Rhythm Pharmaceuticals Inc (RYTM) 2024 Q2 法說會逐字稿

Good day and thank you for standing by. Welcome to the Rhythm Pharmaceuticals second-quarter 2024 earnings conference call. (Operator Instructions) Please be advised that today's conference is being recorded.

美好的一天，感謝您的支持。歡迎參加 Rhythm Pharmaceuticals 2024 年第二季財報電話會議。 （操作員指示）請注意，今天的會議正在錄製中。

I would now like to hand the conference over to your speaker today, David Connolly, Investor Relations and Corporate Communications. Sir, please go ahead.

我現在想把會議交給今天的演講者、投資者關係和企業傳播部門的大衛康諾利 (David Connolly)。先生，請繼續。

Thank you, Michelle. I'm Dave Connolly here at Rhythm Pharmaceuticals. For those of you participating on the conference call, our slides can be accessed and controlled by going to the Investors section on the Investors page of our website, ir.rhythmtx.com. This morning, we issued our press release that provides our second quarter 2024 financial results and business update, and that is available on our website.

謝謝你，米歇爾。我是 Rhythm Pharmaceuticals 的 Dave Connolly。對於參加電話會議的人員，可以透過造訪我們網站 ir.rhythmtx.com 投資者頁面上的投資者部分來存取和控制我們的幻燈片。今天早上，我們發布了新聞稿，其中提供了 2024 年第二季的財務業績和業務更新，可在我們的網站上取得。

Listed on slide 2 is our agenda. On the call are David Meeker, our Chairman, Chief Executive Officer, and President; Jennifer Lee, Executive Vice President, Head of North America; Hunter Smith, our Chief Financial Officer; and Yann Mazabraud, Executive Vice President, Head of International, is on the line joining us from Europe.

第 2 投影片中列出的是我們的議程。參加電話會議的有我們的董事長、執行長兼總裁 David Meeker； Jennifer Lee，執行副總裁，北美區負責人；亨特‧史密斯，我們的財務長；執行副總裁兼國際主管 Yann Mazabraud 從歐洲接聽我們的電話。

And on slide 3, I'll remind you this call contains remarks concerning future expectations, plans and prospects, which constitute forward-looking statements. Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in our most recent annual or quarterly reports on file with the SEC.

在投影片 3 上，我將提醒您，本次電話會議包含有關未來預期、計劃和前景的評論，這些評論構成前瞻性陳述。由於各種重要因素，包括我們向美國證券交易委員會提交的最新年度或季度報告中討論的因素，實際結果可能與這些前瞻性陳述所示的結果有重大差異。

In addition, any forward-looking statements represent our views as of only today and should not be relied upon as representing our views as of any subsequent dates. We specifically disclaim any obligation to update such statements.

此外，任何前瞻性陳述僅代表我們截至今天的觀點，不應被視為代表我們在任何後續日期的觀點。我們特別聲明不承擔更新此類聲明的義務。

With that, I'll turn the call over to David Meeker, who will begin on slide 5.

接下來，我會將電話轉給 David Meeker，他將從投影片 5 開始。

Thank you, Dave. We are pleased to report out another strong quarter with continued steady progress on our commercial opportunity both in North America and internationally. Another regulatory milestone with pediatric approval for IMCIVREE in patients ages two to younger than six in the EU, and broad progress across our development programs.

謝謝你，戴夫。我們很高興地報告又一個強勁的季度，我們在北美和國際上的商業機會持續穩步進展。歐盟兒科批准 IMCIVREE 用於治療 2 歲至 6 歲以下患者，這是另一個監管里程碑，我們的開發項目也取得了廣泛進展。

We remain focused on our three main value drivers shown on slides 5 and 6. In this quarter, we have made advancements in each. First, as noted, the team continues to execute on our global commercial strategy. Second, we remain excited about the hypothalamic obesity and the likelihood of success in our ongoing global Phase 3 trial. And third, we continue to make progress with two new MC4R agonist in Phase 1 and Phase 2 trials. We have completed the Phase 2 DAYBREAK trial, and the Phase 3 M&A trial remains on track to complete enrollment in the two leading cohorts by year-end.

我們仍然專注於幻燈片 5 和 6 所示的三個主要價值驅動因素。首先，如上所述，該團隊繼續執行我們的全球商業策略。其次，我們對下丘腦肥胖以及我們正在進行的全球 3 期試驗的成功可能性仍然感到興奮。第三，我們在第 1 期和第 2 期試驗中繼續在兩種新的 MC4R 激動劑方面取得進展。我們已經完成了第 2 階段的 DAYBREAK 試驗，第 3 階段的併購試驗仍有望在年底前完成兩個主要隊列的入組。

Revenues for the quarter were $29.1 million, driven predominantly by BBS. Two years post approval in the US and with increasing market access in international, what remains most striking to me is the extent to which BBS is a classic rare disease challenge. The obesity and the hunger are there for all to see, but the disease remains relatively invisible to those who are not expert.

該季度的營收為 2,910 萬美元，主要由 BBS 推動。在美國獲得批准兩年後，隨著國際市場准入的不斷增加，對我來說最引人注目的是 BBS 成為經典罕見疾病挑戰的程度。肥胖和飢餓是有目共睹的，但對於那些非專業人士來說，這種疾病仍然相對不易察覺。

Two weeks ago, I attended the BBS Foundation International Conference in Minneapolis, the first in-person meeting at this level in more than four years. More than 200 patients and family members attended, along with a number of the expert physicians. One common refrain was, aren't you tired of having to explain to each new doctor that you see what Bardet-Biedl syndrome is?

兩週前，我參加了在明尼阿波利斯舉行的 BBS 基金會國際會議，這是四年多來首次舉行這一級別的面對面會議。 200多名患者和家屬以及多位專家醫生參加了會議。一個常見的問題是，您是否厭倦了向每位新醫生解釋您所看到的巴代-比德爾綜合症是什麼？

In the opening session, the head of the foundation charged the attendees with one goal, meet someone they did not know from the community. Of the many challenges facing the rare disease patients and families, which include getting to a diagnosis, finding an expert physician, managing their disease, one of the biggest is simply feeling alone.

在開幕典禮上，基金會負責人向與會者提出了一個目標：與社區中不認識的人會面。罕見疾病患者和家人面臨的眾多挑戰包括獲得診斷、尋找專家醫生、控制疾病，其中最大的挑戰之一就是感到孤獨。

Rhythm from the beginning has not focused on selling a drug. Instead, our focus has been on supporting community development with the goal of having more experts, more integrated care centers, and most importantly, more opportunities for patients and their families to interact with other members of the community. That meeting was one big family, and we, as Rhythm were privileged to be part of it.

Rhythm從一開始就沒有專注於銷售藥品。相反，我們的重點是支持社區發展，目標是擁有更多專家、更全面的護理中心，最重要的是，為患者及其家人提供更多與社區其他成員互動的機會。那次會議就像一個大家庭，我們 Rhythm 很榮幸能成為其中的一員。

How does all that relate to revenue growth? We do the right thing for each patient, their family and the community, and the revenues they'll follow. In hypothalamic obesity, our ongoing Phase 3 pivotal trial remains on track for a first half readout in 2025, and our enthusiasm remains high. At this point, the first patients enrolled have completed their placebo-controlled portion and are rolling over into the open-label extension.

這一切與收入成長有何關係？我們為每位患者、他們的家人和社區以及他們將獲得的收入做正確的事情。在下視丘肥胖方面，我們正在進行的 3 期關鍵試驗仍有望在 2025 年上半年公佈結果，我們的熱情仍然很高。此時，第一批入組的患者已經完成了安慰劑對照部分，並正在轉入開放標籤擴展。

A brief reminder, the pivotal cohort for this trial enrolled 120 patients randomized two to one drug to placebo, with the protocol calling for up to eight weeks for dose titration and 52 weeks on the therapeutic dose. The trial is over enrolled, dropout rate remains exceedingly low, and the trial is 99% powered to show a 10% placebo adjusted difference in BMI.

