom of burden associated with their condition.

我們也定期與患者倡導團體合作，以獲取患者對臨床試驗設計的意見。患者對帕圖西汀的潛力充滿熱情，並認識到它不僅可以提供所需的生化控制，而且還可以改善與其病情相關的負擔症狀。

We invested considerable effort to develop the acromegaly symptom diary and are supporting that with psychometric analysis to help document the impact of paltusitine on patient's quality of life.

我們投入了大量精力來開發肢端肥大症症狀日記，並透過心理測量分析來支持這本日記，以幫助記錄帕圖西汀對患者生活品質的影響。

The positive feedback we have received so far indicates that our patient-focused approach and help us develop better therapies that make a meaningful difference to patients.

到目前為止，我們收到的正面回饋表明我們以患者為中心的方法，有助於我們開發更好的療法，為患者帶來有意義的改變。

I'll now hand the call over to Jim to review commercial readiness, strategy and current progress.search for successor and Marc will remain in his current position until a successor is onboarded to ensure a seamless transition.

我現在將把電話轉交給吉姆，以審查商業準備情況、策略和當前進展。

With that, I'll hand it over to Dr. Dana Pizzuti to discuss our clinical and regulatory progress in more detail.

接下來，我將把它交給 Dana Pizzuti 博士，更詳細地討論我們的臨床和監管進展。

Dana?

達納？

Thank you, Scott.

謝謝你，斯科特。

I'll start with our lead candidate out to the team.

我將從團隊的首席候選人開始。

As Scott just mentioned, we remain on track to submit our NDA for Paltusotine in its first indication, acromegaly this year as we have discussed, the Phase three PATHFINDER program was designed to evaluate the safety and efficacy of paltusotine for the treatment of a broad spectrum of patients with acromegaly.

正如Scott 剛才提到的，我們仍在按計劃提交Paltusotine 的新藥上市申請（NDA），用於今年的第一個適應症，即肢端肥大症，正如我們所討論的，第三階段PATHFINDER 計劃旨在評估Paltusotine 治療廣譜疾病的安全性和有效性。

Based on the success of both, phase 3 PATHFINDER studies.

基於這兩項研究的成功，第 3 階段的 PATHFINDER 研究。

We intend to seek approval for all patients, including those switching from the standard of care injected SRLs tip out to the team as studies in PATHFINDER one and those who are not currently treated as studies in Pathfinder two.

我們打算為所有患者尋求批准，包括那些從標準護理注射 SRL 轉為探路者一號研究的患者以及目前未在探路者二號研究中接受治療的患者。

In parallel with our Phase three program, we have laid the foundation to streamline and accelerate the NDA filing, we have held two productive pre-NDA interactions with the FDA to align on clinical, nonclinical, CMC and quality topics.

在第三階段計劃的同時，我們為簡化和加速 NDA 申報奠定了基礎，我們與 FDA 舉行了兩次富有成效的 NDA 前互動，以就臨床、非臨床、CMC 和品質主題進行協調。

The FDA confirmed that our proposed package supports submission for both the two and maintenance of acromegaly.

FDA 確認我們提議的一攬子計劃支持提交這兩種情況和維持肢端肥大症。

This robust package includes data from our two PATHFINDER Phase three studies as well as dose response analyses, data from our long-term safety studies and patient outcomes from the acromegaly symptom diary, which showed significant improvements in patient reported symptoms in both of our studies.

這個強大的資料包包括來自我們兩項PATHFINDER 三期研究的數據以及劑量反應分析、來自我們長期安全性研究的數據以及來自肢端肥大症症狀日記的患者結果，這表明我們兩項研究中患者報告的症狀有顯著改善。

We look forward to updating you as we continue towards the NDA filing in addition, we are diligently conducting health economics and outcome studies to further demonstrate the value proposition of power to the team in acromegaly.

我們期待在繼續提交新藥申請的過程中向您通報最新情況。

This work supports the commercial team's efforts as they engage with payers, physicians and patients.

這項工作支持商業團隊在與付款人、醫生和患者互動時的努力。

We are also making progress in paltusotine second indication, carcinoid syndrome.

我們在帕圖索汀的第二個適應症—類癌症候群方面也取得了進展。

As previously reported, our Phase two study showed highly statistically significant results, demonstrating the potential of paltusotine to treat people living with carcinoid syndrome.

如同先前所報導的，我們的第二階段研究顯示了高度統計顯著性的結果，證明了帕圖索汀治療類癌症候群患者的潛力。

Importantly, the patients who elected to participate in the ongoing open-label extension continue to benefit from power tools to building on this success we are preparing to discuss the Phase two results with the FDA and align on the design of a Phase three protocol.

重要的是，選擇參與正在進行的開放標籤擴展的患者將繼續受益於強大的工具，在這一成功的基礎上，我們正​​準備與FDA 討論第二階段的結果，並就第三階段方案的設計進行協調。

We expect to initiate the Phase three trial by the end of 2024.

我們預計在 2024 年底前啟動第三階段試驗。

Turning now to at a moment, we are excited about the progress and potential of that amendment in both CAH and Cushing's disease.

現在，我們對該修正案在 CAH 和庫欣氏症方面的進展和潛力感到興奮。

As Scott mentioned, the initial results from the open-label Phase two studies, which were featured at Endo have exceeded our expectations to three cohorts evaluating different doses of at a moment.

正如斯科特所提到的，Endo 上展示的開放標籤二期研究的初步結果超出了我們對同時評估不同劑量的三個隊列的預期。

In the CAH.

在CAH。

Phase two study are now fully enrolled.

第二階段研究現已全部入組。

We anticipate additional data will be available this year, and we are excited to advance this program.

我們預計今年將提供更多數據，我們很高興能推進該計劃。

We also expect to share additional data from the ongoing study in ACTH dependent Cushing's syndrome later this year.

我們還希望在今年稍後分享更多正在進行的 ACTH 依賴性庫欣氏症候群研究的數據。

So NetIQ's is fundamentally committed to placing patients at the forefront of everything we do.

因此，NetIQ 從根本上致力於將患者置於我們所做的一切的最前沿。

This patient-centric approach is deeply ingrained in the development activities for each of the programs in our pipeline, we actively seek patient input throughout the drug development process.

這種以患者為中心的方法深深植根於我們管道中每個項目的開發活動中，我們在整個藥物開發過程中積極尋求患者的意見。

We've gained valuable insights by sharing data with patients, particularly from our acromegaly program.

透過與患者分享數據，特別是我們的肢端肥大症計畫的數據，我們獲得了寶貴的見解。

These insights validate our commitment to developing treatments that improve patients' quality of life, such as offering convenient dosing regimens.

這些見解證實了我們對開發改善患者生活品質的治療方法的承諾，例如提供方便的給藥方案。

We have also routinely partnered with patient advocacy groups to obtain patient input on clinical trial design.

