Crinetics Pharmaceuticals Inc (CRNX) 2023 Q4 法說會逐字稿

Welcome to the Chronix Pharmaceuticals Fourth Quarter and Full Year 2023 financial results conference call.

歡迎參加 Chronix Pharmaceuticals 2023 年第四季和全年財務業績電話會議。

At this time, all participants are in a listen-only mode.

此時，所有參與者都處於只聽模式。

Following management's prepared remarks, we will hold a question and answer session.

在管理層準備好發言後，我們將舉行問答會議。

I will now turn the call over to Corey Davis of LifeSci Advisors.

我現在將把電話轉給 LifeSci Advisors 的 Corey Davis。

Please go.

請離開。

Thank you, Sergio, and hello, everyone.

謝謝你，塞爾吉奧，大家好。

Joining me on the call today are Scott Struthers, Founder and Chief Executive Officer, Alan Krasner, chief endocrinologist, and Mark Wilson, Chief Financial Officer.

今天與我一起參加電話會議的有創始人兼首席執行官斯科特·斯特拉瑟斯(Scott Struthers)、首席內分泌學家艾倫·克拉斯納(Alan Krasner) 和首席財務官馬克·威爾遜(Mark Wilson)。

Also joining us for the Q&A portion of the call are Dana pursued a Chief Medical and Development Officer, and Jim has Chief Commercial Officer.

達納 (Dana) 擔任首席醫療和開發官，吉姆 (Jim) 擔任首席商務官，也參加了電話會議的問答部分。

A press release announcing the fourth quarter and full year 2023 financial results was issued today and is also available on the kinetics website.

今天發布了宣布 2023 年第四季度和全年財務業績的新聞稿，該新聞稿也可在 Kinetics 網站上取得。

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.

提醒一下，我們將做出前瞻性陳述，我邀請您詳細了解與這些陳述相關的風險和不確定性。

As disclosed in our SEC filings.

正如我們在美國證券交易委員會 (SEC) 文件中所揭露的那樣。

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，由於與本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.

這些前瞻性陳述完全受到今天新聞稿中包含的警示性陳述的限制。

The Company's other news releases and kinetics SEC filings, including its annual report on Form 10 K.

該公司的其他新聞稿和動力學 SEC 備案，包括其 10 K 表格年度報告。

I'd 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, February 28th, 2024 for critics takes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this call.

我還想指出的是，本次電話會議的內容包含時間敏感的信息，僅截至本次直播之日（2024 年 2 月 28 日）準確，批評者沒有義務修改或更新任何前瞻性陳述反映本次電話會議之後發生的事件或情況。

I'll now hand the call over to Scott Struthers.

我現在將把電話轉給斯科特·斯特拉瑟斯。

Scott, go ahead.

斯科特，繼續吧。

Thanks, Corey, and good afternoon, everyone, and thank you for joining us for our quarterly results call.

謝謝科里，大家下午好，謝謝您參加我們的季度業績電話會議。

As the company progresses towards commercialization.

隨著公司逐步走向商業化。

It's our intent to expand our investor outreach and provide greater opportunities for interactive dialogue.

我們的目的是擴大我們的投資者範圍並提供更多的互動對話機會。

We appreciate your attendance and look forward to our discussion today and on future quarterly calls.

我們感謝您的出席，並期待我們今天的討論以及未來的季度電話會議。

To begin, I'll spend a few moments summarizing our recent accomplishments, but 14 before turning the call over to Alan Krasner, our Chief endocrinologist, to discuss our clinical programs and recently reported data in some more detail before we get started with the review of 2023, I wanted to say how pleased we are to have announced a private placement equity financing of approximately $350 million.

首先，我將花一些時間總結我們最近的成就，但在14 小時後，我將把電話轉給我們的首席內分泌學家艾倫·克拉斯納(Alan Krasner)，在我們開始審查之前更詳細地討論我們的臨床項目和最近報告的數據2023 年，我想說的是，我們非常高興宣布進行約 3.5 億美元的私募股權融資。

Earlier today, we're very appreciative of the continued support that we've received from new and existing shareholders who share our long-term vision for building the premier endocrine company to help patients suffering from a wide range of different endocrine related diseases.

今天早些時候，我們非常感謝新舊股東對我們的持續支持，他們與我們有著共同的長期願景，即建立一流的內分泌公司，幫助患有各種不同內分泌相關疾病的患者。

This financing is simply one more step forward in that strategy.

此次融資只是該策略又向前邁出了一步。

2023 was a tremendously successful year for kinetics on many fronts.

2023 年是動力學在許多方面取得巨大成功的一年。

I'll begin with our lead development candidate.

我將從我們的首席開發候選人開始。

Paltusotine toxicity team continues to deliver impressive results in the two indications for which it is being developed acromegaly and carcinoid syndrome.

帕妥索汀毒性團隊繼續在其正在開發的肢端肥大症和類癌綜合徵這兩個適應症中取得令人印象深刻的成果。

In September, we reported clinical results in acromegaly that exceeded expectations.

九月，我們報告了肢端肥大症的臨床結果超出了預期。

Our Phase three PATHFINDER one trial achieved its primary endpoint of maintaining IGF control and met all secondary endpoints with high statistical significance.

我們的第三階段 PATHFINDER one 試驗實現了維持 IGF 控制的主要終點，並達到了具有高度統計顯著性的所有次要終點。

As a reminder, PATHFINDER one was designed to evaluate oral paltusotine in patients with acromegaly for already controlled on standard of care, which are injected somatostatin receptor ligand depots or SRL. therapy.

提醒一下，PATHFINDER 旨在評估肢端肥大症患者的口服帕妥索汀是否已透過標準護理得到控制，這些患者註射了生長抑素受體配體長效製劑或 SRL。治療。

Our intention for this trial is to support an indication for the maintenance of acromegaly treatment.

我們進行這項試驗的目的是支持肢端肥大症維持治療的適應症。

In other words, to maintain biochemical control in patients switching from standard of care injectables to once-daily oral paltusotine.

換句話說，為了維持從標準護理注射轉為每日一次口服帕圖索汀的患者的生化控制。

In contrast, our second Phase three trial, Pathfinder two is evaluating paltusotine in patients with acromegaly who have elevated IGF-I levels above via the normal range.

相較之下，我們的第二個三期試驗 Pathfinder 2 正在評估帕圖索汀對 IGF-I 水平升高至正常範圍以上的肢端肥大症患者的療效。

These are patients who are either naive to therapy untreated for at least four months for patients who agreed to wash out of the standard of care.

這些患者要不是接受治療至少四個月未接受治療的患者，就是同意退出標準照護的患者。

As part of entering the study, we completed enrollment in PATHFINDER to last year, and we are on track to unblind and report top-line results in March If successful, we intend to submit an NDA supporting supported by these results from both studies to the U.S. FDA in the second half of 2024.

作為進入研究的一部分，我們去年完成了 PATHFINDER 的註冊，我們預計在 3 月揭盲並報告頂線結果。如果成功，我們打算向2024年下半年獲得美國FDA批准。

Overall, our PATHFINDER program is intended to provide a broad label for the treatment of acromegaly.

總體而言，我們的 PATHFINDER 計劃旨在為肢端肥大症的治療提供廣泛的標籤。

Moving now to carcinoid syndrome, our second intended indication for participating in December, we reported initial results from our ongoing open-label Phase two trial in patients with carcinoid syndrome.

現在轉向類癌綜合徵，這是我們 12 月參與的第二個預期適應症，我們報告了正在進行的類癌綜合徵患者開放標籤二期試驗的初步結果。

From a safety point of view, paltusotine continues to be well tolerated in this patient population, consistent with what we've seen from our other clinical studies to date.

從安全角度來看，帕妥索汀在該患者群體中仍然具有良好的耐受性，這與我們迄今為止從其他臨床研究中看到的結果一致。

With regard to efficacy to date, we are seeing clear reductions in the two key symptoms of carcinoid syndrome, which are excess bile movement, frequencies and flushing episodes results from December were from a subset of patients, and the study is now fully complete with a total of 36 patients.

就迄今為止的療效而言，我們看到類癌綜合徵的兩個關鍵症狀（即膽汁運動過多、頻率和潮紅發作）明顯減少，這些症狀來自 12 月的一部分患者，研究現已完全完成，共有36名患者。

And the proof in the profile we reported the initial results in that unit we reported in the initial results is confirmed in the top-line results that we are expected in this first half of this year.

我們在初步結果中報告的該部門的初步結果中的證據在我們預計今年上半年的頂線結果中得到了證實。

We're excited to move forward into Phase three studies in carcinoid syndrome, pending alignment with the FDA on the study design we've been following in the footsteps of Tuscaloosa team.

我們很高興能夠進入類癌症候群的第三階段研究，等待與 FDA 就我們一直追隨塔斯卡盧薩團隊的腳步的研究設計進行協調。

We built a remarkably deep pipeline.

我們建立了一條非常深的管道。

Our second molecule for eight nine four is currently being evaluated in an open-label Phase two trial in patients with congenital adrenal hyperplasia or CAH and a second trial in patients with ACTH. dependent Cushing's disease people or CH. are unable to make cortisol and instead make excess adrenal androgens.

我們的第二個八、九四分子目前正在先天性腎上腺增生或 CAH 患者的開放標籤二期試驗和 ACTH 患者的第二項試驗中進行評估。依賴庫欣氏症的人或CH。無法產生皮質醇，而是產生過量的腎上腺雄性激素。

And 494 is an oral ACTH antagonist designed to normalized levels of adrenal androgens.

494 是一種口服 ACTH 拮抗劑，旨在使腎上腺雄激素水平正常化。

Alan will elaborate on this program, and we anticipate reporting initial results from a subset of patients in the second quarter of the year beyond 49 core.

艾倫將詳細闡述該計劃，我們預計將在今年第二季報告超過 49 名核心患者的初步結果。

We're also advancing multiple preclinical programs, including a parathyroid hormone or PTH receptor antagonist for the treatment of hyperparathyroidism TSH antagonist for the treatment of Grace disease and thyroid eye disease and candidates for metabolic disease diseases, including diabetes and obesity.