簡單提醒一下，這項試驗的關鍵隊列招募了 120 名患者，隨機將兩種藥物與一種藥物分配給安慰劑，該方案要求長達 8 週的劑量滴定和 52 週的治療劑量。該試驗已超額入組，退出率仍然極低，且該試驗的 99% 有效度顯示 BMI 經安慰劑調整後有 10% 的差異。

Of note, we do not counsel these patients on diet or exercise as a formal part of the trial design. Patients receive only what is standard of care for that institution, recognizing almost all of these patients have tried diet and exercise previously without success. Of interest, approximately 25% of patients enrolled in this trial had tried GLP-1 and about 10% of enrolled patients entered the trial on active GLP-1 therapy.

值得注意的是，我們不會將飲食或運動建議作為試驗設計的正式部分。患者僅接受該機構的標準護理，因為幾乎所有這些患者都曾嘗試過節食和運動但沒有成功。有趣的是，參與試驗的約 25% 的患者曾嘗試過 GLP-1，約 10% 的參與試驗的患者接受主動 GLP-1 治療。

We did not exclude patients on or with GLP-1 experience from the trial. They were allowed to enroll as long as their weight was stable over the preceding three months. Our overall position on GLP-1 use in this population informed partly by our engagement with the community but also by the research many of you have done, is that many patients with HO may have some initial response to GLP-1s, but the percent of patients with sustained benefit will be less than 20%, and the magnitude of that benefit may be 10% or less.

我們沒有將有 GLP-1 經驗的患者排除在試驗之外。只要他們的體重在過去三個月內保持穩定，他們就可以報名。我們對 GLP-1 在這一人群中使用的總體立場部分來自我們與社區的接觸，也來自你們許多人所做的研究，即許多 HO 患者可能對 GLP-1 有一些初步反應，但持續獲益的患者將低於20%，且獲益的幅度可能為10%或更少。

In Japan, where we estimate the number of patients with hypothalamic obesity to be 5,000 to 8000, which is on par with European and United States total patient estimates, despite Japan's overall population being much smaller. We have dosed the first patients in our 12 patient cohort and we are actively screening patients at four sites in Japan. This Japanese cohort will enable us to seek regulatory approval in Japan with data from these 12 patients plus the pivotal cohort and not affect timing for US and European regulatory submissions.

在日本，我們估計下丘腦肥胖患者的數量為 5,000 至 8000 人，這與歐洲和美國的患者總數估計相當，儘管日本的總人口要少得多。我們已經對 12 名患者群組中的第一批患者進行了給藥，並且我們正在日本的四個地點積極篩選患者。這個日本隊列將使我們能夠利用這 12 名患者以及關鍵隊列的數據在日本尋求監管部門的批准，並且不會影響美國和歐洲監管機構提交的時間。

Our two next-generation MC4 agonists designed to avoid the hyperpigmentation that comes with MC1R agonism are advancing on schedule. Last month, we announced dosing of the first patient in our 28 patient Phase 2 placebo-controlled trial evaluating the oral MC4R agonist LB54640 in hypothalamic obesity.

我們的兩種下一代 MC4 激動劑旨在避免 MC1R 激動劑帶來的色素沉著過度，正在按計劃推進。上個月，我們宣布對 28 名患者參與的 2 期安慰劑對照試驗中的第一位患者進行給藥，該試驗評估口服 MC4R 激動劑 LB54640 對下丘腦肥胖的治療作用。

The Phase 1 study of RM-718, our weekly injectable built of setmelanotide is progressing through the SAD, the single ascending dose and MAD multiple ascending dose portions of the trial and normal healthy volunteers with obesity. We made the decision to add two additional higher dosing cohorts in the SAD portion with the goal of satisfying the regulatory requirements in this early Phase study potentially avoiding the need for a dedicated QTC study measure of heart rhythm, thereby simplifying the regulatory development path.

RM-718（我們的每週注射劑 setmelanotide）的 1 期研究正在透過 SAD、單次遞增劑量和 MAD 多次遞增劑量部分的試驗以及患有肥胖症的正常健康志願者進行。我們決定在 SAD 部分添加兩個額外的較高劑量組，目的是滿足這項早期研究的監管要求，從而避免對心律進行專門的 QTC 研究測量，從而簡化監管開發路徑。

Finally, we were pleased to receive an expanded marketing authorization for IMCIVREE from the European Commission for patients two to less than six years old with Bardet-Biedl syndrome or POMC, LEPR deficiency. In the US, we completed submission of the supplemental new drug application to the FDA in the second quarter, which keeps us on track for a potential label expansion towards the end of this year.

最後，我們很高興獲得歐盟委員會對 IMCIVREE 的擴大行銷授權，用於治療患有 Bardet-Biedl 症候群或 POMC、LEPR 缺陷的 2 至 6 歲以下患者。在美國，我們在第二季完成了向 FDA 提交補充新藥申請，這使我們有望在今年年底前實現潛在的標籤擴展。

As we have previously highlighted, this approval modestly expands the treatable population, but more importantly, it may offer patients fortunate enough to get a diagnosis at an early age potential for better outcomes. Two key takeaways from the Phase 3 trial were one, patients as young as two can be severely affected; and two, as shown on slide 7, they responded uniformly and well to a treatment with an 18.4% mean reduction in BMI at one year. These are genetic diseases and the defect is present at birth. Yann will share modeling data, which was presented at the European Congress of Obesity in May, that model the impact of early intervention on long-term comorbidities in patients with obesity. Given the potential benefit, why would you not want to start treatment as early as possible?

正如我們之前強調的，這項批准適度擴大了可治療的人群，但更重要的是，它可能為足夠幸運的患者提供早期診斷的潛力，以獲得更好的結果。第三階段試驗的兩個關鍵要點是：一是年僅兩歲的患者可能會受到嚴重影響；第二，如幻燈片 7 所示，他們對治療的反應一致且良好，一年內 BMI 平均降低了 18.4%。這些都是遺傳性疾病，缺陷在出生時就存在。 Yann 將分享五月在歐洲肥胖大會上提交的模型數據，這些數據模擬了早期介入對肥胖患者長期合併症的影響。考慮到潛在的益處，為什麼不想儘早開始治療呢？

So I now turn the call over to Jennifer to provide the North American update. Jennifer?

因此，我現在將電話轉給詹妮弗，以提供北美的最新情況。詹妮弗？

Thank you, David. This quarter marks the eighth full quarter of IMCIVREE sales for BBS since it was approved in June of 2022. Looking back over the last two years, it has been an amazing journey, in many instances better than we expected. Though, we had done our research and heard feedback regarding the need for a tailored therapy to address persistent hyperphagia and early onset obesity in BBS patients, we have learned so much more since our launch.

謝謝你，大衛。自 2022 年 6 月獲得批准以來，本季是 BBS 的 IMCIVREE 銷售額第八個完整季度。儘管我們已經完成了研究並聽取了有關需要定制療法來解決 BBS 患者持續性食慾過盛和早發性肥胖問題的反饋，但自推出以來我們學到了很多東西。

What grounds us and gives us conviction everyday are the stories we have heard with a consistency relating to the benefits patients are receiving on IMCIVREE. In one story, there was a woman who weighed 210 pounds before initiating IMCIVREE. Now coming up on two years on IMCIVREE, she reports reduction in her hunger and her weight is now stable at approximately 135 pounds.