我們也定期與患者倡導團體合作，以獲取患者對臨床試驗設計的意見。

Patients are enthusiastic about the potential of our team, recognizing that it not only delivers the desired biochemical control, but can also improve the symptom of the burden associated with their condition.

患者對我們團隊的潛力充滿熱情，並認識到它不僅可以提供所需的生化控制，而且還可以改善與其病情相關的負擔症狀。

We invested considerable efforts to develop the acromegaly symptom diary and are supporting that with psychometric analyses to help document the impact of power to the team on patients' quality of life.

我們投入了大量精力來開發肢端肥大症症狀日記，並透過心理測量分析來支持這份日記，以幫助記錄團隊權力對患者生活品質的影響。

Positive feedback we have received so far indicates that our patient focused approach can help us develop better therapies that make a meaningful difference to patients.

到目前為止，我們收到的正面回饋表明，我們以患者為中心的方法可以幫助我們開發更好的療法，為患者帶來有意義的改變。

I'll now hand the call over to Jim to review commercial readiness strategy and current progress.

我現在將把電話轉交給吉姆，以審查商業準備策略和當前進展。

Thank you, Dana.

謝謝你，達納。

For many years, Crinetics has been a committed member of the endocrinology community.

多年來，Crinetics 一直是內分泌學界的忠實成員。

We participated in many medical conferences and learn from countless listening sessions with both patients and healthcare providers alike.

我們參加了許多醫學會議，並從與患者和醫療保健提供者等的無數聆聽會議中學習。

We're now on the verge of filing the paltusitine NDA, an opportunity to establish a new standard of care in the treatment of acromegaly.

我們現在即將提交帕圖西汀 NDA，這是建立肢端肥大症治療新護理標準的機會。

For patients, healthcare practitioners and payers.

對於患者、醫療保健從業者和付款人。

Acromegaly is the first indication for paltusitine.

肢端肥大症是帕圖西汀的第一個適應症。

Our launch preparation activities are laying the foundation of a fully integrated organization that can be leveraged for future indications, including carcinoid syndrome, as well as other drug candidates in our pipeline.

我們的上市準備活動正在為一個完全整合的組織奠定基礎，該組織可用於未來的適應症，包括類癌症候群以及我們管道中的其他候選藥物。

Our overarching strategy is to disrupt the established acromegaly marketplace, which has not seen any new molecules in over a decade.

我們的整體策略是顛覆現有的肢端肥大症市場，十多年來沒有出現任何新分子。

We are bringing a clinically differentiated once daily oral medication to market with our commercial infrastructure and differentiated support services.

我們透過我們的商業基礎設施和差異化的支援服務，將臨床差異化的每日一次口服藥物推向市場。

Our commercial strategy is guided by three underlying pillars.

我們的商業策略以三個基本支柱為指導。

First, extending Crinetics's partnership with healthcare practitioners.

首先，擴大 Crinetics 與醫療保健從業人員的合作夥伴關係。

Second, empowering patients; and third, streamlining access to therapy.

第二，賦予病人權力；第三，簡化治療途徑。

The first pillar is extending our partnership with the endocrinology community.

第一個支柱是擴大我們與內分泌學界的合作關係。

We will be launching into a concentrated prescriber base of approximately 200 healthcare practitioners, who are responsible for the vast majority of prescriptions.

我們將建立一個由約 200 名醫療保健從業人員組成的集中處方者群體，他們負責絕大多數處方。

These providers can be reached with a small sales force of approximately 25 to 30 sales representatives in conjunction with other activities across the organization, including medical affairs.

可以透過大約 25 至 30 名銷售代表的小型銷售團隊以及整個組織內的其他活動（包括醫療事務）來聯繫這些提供者。

As we deepen our relationships with prescribers, we are building awareness of the patient experience and burden associated with the current standard of care.

隨著我們加深與處方醫生的關係，我們正在建立對患者體驗和與當前護理標準相關的負擔的認識。

We've conducted multiple lines of market research, and one common theme is a disconnect between what physicians perceive and what their patients actually experience.

我們進行了多方面的市場研究，一個共同的主題是醫生的看法與病人的實際經驗之間的脫節。

For example, we found that endocrinologists believe two-thirds of their acromegaly patients on pharmacotherapy are well-controlled biochemically and symptomatically.

例如，我們發現內分泌學家認為，在接受藥物治療的肢端肥大症患者中，三分之二的生化和症狀得到了良好控制。

However, in our patient surveys, we found that 79% of acromegaly patients report breakthrough symptoms.

然而，在我們的患者調查中，我們發現 79% 的肢端肥大症患者報告了突破性症狀。

Now, these are symptoms that often reemerge toward the end of their monthly treatment cycle.

現在，這些症狀經常在每月治療週期結束時再次出現。

Patients have indicated that the treatment burden and breakthrough symptoms can be detrimental to their lives, but patients may not mention this during their physician appointments.

患者表示治療負擔和突破性症狀可能對其生活有害，但患者在約見醫生時可能不會提及這一點。

So, if doctors aren't asking and patients aren't volunteering this information, the disconnect is not being addressed.

因此，如果醫生不詢問，患者不主動提供這些信息，這種脫節就不會得到解決。

Healthcare practitioners are always seeking the best treatment for their patients, and today they don't always have complete visibility into their patient's experience.

醫療保健從業者一直在為患者尋求最佳治療，但如今他們並不總是能夠完全了解患者的體驗。

We at Crinetics are dedicated to providing an option that addresses the limitations of the current standard of care.

我們 Crinetics 致力於提供一種解決當前護理標準限制的選擇。

We want to bridge the frequent disconnect in dialogue and help healthcare practitioners become more aware of the patient experience, including the pain and challenges associated with Intramuscular and deep subcutaneous injections and the breakthrough symptoms that can occur at the end of the somatostatin receptor ligand injection cycle.

我們希望彌合對話中經常出現的脫節，幫助醫療保健從業者更了解患者的體驗，包括與肌肉內和深層皮下注射相關的疼痛和挑戰，以及生長抑素受體配體注射週期結束時可能出現的突破性症狀。

We believe paltusitine may provide a better treatment option for patients as it was designed to address the limitations of today's standard of care.

我們相信帕圖西汀可能為患者提供更好的治療選擇，因為它旨在解決當今護理標準的局限性。

Our commercial team has recently launched acromegaly truth.com, our disease awareness campaign for endocrinologists treating patients with acromegaly, which you can see on slide 7.

我們的商業團隊最近推出了肢端肥大症 Truth.com，這是我們為治療肢端肥大症患者的內分泌科醫生開展的疾病宣傳活動，您可以在幻燈片 7 中看到。

More than 1500 providers have already interacted with this site so far.