我們也正在推進多個臨床前項目，包括用於治療副甲狀腺功能亢進症的副甲狀腺素或PTH 受體拮抗劑、用於治療格雷斯病和甲狀腺眼病的TSH 拮抗劑以及治療代謝性疾病（包括糖​​尿病和肥胖症）的候選藥物。

These are just a few of the many early stage programs in our pipeline, and we plan to provide you with regular updates on these and other development candidates when appropriate in anticipation of a potential 2025 launch of paltusotine, we also remain focused on building out our commercial organization acromegaly and carcinoid syndrome together present a multi-billion dollar market opportunity for actively developing commercial capabilities for these markets, identifying key prescribers and tailoring our launch strategy.

這些只是我們管道中的眾多早期項目中的幾個，我們計劃在適當的時候為您提供這些和其他開發候選項目的定期更新，以預測2025 年可能推出的帕妥索汀，我們也仍然專注於建立我們的專案商業組織肢端肥大症和類癌綜合徵共同提供了數十億美元的市場機會，可以積極開發這些市場的商業能力，確定主要處方者並定制我們的上市策略。

We know that Pathfinder one data is resonating well, creating excitement among the acromegaly and carcinoid syndrome prescribers and the patients understanding payer perspectives is also crucial.

我們知道，探路者一號的數據引起了很好的共鳴，在肢端肥大症和類癌綜合徵的處方者中引起了興奮，而患者了解付款人的觀點也至關重要。

And Jim hazard and our Chief Commercial is our Chief Commercial Officer is building a market access team to build relationships with these important stakeholders.

吉姆·哈斯特和我們的首席商務官正在建立一個市場准入團隊，以與這些重要的利害關係人建立關係。

We're preparing logistics, finalizing specialty pharmacy agreements and generally preparing the company for commercial readiness on all fronts.

我們正在準備物流，敲定專業藥房協議，並為公司在各個方面做好商業準備做好整體準備。

Looking forward to the rest of 2024 and 25, we anticipate multiple transformative milestones ahead, completing Pathfinder two, completing Phase two, followed by initiation of a Phase three study in carcinoid syndrome, completing a Phase two and initiating a Phase three in CAH, submitting our first NDA and launching how to for acromegaly, if approved for over continuing to advance our pipeline of promising candidates in high prevalence indications that are beginning to emerge from discovery.

展望2024 年及25 年剩餘時間，我們預期未來將出現多個變革性里程碑，完成探路者二期、完成第二期、隨後啟動類癌症候群第三期研究、完成第二期並啟動CAH的第三期研究，提交我們的第一個NDA 並啟動瞭如何治療肢端肥大症，如果獲得批准，將繼續推進我們在高患病率適應症中的有希望的候選藥物的管道，這些適應症已經開始出現。

We are also continuing to invest in our world-class discovery capabilities that are the roots of our long-term success.

我們也持續投資於世界級的發現能力，這也是我們長期成功的根源。

With that, let me hand it over to Dr. Alan Krasner, our Chief endocrinologist, to talk about our clinical program and the results we're seeing today now.

接下來，讓我將其交給我們的首席內分泌學家 Alan Krasner 博士，來談談我們的臨床計劃和我們今天看到的結果。

Thank you, Scott.

謝謝你，斯科特。

Today I will provide a summary of the results we recently reported from our clinical programs and what this means for the continued development, starting with paltusotine.

今天，我將總結我們最近從臨床計畫中報告的結果，以及這對從帕圖索汀開始的持續開發意味著什麼。

As Scott already mentioned our Phase three PATHFINDER one study of oral paltusotine in patients with acromegaly achieved all the goals set out for the study.

正如史考特已經提到的，我們對肢端肥大症患者口服帕妥索汀的第三期探路者一期研究實現了該研究設定的所有目標。

In September, we reported highly statistically significant results in our primary endpoint and all secondary endpoints.

九月，我們報告了主要終點和所有次要終點的高度統計顯著性結果。

Before I dive into the data, I'd like to reiterate that this trial was designed to evaluate patients participating in patients who are already biochemically controlled on injectable SRL therapy and switch to participate in acromegaly excess growth hormone axis at the liver to secrete excess insulin-like growth factor one or IGF-1 participants in the Pathfinder one trial were previously treated with injectable SRL therapy and had IGF-1 levels at baseline of less than or equal to one times the upper limit of normal.

在深入研究數據之前，我想重申一下，這項試驗的目的是評估參與注射 SRL 療法的生化控制已得到控制並轉而參與肢端肥大症肝臟生長激素軸過量以分泌過量胰島素的患者Pathfinder one 試驗中的類生長因子1 或IGF-1 參與者之前曾接受過注射SRL 治療，且基線時的IGF-1 水準小於或等於正常上限的一倍。

The goal for participating in this trial was to maintain this level of biochemical control.

參與試驗的目標是維持這種生化控制水準。

Therefore, the primary endpoint was the proportion of participants who maintained IGF-1 levels of less than or equal to one times the upper limit of normal on paltusotine compared to placebo.

因此，主要終點是與安慰劑相比，使用帕妥索汀維持 IGF-1 水平低於或等於正常上限一倍的參與者比例。

We also prespecified clinically important metrics as secondary endpoints.

我們也預先指定了臨床重要指標作為次要終點。

The change from baseline in IGF one, the change in acromegaly symptoms using a fit for purpose, acromegaly symptom diary and the proportion of patients participants able to maintain growth hormone levels of less than one nanogram per milliliter.

IGF 相對於基線的變化、使用適合目的的肢端肥大症症狀的變化、肢端肥大症症狀日記以及能夠將生長激素水平維持在每毫升 1 納克以下的患者參與者的比例。

In the study, we saw a remarkable 83% or 25 of 30 patients who received paltusotine meet the primary endpoint.

在這項研究中，我們發現接受帕妥索汀治療的 30 名患者中，有 83%（即 25 名）達到了主要終點。

This is compared to only 4% or one out of 28 patients receiving placebo.

相較之下，只有 4%（即 28 名患者中就有 1 名）接受安慰劑。

The magnitude of this difference is highly statistically significant with a p-value of less than 0.0001 in all secondary endpoints.

此差異的大小具有高度統計顯著性，所有次要終點的 p 值均小於 0.0001。

We also achieved statistical statistical significance participants in the participating Group maintained control of IGF-1 levels, while those on placebo rose markedly.

我們也取得了統計顯著性，參與組的參與者保持了 IGF-1 水準的控制，而安慰劑組的參與者則顯著上升。

And this difference was statistically significant with a p-value of 0.0001 in addition, overall symptom control was measured using the acromegaly symptom diary or ASD. score participants receiving paltusotine maintain control of their symptoms as measured by the total ASD. score as compared to an overall increase from baseline as reported by the placebo group.

而且這種差異具有統計顯著性，p 值為 0.0001。此外，整體症狀控制是使用肢端肥大症症狀日記或 ASD 來測量的。根據總自閉症譜系障礙 (ASD) 衡量，接受帕圖索汀治療的參與者保持對症狀的控制。與安慰劑組報告的基線整體增加相比。

This difference was statistically significant with a P value of 0.02.

此差異具有統計學意義，P 值為 0.02。

Finally, 87% of participants receiving paltusotine maintained growth hormone levels less than one nanogram per milliliter compared to 28% in placebo.

最後，接受帕妥索汀治療的參與者中有 87% 的生長激素水平維持在每毫升 1 奈克以下，而安慰劑組的比例為 28%。

This difference was also highly statistically significant with a p-value of 0.0003. And we are very excited about these results that demonstrate durable symptom and biochemical control, driven through a convenient, once-daily oral option for patients who are currently burdened by depot injections.

這種差異也具有高度統計顯著性，p 值為 0.0003。我們對這些結果感到非常興奮，這些結果表明，透過為目前承受長效注射負擔的患者提供方便的每日一次口服選擇，可以實現持久的症狀和生化控制。

These data are very clear that paltusotine effectively maintains IGF-1 levels in the normal range in the draft guidance on the development of drugs for the treatment of acromegaly issued in January 2023, the FDA identified to acromegaly population pick up to a acromegaly patient populations of interest.

這些數據非常清楚地表明，帕妥索汀有效地將IGF-1水平維持在正常範圍內，在2023年1月發布的治療肢端肥大症藥物開發指南草案中，FDA確定肢端肥大症人群回升到肢端肥大症患者族群興趣。

Firstly, the maintenance population who are evaluated in the Pathfinder one trial.

首先，在探路者一項試驗中評估的維持人群。

And secondly, the treatment population that we are currently evaluating in our Pathfinder to study the treatment population includes those with active acromegaly who are not who are not currently on medical therapy and therefore have an IGF-1 level that is greater than the upper limit of normal.

其次，我們目前在探路者中評估以研究治療人群的治療人群包括那些患有活動性肢端肥大症的人，他們目前沒有接受藥物治療，因此 IGF-1 水平高於上限普通的。

The goal here is to show that a new agent can treat active disease as measured by lowering elevated IGF-1 level.

這裡的目標是證明一種新藥物可以透過降低升高的 IGF-1 水平來治療活動性疾病。

Srls are currently used in practice as first-line medical therapy for acromegaly.

Srls 目前在實務上用作肢端肥大症的第一線藥物治療。

Because published studies have demonstrated that most untreated patients when treated with SRL monotherapy have meaningful lowering of IGF-1, although only the minority of patients, particularly among those who are naive to medical therapy normalized IGF-1, it is not possible to predict which untreated patients who start out with a potentially wide range of baseline IGF-1 elevations will actually normalize.

因為已發表的研究表明，大多數未經治療的患者在接受SRL 單一療法治療時，IGF-1 均出現有意義的降低，儘管只有少數患者，特別是那些未曾接受過藥物治療的患者，IGF- 1 已正常化，但無法預測哪些患者會出現IGF-1 正常化。未經治療的患者一開始基線 IGF-1 升高的範圍可能很大，實際上會恢復正常。

But it is known that the majority of patients treated with an SRL in previous studies benefited from therapy for regulatory purposes.

但眾所周知，在先前的研究中，大多數接受 SRL 治療的患者都從出於監管目的的治療中受益。

The primary objective of Pathfinder two is to demonstrate a statistically greater proportion of subjects on paltusotine with normal IGF-1 at end of treatment compared to that achieved with placebo treatment.