我們每天聽到的與患者在 IMCIVREE 上獲得的福利相關的故事始終是我們的基礎和信念。在一個故事中，有一位女性在開始使用 IMCIVREE 之前體重為 210 磅。現在，她已經服用 IMCIVREE 兩年了，她報告飢餓感減輕了，體重現在穩定在約 135 磅。

While there is patient by patient variability in the amount of weight loss experienced, what stands out with consistency is the positive impact of both hunger and weight reduction. For this particular patient, after several years of not working, she recently started a job as a customer service representative working from home as the first visually impaired employee for this company.

雖然不同患者的體重減輕程度有差異，但飢餓和體重減輕的正面影響具有一致性。對於這位特殊的患者來說，在幾年沒有工作之後，她最近開始擔任客戶服務代表，在家工作，成為該公司第一位視障員工。

She also told us about her first solo plane trip to see a friend, and she's now looking forward to more trips in the future. Stories like this motivate everyone at Rhythm to ensure all eligible patients are able to have access to IMCIVREE, and we continue to make progress with a sense of urgency as a collective team.

她還向我們講述了她第一次獨自乘飛機去看朋友的經歷，她現在期待著未來更多的旅行。這樣的故事激勵 Rhythm 的每個人確保所有符合條件的患者都能獲得 IMCIVREE，並且我們作為一個集體團隊帶著緊迫感繼續取得進展。

Now to the quarter, beginning on slide 9. On a high level, our results for the second quarter are strong and consistent with our expectations. We're continuing to see steady growth in prescriptions and prescribers breadth and depth quarter-over-quarter, as well as ongoing positive reimbursement decisions for both initial as well as reauthorization approvals.

現在到本季度，從幻燈片 9 開始。我們繼續看到處方和處方者的廣度和深度逐季度穩步增長，以及初始和重新授權批准的持續積極報銷決策。

On to slide 10, here are the top level metrics we've been sharing since launch. We received approximately 100 new prescriptions for IMCIVREE to treat patients with BBS here in the United States. In addition to gaining approximately 70 approval for reimbursement, which is representative of the steady growth quarter-over-quarter. While not detailed on the slide, we had approximately 70 prescribers this quarter. Launch to-date, more than 30% of prescribers have written two or more prescriptions.

在投影片 10 上，以下是我們自發布以來一直在分享的頂級指標。我們收到了大約 100 個 IMCIVREE 新處方，用於治療美國的 BBS 患者。此外還獲得了約 70 個報銷批准，這代表了季度環比的穩定增長。雖然幻燈片上沒有詳細說明，但本季我們有大約 70 名處方者。迄今為止，已有超過 30% 的處方醫生開過兩張或更多處方。

Lastly, the breakdown by physician specialty remains consistent with what we have reported in past quarters with endocrinologists being the lead prescribers of IMCIVREE. With access, the story is also consistent as we have seen positive reimbursement decisions by state Medicaid programs that represent more than 90% of Medicaid covered lives.

最後，按醫生專業劃分的細分與我們過去幾季的報告一致，內分泌科醫生是 IMCIVREE 的主要處方者。就准入而言，這個故事也是一致的，因為我們看到州醫療補助計劃做出了積極的報銷決定，這些計劃代表了超過 90% 的醫療補助覆蓋人群。

Our success in the reauthorization process continues to be strong. With reauthorizations, we are still seeing the vast majority approved right away. By the beginning of the second quarter, less than 10 had not yet been reauthorized. And we are working through the appeals process for these patients.

我們在重新授權過程中繼續取得巨大成功。透過重新授權，我們仍然看到絕大多數立即獲得批准。截至第二季初，尚未重新授權的項目還不到 10 個。我們正在為這些患者辦理上訴程序。

With the consistency of these metrics over the last several quarters, and knowing what we know now, we look forward with confidence in the long-term BBS opportunity.

鑑於過去幾季這些指標的一致性，並且了解我們現在所知的情況，我們對長期 BBS 機會充滿信心。

On to slide 11, we are pleased with the progress we have made across our areas of focus and we are constantly evaluating to see if there are ways we may refine moving forward. One example we identified was within our patient support program with Rhythm InTune, we started with one group of patient education managers when we launched. As we have grown, we have evolved how our teams are organized and split out the responsibilities into patient support services group by adding field access managers. This group focuses on gaining initial payer approvals and ensuring ongoing reimbursement through the reauthorization processes or insurance changes throughout the year. This change has freed up our patient education managers so they can focus on providing education and support directly to patients and their families to ensure they understand treatment expectations and help manage through the process of treatment initiation and long-term maintenance.

在投影片 11 上，我們對我們在重點領域的進展感到滿意，並且我們正在不斷評估，看看是否有可以改進的方法。我們發現的一個例子是 Rhythm InTune 的患者支援計劃，啟動時我們從一組患者教育經理開始。隨著我們的成長，我們改變了團隊的組織方式，並透過增加現場訪問經理將職責劃分到患者支援服務小組。該小組的重點是獲得付款人的初始批准，並確保透過全年的重新授權流程或保險變更進行持續報銷。這項變革解放了我們的患者教育經理，使他們能夠專注於直接向患者及其家人提供教育和支持，以確保他們了解治療期望並幫助管理治療開始和長期維持的過程。

On to physician engagement, we continue finding and engaging with new potential prescribers and see more physicians gaining experience with IMCIVREE and see their patients benefit from therapy. Through their experiences, there have been healthcare providers who have been inspired and motivated to optimize care of BBS patients, including the recognition of the benefit and need of multidisciplinary involvement in the diagnosis and care of patients.

在醫生參與方面，我們繼續尋找新的潛在處方者並與之接觸，並看到更多的醫生獲得 IMCIVREE 的經驗，並看到他們的患者從治療中受益。透過他們的經驗，一些醫療保健提供者受到啟發和激勵來優化 BBS 患者的護理，包括認識到多學科參與患者診斷和護理的好處和需求。

Each rare disease is unique and comes with its own opportunities and challenges. I am proud of the success and progress our teams have made to help increase awareness and build community through active education, engagement, and support. We are thrilled to see hundreds of patients and families benefiting from IMCIVREE every day.

每種罕見疾病都是獨特的，都有其自身的機會和挑戰。我為我們的團隊在透過積極的教育、參與和支持來幫助提高認識和建立社區方面所取得的成功和進步感到自豪。我們很高興每天看到數百名患者和家庭從 IMCIVREE 中受益。

Now, I'll turn the call over to Yann.

現在，我將把電話轉給 Yann。

Thank you, Jennifer. I begin on slide 13 with the great news from last week that the European Commission expanded the marketing authorization for IMCIVREE to now include children with BBS, POMC and LEPR deficiency who are as young as two years old. This decision to allow for pediatric use of IMCIVREE in patients this young, a decision which came one month before it was expected, underscores the severe impact of the disruption of the MC4R pathway and the significant unmet medical need for young children.

謝謝你，詹妮弗。我從第 13 張幻燈片開始，介紹了上週的好消息：歐盟委員會擴大了 IMCIVREE 的營銷授權，現在包括患有 BBS、POMC 和 LEPR 缺陷的年僅兩歲的兒童。這項允許兒童使用 IMCIVREE 的決定比預期提前了一個月，強調了 MC4R 途徑破壞的嚴重影響以及幼兒的重大未滿足的醫療需求。

In Germany, the exemption process, which will allow us to get federal reimbursement, has already started. We have also already submitted the reimbursement dossier to the French and Italian authorities and we will do the same with several other key European countries in coming weeks and months.

在德國，豁免程序已經啟動，這將使我們能夠獲得聯邦報銷。我們也已經向法國和義大利當局提交了報銷文件，我們將在未來幾週和幾個月內向其他幾個主要歐洲國家提交相同的文件。

This is an important milestone for IMCIVREE. We know it is important to diagnose patients with these diseases early in life before the commodities of severe obesity take hold and now we look forward to working with the physicians and caregivers to provide access to IMCIVREE beginning at a young age and making a positive difference for the patients.