迄今為止，已有 1500 多家供應商與該網站進行了互動。

Acromegalytruth.com includes perspectives from patients on injectable SSLs, including injection site reactions, GI side effects, breakthrough symptoms, and emotional impact of treatment.

Acromegalytruth.com 收錄了患者對注射 SSL 的看法，包括注射部位反應、胃腸道副作用、突破性症狀和治療的情緒影響。

In addition, we believe that positive data from the acromegaly symptom diary, which was one of the secondary endpoints used in the Pathfinder Phase 3 program, will help healthcare practitioners understand the clinical benefits of paltusitine, which go well beyond biochemical control.

此外，我們相信肢端肥大症症狀日記的積極數據（探路者第3 期計劃中使用的次要終點之一）將幫助醫療保健從業者了解帕圖西汀的臨床益處，這遠遠超出了生化控制。

In fact, we have already shared some of this data from the acromegaly symptom diary at Endo this past June.

事實上，我們已經在去年六月分享了一些關於遠藤肢端肥​​大症症狀日記的數據。

We hope this data will help physicians understand the potential transformative impact of paltusitine for their patients.

我們希望這些數據能幫助醫生了解帕圖西汀對病患的潛在變革性影響。

We already have strong relationships with academic key opinion leaders in the pituitary treatment centers.

我們已經與腦下垂體治療中心的學術關鍵意見領袖建立了牢固的關係。

As another example of our commercial execution, we are looking to expand our relationship with endocrinologists in the community setting.

作為我們商業執行的另一個例子，我們希望在社區環境中擴大與內分泌學家的關係。

To that end, we've assembled an initial team of thought leader liaisons who are in the field, deepening our relationships with clinical endocrinologists who are managing patient’s day in and day out.

為此，我們組成了一個由現場思想領袖聯絡人組成的初始團隊，加深了我們與日復一日管理患者的臨床內分泌學家的關係。

The second pillar of our commercial plan is empowering patients to ask for better care and improved control of their symptoms.

我們商業計劃的第二個支柱是讓患者能夠要求更好的護理並改善對症狀的控制。

We recognize the vital role patients play in advocating for their diagnosis, managing their disease, and seeking optimal treatment.

我們認識到患者在倡導診斷、管理疾病和尋求最佳治療方面發揮的重要作用。

To this end, we plan to launch next year an expanded disease awareness campaign targeted towards patients with acromegaly.

為此，我們計劃明年針對肢端肥大症患者發起一項擴大疾病認識活動。

The goal is to help patients realize that better control of their acromegaly symptoms and the lower treatment burden may be possible.

目標是幫助患者認識到更好地控制肢端肥大症症狀並減輕治療負擔是可能的。

Ultimately, we want to empower patients to ask their healthcare practitioner for paltusitine once approved.

最終，我們希望患者能夠在獲得批准後向其醫療保健醫生索取帕圖西汀。

As Dana mentioned, our patient advocacy team has been engaging with the acromegaly patient organizations since early in clinical development.

正如達納所提到的，我們的病患倡議團隊從臨床開發早期就開始與肢端肥大症患者組織合作。

We are continuing to strengthen our relationship with the patient community to ensure we are addressing the needs of patients.

我們將繼續加強與患者社區的關係，以確保我們滿足患者的需求。

The third pillar of our commercial plan is to ensure optimal patient access to our best-in-class therapy.

我們商業計劃的第三個支柱是確保患者能夠獲得我們一流的治療。

The national account team responsible for all payer interactions is in place and onboarded.

負責所有付款人互動的國家客戶團隊已就位並已就職。

We have had discussions with the top commercial and government payers covering the majority of lives in the country, and initial feedback from those payer advisory meetings has been encouraging.

我們與涵蓋該國大多數人生活的頂級商業和政府付款人進行了討論，這些付款人諮詢會議的初步反饋令人鼓舞。

We are finalizing a highly differentiated patient support center to help streamline the prescribing, dispensing and reimbursement process.

我們正在最終確定一個高度差異化的患者支援中心，以幫助簡化處方、配藥和報銷流程。

This support center is being designed based on our ongoing market research and discussions with patients to develop best practices and close the gaps in the current reimbursement processes.

這個支援中心的設計是基於我們正在進行的市場研究以及與患者的討論，以製定最佳實踐並縮小當前報銷流程中的差距。

We have also finalized our distribution channel.

我們也最終確定了我們的分銷管道。

We look forward to sharing more details at our next earnings call.

我們期待在下次財報電話會議上分享更多細節。

In addition to establishing the commercial foundation for a successful launch.

除了為成功發布奠定商業基礎之外。

Our medical affairs team is engaging in robust scientific discussions throughout the medical community.

我們的醫療事務團隊正在整個醫學界進行激烈的科學討論。

We've hired Dr. Bob Cudahy, an experienced endocrinologist who has dedicated much of his career to treating patients, including those with Acromegaly, and has built and led medical affairs functions at other organizations such as Janssen, Sanofi, and Amgen.

我們聘請了Bob Cudahy 博士，他是一位經驗豐富的內分泌學家，他的大部分職業生涯都致力於治療患者，包括肢端肥大症患者，並在楊森、賽諾菲和安進等其他組織建立和領導了醫療事務職能部門。

In conclusion, Crinetics continues our evolution to ensure that we are in the best position to execute our launch strategy following approval.

總之，Crinetics 繼續不斷發展，以確保我們處於最佳位置，在獲得批准後執行我們的發布策略。

The paltusitine data that have been generated to date puts us in a unique position to demonstrate a highly differentiated clinical profile across multiple dimensions, including biochemical control, symptom control, tolerability, and the overall patient experience.

迄今為止產生的帕圖西汀數據使我們處於獨特的地位，可以在多個維度上展示高度差異化的臨床特徵，包括生化控制、症狀控制、耐受性和整體患者體驗。

We know what is important to patients to the physicians, who treat them and to the healthcare system, and we believe the value proposition of paltusitine, which serves each of these constituencies well.

我們知道什麼對患者、治療他們的醫生以及醫療保健系統來說是重要的，我們相信帕圖西汀的價值主張，它很好地服務於這些群體。

Over the coming months leading up to the expected launch in 2025, we will continue to implement our commercial strategy and share updates along the way.

在預計 2025 年推出之前的未來幾個月，我們將繼續實施我們的商業策略並分享最新動態。

I believe in the transformative potential of paltusitine for patients with acromegaly, and I'm excited to be leading our commercial team to launch this therapy.

我相信帕圖西汀對肢端肥大症患者俱有變革潛力，我很高興能夠領導我們的商業團隊推出這種療法。

We are laying the foundation for a fully integrated pharmaceutical company that will be prepared for future paltusitine indications, as well as other products in the Crinetics pipeline.

我們正在為一家完全整合的製藥公司奠定基礎，該公司將為未來的帕圖西汀適應症以及 Crinetics 管道中的其他產品做好準備。

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

現在，我將把它交給馬克來審查財務狀況。

Thank you, Jim.