探路者二號的主要目標是證明與安慰劑治療相比，帕圖索汀治療結束時 IGF-1 正常的受試者比例在統計上更高。

This was the same primary objective of Pathfinder one.

這與探路者一號的主要目標相同。

However, it is important to note that the absolute IGF-1 normalization rates and Pathfinder two is expected to be lower than that observed in the Pathfinder one population.

然而，值得注意的是，Pathfinder 2 的絕對 IGF-1 正常化率預計低於 Pathfinder 1 族群中觀察到的水平。

Remember, the Pathfinder one population were all known to have normal IGF-1 on SRL monotherapy at baseline test one or two patients would be expected to have a wide range of IGF one belt elevations at baseline based on published data, our best estimate of the overall percentage of patients who achieved normalized IGF-1 on drug at the end of treatment in PATHFINDER two should be approximately 30%.

請記住，在基線測試中，探路者一人群在接受SRL 單藥治療時均具有正常IGF-1，根據已發表的數據（我們對這一數據的最佳估計），預計一到兩名患者在基線時會出現大範圍的IGF 1 帶升高。在 PATHFINDER 2 治療結束時，藥物 IGF-1 達到正常化的患者總體百分比應約為 30%。

And this study is powered to show that this is different than that expected in the placebo group.

這項研究有力地表明，這與安慰劑組的預期不同。

This normalization rate would indicate that paltusotine is similarly effective to injected SRLs in this patient population and should be able to compete with the injections as a first line therapy, although IGF-1 normalization is of interest, perhaps even more relevant to clinical practice is the reduction from elevated baseline that can be achieved with publicity.

這種正常化率表明，帕妥索汀在該患者群體中與注射 SRL 相似，並且應該能夠與注射作為一線治療競爭，儘管 IGF-1 正常化很有趣，也許與臨床實踐更相關的是可以通過宣傳來實現從較高基線的減少。

And this is a prespecified key secondary endpoint in Pathfinder two pending results.

這是探路者兩個待定結果中預先指定的關鍵輔助端點。

We hope that Pathfinder two will complement Pathfinder one and allow us to seek a broad indication for paltusotine in the treatment of acromegaly, PATHFINDER two completed enrollment with 111 enrolled participants.

我們希望探路者二號能夠補充探路者一號，使我們能夠尋求帕圖索汀治療肢端肥大症的廣泛適應症，探路者二號已完成入組，共有 111 名參與者。

We look forward to sharing top-line results from PATHFINDER two with you in the next month, paltusotine second target indication.

我們期待在下個月與您分享 PATHFINDER 2 的頂線結果，帕圖索汀第二個目標適應症。

Carcinoid syndrome is also showing promising results to date.

迄今為止，類癌綜合徵也顯示出有希望的結果。

In December, we reported initial results from the ongoing open-label Phase two trial.

12 月，我們報告了正在進行的開放標籤第二階段試驗的初步結果。

As a brief reminder, SRLs are the first-line medical therapy for carcinoid syndrome.

簡單提醒一下，SRL 是類癌症候群的第一線藥物治療方法。

And we would expect that oral paltusotine would compete with the injections in this patient population as well.

我們預期口服帕妥索汀也將與該患者族群的注射劑競爭。

Carcinoid syndrome arises from neuro endocrine tumors that most commonly originate in the small intestine.

類癌症候群是由最常見起源於小腸的神經內分泌腫瘤所引起。

The syndrome is caused by tumor production of serotonin and other factors.

此症候群是由腫瘤產生血清素和其他因素引起的。

The two key symptoms that patients experience in this disease are diarrhea and flushing.

患者在這種疾病中經歷的兩個主要症狀是腹瀉和潮紅。

Our goal in treating carcinoid syndrome patients with paltusotine is to reduce their total symptom burden.

我們用帕妥索汀治療類癌症候群患者的目標是減輕他們的總症狀負擔。

The ongoing Phase two study is an open-label parallel group study that enrolled patients who are either naive to SRL treatment or or are currently treated untreated and actively symptomatic or who are controlled on SRL therapy and willing to wash out prior to entry.

正在進行的第二階段研究是一項開放標籤平行組研究，入組的患者要么未接受過 SRL 治療，要么目前未接受治療但症狀活躍，要么接受 SRL 治療得到控制並願意在進入之前退出。

The initial results we presented in December included 27 participants.

我們在 12 月公佈的初步結果包括 27 名參與者。

The trial is fully enrolled with a total of 36 participants and top line results from the full study are anticipated in the first half of this year.

該試驗已全部入組，共有 36 名參與者，完整研究的主要結果預計今年上半年公佈。

From a safety point of view, paltusotine was well-tolerated with no new safety findings consistent with what we've seen in our previous studies.

從安全性的角度來看，帕妥索汀具有良好的耐受性，沒有與我們在先前的研究中看到的一致的新的安全性發現。

In addition, pharmacokinetics in this patient population remains consistent with what we expected to see from prior experience and healthy volunteers.

此外，該患者群體的藥物動力學與我們從先前的經驗和健康志願者中預期看到的結果保持一致。

We are also very pleased to have already observed meaningful reductions in the two key symptoms of carcinoid syndrome, it says bowel movements and flushing episodes.

我們也非常高興地發現類癌症候群的兩個關鍵症狀（即排便和潮紅發作）顯著減少。

Even in the initial look at the data so far, paltusotine is associated with a 65% reduction in excess of movement frequency in patients who entered the study with greater than three bowel movements per day in patients who experienced one or more fleshing out events per day at baseline paltusotine and also associated with a 65% reduction.

即使從迄今為止的初步數據來看，對於每天排便次數超過 3 次的患者以及每天經歷一次或多次充實事件的患者，帕圖索汀與過度運動頻率減少 65% 相關帕圖索汀基線水平也降低了65%。

And these EpiCept as part of this study, design participants had the opportunity to up titrate their dose of paltusotine based on prespecified symptom criteria.

作為本研究的一部分，這些 EpiCept 設計參與者有機會根據預先指定的症狀標準增加帕圖索汀的劑量。

However, few patients in the study at the time of the initial analysis required an increase in dose.

然而，在初步分析時，研究中很少有患者需要增加劑量。

So we believe we're on the correct range to observe a response results of biomarker and other supplemental exploratory endpoints will be analyzed and reported with final results.

因此，我們相信我們處於觀察生物標記反應結果的正確範圍內，其他補充探索性終點將被分析並報告最終結果。

We are excited about this initial data and look forward to reviewing the full top line results which are anticipated in the first half of this year.

我們對這項初步數據感到興奮，並期待審查預計在今年上半年的完整營收結果。

Based on the results thus far, we believe paltusotine is acting like an SRL in terms of its ability to provide symptom relief, and we think the full dataset will confirm this.

根據迄今為止的結果，我們認為帕妥索汀在緩解症狀的能力方面類似於 SRL，並且我們認為完整的數據集將證實這一點。

We will submit the final data to the FDA to discuss at an end of Phase two meeting.

我們將在第二階段會議結束時向 FDA 提交最終數據進行討論。

We look forward to updating you on the Phase three trial design details, including dose registrational endpoint and timing.

我們期待向您提供第三階段試驗設計細節的最新信息，包括劑量註冊終點和時間安排。

Once we've had these discussions, our second candidate following paltusotine is 0.04894 4894 is an ACTH receptor antagonist in development for the treatment of congenital adrenal hyperplasia or CH. classic CH. is a genetic disorder that affects approximately 27,000 patients in the US.

一旦我們進行了這些討論，我們繼帕妥索汀之後的第二個候選藥物是 0.04894 4894 是一種 ACTH 受體拮抗劑，正在開髮用於治療先天性腎上腺增生或 CH。經典 CH.是一種遺傳性疾病，影響美國約 27,000 名患者。

These patients have impaired quarters of production, which causes high levels of ACTH.

這些患者的生產能力受損，導致促腎上腺皮質激素水平升高。

This excess ACTH causes over stimulation of the adrenal cortex, resulting an overproduction of androgen as an ACTH antagonist, 4894 is designed to act directly at the adrenal gland to normalize adrenal androgen production. 4894 is currently being studied in a Phase two open label sequential dose study in participants with CH.

這種過量的 ACTH 會導致腎上腺皮質過度刺激，導致雄性激素過度產生。作為 ACTH 拮抗劑，4894 旨在直接作用於腎上腺，使腎上腺雄激素的產生正常化。目前，4894 正在一項針對 CH 參與者的第二階段開放標籤序貫劑量研究中進行研究。

At this stage of development, we are primarily interested in evaluating safety and pharmacokinetics of 49 for, however, we are also interested in looking at pharmacodynamics and NCAH.

在這個開發階段，我們主要感興趣的是評估 49 的安全性和藥物動力學，但我們也有興趣研究藥效學和 NCAH。

This is measured primarily using the biomarker interesting diagram or a four similar to how we presented the carcinoid syndrome data in December, we plan to report initial data from the open label Phase two study in the second quarter of 2024.

這主要是使用生物標記有趣的圖表或類似於我們在 12 月呈現類癌綜合徵數據的方式進行的四次測量，我們計劃在 2024 年第二季度報告開放標籤第二階段研究的初始數據。

This will not be full data, but initial data from a small number of enrolled participants.

這不是完整的數據，而是來自少數註冊參與者的初始數據。

We hope that will give us an early picture of how 4894 is acting in CAH. patients.

我們希望這能讓我們儘早了解 4894 在 CAH 的表現。患者。

With that, I will now hand it over to Mark for a review of the financials.

現在，我將把它交給馬克來審查財務狀況。

Thank you, Alan.

謝謝你，艾倫。

We ended 2023 on strong financial footing with $558.6 million in cash and investments.

截至 2023 年，我們的財務基礎雄厚，擁有 5.586 億美元的現金和投資。

In addition, earlier today, we announced a $350 million private placement equity financing.

此外，今天早些時候，我們還宣布了 3.5 億美元的私募股權融資。

This private placement further strengthened our financial position with approximately $900 million on a pro forma basis.

這次私募進一步增強了我們的財務狀況，預計財務狀況約為 9 億美元。

We have a solid financial foundation as we prepare for multiple upcoming data readouts and regulatory milestones.