這是 IMCIVREE 的一個重要里程碑。我們知道，在嚴重肥胖症流行之前儘早診斷患有這些疾病的患者非常重要，現在我們期待與醫生和護理人員合作，從年輕時開始提供 IMCIVREE 的使用機會，並為患者帶來積極的影響。 。

Next slide, and since we are talking about this topic in May, at the European Congress on Obesity, we presented research showing the negative impact early onset obesity can have on comorbidities and life expectancy and we also showed the positive impact of early intervention on weight prediction have in reducing the risk of comorbidities and increasing life expectancy.

下一張投影片，由於我們在五月份的歐洲肥胖大會上討論了這個主題，我們提出的研究表明早發性肥胖可能對合併症和預期壽命產生負面影響，我們也展示了早期幹預對體重的正面影響預測有助於降低合併症風險並延長預期壽命。

As you can see in the table, this early onset of obesity model developed based on a detailed assessment of more than 200 published studies, shows that the patient with a BMISD score of 2.5 at the age of 2 or BMISD score of 4 at the age of 4, which is typical of patients with rare MC4R pathway disease has increased likelihood of several key comorbidities such as type 2 diabetes, cardiovascular disease, asthma, MASLD, and cancer. The life expectancy of such a patient is 37 years of age. With an intervention that reduces BMISD by 2 points, life expectancy almost doubles to 64 years old and as you can see in the table, the risk of several comorbidities is greatly reduced, for example for cardiovascular events or asthma, or obstructive sleep apnea.

如表中所見，這個早期肥胖模型是根據對 200 多項已發表研究的詳細評估而開發的，顯示 2 歲時 BMISD 評分為 2.5 或 2 歲時 BMISD 評分為 4 的患者4 是罕見MC4R 通路疾病患者的典型症狀，它增加了幾種關鍵合併症的可能性，如2 型糖尿病、心血管疾病、氣喘、MASLD 和癌症。該患者的預期壽命為 37 歲。透過將BMISD 降低2 個點的干預措施，預期壽命幾乎增加一倍，達到64 歲，並且如表中所示，多種合併症的風險大大降低，例如心血管事件或氣喘或阻塞性睡眠呼吸中止症。

Next slide, the organizer of the European Congress on Obesity selected this compelling research for inclusion in the conference official press release. More than 30 media outlets reported on these results and as our presenters told the British news outlet the Guardian, it is vital that treatment isn't put off until the development of type 2 diabetes, high blood pressure or other warning signs, but starts early.

在下一張投影片中，歐洲肥胖大會的組織者選擇了這項引人注目的研究，將其納入會議官方新聞稿中。超過30 家媒體報導了這些結果，正如我們的主持人告訴英國新聞媒體《衛報》的那樣，重要的是，治療不要推遲到出現2 型糖尿病、高血壓或其他警告信號時才開始，而是儘早開始。

On the next slide, slide 16, we are also pleased to share the news that NICE recommended that the National Health Service reimburse IMCIVREE for treatment of obesity and hyperphagia in patients with BBS between the ages of 6 and 17 years old. Patients who begin therapy before 18 years old can remain on reimburse therapy if they continue to show benefit. We are very pleased with the successful negotiation and very grateful for the support we received from leading UK BBS experts and the UK BBS patient association.

在下一張幻燈片（幻燈片 16）中，我們也很高興地分享這樣的消息：NICE 建議國家衛生服務機構報銷 IMCIVREE，用於治療 6 歲至 17 歲之間 BBS 患者的肥胖和食慾過盛。 18 歲前開始治療的患者如果繼續表現出獲益，可以繼續接受報銷治療。我們對談判的成功感到非常高興，並非常感謝英國 BBS 領先專家和英國 BBS 患者協會的支持。

We now expect IMCIVREE to be funded for BBS in England and Wales in the third quarter and we anticipate Northern Ireland authorities to follow and adopt the NAIC guidance in the next several months and the Scottish Medicines Consortium to do the same in 2025.

我們現在預計 IMCIVREE 將在第三季度為英格蘭和威爾斯的 BBS 提供資金，我們預計北愛爾蘭當局將在未來幾個月內遵循並採用 NAIC 指南，蘇格蘭藥品聯盟將在 2025 年採取同樣的做法。

In terms of the two years to six years indication, we expect an MHRA approval before the end of the year following the EMA approval from last week, which will be then followed by an automatic National Health Service funding for this expanded population.

就兩年至六年的指示而言，繼上週獲得 EMA 批准後，我們預計 MHRA 將在年底前獲得批准，隨後將為這一擴大的人口自動提供國家醫療服務資金。

Lastly, on slide 17, you can see the landscape of where we have achieved reimbursement for IMCIVREE for BBS and our POMC, LEPR deficiency, and where we have named patient cells in place, mostly reimbursed by the way. Germany and France remain the main driver of revenues from the international region. The Germany launch continue as we expected, a typical rare disease launch not dissimilar to the steady trajectory in United States.

最後，在幻燈片 17 上，您可以看到我們為 BBS 和 POMC、LEPR 缺陷實現 IMCIVREE 報銷的情況，以及我們已就位命名患者細胞的情況，順便說一下，大部分報銷。德國和法國仍然是國際地區收入的主要驅動力。德國的上市正如我們預期的那樣繼續進行，這是一種典型的罕見疾病的上市，與美國的穩定軌跡沒有什麼不同。

France also is contributing with both the pre-EMA approval paid early access program for hypothalamic obesity and the paid early access program for BBS. We also now are seeing increased commercial patient activity for BBS in both Italy and Spain.

法國也為 EMA 批准前的下丘腦肥胖付費早期訪問計劃和 BBS 付費早期訪問計劃做出了貢獻。我們現在也看到義大利和西班牙 BBS 的商業患者活動增加。

And importantly, and this is recent news that is new today, we received an exceptional pre-EMA marketing authorization from the Italian Ministry of Health for the inclusion of IMCIVREE under the Law 648 for the treatment of obesity and hunger control associated with hypothalamic obesity for patients between 6 and 24 years old. And similar to France, we will begin receiving reimbursement to treat these patients. This development speaks to the severity of the disease, significance of unmet medical need in treating hypothalamic obesity, and just how compelling the data from a Phase 2 trial and its open-label extension are.

重要的是，這是今天的最新消息，我們收到了義大利衛生部的特殊預 EMA 行銷授權，根據第 648 號法律將 IMCIVREE 納入其中，用於治療與下丘腦肥胖相關的肥胖和飢餓控制6至24歲之間的患者。與法國類似，我們將開始獲得治療這些患者的報銷。這項進展說明了該疾病的嚴重性、治療下丘腦肥胖未得到滿足的醫療需求的重要性，以及來自 2 期試驗及其開放標籤擴展的數據是多麼令人信服。

Now, over to Hunter.

現在，轉到亨特。

Thank you, Yann. Turning to slide 19, net revenue from global sales of IMCIVREE in Q2 came in at $29.1 million, which represents almost 12% growth over the prior quarter. As we show here on this slide, net revenue has continued to grow steadily during the two years since the launch of IMCIVREE for BBS in the United States.

謝謝你，揚。轉向投影片 19，第二季 IMCIVREE 全球銷售淨收入為 2,910 萬美元，比上一季成長近 12%。正如我們在此幻燈片中所示，自 IMCIVREE for BBS 在美國推出以來的兩年裡，淨收入持續穩定成長。

IMCIVREE revenue generated in the United States accounted for 74% of net sales this quarter, consistent with the first quarter of the year. US revenue of $21.6 million increased $2.2 million, or nearly 11% versus Q1. Driving US revenue growth was an increase in the number of reimbursed patients on therapy and a resulting increase in vials dispensed. Changes in inventory levels at the specialty pharmacy did not have a meaningful impact on US revenue.