謝謝你，吉姆。

As Scott mentioned, I will be stepping down from my role as CFO at Crinetics for personal reasons.

正如 Scott 所提到的，由於個人原因，我將辭去 Crinetics 財務長的職務。

Crinetics is in very capable hands with its deep bench of leaders across the organization.

Crinetics 掌握在非常有能力的手中，在整個組織中擁有深厚的領導階層。

I'm proud of all we have accomplished during my tenure, and I look forward to the company's continued success as it evolves into a fully integrated endocrinology franchise.

我為我們在我任職期間所取得的成就感到自豪，我期待著公司在發展成為完全一體化的內分泌專營公司的過程中不斷取得成功。

With that, I'll now return review the second quarter financial results.

現在，我將回顧第二季的財務表現。

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

Crinetics 持續保持強勁的財務狀況，第二季末現金和投資約為 8.63 億美元。

Our solid financial foundation is projected to fund our current operating plan into 2028.

我們堅實的財務基礎預計將為我們目前的營運計畫提供資金直至 2028 年。

This includes plans to commercialize paltusitine for acromegaly, the initiation of multiple later-stage clinical trials in additional indications with paltusitine and Atumelnant, as well as continued investment in our pipeline.

這包括將帕圖西汀用於肢端肥大症的商業化計劃、針對帕圖西汀和 Atumelnant 的其他適應症啟動多項後期臨床試驗，以及對我們的管道的持續投資。

With respect to the second quarter financial results, research and development expenses were $58.3 million for the quarter end of June 30th, 2024, compared to $40.6 million for the same period in 2023.

就第二季財務表現而言，截至 2024 年 6 月 30 日季末的研發費用為 5,830 萬美元，而 2023 年同期為 4,060 萬美元。

The increase was primarily attributable to higher personnel costs and manufacturing and development activities, both of which were driven by the advancement of our clinical programs and the expansion of our preclinical portfolio.

這一增長主要歸因於人員成本以及製造和開發活動的增加，這兩者都是由我們的臨床項目的進步和臨床前產品組合的擴展所推動的。

For the quarter ended June 30th, 2024, General and Administrative expenses were $24.8 million compared to $13.3 million for the same period in 2023.

截至 2024 年 6 月 30 日的季度，一般及行政費用為 2,480 萬美元，而 2023 年同期為 1,330 萬美元。

The change was primarily due to an increase in personnel costs and an increase in outside services as we continue to build the infrastructure to support our growing pipeline.

這項變更主要是由於人員成本的增加和外部服務的增加，因為我們繼續建造基礎設施來支援我們不斷增長的管道。

Net loss for the quarter ended June 30th, 2024 was $74.1 million compared to a net loss of $51 million for the same period in 2023.

截至 2024 年 6 月 30 日的季度淨虧損為 7,410 萬美元，而 2023 年同期淨虧損為 5,100 萬美元。

Revenues were $0.4 million for the quarter end of June 30th compared to $1 million for the same period in 2023.

截至 6 月 30 日的季度營收為 40 萬美元，而 2023 年同期營收為 100 萬美元。

Revenues during the current year’s quarter were derived from the paltusitine licensing arrangement with our Japanese partner, SKK.

本季的收入來自與我們的日本合作夥伴 SKK 的帕圖西汀授權安排。

Net cash used for operating activities for the quarter end of June 30th, 2024 was $45.6 million.

截至 2024 年 6 月 30 日季末，用於經營活動的淨現金為 4,560 萬美元。

We expect our cash burn to be approximately $50 million to $60 million per quarter for the remainder of 2024.

我們預計 2024 年剩餘時間內每季的現金消耗約為 5,000 萬至 6,000 萬美元。

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

現在，在我們開始問答之前，我將把它交還給斯科特，讓他作結束語。

Thank you, Marc.

謝謝你，馬克。

Looking to the rest of '24 and '25, we'll continue to build on the strong progress today.

展望 24 年和 25 年剩下的時間，我們將繼續在今天取得的強勁進展的基礎上再接再厲。

We look forward to upcoming clinical and regulatory milestones from paltusitine and Atumelnant and continued advancement of our deep pipeline of emerging candidates.

我們期待 paltusitine 和 Atumelnant 即將實現的臨床和監管里程碑，並繼續推進我們的新興候選藥物的深入研發。

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

Crinetics 繼續處於有利地位，成為首屈一指的、完全整合的、專注於內分泌的製藥公司。

Thank you all for your attention.

感謝大家的關注。

Operator, we're ready to take questions for folks on the call.

接線員，我們已準備好回答通話中的人員問題。

We'd appreciate it if you could limit yourself to one question.

如果您能只回答一個問題，我們將不勝感激。

We have a lot of analysts on the call, want to ensure that we can provide each of you with a thoughtful response.

我們有很多分析師正在通話，希望確保我們能夠為你們每個人提供深思熟慮的答案。

Thank you everybody.

謝謝大家。

(Operator Instructions).

（操作員說明）。

Jessica Fye, JP Morgan

潔西卡‧菲伊，摩根大通

Good afternoon.

午安.

Thanks for taking my question.

感謝您提出我的問題。

Marc, it's been great working with you over the years.

馬克，這些年來與你合作非常愉快。

I was wondering how we should think about what additional insights we could expect to gain from the Phase 2 updates in CAH and Cushing's coming later this year.

我想知道我們應該如何思考我們可以從今年稍後發布的 CAH 和庫欣的第二階段更新中獲得哪些額外的見解。

And what venue or venues we should look for those at?

我們應該在哪些場所或哪些場所尋找這些？

Thank you.

謝謝。

Just let me hand that over to Alan to give you a brief.

讓我把它交給艾倫，讓他給你一個簡短的介紹。

We will have final or top line results in CAH and Cushing's disease hopefully.

我們有望獲得 CAH 和庫欣氏症的最終或頂線結果。

And we will be able to sort of continue to support the messages.

我們將能夠繼續支持這些訊息。

I believe that we have already communicated at the endocrine society, meaning this appears to be a uniquely effective agent in these disease states that in terms of biomarker responses.

我相信我們已經在內分泌學會上進行了溝通，這意味著就生物標記反應而言，這似乎是這些疾病狀態中獨特有效的藥物。

I think, with higher sample sizes, we'll have a greater variety, a greater number of patients evaluated and we'll have, most importantly probably from the regulatory standpoint is the dose response relationship fully described.

我認為，隨著樣本量的增加，我們將有更多的種類、更多的患者進行評估，最重要的是，從監管的角度來看，我們將充分描述劑量反應關係。

And I think that's what will trigger, that's the information we need to really fully design our Phase 3 program and go forward in development.