我們擁有堅實的財務基礎，為即將到來的多個數據讀數和監管里程碑做好準備。

And as we continue investing in the expansion of our deep pipeline.

隨著我們繼續投資擴大我們的深層管道。

Research and development expenses were $45.6 million and $168.5 million for the quarter and full year ended December 31st, 2023, compared to $37 million and $130.2 million for the same periods in 2022.

截至 2023 年 12 月 31 日的季度和全年，研發費用分別為 4,560 萬美元和 1.685 億美元，而 2022 年同期分別為 3,700 萬美元和 1.302 億美元。

The increases were primarily attributable to higher personnel costs and increased outside services, both of which were driven by the advancement and expansion of our portfolio of programs.

增加的主要原因是人員成本增加和外部服務增加，這兩者都是由我們專案組合的進步和擴展所推動的。

General and administrative expenses were $17.1 million and $58.1 million for the quarter and full year ended December 31st, 2023, compared to $11.3 million and $42.4 million for the same periods in 2022.

截至 2023 年 12 月 31 日的季度和全年，一般及管理費用分別為 1,710 萬美元和 5,810 萬美元，而 2022 年同期為 1,130 萬美元和 4,240 萬美元。

These increases were primarily attributable to higher personnel costs.

這些成長主要歸因於人員成本增加。

Our net loss for the quarter ended December 31st, 2023 was $60.1 million compared to a net loss of $45 million for the same period in 2022.

截至 2023 年 12 月 31 日的季度，我們的淨虧損為 6,010 萬美元，而 2022 年同期的淨虧損為 4,500 萬美元。

For the year ended December 31st, 2023, the Company's net loss was $214.5 million compared to a net loss of $163.9 million for the same period in 2022.

截至2023年12月31日止年度，該公司的淨虧損為2.145億美元，而2022年同期的淨虧損為1.639億美元。

Revenues were $4 million for the full year ended December 31st, 2023, compared to $4.7 million for the same period in 2022.

截至 2023 年 12 月 31 日的全年收入為 400 萬美元，而 2022 年同期收入為 470 萬美元。

There were no revenues for the quarter ended 2023 compared to $0.7 million for the same period in 2022.

2023 年終了的季度沒有收入，而 2022 年同期為 70 萬美元。

Revenues in both periods were primarily derived from licensing arrangements associated with our path to CRN01941 product candidates.

這兩個時期的收入主要來自與我們的 CRN01941 產品候選路徑相關的授權安排。

Net cash used for operating activities during the quarter ended December 31st, 2023 was $38.5 million and was $166.3 million for the year ended December 31st, 2023.

截至2023年12月31日的季度用於經營活動的現金淨額為3,850萬美元，截至2023年12月31日的年度為1.663億美元。

In 2024, we anticipate our cash burn to be approximately $50 million to $60 million per quarter, and we expect that following the $350 million private placement announced earlier today that our pro forma cash, cash equivalents and short-term investments of approximately $900 million will be sufficient to fund our current operating plan into 2028.

到2024 年，我們預計每季的現金消耗約為5,000 萬至6,000 萬美元，我們預計，繼今天稍早宣布的3.5 億美元私募之後，我們預計現金、現金等價物和短期投資將達到約9億美元。足以為我們目前到 2028 年的營運計劃提供資金。

I will now hand it back to Scott for closing remarks before we begin the 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, Mark for extremely proud of the progress we made throughout 2023 and so far in 2024 and 2024 is poised to be a transformative year for kinetics.

謝謝馬克，他對我們在 2023 年的進展感到非常自豪，到目前為止，2024 年和 2024 年將成為動力學變革的一年。

We look forward to providing continued updates throughout the year as we progress paltusotine to regulatory submissions and commercialization, make continued advancements in our pipeline and continue to create exciting new drug candidates with our discovery efforts.

我們期待在全年中提供持續更新，隨著我們將帕妥索汀推進監管提交和商業化，在我們的管道中不斷取得進展，並繼續透過我們的發現努力創造令人興奮的新候選藥物。

Thank you all for your attention.

感謝大家的關注。

Operator, we're ready to take questions.

接線員，我們準備好回答問題了。

Thank you.

謝謝。

Ladies and gentlemen, we will now begin the question and answer session.

女士們、先生們，我們現在開始問答環節。

Should you have a question, please press star followed by number one on your touchtone phone.

如果您有疑問，請在按鍵式電話上按星號，然後按數字一。

Should you wish to the grant from the polling process, please press star followed by the number two.

如果您希望透過投票過程獲得資助，請按星號，然後按數字二。

If you are using a speakerphone, please lift the handset before pressing any keys.

如果您使用免持電話，請在按任何按鍵之前拿起聽筒。

One moment, please, for your first question.

請稍等一下，回答你的第一個問題。

First question comes from Joseph Schwartz from Leerink Partners.

第一題來自 Leerink Partners 的 Joseph Schwartz。

Please go ahead.

請繼續。

Thanks very much and congrats on all the progress on one.

非常感謝並祝賀在一項工作上取得的所有進展。

So first question on Pathfinder two, um, for the patients who are enrolled in this trial that are not currently receiving medical therapy, do you have a sense of how many of them had previously responded to SRLs versus those that didn't?

那麼關於探路者二的第一個問題，嗯，對於參加本試驗但目前未接受藥物治療的患者，您是否知道他們中有多少人之前對 SRL 做出了反應，而哪些人沒有？

Well, Joe, and thanks.

好吧，喬，謝謝。

I let Alan answer that question for you.

我請艾倫為你回答這個問題。

So in the group where patients haven't been recently treated private screening for this study.

因此，在最近未接受過治療的患者組中，我們對本研究進行了私人篩檢。

Basically, patients who are known not to have responded to route in the past or medical therapy in the past are not eligible for this study now that is largely left to the discretion of the principal investigator of the doctor at the research site.

基本上，已知對過去的途徑或過去的藥物治療沒有反應的患者現在不符合這項研究的資格，這在很大程度上由研究地點的醫生的首席研究員自行決定。

But those patients in periods where they're known not to be responsive to medical therapy, they should not really be in a trial in which medical therapy is being evaluated.

但那些已知對藥物治療沒有反應的時期的患者，他們不應該真正參加評估藥物治療的試驗。

Right.

正確的。

Okay.

好的。

That's helpful.

這很有幫助。

Thanks.

謝謝。

And then actually another question on Pathfinder two do you have a sense for how the assay you're using to measure IGF-1 in the patients in PATHFINDER?

實際上，關於探路者二號的另一個問題，您是否了解探路者中用於測量患者 IGF-1 的檢測方法如何？

Two compares to the assay that was used for the studies that were done many years ago for octreotide and lanreotide in the same population?

與多年前在同一人群中進行的奧曲肽和蘭瑞肽研究中使用的測定法進行兩次比較？

And could any differences in the assays rigor influenced the results?

檢測嚴格程度的差異是否會影響結果？

And if so, do you have any estimate for how much that could come from translate into.

如果是這樣，您是否估計可以將其轉換為多少。

But yes, so we are using what is currently the gold standard assay for IGF-1 measured in a central laboratory in immunoassay.

但是，是的，所以我們正在使用目前在免疫測定中心實驗室測量的 IGF-1 黃金標準測定法。

That is very rigorously validated and probably more important than the assay itself is the uptick up to date reference ranges by age for IGF-1.

這是經過非常嚴格驗證的，並且可能比測定本身更重要的是 IGF-1 按年齡劃分的最新參考範圍的上升。

That's been a major area of research over the last 50 years.

這是過去 50 年來的一個主要研究領域。

And so we are using the state of the art measurement technique.

因此，我們正在使用最先進的測量技術。

And you're right, the older studies used our previous assays and also previous reference ranges that were available at the time.

你是對的，較早的研究使用了我們之前的檢測方法以及當時可用的參考範圍。

However, we have worked with the world world's experts on assay potential assay differences, and we have taken that into account for our sample size calculations for this study, there could be minor differences.

然而，我們與世界各地的專家合作研究了潛在的檢測差異，並且我們在本研究的樣本量計算中考慮到了這一點，可能存在細微的差異。

But in the more recent, I mean, there could be more significant differences with older versions of the assay.

但我的意思是，最近的檢測與舊版的檢測可能有更顯著的差異。

But we think we have a good handle on comparing to more recently done research, particularly in naive patients with acromegaly.

但我們認為我們可以很好地與最近進行的研究進行比較，特別是在肢端肥大症患者中。

So majority.

所以大多數。

But I think also, Scott, to add that, that does get more and more difficult.

但史考特，我還想補充一點，這確實變得越來越困難。

The further back in time, you go to compare our data with those earlier studies and largely because of the assay and perhaps more importantly, the reference ranges for the assay.

時間越早，您就可以將我們的數據與早期的研究進行比較，這很大程度上是因為檢測，也許更重要的是，檢測的參考範圍。

Thanks for your questions.

感謝您的提問。

And thank you.

謝謝你。

Your next question comes from Yasmeen Rahimi from Piper Sandler.

您的下一個問題來自 Piper Sandler 的 Yasmeen Rahimi。

Please, we'll have some good afternoon team, and congrats on all the progress on maybe the first question that has been submitted to us all throughout the whole morning has been investors.

拜託，我們將會有一些下午好團隊，並祝賀整個上午向我們提交的第一個問題可能是投資者的所有進展。

Wondering if the PIPE investors were previewed, any data related to Pathfinder two or and carcinoid or CAH would love to hear your color.

想知道 PIPE 投資者是否已預覽，任何與探路者二號或類癌或 CAH 相關的數據都希望聽到您的顏色。

And then my second question is for Alan.

我的第二個問題是問艾倫的。

If you could maybe share what could be a reasonable sample size for the interim readout for OCA and also maybe a little bit of a reminder or what is considered a clinically meaningful difference and a four level and maybe other key endpoints that we should be looking forward to from from the unmet need that exists in these patients?

如果您可以分享 OCA 臨時讀數的合理樣本量，也許還有一點提醒，或者什麼被認為是臨床上有意義的差異和四級，也許還有我們應該期待的其他關鍵終點從這些患者存在的未滿足的需求中如何解決？

Thank you.