IMCIVREE 在美國產生的收入佔本季淨銷售額的 74%，與今年第一季一致。美國營收為 2,160 萬美元，與第一季相比增加了 220 萬美元，成長近 11%。推動美國收入成長的是接受治療的報銷患者數量的增加以及由此導致的藥瓶分配量的增加。專業藥房庫存水準的變化並未對美國收入產生重大影響。

In Q2, the proportion of IMCIVREE net revenue generated outside the United States was 26%, or $7.5 million, majority of which came from the BBS launch in Germany and from our two early access programs in France, including the AP1 program for hypothalamic obesity. Ex-US, revenue increased by 14% quarter over quarter. While quarterly revenue growth may be variable, the trend is steady as we've described. This reinforces our confidence in the long-term growth prospects for IMCIVREE and BBS.

第二季度，IMCIVREE 在美國以外地區產生的淨收入比例為26%，即750 萬美元，其中大部分來自在德國推出的BBS 以及我們在法國的兩個早期訪問項目，包括針對下丘腦肥胖的AP1專案.除美國外，營收季增 14%。雖然季度收入成長可能會有所變化，但正如我們所描述的，趨勢是穩定的。這增強了我們對 IMCIVREE 和 BBS 長期成長前景的信心。

On slide 20 is a snapshot of the Q2 P&L. Q2's $29.1 million in net revenue compares to $19.2 million during the second quarter of last year. Gross-to-net for US sales in the second quarter increased slightly quarter over quarter to 86% from 85% in the first quarter of the year. Cost of sales during the second quarter was almost $3 million or approximately 10.1% of net product revenue versus 10.8% of net product revenue in the first quarter and compared to 11.6% during the same quarter last year. The primary driver of COGS was the 5% royalty to Ipsen under our licensing agreement as well as minor fluctuations due to product costs, volumes, and inventory.

第 20 張投影片是第二季損益表的快照。第二季的淨收入為 2,910 萬美元，而去年第二季的淨收入為 1,920 萬美元。第二季美國銷售額的毛淨額比上一季略有成長，從今年第一季的 85% 增至 86%。第二季的銷售成本接近 300 萬美元，約佔產品淨收入的 10.1%，而第一季佔產品淨收入的 10.8%，去年同期為 11.6%。銷貨成本的主要驅動因素是根據我們的授權協議向 Ipsen 收取 5% 的特許權使用費，以及由於產品成本、銷售和庫存而產生的小幅波動。

R&D expenses were $30.2 million for the second quarter, compared to $33.5 million during the second quarter of last year. Sequentially, Q1 R&D expenses were $128.7 million, driven by $92.4 million in costs related to LB54640. Separate from the consideration related to the licensing agreement in the first quarter, we experienced a decrease in R&D expenses due to a reduction in cost of our DAYBREAK, M&A, and Phase 3 HO studies, as well as lower costs relating to our ongoing open-label extension trial.

第二季的研發費用為 3,020 萬美元，而去年第二季的研發費用為 3,350 萬美元。隨後，第一季研發費用為 1.287 億美元，其中 LB54640 相關成本為 9,240 萬美元。除了與第一季授權協議相關的對價之外，由於我們的 DAYBREAK、併購和第 3 階段 HO 研究的成本降低，以及與我們正在進行的開放相關的成本降低，我們的研發費用有所減少。延伸試驗。

SG&A expenses were $36.4 million for the second quarter compared to $30 million for the same quarter last year. Q2 SG&A represent the 6% decrease sequential quarterly -- on a sequential quarterly basis versus $34.4 million for the first quarter of 2024. The quarter-over-quarter increase was due to increased levels of stock compensation. For the second quarter, weighted common shares outstanding were $61 million.

第二季的 SG&A 費用為 3,640 萬美元，而去年同期為 3,000 萬美元。第二季的 SG&A 比上一季下降 6%，而 2024 年第一季的 SG&A 為 3,440 萬美元。第二季度，已發行加權普通股為 6,100 萬美元。

Let's move to the next slide for a more fulsome discussion of EPS and cash on hand. On slide 20 -- 21, as of June 30, 2024, we reported $319 million in cash and cash equivalents, which includes net proceeds from the convertible preferred financing, that closed in April. Cash used in operations is approximately $28 million in Q2 and has averaged approximately $30 million in the prior four quarters.

讓我們轉到下一張投影片，對每股盈餘和手頭現金進行更全面的討論。在投影片 20 - 21 上，截至 2024 年 6 月 30 日，我們報告了 3.19 億美元的現金和現金等價物，其中包括 4 月結束的可轉換優先融資的淨收益。第二季營運中使用的現金約為 2,800 萬美元，前四個季度平均約為 3,000 萬美元。

Second-quarter operating expenses included total stock-based compensation of $10.4 million for the quarter compared to $7.8 million in the previous quarter. Reported GAAP EPS for the second quarter of negative $0.55 reflects a one-time non-cash gain of $8.9 million, resulting from a decrease in fair value of the issued convertible preferred stock between the deal execution date of April 1 and the closing date of April 15. This is strictly a non-cash gain with no impact to the preferred shares issued. GAAP EPS also includes accrued dividends on convertible preferred stock of $1.3 million, while no cash dividends are payable prior to the end of the second quarter post closed second year post closing.

第二季營運支出包括本季以股票為基礎的薪酬總額 1,040 萬美元，而上一季為 780 萬美元。報告的第二季GAAP 每股收益為負0.55 美元，反映了一次性非現金收益890 萬美元，這是由於4 月1 日交易執行日至4 月截止日期間已發行可轉換優先股的公允價值下降所致15. 這嚴格來說是非現金收益，對已發行的優先股沒有影響。 GAAP 每股盈餘還包括 130 萬美元的可轉換優先股應計股息，而在交屋後第二年第二季末之前不支付現金股息。

US GAAP classifies these pending payments as increasing rate dividends, i.e., 0% dividends in years one to two, and 6% dividends thereafter, and requires that we accrue for a portion of those dividends payable in future years. For those of you modeling at home, this ongoing accrual will be $1.3 million per quarter or $0.02 per share at the current share count.

美國公認會計準則將這些待支付的股息分類為遞增利率股息，即第一年至第二年的股息為0%，此後的股息為6%，並要求我們在未來幾年中提列部分應付股息。對於那些在家做模特兒的人來說，持續的應計費用將為每季 130 萬美元，或按當前股數計算每股 0.02 美元。

Now on to slide 22. Today, we reiterate our OpEx guidance of approximately $250 million to $270 million in non-GAAP operating expenses for 2024, comprised of R&D non-GAAP operating expenses of $145 million to $160 million and SG&A non-GAAP operating expenses of $105 million to $110 million. And lastly, with the convertible preferred financing of $150 million completed during the second quarter, we expect cash on hand to be sufficient to fund planned operations well into 2026.

現在轉到幻燈片 22。 1.05 億至1.1 億美元。最後，隨著第二季完成 1.5 億美元的可轉換優先融資，我們預計手頭現金足以為 2026 年的計畫營運提供資金。

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

這樣，我會將電話轉回大衛。

Thank you, Hunter. So as I was reflecting, listening to our update here, it was almost two years ago to date when we presented the first six weeks of data on the BBS launch in August of 2022. At that point I mean, there were a ton of questions. You had questions, we had many questions. And two years later, it's quite remarkable.