我認為這就是我們真正全面設計第三階段計劃並繼續開發所需的資訊。

And maybe as a quick reminder to those, not as close to it as us, we now have the 40 milligram, 80 milligram and one 20 milligram cohorts enrolled, and the data from those groups will be available later this year.

也許是為了快速提醒那些不像我們那麼密切的人，我們現在登記了 40 毫克、80 毫克和一個 20 毫克隊列，這些組的數據將於今年稍後提供。

Yasmeen Rahimi, Piper Sandler.

亞斯明·拉希米，派珀·桑德勒。

Marc, we're going to greatly miss you.

馬克，我們會非常想念你的。

It's been really a pleasure working with you and we have done a tremendous job.

與您合作真的很愉快，我們做得非常出色。

So, we will definitely miss you and hope the search continues for a little longer so we can continue working with you.

因此，我們一定會想念您，並希望搜尋能持續更長時間，以便我們能夠繼續與您合作。

Wanted to ask just a question on carcinoid.

只是想問一個關於類癌的問題。

If you could provide some color around engagement with the agency.

如果您可以提供一些有關與該機構的互動的資訊。

Where are you in terms of the sign off?

就簽核而言，你在哪裡？

And what's sort of left to do to kick off the registrational study and I'll jump back into the queue.

還需要做什麼才能開始註冊研究，我將重新加入隊列。

Thanks guys.

謝謝你們。

Dana, you want to handle that one?

達納，你想處理那個嗎？

Yes, we've just completed all the analysis that we needed to do and are essentially ready to start the process of engaging with them.

是的，我們剛剛完成了需要做的所有分析，基本上準備好開始與他們合作的過程。

So, it shouldn't take too long to get that squared away.

因此，解決這個問題應該不會花太長時間。

As we mentioned, we're expecting to get the trial up and running by the end of the year, we have not yet completed the discussions with them.

正如我們所提到的，我們預計在今年年底前啟動並運行試驗，但我們尚未完成與他們的討論。

So, we're sort of actively involved.

所以，我們有點積極參與。

Jeff Hung, Morgan Stanley

傑夫洪，摩根士丹利

Thank you for taking my question, and best wishes to Marc.

感謝您提出我的問題，並向馬克致以最美好的祝愿。

You mentioned that you may advance your ADPKD program with a partner independently.

您提到您可以與合作夥伴獨立推進您的 ADPKD 專案。

What would be the deciding factors for Crinetics to go with one strategy versus the other?

Crinetics 採用一種策略與另一種策略的決定因素是什麼？

And is that the only, is that only relevant to this program, or are there specific early-stage programs that you would not be opening open to partnering?

這是唯一的嗎？

Thanks.

謝謝。

Well, so there's a couple considerations.

嗯，有幾個考慮因素。

Thanks for the question, Jeff.

謝謝你的提問，傑夫。

Couple considerations.

夫婦的考慮。

One is, we've built a remarkably strong team in the endocrinology area and we would need to start building out our kidney capabilities, our nephrology capabilities, in order to do justice for this program.

一是，我們在內分泌領域建立了一支非常強大的團隊，我們需要開始增強我們的腎臟能力，我們的腎臟病學能力，以便公正地對待這個計畫。

And that being said, I think that's quite a reasonable thing for us to do.

話雖這麼說，我認為這對我們來說是一件非常合理的事情。

As a reminder, the polycystic kidney program and the PTH antagonist program both address nephrology populations, so there would be some synergy there.

提醒一下，多囊性腎臟計畫和 PTH 拮抗劑計畫都針對腎臟病族群，因此兩者之間會有一些協同作用。

On the other hand, there may be groups out there that are further advanced than us in the field and could do better justice to this program more rapidly.

另一方面，可能有一些團體在該領域比我們更先進，並且可以更快地更好地實施該計劃。

And I'll also just say that, given the productivity of our discovery group and the depth of our pipeline, I want to make sure that from an internal perspective, we can grow adequately to give each program its due resources and attention.

我還要說的是，考慮到我們發現團隊的生產力和管道的深度，我想確保從內部角度來看，我們能夠充分發展，為每個專案提供應有的資源和關注。

And so that growth of the company is a factor as well.

因此，公司的成長也是一個因素。

We're in a very fortunate position to be able to have to make choices like this.

我們非常幸運能夠做出這樣的選擇。

Dennis Ding, Jefferies

丹尼斯丁，傑弗里斯

Thanks for taking my question.

感謝您提出我的問題。

Maybe if I can ask one on Atumelnant, here how you're thinking about the pricing strategy once you guys eventually get approved next year if you plan a price at a premium given.

也許我可以問一下 Atumelnant，如果你們計劃以給定的溢價定價，那麼一旦你們明年最終獲得批准，你們會如何考慮定價策略。

Thank you so much.

太感謝了。

Thanks, Dennis.

謝謝，丹尼斯。

I'll let Jim handle that one.

我會讓吉姆來處理那件事。

Thanks, Dennis.

謝謝，丹尼斯。

Still too early to talk about pricing.

談論定價還為時過早。

We are engaged, as we mentioned, we are engaged with payers and sharing the value proposition.

正如我們所提到的，我們與付款人合作並分享價值主張。

And again, it has been some encouraging conversations date.

再說一次，這是一些令人鼓舞的對話。

But again, we just need to have a deeper look at a number of factors before we disclose pricing probably next year.

但同樣，我們只需要更深入地研究一些因素，然後我們可能會在明年公佈定價。

Joseph Schwartz, Leerink Partners.

約瑟夫‧施瓦茨，Leerink Partners。

Thanks, very much.

非常感謝。

Best wishes to Marc, of course, that's been great to work with you.

當然，我向馬克致以最良好的祝愿，與您合作真是太好了。

Are specific clinical outcomes being systematically measured in Tucan, or was the observation of two patients who resumed menstruation?

是在圖坎系統地測量具體的臨床結果，還是對恢復月經的兩名患者進行觀察？

Something that was just noticed.

剛剛注意到的東西。

I'm just wondering if there are other clinical benefits that might arise when you report top-line data in the second half.

我只是想知道當您在下半年報告頂線數據時是否可能會出現其他臨床益處。

Alan, would you like to answer Joe?

艾倫，你願意回答喬嗎？

So, in addition to our standard endocrine biomarkers to assess disease state in CAH, there's a large number of clinical parameters that are observed as part of any clinical trial.

因此，除了我們用於評估 CAH 疾病狀態的標準內分泌生物標記外，還有大量臨床參數可作為任何臨床試驗的一部分進行觀察。

But in particular, this one we do follow certain things very carefully, particularly menstrual function.

但特別是，我們確實非常仔細地關注某些事情，特別是月經功能。

We have menstrual diaries in these trials, for example.

例如，我們在這些試驗中有月經日記。

We also look at metabolic control in other ways using various kinds of blood testing.