謝謝。

As you know, I can't answer discuss the inner workings of that deal process and Pathfinder two remains blinded to you me and everyone will know the outcome of that trial next month, but it should be obvious to everybody from the list of great funds that we disclosed in our press release, they were willing to be named and were included in the deal.

如你所知，我無法回答討論該交易流程的內部運作情況，而探路者二號仍然對您、我和每個人都視而不見，下個月就會知道該試驗的結果，但這對每個人來說都應該是顯而易見的，從偉大的基金名單中我們在新聞稿中透露，他們願意透露姓名並參與交易。

But this isn't a deal or wasn't a deal about handicapping some single short term.

但這不是一項協議，也不是一項旨在阻礙某些短期目標的協議。

Rita.

麗塔。

This is a high-quality list of new and existing investors with a long-term view that understand and want to support long-term growth and vision of our company.

這是一份高品質的新舊投資者名單，他們具有長遠的眼光，理解並希望支持我們公司的長期成長和願景。

And Justin, I think that was very helpful.

賈斯汀，我認為這非常有幫助。

On the FTTH side.

在FTTH側。

Yes.

是的。

So yes, those are all great questions about the CH. study.

是的，這些都是關於 CH 的好問題。學習。

What is an appropriate sample size for us to reach some conclusions about safety, pharmacokinetics and efficacy.

我們需要多少樣本量才能得出有關安全性、藥物動力學和功效的結論。

So I would say right off the bat that this is not a pre-specified up a statistical exercise.

所以我會立即說，這不是預先指定的統計練習。

This is more of a qualitative look at directional data which is exactly what we did recently with carcinoid syndrome.

這更多的是對方向資料的定性觀察，這正是我們最近對類癌症候群所做的研究。

This is a rare disease.

這是一種罕見的疾病。

But in general, we are look, you asked what's the most?

但總的來說，我們都是看看，你問什麼最多？

What's the clinically meaningful change in the pharmacodynamic biomarker of most interest.

最感興趣的藥效生物標記有什麼臨床意義的變化？

And that's interesting, Diane has mentioned, and I think you know, what we'll be looking for, of course, is easily our chain are easily visualized changes from baseline in a four level on the pharmacodynamic front.

這很有趣，黛安提到過，我想你知道，我們當然要尋找的是，我們的鏈很容易在藥效學方面從基線的四個水平上輕鬆可視化變化。

And in fact, most importantly, can we achieve normalization of a score, I think is probably what's most clinically meaningful based on what we know now from elevated baseline.

事實上，最重要的是，我們能否實現分數的標準化，我認為根據我們現在從升高的基線了解到的情況，這可能是最有臨床意義的。

And as you mentioned, there are many other potential endpoints.

正如您所提到的，還有許多其他潛在的終點。

Besides a four on the pharmacodynamic front, we can look at and that we are exploring a lot of these in this, even this small study in Phase two for CH.

除了藥效學的四個項目之外，我們還可以研究並探索其中的許多內容，甚至是 CH 的第二階段的小型研究。

I mean some examples of things that are also important.

我指的是一些同樣重要的事情的例子。

There are other biomarkers that are of relevance to like 17 hydroxy progesterone, which is another biomarker used by clinicians to assess dose and response to therapy as well as the diagnosis of the disease.

還有其他與 17 羥基孕酮相關的生物標記物，這是臨床醫生用來評估治療劑量和反應以及疾病診斷的另一種生物標記。

But also things like how are the patients doing clinically.

還有諸如患者臨床表現如何之類的事情。

A lot of these patients, for example, of a female patients with this disorder have irregular menses and can be in personal.

許多此類患者，例如患有這種疾病的女性患者，月經不規則並且可能是個人的。

And we would, of course, we monitor menstrual cycling in women very closely, and there are many other clinically important things like that, that we will follow carefully.

當然，我們會非常密切地監測女性的月經週期，還有許多其他類似的臨床重要事情，我們將仔細追蹤。

And I hope we have a good directional signal from our interim analysis that we'll be doing and reporting on by the end of the first half.

我希望我們能從中期分析中得到一個良好的方向性訊號，我們將在上半年結束時進行並報告。

Thank you, Alan, Ryan.

謝謝你，艾倫，瑞安。

Thank you.

謝謝。

Your next question comes from Jessica Fye from JPMorgan Chase.

您的下一個問題來自摩根大通的傑西卡·菲伊。

Please go ahead.

請繼續。

Hey, guys, this is Noss on on for Jess.

嘿，夥計們，這是諾斯為傑西辯護的。

So we are very close to on full data for carcinoid.

所以我們非常接近類癌的完整數據。

Can you help us set some expectations there.

您能幫助我們在那裡設定一些期望嗎？

Maybe like what would represent a win for that update?

也許就像什麼代表該更新的勝利？

And then can you provide any updated thoughts on your office three plans for carcinoid syndrome?

那麼您能否提供有關您辦公室的類癌綜合徵三項計劃的最新想法？

Thank you.

謝謝。

Yes.

是的。

So I mean, I was pretty impressed with our interim data reported in December.

所以我的意思是，我們 12 月報告的中期數據給我留下了深刻的印象。

I thought that was a pretty winning stuff already.

我認為這已經是一件非常成功的事了。

And some of these very important endpoints kind of reached a statistical significance even in this small in this small our study.

即使在我們這項小型研究中，其中一些非常重要的終點也達到了統計顯著性。

So I would say a win for the final dataset is really confirming kind of what we saw in our interim data.

所以我想說，最終數據集的勝利確實證實了我們在中期數據中看到的情況。

And also we hope to have more information and expanded information on other exploratory endpoints like key biomarkers and other sort of supplemental data points.

我們還希望獲得有關其他探索性終點的更多資訊和擴展信息，例如關鍵生物標誌物和其他類型的補充數據點。

For example, you may recall from our interim data report, we I was very excited to see not only have the numbers of excess bowel movements and flushing episodes reduced on paltusotine, but also the urgency of the dose associated bowel movements and also the severity of those flushing episodes were also it's very meaningfully reduced.

例如，您可能還記得我們的中期數據報告，我們非常興奮地看到帕妥索汀不僅減少了過度排便和潮紅發作的次數，而且還減少了與劑量相關的排便的緊迫性以及排便的嚴重程度。那些潮紅的情況也得到了非常有意義的減少。

That goes beyond just number as it goes to the what the patient is actually experiencing and what's most important to patients.

這不僅僅是數字，還涉及患者實際經歷的情況以及對患者最重要的事情。

So I'm hoping we'll have additional kind of patient centric information as well.

因此，我希望我們還能獲得更多以患者為中心的資訊。

And maybe comment on Phase three for our Phase three?

也許對我們的第三階段的第三階段發表評論？

Thank you.

謝謝。

Yes, we are actively designing Phase three obviously, and we're using our Phase two database to help with that a great deal.

是的，顯然我們正在積極設計第三階段，我們正在使用第二階段資料庫來幫助實現這一目標。

In fact, the Phase two database is really essential for this process.

事實上，第二階段資料庫對於這個過程確實至關重要。

I do anticipate, based on our regulatory history that we will be designing a likely a placebo-controlled parallel-group Phase three trial where exploring a variety of important potential primary endpoints that we will discuss with the FDA as well as the key secondary endpoints for the Phase three trial on we based on historical precedent, we know that the general sample size for Phase three trials in this area are roughly say, between 80 and 150 patients.

我確實預計，根據我們的監管歷史，我們將設計一項可能的安慰劑對照平行組第三期試驗，其中探索我們將與 FDA 討論的各種重要的潛在主要終點以及關鍵的次要終點我們根據歷史先例進行的三期試驗，我們知道該領域三期試驗的一般樣本量大致在80 至150 名患者之間。

And I think that's the kind of study we will end up proposing to the FDA.

我認為這就是我們最終向 FDA 提議的研究類型。

And again, we'll report back once we've had those discussions with them full.

再次強調，一旦我們與他們進行了充分的討論，我們就會進行報告。

Thanks.

謝謝。

Just Frank.

只是弗蘭克。

Your next question comes from Jeff Hung from Morgan Stanley.

您的下一個問題來自摩根士丹利的 Jeff Hung。

Please go ahead.

請繼續。

Thanks for taking my questions.

感謝您回答我的問題。

Can you talk about the importance of the acromegaly symptoms, diary and the strategy for having that included in the label?

您能談談肢端肥大症症狀、日記的重要性以及將其納入標籤的策略嗎？

And then I have a follow-up.

然後我有一個後續行動。

Actually, I think it's important to point out that that's fairly unique amongst the SRLs, and we're very excited about it.

事實上，我認為有必要指出這一點在 SRL 中相當獨特，我們對此感到非常興奮。

And maybe Jim, our Chief Commercial Officer, can answer a little more in-depth.

也許我們的首席商務官吉姆可以回答得更深入一些。

So thanks, Scott.

所以謝謝，斯科特。

So as Scott mentioned, I symptom diary or quality of life is not been a component of the competitive label.

正如史考特所提到的，我的症狀日記或生活品質並不是競爭標籤的組成部分。

So is something that we do look forward to and whether it's in the label or whether it's in publication, it's certainly something that will be communicated to key opinion leaders within the United States and globally symptom control among patients with acromegaly is a big deal of there.

因此，我們確實期待一些東西，無論是在標籤中還是在出版物中，它肯定會傳達給美國境內的主要意見領袖，全球肢端肥大症患者的症狀控制是一件大事。 。

Certainly biochemical control is the regulatory endpoint, but as we speak to patients, it is all about symptoms and how they feel.

當然，生化控制是監管終點，但當我們與患者交談時，一切都與症狀和他們的感受有關。

And so it will be a big part of the conversation from a commercial standpoint.

因此，從商業角度來看，這將成為對話的重要組成部分。

And it certainly would be an important component of helping to sustain performance for both patients and physicians.

這肯定是幫助病人和醫生維持績效的重要部分。

Great.

偉大的。

Thanks.

謝謝。

And then what is your latest thinking on the commercial strategy for pulse in and what has been the payer feedback been so far?