謝謝你，亨特。因此，正如我在此處聆聽我們的更新時所反思的那樣，我們在2022 年8 月發布BBS 發布的前六週數據時，已經是大約兩年前的事了。很多問題。你有問題，我們有很多問題。兩年後，這是相當了不起的。

I think you've heard quarter on quarter, as we've reported, really how in a way thrilled and in some level a bit unsurprised by the extent of approval, the extent of progress that we've made and the number of approvals we've had around the world. So from a BBS standpoint, we're in a really good place. We're incredibly excited about the progress to date, and we're increasingly excited about what is ahead.

正如我們所報導的那樣，我認為您每個季度都聽說過，對於批准的程度、我們取得的進展的程度以及我們獲得的批准的數量，確實在某種程度上感到興奮，並且在某種程度上感到有點驚訝。因此，從 BBS 的角度來看，我們處於一個非常好的位置。我們對迄今為止的進展感到非常興奮，並且對未來也越來越感到興奮。

So with that, I will open it up for questions.

因此，我將開放提問。

Thank you. (Operator Instructions)

謝謝。 （操作員說明）

Jeff Hung, Morgan Stanley.

傑夫洪，摩根士丹利。

The first is the number of the new prescriptions for BBS has been consistent over the last three quarters with 100 new scripts and 70 payer approvals for reimbursement per quarter. What remaining levers do you have to further increase numbers of new scripts per quarter, or proportion of payer approvals? Or is the launch fairly mature for BBS, where numbers are likely to remain consistent or decrease over time? And then I have a follow-up.

首先，BBS 的新處方數量在過去三個季度保持穩定，每個季度有 100 個新處方和 70 個付款人批准報銷。您還有哪些剩餘手段可以進一步增加每季新腳本的數量或付款人批准的比例？或者 BBS 的推出是否相當成熟，隨著時間的推移，數量可能會保持一致或減少？然後我有一個後續行動。

Jeff, maybe I'll make one comment and then turn it over to Jennifer for any color. I think, yeah, to be honest, the 100, quote-unquote, approximate 100 for the past few quarters is a bit almost remarkably consistent for a rare disease. We've highlighted from the beginning these ultra-rare opportunities, of course, tend to be lumpy. I would not necessarily anticipate a pure trend line even now that we're two years out, but we acknowledge the fact that it's been somewhat consistent.

傑夫，也許我會發表一條評論，然後將其交給珍妮佛以獲取任何顏色。我認為，是的，說實話，對於一種罕見疾病來說，過去幾個季度的 100（引用不引用）大約 100 幾乎是非常一致的。我們從一開始就強調了這些極為罕見的機會，當然，它們往往是不穩定的。即使現在已經過去兩年了，我也不一定會預期一條純粹的趨勢線，但我們承認它在某種程度上是一致的。

But with that, I'll turn over to Jennifer for any additional color on the numbers we have.

但這樣一來，我將向珍妮佛詢問我們所掌握的數字的任何其他顏色。

So I think like relating to the prescriptions in terms of that steady number, even two years out of launch, we're actually very happy with. We also recognize that there's still a lot of opportunity that remains out there. And I think one example was just in terms of the patient meeting that David had outlined, there were many patients there that had also just recently been diagnosed, many patients that were already diagnosed, and hearing about IMCIVREE for the first time.

所以我認為，就處方數量而言，即使在推出兩年後，我們實際上也非常滿意。我們也認識到，仍然存在著許多機會。我認為一個例子是 David 概述的患者會議，那裡有許多患者最近剛被診斷，許多患者已經被診斷，並且是第一次聽說 IMCIVREE。

So we know that the patients are out there in terms of those that have been diagnosed already and may not have yet understood there's a tailored therapy for them, as well as the opportunity to get patients to a quicker diagnosis moving forward. I think that we get better over time in terms of understanding where to have our field teams target in terms of their education and we also get more information in terms of our non-personal promotion efforts, just to be able to most effectively and efficiently use our resources moving forward and are constantly looking for new ways to actually supplement these efforts.

因此，我們知道，那些已經被診斷出來的患者可能還不知道有針對他們的量身定制的治療方法，以及讓患者更快獲得診斷的機會。我認為，隨著時間的推移，我們會更好地了解我們的現場團隊在教育方面的目標，並且我們還獲得了更多有關非個人推廣工作的信息，以便能夠最有效和高效地利用我們的資源不斷向前發展，並不斷尋找新的方法來真正補充這些努力。

I think one example is that more recently; there are other labs that actually have BBS testing done and genetic results. And there are opportunities for us to understand who are the physicians with positive BBS patients. So when new opportunities like that pop up, those are opportunities that we explore and evaluate in terms of if it's worth being able to execute on.

我認為最近的一個例子是：還有其他實驗室實際上已經完成了 BBS 測試和基因結果。我們還有機會了解誰是治療 BBS 陽性患者的醫生。因此，當出現這樣的新機會時，我們會探索和評估這些機會是否值得執行。

From a payer perspective, I would say, that we're very happy in terms of our current status and the number across each of the different payer types of folks who have IMCIVREE specific policies in place. I think the one lever that still remains and still ongoing dialogue is this space around Medicare, which has been a challenge for many other drugs as well.

從付款人的角度來看，我想說，我們對目前的狀況以及擁有 IMCIVREE 具體政策的不同付款人類型的人數感到非常滿意。我認為仍然存在且仍在持續對話的一個槓桿是醫療保險周圍的空間，這對許多其他藥物來說也是一個挑戰。

Great. And then second question is, can you just remind us of what you hope to see in Stage 2 of DAYBREAK later this year? And what kind of placebo adjusted benefit would be considered clinically meaningful? Would there be sufficient numbers of patients to get a sense by gene? And if not, like, how do you decide which genotypes to advance?

偉大的。第二個問題是，你能提醒我們一下你希望在今年稍後的 DAYBREAK 第二階段看到什麼嗎？什麼樣的安慰劑調整後的益處被認為具有臨床意義？是否有足夠數量的患者可以透過基因來感知？如果不是，例如，你如何決定要推進哪些基因型？

Yes, Jeff. Yes, that is a challenge with DAYBREAK. Again, as we've said, that was a very ambitious effort starting out with a very large number of genes. And we knew that is coming out of this, we would likely have relatively small number of patients per gene. So with that qualification, we presented the data in December. What happened in the Stage 1? And so by definition, patients who went into Phase 2 of DAYBREAK had had a 5% or more loss of or decrease in their BMI. So they were responders by that definition.

是的，傑夫。是的，這對 DAYBREAK 來說是一個挑戰。正如我們所說，這是一項非常雄心勃勃的努力，從大量的基因開始。我們知道，由此而來，每個基因的患者數可能相對較少。因此，有了這個資格，我們在 12 月提供了數據。第一階段發生了什麼事？因此，根據定義，進入 DAYBREAK 第 2 階段的患者的 BMI 下降或下降了 5% 或更多。所以按照這個定義，他們是響應者。

I think that, that data was encouraging. What you should expect to see coming out of this is that of those genes that look interesting, there will provide more color on two things. One did the DAYBREAK trial design work, meaning that definition of responder, if you went on a placebo, did you regain weight? If you continued on IMCIVREE, did you continue to lose more? And so that additional color on the genes you had there. And again, I think what we would expect and hope coming out of this is that out of that big effort, there's minimally one to three additional genes that we might find interesting to pursue.

我認為這些數據令人鼓舞。你應該期望看到的是那些看起來有趣的基因，它們將為兩件事提供更多的色彩。其中一個進行了 DAYBREAK 試驗設計工作，這意味著響應者的定義是，如果您服用安慰劑，您的體重會反彈嗎？如果您繼續使用 IMCIVREE，您是否會繼續失去更多？所以你那裡的基因會有額外的顏色。再說一次，我認為我們所期望和希望的結果是，經過巨大的努力，我們可能會發現至少一到三個額外的基因有興趣去追求。

Phil Nadeau, TD Cowen.