我們也透過各種血液檢測以其他方式研究代謝控制。

We know that for example, glucose is an important parameter in these patients and other like measures.

例如，我們知道，血糖是這些患者和其他類似指標的重要參數。

There's actually going to be a large number of what I would call patient reported outcomes and also physician reported outcomes both in Phase 2, but even more importantly in Phase 3 when we have larger numbers of patients to assess of both genders.

實際上，在第二階段中將會有大量我稱之為患者報告的結果和醫生報告的結果，但更重要的是在第三階段，當我們有更多的患者來評估兩性時。

Very helpful.

非常有幫助。

Thanks, Alan.

謝謝，艾倫。

Gavin Clark-Gartner, Evercore ISI

Gavin Clark-Gartner，Evercore ISI

Thank for taking my question.

感謝您提出我的問題。

I just wanted to ask more specifically on the carcinoid regulatory feedback as we're getting close to that.

我只是想更具體地詢問類癌監管回饋，因為我們已經接近這一點。

What's your desired base case or expectation on primary endpoint confidence that a placebo comparator arm will be viable?

您對安慰劑比較組可行的主要終點信心期望的基本情況或期望是什麼？

And also, just reconfirm you're looking at both switch and new starts and confirming those would be within the same one trial.

另外，只需再次確認您正在查看切換和新的開始，並確認它們將在同一個試驗中。

Thank you.

謝謝。

Thanks.

謝謝。

As far as the patient population, we're definitely intending to include both previously treated and naive patients.

就患者群體而言，我們肯定打算包括先前接受過治療的患者和未接受過治療的患者。

I think, we have looked at a lot of different ways to estimate efficacy.

我認為，我們已經研究了很多不同的方法來估計療效。

And since there's no real sort of guidances from FDA in this indication, it's a little bit sort of ours to propose.

由於 FDA 沒有針對這種適應症提供真正的指導，因此這有點像是我們的提議。

So, I think that we'd rather kind of have the discussions first and then disclose where we're going after we've designed the trial.

因此，我認為我們寧願先進行討論，然後在設計試驗後披露我們的進展。

Is there anything else, Gavin, that you asked?

加文，你還有什麼想問的嗎？

It's just reconfirming whether placebo or an active compared to arm maybe required.

這只是再次確認是否需要安慰劑或活性藥物與手臂相比。

Our plan is that a placebo trial will be required.

我們的計劃是需要進行安慰劑試驗。

Brian Skorney, Baird.

布萊恩·斯科尼，貝爾德。

This is Charlie on for Brian.

這是查理為布萊恩代言的。

Thanks for taking our question.

感謝您提出我們的問題。

So just thinking about the profile of paltusitine we've seen so far, do you have any plans to investigate it in the treatment of neuroendocrine tumors in the future?

那麼，想想我們迄今為止所看到的帕圖西汀的概況，您是否有計劃在未來研究它在神經內分泌腫瘤治療中的應用？

So, we are using it to treat neuroendocrine tumors in those patients that experience the symptoms of carcinoid syndrome.

因此，我們用它來治療那些出現類癌症候群症狀的患者的神經內分泌腫瘤。

So perhaps you're referring to understanding the anti-tumor activity that's well described as part of somatostatin receptor ligands on these tumor types.

因此，也許您指的是了解抗腫瘤活性，這種活性已被充分描述為生長抑素受體配體對這些腫瘤類型的一部分。

And so, we are thinking that as part of our Phase 3, we will be observing tumors both in the Phase 3 study in itself and in open-label extensions, but we're not designing the trial to measure anti-tumor activities as we think we've got a wide range of other areas we should be investing in.

因此，我們認為，作為第 3 期研究的一部分，我們將在第 3 期研究本身和開放標籤擴展中觀察腫瘤，但我們不會設計試驗來測量抗腫瘤活性，因為我們我認為我們還有很多其他領域值得投資。

And that the treatment of patients with neuroendocrine tumors is moving more and more to somatostatin analogs for symptom control and other modalities are coming in play for treatment of the tumor growth itself.

神經內分泌腫瘤患者的治療越來越多地轉向生長抑素類似物來控制症狀，其他治療方式也開始用於治療腫瘤生長本身。

And I think, you'll hear more from us in the coming quarters about some of these details.

我認為，在接下來的幾個季度中，您會從我們這裡聽到更多有關其中一些細節的資訊。

Thank you.

謝謝。

Thank you.

謝謝。

Catherine Novack, Jones Research

凱瑟琳諾瓦克，瓊斯研究中心

Hey, good afternoon, guys.

嘿，下午好，夥計們。

If I can just one about the pipeline again.

如果我能再談談管道的話。

I'm curious about the role of SST3 agonism in ADPKD.

我很好奇 SST3 激動劑在 ADPKD 中的作用。

If you can just talk about your decision to go into ADPKD and how this approach might differentiate from earlier studies that looked at anti-proliferative drugs, which seemed to reduce kidney volume, but not necessarily improve kidney function per se.

您能否談談您進入 ADPKD 的決定，以及這種方法與早期抗增殖藥物的研究有何不同，後者似乎減少了腎臟體積，但不一定能改善腎功能本身。

Yes, no, thanks, Catherine.

是的，不，謝謝，凱瑟琳。

And that question could justify a half a day conversation about, the science here.

這個問題可能值得花半天的時間來討論這裡的科學。

But it is fairly remarkable that as we were looking through the literature just in our day-to-day scientific reading.

但值得注意的是，當我們在日常科學閱讀中瀏覽文獻時。

We noticed that the people studying Crinetics of which polycystic kidney is a one of the manifestations of the Crinetics, that everybody was using an antibody against SST 3 as a cytologic marker for immuno staining of the Cilia.

我們注意到，研究 Crinetics 的人（其中多囊腎是 Crinetics 的表現之一），每個人都使用抗 SST 3 的抗體作為纖毛免疫染色的細胞學標記。

So SST3 is expressed very cleanly in cilia, and we know that the Crinetics that are caused by mutations in poly systems, which result in an imbalance of the cyclic AMP and calcium ratio in the cilia and all somatostatin with too much cyclic AMP, and all somatostatin analogs are acting all somatostatin receptors are acting to decrease cyclic AMP levels in cells and in this case in the primary cilia.

所以SST3在纖毛中表達得非常乾淨，我們知道Crinetics是由多系統突變引起的，導致纖毛中環AMP和鈣比例不平衡以及所有環AMP過多的生長抑素，以及所有生長抑素類似物的作用是所有生長抑素受體都可以降低細胞中的環磷酸腺苷水平，在這種情況下是初級纖毛中的環磷酸腺苷水平。

So, we'll be coming out with more and more data around this.

因此，我們將提供越來越多的相關數據。

But we've developed animal models in genetically engineered mice.

但我們已經在基因工程小鼠中開發了動物模型。

We've done cyst models and dispersed kidney cells.