那麼，您對 Pulse in 商業策略的最新想法是什麼？到目前為止，付款人的回饋如何？

And so our commercial strategy is I think as element Scott have mentioned, Pathfinder one and Pathfinder two will provide us with.

因此，我認為我們的商業策略是史考特所提到的，探路者一號和探路者二號將為我們提供。

We hope that the broadest possible label that will allow us to treat and market to both naive patients and patients that are currently going under under therapy.

我們希望盡可能廣泛的標籤將使我們能夠向初治患者和目前正在接受治療的患者進行治療和行銷。

In terms of we've had a number of advisory boards with physicians and also market research with payers.

就我們而言，我們已經成立了許多由醫生組成的諮詢委員會，以及與付款人一起進行的市場研究。

And I will tell you that based on the PATHFINDER one data, the response has been very, very enthusiastic on in terms of a value proposition.

我會告訴你，根據 PATHFINDER one 的數據，人們對價值主張的反應非常非常熱情。

We also have been speaking with payers just about the relative pricing within the marketplace, both for the standard of care injectables and depending on channel as well.

我們也一直在與付款人討論市場內的相對定價，包括護理注射劑的標準和管道的相對定價。

And within the hospital segment, there is a markup system that that occurs where the average markup for payers and and for patients in terms of their co-pay within injectable somatostatin analogs that are delivered within the hospital outpatient setting the markup can be as high as or on average, about 300% as high as in some cases, 700%.

在醫院領域內，存在一個加價系統，付款人和患者在醫院門診內提供的注射生長抑素類似物的共同支付中的平均加價可以高達或者平均而言，大約為300%，在某些情況下高達700%。

So this is certainly a savings that an oral pill to the team delivered through specialty pharmacy can offer to the payer community and something that we're having continued discussions with payers on that on that level.

因此，透過專業藥局向團隊提供口服藥丸無疑可以為付款人社區帶來節省，我們正在與付款人就這一層面繼續進行討論。

Thank you.

謝謝。

Thank you.

謝謝。

Your next question comes from George Hill from analyst.

您的下一個問題來自分析師喬治·希爾。

Please go ahead.

請繼續。

Thanks for taking our questions and congrats on all the progress you've made last year on question quick question on acromegaly.

感謝您提出我們的問題，並祝賀您去年在肢端肥大症快速問題上取得的所有進展。

So taking a look across all the historical data processing, i.e., acromegaly, for the strong correlation between treatment response in certain baseline characteristics such as age or whether a patient has entered the study with a macro versus micro at Inova.

因此，請查看所有歷史資料處理（即肢端肥大症），以了解某些基線特徵（例如年齡）的治療反應之間的強相關性，或者患者是否已進入 Inova 的宏觀與微觀研究。

Can you give us a better understanding or insight more broadly to how these patient demographics for path there too aligned across the spectrum of previous studies that are in this group.

您能否讓我們更好地理解或更廣泛地了解這些患者的人口統計數據如何與該組先前的研究範圍保持一致。

I think the simple answer is we haven't done that analysis yet, and some of those sensitivity and subsets will be part of the Phase three workup.

我認為簡單的答案是我們還沒有進行分析，其中一些敏感性和子集將成為第三階段檢查的一部分。

But broadly, this is a global study with acromegaly patients that we think are representative of the general population.

但總的來說，這是一項針對肢端肥大症患者的全球研究，我們認為這些患者代表了一般人群。

I think in the literature from previous studies done over the years.

我認為在多年來所做的研究文獻中。

It is not easy to identify a clear predictor of response to treatment in acromegaly.

確定肢端肥大症治療反應的明確預測因子並不容易。

Probably if one thing is most useful, it's just looking at the baseline IGF-1 level.

也許如果說一件事最有用的話，那就是查看基線 IGF-1 水平。

If it's if it's very high, it's C&O, this are going to take more lowering to get to normal.

如果它非常高，那就是 C&O，這將需要更多的降低才能恢復正常。

And that's why we reiterate that in this kind of study where patients in PATHFINDER two are patients can start out sometimes with very high IGF-1 levels.

這就是為什麼我們重申，在此類研究中，PATHFINDER 2 中的患者有時一開始就具有非常高的 IGF-1 水平。

And we should expect a lower rate of IGF-1 normalization compared to what we saw in PATHFINDER one where we knew everybody there was controlled at baseline on medication.

與我們在 PATHFINDER 中看到的情況相比，我們應該預期 IGF-1 正常化率會較低，在 PATHFINDER 中我們知道每個人都在藥物治療的基線上得到控制。

And we've been trying for years, you've been telling other folks to be sure and remind people that this is not the same population that we studied in PATHFINDER one.

我們多年來一直在努力，你一直在告訴其他人要確定並提醒人們，這與我們在探路者一號中研究的人群不同。

And that overall, our blended estimate for this study is a response rate in the low 30s ballpark in the end.

總的來說，我們對這項研究的綜合估計是最終的回應率在 30 左右。

You've previously, you know, building off of that.

你知道，你之前已經以此為基礎來建構。

You previously mentioned that you've used the head to head passively a diverse octreotide study in your assumptions for at least the Stratum one group.

您之前提到過，在您的假設中，您至少在階層一組中被動地進行了一項不同的奧曲肽研究。

Can you walk us through that rationale behind looking at that study to inform potential patent matter to outcomes?

您能否向我們介紹一下該研究背後的基本原理，以了解潛在的專利問題與結果？

And especially given when you look across these studies historically, that's probably one of the more conservative response rates we've seen well.

尤其是當你回顧這些歷史研究時，你會發現這可能是我們所見過的較保守的反應率之一。

It's also one of the most modern and comprehensive studies in the naive population and using the same assay with a close to modern reference range.

這也是對幼稚人群進行的最現代、最全面的研究之一，並使用具有接近現代參考範圍的相同測定法。

So I think it's actually a pretty good analogue, and we did use that in our powering assumptions.

所以我認為這實際上是一個非常好的模擬，我們確實在我們的動力假設中使用了它。

And in that study, the control arm was octreotide and it was a large number of naive patients and octreotide reduced IGF levels and the vast majority of patients, but only 24% achieved IGF levels within the normal range and so that's where we had the powering for that group.

在那項研究中，對照組是奧曲肽，有大量未接受治療的患者，奧曲肽降低了絕大多數患者的 IGF 水平，但只有 24% 的 IGF 水平達到正常範圍內，這就是我們的動力所在對於那個群體。

Our Stratum one of the Pathfinder two study.

我們的地層之一探路者兩項研究。

Yes.Thank you.

是的，謝謝。

Your next question comes from Brian Skorney from Baird.

您的下一個問題來自貝爾德 (Baird) 的布萊恩·斯科尼 (Brian Skorney)。

Please go ahead.

請繼續。

Hey, good afternoon, everyone.

嘿，大家下午好。

Thanks for taking my questions.

感謝您回答我的問題。

I guess just following on on that last question, can you say anything about the baseline for respects in terms of what the baseline IGF-I level, what does wall target Pathfinder two study?

我想接著最後一個問題，您能談談基線 IGF-I 水平方面的基線嗎？牆目標探路者二號研究什麼？

And I mean, it sounds like it was reasonable.

我的意思是，這聽起來似乎很合理。

Is it fair to say that there's sort of a trade-off between the primary and secondary endpoint, where a lower baseline IGF-1 would mean better response rate, but lower IGF production and higher baseline in the reverse?

是否可以公平地說，主要終點和次要終點之間存在某種權衡，其中較低的基線 IGF-1 意味著更好的緩解率，但相反，較低的 IGF 產量和較高的基線？

Yes, I think we'll just have to wait another month for every brand to come.

是的，我想我們還需要再等一個月才能看到每個品牌的到來。

And I know everybody wants to see it, but nobody worse than me so soon is the answer was there part of that, that I could really answer, and I kind of lost it at the at all.

我知道每個人都想看到它，但沒有人比我更糟糕，這麼快就有答案了，我真的可以回答，但我根本就失去了它。

Just if you could say anything about sort of the baseline IGF-1 level?

您能談談 IGF-1 基線水平嗎？

Yes, not at not at this time.

是的，不是現在。

And then maybe as a follow-up, ask something more in the pipeline today, it seems like your thyroid stimulating hormone antagonist was moving along nicely.

然後也許作為後續行動，今天要問更多的事情，看起來你的促甲狀腺激素拮抗劑進展順利。

I guess do you think you have the capability to get an oral agent here?

我想你認為你有能力在這裡買到口服製劑嗎？

And and I was just wondering about the specific target, is it the TITSH. receptor is that IG at one receptor?

我只是想知道具體目標是 TITSH 嗎？受體是 IG 的一種受體嗎？

I'm just trying to think about how to get a handle on on how comparable this could be the opportunity, any differences between where it's finding to think about?

我只是想思考如何了解這個機會的可比性，它發現的地方之間有什麼區別嗎？

Oh, yes, no, great.

哦，是的，不，太好了。

Yes.

是的。

Just bumped into one of the chemists in the hall who is really excited about the latest batch of molecules, and we already have good molecules that are orally available and polishing the last few, I think we're getting pretty close in this program.

剛剛在大廳裡遇到了一位化學家，他對最新一批分子感到非常興奮，我們已經有了可以口服的良好分子，並正在完善最後幾個分子，我認為我們在這個計劃中已經非常接近了。

The target is the TSH receptor and just remind people because this isn't something we've talked a ton about in our pipeline.

目標是 TSH 受體，只是提醒人們，因為這不是我們在管道中討論過的東西。

Graves disease is caused by antibodies that people develop that activate this TSH receptor.

格雷夫茲病是由人們產生的激活這種 TSH 受體的抗體引起的。

And so the notion is to block that in grave eye disease or thyroid eye disease is it's been branded.

因此，我們的想法是阻止嚴重眼疾或甲狀腺眼疾被標記。

The more formal name is Grace off them apathy, but it's such a mouthful that people call it thyroid eye disease that's caused by the binding of these antibodies to TSH receptors and the cells at the back the back of the eye, those receptors then act on those cells.

更正式的名字是Grace off the apathy，但它太拗口了，人們稱之為甲狀腺眼病，它是由這些抗體與TSH受體和眼睛後部的細胞結合引起的，這些受體然後作用於那些細胞。

And on the IGF receptors on those cells to cause the hypertrophy that results in the protruding and other problems in the back of the eye.