菲爾·納多，TD·考恩。

Congrats on a solid quarter. A few commercial questions. First, in North America, can you give us your most recent estimates for the persistence and compliance on therapy? Have the rates of compliance in particular or persistence changed over the last few quarters?

恭喜季度業績穩健。一些商業問題。首先，在北美，您能為我們提供您對治療持續性和依從性的最新估計嗎？在過去幾個季度中，特別是合規率或堅持率是否發生了變化？

Yeah, from a pure discontinuation rate, I mean, we're still in that 20% to 30% range. We're pushing toward the upper end there, which is where we've been. But that looks like it's holding and solid there. We have a little less insight into overall compliance. That's more challenging to get at.

是的，從純粹的停藥率來看，我的意思是，我們仍然處於 20% 到 30% 的範圍內。我們正在向上游邁進，這就是我們曾經去過的地方。但看起來它在那裡很牢固。我們對整體合規性的了解較少。這更具挑戰性。

But with that, I will turn it over to Jennifer.

但這樣一來，我就把它交給珍妮佛了。

I think from a compliance standpoint, similar to the experience that I've had in some other diseases, for areas where patients start to feel something, if they don't take the drug, they tend to have -- when they feel something, when they don't take the drug or reoccurrence of symptoms, they tend to have a higher compliance rate overall. So we are really happy in terms of that being similar with our area as it relates to the compliance rate that we are seeing today with IMCIVREE.

我認為從依從性的角度來看，類似於我在其他一些疾病中的經驗，對於患者開始有某種感覺的領域，如果他們不服用藥物，他們往往會——當他們有某種感覺時，當他們不服藥或症狀再次出現時，他們的整體依從率往往較高。因此，我們非常高興與我們的領域相似，因為這與我們今天在 IMCIVREE 看到的合規率有關。

That's helpful. And then one international question on the use of IMCIVREE for HO in France. Can you talk about the kinetics of the uptake in the HO community in France? How quickly is it being adopted? Do you have any sense of the number of HO patients on therapy? And should we expect a similar rate of adoption in Italy now that early access is opening?

這很有幫助。然後是關於在法國使用 IMCIVREE 進行 H2O 的國際問題。能談談法國 HO 社群的吸收動態嗎？它被採用的速度有多快？您了解接受治療的 HO 患者人數嗎？既然搶先體驗已經開放，我們是否應該期待義大利也有類似的採用率？

So maybe one quick reminder about France, which is important. We did achieve this pre-EMA approval access based on Phase 2 data, which is extremely rare. And to be more precise, there are just two rare disease therapies with such status inference in the last 10 years. So I will not give a precise number of patients. But yes, we are happy with the uptake. We are happy with the willingness to treat coming from the rare endocrine disease community and the urgency also to treat. So that's for France.

因此，也許可以快速提醒法國，這一點很重要。我們確實根據第二階段的數據實現了 EMA 前的批准訪問，這是極其罕見的。更準確地說，在過去 10 年裡，只有兩種罕見疾病療法具有這樣的狀態推論。所以我不會給出特定的患者人數。但是，是的，我們對這種採用感到滿意。我們對罕見內分泌疾病社群的治療意願和治療的緊迫性感到高興。這就是法國的情況。

And for Italy, it will -- the first patient will be likely started at the end of the year. We also expect, because we have already conversations with many of the stakeholders and experts. We also expect a significant traction. Of course, the number of the population is a bit different. As you've heard, it's between 6 and 24 years old, but it's comparable to France, we expect patients to start at the year-end and early next week.

對於義大利來說，第一位患者可能會在今年底開始治療。我們也期待如此，因為我們已經與許多利害關係人和專家進行了對話。我們也預計會有很大的吸引力。當然，人口數量略有不同。正如你所聽說的，年齡在 6 歲到 24 歲之間，但與法國相當，我們預計患者會在年底和下週初開始。

Whitney Ijem, Canaccord Genuity.

惠特尼·艾傑姆，Canaccord Genuity。

Hey, guys, add my congrats on the quarter. Just to follow-up on Phil's question on the HO patients in France, are there -- is there any data being collected on those patients to kind of put together some real world data that you could be able to use to help from a reimbursement perspective or any other perspective in the relative near-term?

嘿，夥計們，對本季表示祝賀。只是為了跟進 Phil 關於法國 HO 患者的問題，是否有 - 是否正在收集這些患者的任何數據，以匯總一些現實世界的數據，您可以使用這些數據從報銷的角度提供幫助或相對近期的任何其他觀點？

Yann?

揚？

So thank you. There is -- yes, thank you. There is indeed a national data collection led by the French Ministry of Health. We don't have access directly to these clinical data yet, but we know that the HCP and the Federal Joint Committee plan to publish on them soon. What I can say beyond the data is that what we hear from the physicians directly is that they are very pleased with the efficacy of the drug.

所以謝謝你。有——是的，謝謝。確實有一個由法國衛生部領導的國家數據收集工作。我們還無法直接存取這些臨床數據，但我們知道 HCP 和聯邦聯合委員會計劃很快發布這些數據。除了數據之外，我還能說的是，我們直接從醫生那裡聽到的是，他們對藥物的功效非常滿意。

Great. Thanks. And then just on 718, can you expand, I guess, on the progress of that study and timelines? And I guess, thinking through, are there any updated thoughts on your side about if the timeline of the oral and 718 end up being more similar kind of the value of moving them both forward versus maybe just the oral?

偉大的。謝謝。然後就在 718，我猜你能詳細介紹一下這項研究的進展和時間表嗎？我想，想一想，您是否有任何更新的想法，關於口頭和 718 的時間線最終是否更相似，以及推動它們前進的價值而不是僅僅口頭？

Yeah. I mean, the answer to the second part of that is, we assuming success in both trials. We will continue to move both of them forward. I mean, again, the goal all along here is than to have two options, a weekly injectable and a daily oral. So yes, if they're successful, we'll move both of them forward.

是的。我的意思是，第二部分的答案是，我們假設這兩項試驗都成功。我們將繼續推動兩者向前發展。我的意思是，這裡的目標始終是有兩種選擇，每週注射一次和每天口服一次。所以，是的，如果他們成功了，我們將推動他們前進。

In terms of additional color around 718, as we said, it's progressing well through the SAD, MAD. I mean, the decision to add a couple of additional cohorts is obviously predicated on having done well up through the cohorts treated to-date. And that decision to go to two higher dosing cohorts is, if we can avoid having to do a PPC study, it saves both some time and expense those are not cheap studies. So that's the reason for that.

就 718 周圍的附加顏色而言，正如我們所說，它在 SAD、MAD 方面進展順利。我的意思是，增加幾個額外隊列的決定顯然是基於迄今為止接受治療的隊列中表現良好。進行兩個較高劑量組的決定是，如果我們可以避免進行 PPC 研究，那麼它可以節省一些時間和費用，這些研究並不便宜。這就是原因。

I think in terms of part starting, Part C, we'll complete these two additional higher dosing cohorts. The other thing is that we need to finish the six-month talk study to be able to treat patients for longer than the four weeks. And so that will be a key aspect. And so that will finish up in mid to late fall here and will be a key trigger for moving on into the Part C.

我認為就開始部分（C 部分）而言，我們將完成這兩個額外的較高劑量組。另一件事是，我們需要完成為期六個月的談話研究，以便能夠治療患者的時間超過四週。所以這將是一個關鍵方面。因此，這將在秋季中後期結束，並將成為進入 C 部分的關鍵觸發因素。

Dae Gon Ha, Stifel.