我們製作了囊腫模型和分散的腎細胞。

We've done signaling, we've done a variety of things to begin to shore up the hypothesis that activating the SST3 will be effective in polycystic kidney disease.

我們已經完成了信號傳導工作，我們已經做了各種各樣的事情來開始支持激活 SST3 將有效治療多囊性腎病的假設。

But of course, the real test is to get it into patients and see what it does.

但當然，真正的測試是將其註入患者體內並觀察其作用。

So that's what we're trying to figure out how to get there, whether either ourselves or through partners, but a huge unmet need.

因此，這就是我們正在努力弄清楚如何實現這一目標的方法，無論是我們自己還是透過合作夥伴，但這是一個巨大的未滿足的需求。

Just as a hint we don't expect based on the location in the renal tubules that this will cause the type of very high urine volumes that you see with the vasopressin antagonists.

提示一下，根據腎小管的位置，我們預計這不會導致您在使用加壓素拮抗劑時看到的非常高的尿量。

And that's one of the major limiting tolerability issues.

這是限制耐受性的主要問題之一。

Well, thanks that definitely looking forward to hearing more from that program in the future.

好吧，謝謝您，我們非常期待將來從該計劃中聽到更多。

Super exciting.

超級刺激。

Very high unmet need.

未滿足的需求非常高。

Jon Wolleben, Citizens JMP

Jon Wolleben，公民 JMP

Best wishes to Marc.

向馬克致以最美好的祝愿。

Was hoping you guys could talk a little bit about how you're thinking about next steps, specifically in CAH?

希望你們能談談你們對下一步的想法，特別是在 CAH 方面？

if you think you'd have enough information to move forward to a Pivotal trial, and then how you're thinking about integrating younger patients into the program as well?

如果您認為自己有足夠的資訊來推進關鍵試驗，那麼您如何考慮將年輕患者也納入該計劃？

Those are definitely key areas for us in the future.

這些絕對是我們未來的關鍵領域。

As Alan mentioned, and Scott mentioned before, that we're really encouraged by the data so far for CAH, and we think that once we have the full complement of patient data, we'll definitely be able to talk to the FDA about the design of Phase 3.

正如 Alan 和 Scott 之前提到的，迄今為止 CAH 的數據讓我們深受鼓舞，我們認為一旦我們掌握了完整的患者數據，我們肯定能夠與 FDA 討論該問題三期設計。

So, I think the data that we generate from those three cohorts in that trial will certainly be enough to go talk to the agency about our Phase 3 design.

因此，我認為我們在該試驗中從這三個隊列中產生的數據肯定足以與該機構討論我們的第三階段設計。

And as far as the pediatric program, we're also actively putting together protocol designs to evaluate that in Phase 2 and then be able to use that to very quickly move into Phase 3 because that obviously is a significant unmet medical need with profound morbidity for those kids.

就兒科計畫而言，我們也積極整合方案設計，以在第二階段進行評估，然後能夠利用它快速進入第三階段，因為這顯然是一個重大的未滿足的醫療需求，其發病率很高。那些孩子。

So, we're very focused on that.

所以，我們非常關注這一點。

Thank you very much.

非常感謝。

Leland Gershell, Oppenheimer

利蘭·格謝爾、奧本海默

Good afternoon.

午安.

Thanks for taking my question.

感謝您提出我的問題。

Marc, it has been great working with you and best of luck in the future.

馬克，與您合作非常愉快，祝福您未來一切順利。

Scott, wanted to ask on your thyrotropin receptor program, you'd mentioned recent calls that you've been moving nicely along with potential candidates.

斯科特，想詢問您的促甲狀腺素受體計劃，您提到最近的電話顯示您與潛在候選人的進展順利。

Just wondering where you may be there?

只是想知道你可能在那裡？

Could we see a clinical candidate nominated in the next few months or perhaps in 2025?

我們能否在未來幾個月或 2025 年看到臨床候選人被提名？

Yes, thanks.

是的，謝謝。

It's always hard to say when you're going to get there on the process of drug discovery is very much an asymptote.

藥物發現的過程在很大程度上是一條漸近線，很難說你什麼時候能到達那裡。

You just keep getting closer and closer and closer to what you think is an ideal candidate and a certain point you say that's good.

你只是不斷地接近你認為的理想候選人和你認為好的某一點。

That's good enough.

這就足夠了。

And I got to say that in the TSH antagonist where 1% to 2% of the population can have this disease.

我必須說，在 TSH 拮抗劑中，1% 到 2% 的人口可能患有這種疾病。

And we just saw I just saw the news this morning that one of my favorite characters, Ray and Star Wars was just diagnosed with grave disease, but this molecule needs to be really high quality.

我們剛剛看到今天早上我剛剛看到新聞，我最喜歡的角色之一，雷和星球大戰剛剛被診斷出患有嚴重疾病，但這種分子需要非常高品質。

So we are working hard on that.

所以我們正在為此努力。

I can I can tell we're really close but whether that's this quarter, next quarter or early next year, I don't know for sure, but it is right around the corner.

我可以說我們已經非常接近了，但無論是本季、下季還是明年初，我不確定，但它就在眼前。

Great, Thanks.

太好了，謝謝。

Douglas Tsao, H.C. Wainwright

雪兒 (Douglas Tsao)溫賴特

I'll join the chorus of people saying how much we've enjoyed working with Marc over the years.

我將和人們一起表達這些年來我們是多麼享受與馬克的合作。

I guess maybe a question for Jim, since he mentioned the fact that patients often have a very different experience with acromegaly than clinicians realize.

我想這可能是吉姆的問題，因為他提到了這樣一個事實，即肢端肥大症患者的經歷通常與臨床醫生意識到的非常不同。

So, I guess in terms of driving adoption how do you plan to get around that?

那麼，我想在推動採用方面，您打算如何解決這個問題？

Because I think that has been a factor that has hampered.

因為我認為這是一個阻礙因素。

There was the launch of CAH so in terms of converting that product.

CAH 的推出，就轉換該產品而言。

And I know that this profile is very different.

我知道這個檔案非常不同。

You have much, much stronger data, but just how do you from a tactical standpoint, plan to address that aspect of the launch?

您擁有非常非常強大的數據，但從戰術角度來看，您計劃如何解決發布的這方面問題？

Thank you.

謝謝。

Thanks Doug.

謝謝道格。

And I think, I'll start where, where you left off, which is, yes, we've got a great product paltusitine.

我想，我將從你停下的地方開始，是的，我們有一個很棒的產品帕圖西汀。

And that's something that does differentiate us certainly from most recent launches.

這確實是我們與最近推出的產品的不同之處。

But however, it is true that even with such a great product, what we hear from physicians is, if it's not broken, I'm not going to fix it.