這些細胞上的 IGF 受體會導致肥大，導致眼睛後部突出和其他問題。

So we're going to the root of the problem that there hasn't been a new drug for GRACE disease itself since the 1940s and the TSH receptor is the root problem.

因此，我們要解決問題的根源，自 20 世紀 40 年代以來，一直沒有針對 GRACE 疾病本身的新藥，而 TSH 受體是根本問題。

If you block that and you have an effective drug for Grace itself.

如果你阻止了它，你就擁有了一種對格雷斯本身有效的藥物。

We think you won't be getting great side disease.

我們認為您不會患上嚴重的副作用。

And if you block that receptor for patients who already have Graves eye disease, we think we can treat it.

如果你阻斷已經患有格雷夫斯眼病的患者的這種受體，我們認為我們可以治療它。

That's the hypothesis.

這就是假設。

And this is yet another peptide hormone receptor that we're trying to replace or trying to block with a small molecule.

這是我們試圖用小分子取代或阻斷的另一種勝肽激素受體。

And maybe I'm too in our horn a little bit.

也許我也有點自暴自棄了。

But I think the guys in the next labs down the hall here, some of the best in the world guys and gals.

但我認為大廳裡隔壁實驗室的人都是全世界最優秀的人。

So for some of the best in the world at making drugs like that.

對於世界上一些最擅長製造此類藥物的人來說。

So yes, we're going to get it.

所以是的，我們會得到它。

Thank you.

謝謝。

Your next question comes from Douglas Tsao from H.C. Wainwright.

您的下一個問題來自 H.C. 的 Douglas Tsao。溫賴特。

Please go ahead, ma'am.

請繼續，女士。

Good afternoon and thanks for taking the questions.

下午好，感謝您提出問題。

And maybe as a starting point, I'm just curious on with the CAH. readout on the interim, look that we'll get, I'm just curious sort of is there on an operational decision you make from getting that versus the full readout and Unisom, but it's similar to carcinoid syndrome where it sort of really helps you jump start thinking about the Phase three study?

也許作為一個起點，我只是對 CAH 感到好奇。臨時讀數，看看我們會得到的，我只是好奇你是否會根據完整讀數和 Unisom 做出操作決策，但這與類癌綜合症類似，它確實對你有幫助開始考慮第三階段研究？

Or are there potential changes that you would make to the fit the CH. study itself that on new sort of mid-course adjustments on on that would help you sort of better understand and how the molecules behave?

或者您是否需要進行一些潛在的更改以適應 CH。研究新的中途調整會幫助你更理解分子的行為嗎？

Yes, Doug, it's like all the core endocrinology studies, including the Phase one we did with paltusotine, where in the earliest cohorts of our SAD study, we knew the drug was working and we knew the pharmacology that was coming out by these changes in hormonal biomarkers and as this ICH. study progresses and we begin to get that type of information, it's you know, it's an open-label study.

是的，道格，就像所有核心內分泌學研究一樣，包括我們用帕妥索汀進行的第一階段研究，在我們SAD 研究的最早隊列中，我們知道該藥物正在發揮作用，並且我們知道這些變化所產生的藥理作用。荷爾蒙生物標記和 ICH 一樣。研究取得進展，我們開始獲得此類信息，你知道，這是一項開放標籤研究。

So we're looking at it all the time and we're getting all this information to guide our Phase three design.

因此，我們一直在關注它，並獲取所有這些資訊來指導我們的第三階段設計。

But until we start to instill it until we disclose that, we can't be talking about it publicly either with our investors or with a broader group of physicians outside of our investigators and our advisory boards.

但在我們開始灌輸它直到我們披露這一點之前，我們不能與我們的投資者或與我們的調查人員和諮詢委員會之外的更廣泛的醫生群體公開談論它。

So we want to be able to talk to a broader community about how we advance this program forward.

因此，我們希望能夠與更廣泛的社區討論如何推進該計劃。

And that's and it's been moving well.

這就是並且進展順利。

So that's why we decided that our current estimate is we'll be able to start talking about it next quarter.

因此，我們決定目前的估計是我們將能夠在下個季度開始討論它。

Okay.

好的。

Great.

偉大的。

And then just a quick follow-up on the TSH antagonist.

然後是 TSH 拮抗劑的快速跟進。

I'm just curious, what are you looking at on, I guess, in a preclinical setting to determine or select your molecule I'm just curious what sort of you're most focused on in terms of lead candidate selection ahead of obviously going into the clinic and seeing the sort of the impact on power levels on, et cetera?

我只是好奇，我想，在臨床前環境中，你在看什麼來確定或選擇你的分子，我只是好奇，在明顯的選擇之前，你最關注的是哪種主要候選藥物進入診所並查看對功率等級的影響等等？

Yes.

是的。

So it's very much like our other programs in finding the right molecule.

因此，這與我們尋找正確分子的其他程序非常相似。

You're trying to optimize 2030 different characteristics.

您正在嘗試優化 2030 個不同的特徵。

And we've had molecules for a long time that were potent at the receptor and able to normalize hormone levels in a mouse model.

長期以來，我們已經找到了對受體有效的分子，並且能夠使小鼠模型中的荷爾蒙水平正常化。

But we're really working on all those other little polishing to make a good molecule to make sure it's highly orally absorb, doesn't have drug interactions has good toxicology profile.

但我們確實正在努力進行所有其他的小改進，以製造出良好的分子，以確保其具有高度口服吸收性、沒有藥物相互作用、具有良好的毒理學特徵。

But if you're interested in efficacy, I'll point you towards our corporate deck where there's a slide towards the back where we give mice and antibody, just like the humans have that cause activation of the TSH receptor, their thyroid hormone levels go up remarkably and then we start treating them with one of our oral candidates and those hormone levels go back to normal.

但如果你對功效感興趣，我會帶你去我們公司的平台，那裡有一個滑向後面的幻燈片，我們給小鼠和抗體，就像人類有導致TSH 受體激活的物質一樣，他們的甲狀腺激素水平會升高。顯著上升，然後我們開始用我們的一種口服候選藥物治療它們，這些激素水平就會恢復正常。

So we'll do that same type of study in patients with greatest disease.

因此，我們將對患有最嚴重疾病的患者進行同樣類型的研究。

So I think it's quite relevant as an efficacy model.

所以我認為它作為一個功效模型非常相關。

But like I said, in many of our programs, it's not about the efficacy.

但就像我說的，在我們的許多計劃中，這與功效無關。

It's about finding a great drug that also has the great efficacy.

這是為了找到一種具有巨大功效的好藥物。

Thank you.

謝謝。

Your next question comes from Jon Wolleben from Citizens GMP.

您的下一個問題來自 Citizens GMP 的 Jon Wolleben。

Please go ahead.

請繼續。

Say thanks for taking the question.

感謝您提出問題。

Two for me.

給我兩個。

Just wondering if you could give some context about how you think the opportunity to propel to strategic changes in acromegaly, if you just have a maintenance label versus a maintenance and treatment label?

只是想知道，如果您只有維護標籤與維護和治療標籤，您是否可以提供一些背景信息，說明您如何看待推動肢端肥大症戰略變革的機會？

And then it seems like a lot of excitement for United for in CAH and Cushing's has been a difficult and indication and the dynamics are changing there.

然後，對於曼聯來說，CAH 和庫欣的情況似乎很令人興奮，這一直是一個困難和跡象，那裡的動態正在改變。

You know, are you still thinking about moving forward.

你知道，你還在考慮繼續前進嗎？

The question was as well as eight nine four.

問題是八九四。

We're going to be focused on.

我們將重點關注。

Cah will report.

曹會報告。

Thanks.

謝謝。

Well, let me address 49 for and then I'll hand it over to Jim to think about the commercial opportunity, talk about personal opportunity, but four eight nine four addresses the ACTH receptor, which is the heart of the body at the center of the body's endocrine response to stressors and when things go wrong in that pathway, bad things happen.

好吧，讓我談談 49，然後我會把它交給吉姆來思考商業機會，談論個人機會，但是四八九四涉及 ACTH 受體，它是身體的心臟，位於身體的中心。身體內分泌對壓力源的反應，當該途徑出現問題時，就會發生不好的事情。

So in Cushing's disease with excess glucocorticoids or in CAH patients with that first glucocorticoid you're adding you're adding too much capacity or increasing blood pressure on your damaging bone.

因此，對於使用過量糖皮質激素的庫欣氏症或使用第一種糖皮質激素的 CAH 患者，您會增加過多的容量或增加損壞骨骼的血壓。

It's a problem.

這是一個問題。

So we if we were out front in CAH, we have an exciting ongoing study with the NIH in Cushing's disease, and we're continuing to work on that.

因此，如果我們在 CAH 領域處於領先地位，我們將與 NIH 合作進行一項令人興奮的庫欣氏症研究，並且我們將繼續致力於此。

And we're thinking about what else we might do down the road with an ACTH antagonist.

我們正在考慮未來我們還可以用 ACTH 拮抗劑做些什麼。

This is something nobody else in the world has ever evaluated in humans, and we're going to learn a lot about the pathway in these studies.

這是世界上沒有其他人在人類身上評估過的東西，我們將在這些研究中了解很多關於這一途徑的資訊。

So Jim, maybe you want to comment on indications and expectations for how to succeed in acromegaly?

那麼吉姆，也許您想評論如何在肢端肥大症方面取得成功的適應症和期望？

Sure.

當然。

Thanks, Scott.

謝謝，斯科特。

And I think the question was specifically kind of maintenance versus naive.

我認為問題在於維護與天真。

I mean, from a from a an addressable patient population standpoint, the majority of the patients are currently on treatment.

我的意思是，從可尋址患者群體的角度來看，大多數患者目前正在接受治療。

So in any given year, we estimate maybe 500 new patients are naive patients enter enter the marketplace so that gives you approximately 10,000 patients that are maintenance arm patients.

因此，在任何一年中，我們估計可能有 500 名新患者進入市場，因此大約有 10,000 名患者屬於維持組患者。

And that's the importance of the Pathfinder one data already in hand is that group of approximately 10,000 patients, however, don't want to minimize the value of a pathfinder two because again, Pathfinder two gives us the broadest possible label to really address patients across the continuum.