但事實上，即使有這麼好的產品，我們從醫生那裡聽到的是，如果它沒有壞，我就不會修理它。

And that's exactly the purpose and the rationale behind our disease state campaign acromegaly truth.com.

這正是我們進行疾病狀態運動 acromegaly Truth.com 的目的和基本原理。

Already, there's a small contingent of endocrinologists that are behind a lot of the data in this area of, again, trying to address this discord in dialogue.

已經有一小群內分泌學家在這個領域的大量數據背後，再次試圖解決對話中的不和諧。

And it is really making sure that physicians are aware of the patient experience and then ensuring that as we get closer to launch that we really do empower patients to have that discussion with their endocrinologist.

它確實確保醫生了解患者的體驗，然後確保當我們接近啟動時，我們確實能夠讓患者與內分泌科醫生進行討論。

Based on the research that we've done, Doug, it's a powerful message and I know that the physicians have reacted well to the awareness.

道格，根據我們所做的研究，這是一個強有力的信息，我知道醫生們對這一認識反應良好。

And I will tell you that patients even react better to it when they see the campaign, and realize that yes, this is the kind of discussion, these are the kinds of symptoms that they're feeling.

我會告訴你，當患者看到該活動時，他們甚至會對此做出更好的反應，並意識到是的，這就是這種討論，這些就是他們所感受到的症狀。

This is what they want, this is the kind of discussion they want to have with their endocrinologist.

這就是他們想要的，這就是他們想要與內分泌科醫生進行的討論。

So more to come and we'll be providing details as to how impactful this is and what the metrics are from the campaign.

因此，接下來會有更多內容，我們將提供有關此活動的影響力以及活動指標的詳細資訊。

But it is really that the underpinning of a great product is the awareness around the problem.

但事實上，優秀產品的基礎是對問題的認知。

Okay, great.

好的，太好了。

Thank you so much and that's helpful.

非常感謝你，這很有幫助。

Thanks, Doug.

謝謝，道格。

Cory Jubinville, LifeSci Capital

朱賓維爾 (Cory Jubinville)，生命科學資本

Congrats on all the progress.

祝賀所有的進展。

Marc congrats on everything you've helped build over the years.

馬克對您多年來幫助建立的一切表示祝賀。

Will definitely be sad to see you go, but of course, wish you well and whatever comes next.

看到你離開肯定會很難過，但當然，祝你一切順利，無論接下來會發生什麼。

But I guess can you help give us a bit of context in how your launch efforts in acromegaly could potentially help support a launch in carcinoid syndrome down the line?

但我想您能否幫助我們介紹一下您在肢端肥大症方面的推出工作如何可能有助於支持類癌綜合徵的推出？

Thinking about these prescriber groups as almost like a Venn diagram, how might a carcinoid patient, how often might a carcinoid patient be coming in contact with an endocrinologist that might have had previous experience with paltusitine treating acromegaly?

將這些處方者群體視為幾乎像維恩圖一樣，類癌患者與可能有過帕圖西汀治療肢端肥大症經驗的內分泌科醫生接觸的頻率如何？

While it's certainly been several years ago, are there any learnings you're taking from the expansion of octreotide or lanreotide into these patient groups from acromegaly to carcinoid syndrome or get net that that can be applied to your strategy with paltusitine?

雖然已經是幾年前的事了，但您是否從將奧曲肽或蘭瑞肽擴展到從肢端肥大症到類癌綜合徵的這些患者群體中學到了什麼，或者是否可以將其應用於您的帕圖西汀策略？

Thanks, Cory.

謝謝，科里。

We have already started to look at the overlap in terms of the customer base.

我們已經開始考慮客戶群的重疊情況。

And I'll tell you where we see a great deal of overlap is in the pituitary treatment centers.

我會告訴你我們在腦下垂體治療中心看到大量重疊的地方。

The same academic centers.

相同的學術中心。

There are about 45 of these pituitary treatment centers.

大約有 45 個這樣的腦下垂體治療中心。

And there is a good deal of overlap with, for example, the NCCN cancer network, the national comprehensive Cancer Network.

與 NCCN 癌症網絡、全國綜合癌症網絡等有許多重疊。

So, places like Memorial Sloan Kettering, Dr. Eliza Geer is at MSK, that's also obviously a cancer institution.

所以，像斯隆凱特琳紀念館、伊麗莎吉爾醫生就在 MSK 斯隆這樣的地方，那顯然也是一個癌症機構。

And as well, to your point, there are specific endocrinologists that are very much involved in neuroendocrine tumors as well.

而且，就你的觀點而言，也有一些特定的內分泌學家也非常參與神經內分泌腫瘤的研究。

So, there is also an overlap.

所以，也存在重疊。

It will be though it will be a new indication for us to get into and oncologists are going to be a new audience for us.

儘管這將是我們進入的新適應症，腫瘤學家將成為我們的新受眾。

But again, where they're located is a lot of co-location and a great opportunity for us.

但同樣，他們所在的地方有很多協同辦公的地方，這對我們來說是一個很好的機會。

And maybe I'll just add to that, Corey, that beyond the actual practicing physicians and their staffs launching your first drug is an exercise in building out a range of different capabilities, relationships with those institutions, the pharmacies at those institutions, relationships with the payers, and as I mentioned, just our internal capabilities.

也許我會補充一點，科里，除了實際的執業醫生及其工作人員推出你的第一種藥物之外，還需要建立一系列不同的能力、與這些機構的關係、這些機構的藥房、與付款人，如我所提到的，只是我們的內在能力。

So, there's a huge amount of synergy between this and then the second launch.

因此，本次發布與第二次發布之間存在著巨大的協同作用。

And then that of course also support the third launch and fourth launches with at, and then the many, many other launches we anticipate with other things coming out of the pipeline.

當然，這也支援第三次發射和第四次發射，以及我們預期的許多其他發射以及其他即將推出的產品。

Thank you.

謝謝。

And there are no further questions at this time.

目前沒有其他問題。

I'd be happy to return the call to our host for any closing comments.

我很樂意回電給我們的主持人以徵求任何結束意見。

Thank you all for being here and listening to us.

感謝大家來到這裡並聆聽我們的演講。

And those of you who have such affection for Marc, he's not going anywhere right away and you know how to find him and I'm sure he'd be happy to have a drink and or lunch or ice cream and catch up sometime.

你們中那些對馬克如此有感情的人，他不會立即去任何地方，你們知道如何找到他，我相信他會很高興找個時間喝一杯、或吃午餐或吃冰淇淋，然後聊聊。

Thank you all for listening.

感謝大家的聆聽。

This does conclude today's Crinetics Pharmaceuticals second quarter 2024 earnings conference call.

今天的 Crinetics Pharmaceuticals 2024 年第二季財報電話會議到此結束。

Thank you for participating.

感謝您的參與。

You may now disconnect your line and have a great day.

您現在可以斷開線路並度過美好的一天。