這就是現有的探路者一號資料的重要性，即大約10,000 名患者，但是，我們不想最小化探路者二號的價值，因為探路者二號再次為我們提供了最廣泛的標籤，以真正解決跨性別患者的問題連續體。

It's differentiated from several products that are in the marketplace.

它與市場上的幾種產品不同。

So it will be an important readout for us as we move forward.

因此，隨著我們的前進，這對我們來說將是一個重要的讀數。

And I think we hope to glean more than just an indication from PATHFINDER two.

我認為我們希望從探路者二號中收集到的不僅僅是一個指示。

We hope that there's some important data that will differentiate paltusotine from the injectable somatostatin receptor ligands additionally.

我們希望有一些重要的數據能夠將帕妥索汀與注射生長抑素受體配體區分開來。

And if I can just add to that a little bit as amazing as the data was from PATHFINDER one, it was all about maintaining a level of control in patients who were control in Pathfinder two, we're starting with patients who are sick and demonstrating to Pogo's well that's helped us attain can help them lower their IGF levels, lower their symptoms, make them feel better.

如果我可以補充一點，就像探路者一號的數據一樣令人驚奇，這一切都是為了維持探路者二號中控制的患者的控制水平，我們從生病的患者開始並展示Pogo 的井幫助我們實現了可以幫助他們降低IGF 水平，減輕他們的症狀，讓他們感覺更好。

And there's something visceral about being able to communicate an improvement in a disease condition rather than just a maintenance in the disease condition.

能夠傳達疾病狀況的改善而不僅僅是疾病狀況的維持，這是一種發自內心的感覺。

And so we're very excited to see how this plays out next month.

因此，我們很高興看到下個月的情況如何。

Thank you.

謝謝。

Your next question comes from Dave Windley from Jefferies.

您的下一個問題來自 Jefferies 的 Dave Windley。

Please go ahead.

請繼續。

I can afternoon.

下午可以。

Thanks for taking our question.

感謝您提出我們的問題。

Some we have to for CA to own, if I may.

如果可以的話，有些我們必須讓 CA 擁有。

So number one just around A4 reductions at week 12 and others actually surprising not surprisingly not a lot of data out at week 12 and most are for weeks two to four.

因此，排名第一的數據大約是第12 週的A4 減少量，而其他數據實際上令人驚訝，這並不奇怪，第12 週發布的數據並不多，而且大多數數據都是第二周到第四周的數據。

So I'm curious to hear what level of percentage a four reduction do you think will be competitive at least two given we already have from the data out there from others, but those are from earlier time points.

因此，我很想知道，考慮到我們已經從其他人那裡得到的數據，您認為四次減少的百分比水平是多少至少有競爭力，但這些都是來自較早時間點的數據。

And then question two is around based Europe, one competitor who will obviously have some Phase IIb data in March.

第二個問題是圍繞歐洲的，一個競爭對手顯然會在 3 月獲得一些 IIb 期數據。

How do you frame that update given you will report data soon after in Q2?

鑑於您很快將在第二季度報告數據，您如何制定更新？

And maybe if I can be a little bit more specific, can you comment on how we should think about percentage a four change versus the absolute magnitude of a board change and which should people focus on paying so much yet?

也許如果我可以更具體一點，您能否評論一下我們應該如何考慮四次變化的百分比與董事會變化的絕對幅度以及人們應該關注哪些方面？

Thanks, Dennis.

謝謝，丹尼斯。

Um, let's see how the best way to answer that is first up in our study, we're measuring time courses of A4 and other adrenal markers throughout the treatment period.

嗯，讓我們看看在我們的研究中首先如何回答這個問題的最佳方法，我們正在測量整個治療期間 A4 和其他腎上腺標記物的時間進程。

So the comparator time points at different places for the other, really innovative things that Allen is doing in that study.

因此，艾倫在該研究中所做的其他真正創新的事情的比較器時間點位於不同的地方。

And we'd like to make our studies as informative as possible because we have an option for patients to enroll in what we call the circadian are where we measure A4 and other markers throughout the day because as you know, those fluctuate.

我們希望讓我們的研究提供盡可能豐富的信息，因為我們可以讓患者選擇參加我們所謂的晝夜節律，我們全天測量 A4 和其他標記物，因為如您所知，這些標記物會波動。

And so understanding the timing of measurements in the day, not just in the weeks is also important, and I think you know, but I've been around the center consistently since the earliest days of my career.

因此，了解一天中的測量時間，而不僅僅是幾週內的測量時間也很重要，我想你知道，但從我職業生涯的最初幾天起，我就一直在該中心工作。

And CRF is a very exciting molecule that has some wonderfully interesting biologies, but at the pituitary, it is only a portion of the signal that goes into the cortex trough cells that make ACTH.

CRF 是一種非常令人興奮的分子，具有一些非常有趣的生物學特性，但在腦下垂體中，它只是進入皮質槽細胞產生 ACTH 的訊號的一部分。

And we now have an estimate from the recent data on crinecerfont that by blocking that signal, you can reduce 45% of the A4 output by the adrenal.

現在，我們根據 crinecerfont 的最新數據估計，透過阻斷該訊號，可以減少腎上腺 A4 輸出的 45%。

So that says there's another 65% of signal going into the pituitary from probably bears a person or some other things.

也就是說，還有 65% 的訊號可能來自人或其他物體進入腦下垂體。

However, mechanistically at the adrenal, there's only one way that ACTH can act and that's through its receptor, which is called MC. two and Landqart receptor two, and that's what we're blocking.

然而，從機制上講，ACTH 在腎上腺的作用只有一種方式，那就是透過其受體，即 MC。 2 和 Landqart 受體 2，這就是我們要阻斷的。

So I would expect an ACTH antagonist to have a much more if you can fully block the receptor to have a much larger effect on adrenal, et cetera.

因此，如果你能完全阻斷受體，對腎上腺等產生更大的影響，我預期 ACTH 拮抗劑的作用會更大。

But and we'll know what that effect is in the coming months.

但是，我們將在未來幾個月內知道這種影響是什麼。

So super excited to see that and I think the community has as well.

看到這一點我非常興奮，我認為社區也是如此。

We've known about ACTH in Cushing's disease since Cushing's disease since 1910, but nobody has ever had an antagonist in that receptor before so it's a very exciting advancement in the field.

自 1910 年庫欣氏症以來，我們就知道 ACTH 在庫欣氏症中的作用，但之前沒有人發現過該受體的拮抗劑，因此這是該領域非常令人興奮的進展。

And thank you.

謝謝你。

Your next question comes from Leland Gershell from Oppenheimer.

您的下一個問題來自奧本海默的利蘭·格謝爾。

Please go ahead.

請繼續。

Thanks and congratulations on all the accomplishments that have been made and thank you for the updates across the board.

感謝並祝賀所取得的所有成就，並感謝您的全面更新。

Just curious, Scott, as we look forward to the annual meeting of the Endocrine Society, not too long from now, I want to know if you might be able to give us indication of any updates perhaps on some of the earlier pipeline programs that you're moving forward?

只是好奇，斯科特，當我們期待不久之後的內分泌學會年會時，我想知道您是否能夠向我們提供任何更新，也許是您之前的一些管道計劃的更新。正在前進嗎？

I look forward to that.

我對此很期待。

Yes, thanks.

對了謝謝。

That's a annual pilgrimage of endocrinologists from around the world to get together and talk about the latest in endocrinology.

這是來自世界各地的內分泌學家一年一度的朝聖之旅，他們齊聚一堂，討論內分泌學的最新進展。

And I've been going since the 1980s, I love that meeting.

我從 20 世紀 80 年代就開始參加這次會議，我很喜歡那次會議。

We will be sending, as usual, a large contingent of we're submitting many abstracts.

像往常一樣，我們將發送大量的摘要。

I frankly don't know the final list of abstracts, but that will be coming out as we see the acceptances.

坦白說，我不知道最終的摘要清單，但當我們看到接受時就會出來。

And I think you can look for a strong presence from there from us there in Boston this June.

我認為今年六月您可以在波士頓尋找我們的強大影響力。

Great.

偉大的。

And then just a question just to clarify and on freight going forward between Cushing and CHQ. and your press release had mentioned the CHM. three, that would be next quarter.

接下來是一個問題，旨在澄清庫欣和 CHQ 之間的貨運情況。你們的新聞稿中提到了 CHM。三，那是下個季度。

I think you had indicated previously that we may see switching data in Q2, but that wasn't mentioned.

我認為您之前曾表示我們可能會在第二季度看到轉換數據，但沒有提到。

So what is the cushions reveals going to be perhaps from two Q3?

那麼第三季的兩個緩衝墊可能會透露什麼呢？

Or I'm just wondering if you might have any indication.

或者我只是想知道你是否有任何指示。

You know, I think we just didn't do a deal between the two discussions and maybe didn't spend enough time talking about Cushing.

你知道，我認為我們只是在兩次討論之間沒有達成協議，也許沒有花足夠的時間討論庫欣。

So let's let's see how it plays out.

那麼讓我們看看結果如何。

I think there's a chance we'll hear about both but 49 for us, certainly something of great interest on many fronts, but don't interpret any subtlety in the way we face things as any loss of interest in Cushing's disease.

我認為我們有可能會聽到除49 以外的其他信息，這肯定是在許多方面都引起人們極大興趣的事情，但不要將我們面對事物的方式中的任何微妙之處解釋為對庫欣病失去興趣。

Thank you.

謝謝。

That's all the time we have for questions today.

這就是我們今天提問的全部時間。

So I will turn it back to Scott for closing remarks.

因此，我將把它轉回斯科特以供結束語。

Thank you, everybody, for joining us today.

謝謝大家今天加入我們。

We appreciate your attention and your support and look forward to talking to more to you more in the future.

我們感謝您的關注和支持，並期待將來與您進行更多交流。

Thank you.

謝謝。

Ladies and gentlemen, this concludes your conference call for today.

女士們、先生們，今天的電話會議到此結束。

We thank you for participating and ask that you please disconnect your lines.

我們感謝您的參與，並請您斷開線路。