大貢河，斯蒂菲爾。

Two from our side as well. One, if I could maybe get Yann's take on Italy, just to kind of clarify for that access, what additional data were submitted to get that reimbursement and early access and aid show beyond the Phase 2 data. I guess what we've seen from obesity week last year. And then second question is, ex-US commercial question for Yann as well. As you look at Germany, I think in the prepared remarks, you talked about sort of similar trajectory as the US. I mean, is there anything unique about Germany that whether it's compliance or persistence or even the way the healthcare system is structured such that the uptake could be more robust than the US? Just kind of curious on that.

我們這邊也有兩個。第一，如果我能了解 Yann 對義大利的看法，只是為了澄清該訪問，提交了哪些額外數據以獲得超出第二階段數據的報銷、早期訪問和援助顯示。我想我們從去年的肥胖週看到了什麼。第二個問題是 Yann 的前美國商業問題。當你看看德國時，我認為在準備好的演講中，你談到了與美國類似的軌跡。我的意思是，德國有什麼獨特之處嗎？只是對此有點好奇。

So first question, Italy HO, in fact, it is coming from the physicians and from the experts. It's -- so in France, we submit a dossier. The dossier is evaluated by the authorities. In Italy, it's different. It's based on the request from the physician. Then we are asked to submit a dossier and it is evaluated. And then we heard from the decision in the official journal of Italy. So it's a bit a different process, but in terms of data submitted, at the end of the day, it's the same set of data.

所以第一個問題，義大利HO，其實它是來自醫生和專家的。所以在法國，我們提交了一份檔案。該檔案由當局評估。在義大利，情況有所不同。這是根據醫生的要求。然後我們被要求提交一份檔案並對其進行評估。然後我們在義大利官方雜誌上聽到了這個決定。所以這是一個有點不同的過程，但就提交的數據而言，歸根結底，這是同一組數據。

Now back to France, back to Germany. Sorry, your question was about how the market look like. So I would say that to summarize, it's between France, which is very centralized, and the US, which is fairly decentralized. So there are important university hospitals and currently, for your information, we have 15 of these university hospitals were already treated -- treating BBS patients. There is a major center in the West of Germany with many, many BBS patients. So one of the key factor success for us is to continue further this decentralization and to speak to more hospitals and more physicians in terms of compliance or in terms of patient adherence, we have a very strong patient support program in place with nurses and a tailor program. So sometimes the nurse will be at home for each injection, sometimes once a week, sometimes once a month.

現在回到法國，回到德國。抱歉，您的問題是關於市場的情況。所以我想說，總而言之，這是在非常集中的法國和相當分散的美國之間進行的。因此，有一些重要的大學醫院，目前，供您參考，我們已經對其中 15 所大學醫院進行了治療——治療 BBS 患者。德國西部有一個主要中心，有很多很多 BBS 患者。 So one of the key factor success for us is to continue further this decentralization and to speak to more hospitals and more physicians in terms of compliance or in terms of patient adherence, we have a very strong patient support program in place with nurses and a tailor程式.因此有時護士會在家中進行每次注射，有時每週一次，有時每月一次。

They are in touch with the patient, they call them, they text them, et cetera. And it's one of the country in the world with the best adherence, thanks to this patient support program. So those are, I would say, the major facts about Germany that I can talk to you about.

他們與患者保持聯繫，給他們打電話，給他們發短信等等。由於這項患者支持計劃，它是世界上依從性最好的國家之一。我想說，這些是我可以與您談論的有關德國的主要事實。

Corinne Johnson, Goldman Sachs.

科琳·約翰遜，高盛。

You talked a little bit about adherence and compliance in the BBS launch. I'm curious if you could talk to us about how we should think about read across from what you see in BBS to the HO population and note any key similarities or differences between those two groups. And then, on a similar note, I think you mentioned a number of prescribers with 30% of those having written two or more scripts in BBS. I'm curious if you could talk again about the overlap between the prescriber population that you've had come on Board in BBS to the potential prescribers for an HO launch coming hopefully in the next couple of years.

您在 BBS 發布中談到了一些關於遵守和合規的問題。我很好奇你是否可以和我們談談我們應該如何考慮將你在 BBS 中看到的內容閱讀給 HO 人群，並注意這兩個群體之間的任何關鍵相似點或差異。然後，類似地，我認為您提到了一些處方者，其中 30% 的人在 BBS 中編寫了兩個或更多腳本。我很好奇您是否可以再次談論您在 BBS 中加入的處方者人群與預計在未來幾年內推出 HO 的潛在處方者之間的重疊。

So maybe I'll take the first one and Jennifer take the second one. So I think the read through to HO again, they're very different diseases as we know, they both have significant comorbidities which make them challenging diseases in general. And on top of that, they're dealing with this MC4 pathway defect. So hard to say, Corinne, I think the hyperpigmentation aspect will be similar in both groups.

所以也許我會選擇第一個，珍妮佛選擇第二個。因此，我認為再次通讀 HO，正如我們所知，它們是非常不同的疾病，它們都有顯著的合併症，這使得它們對一般疾病具有挑戰性。最重要的是，他們正在處理 MC4 通路缺陷。很難說，科琳，我認為兩組的色素沉澱方面都會相似。

Now, the extent to which they find it's all a benefit weight against that and we'll see. But that's one aspect that might be somewhat similar, if you remember this on the order of 5% of patients are discontinuing because of concern over the hyperpigmentation. I think we're getting better and better at managing the other side effects of the drug. As Jennifer said, talking, helping set expectations at the patient level in terms of what to expect early on, in terms of the nausea and the like. I think physicians are getting more experience in terms of titrating the drug, maybe going a little slower if patients are again struggling with that.

現在，他們發現這在多大程度上是一種利益權重，我們拭目以待。但這是一個可能有些相似的方面，如果你還記得這一點的話，大約有 5% 的患者因為擔心色素沉著而停止用藥。我認為我們在控制藥物的其他副作用方面做得越來越好。正如珍妮佛所說，透過交談，幫助患者設定早期預期的期望，包括噁心等。我認為醫生在滴定藥物方面正在獲得更多經驗，如果患者再次遇到這種情況，可能會放慢一點。

And the general approach in terms of our patient support system, patient education managers, and the like, Jennifer highlighted, we've continued to get better at that, and so we'll bring all of that experience to the HO world. So I'm optimistic we do better, but there's obviously a lot more to learn. Jennifer, feel free to add any color to that answer, as well as talking about the prescriber base.

Jennifer 強調，在我們的病患支援系統、病患教育經理等方面的一般方法，我們在這方面一直在不斷進步，因此我們將把所有這些經驗帶到 HO 世界。所以我很樂觀我們會做得更好，但顯然還有很多東西要學習。詹妮弗，請隨意為這個答案添加任何色彩，以及談論處方者基礎。

Yes. So, to iterate with David said that the product is the product and everything that we've learned, just in terms of the nuances of being able to educate and onboard patients and maintain them on therapy and the challenges that we have faced and the lessons that we have learned all apply to any future indication I think. I think we have a very solid baseline in place with the teams in place.

是的。因此，大衛重申，產品就是產品，也是我們學到的一切，只是就能夠教育和引導患者並維持他們接受治療的細微差別以及我們面臨的挑戰和教訓而言我們所了解到的一切都適用於我認為的任何未來跡象。我認為我們已經有了非常堅實的基線和團隊。

And as I outlined in my opening, we have also learned in terms of the positive aspect of focus, which is within the patient support team, they were responsible for two key areas of focus, which included gaining and maintaining reimbursement for patients. And the second area being the education support to also allow for onboarding and persistence. So even that learning and split, you'll have two teams now in place to really help with the BBS ongoing efforts as well as any future launches. I think is a good learning and implementation in terms of how we adapt.

正如我在開場白中概述的那樣，我們還了解到患者支援團隊內部關注的積極方面，他們負責兩個關鍵的關注領域，其中包括獲得和維持患者的報銷。第二個領域是教育支持，也允許入職和堅持。因此，即使是學習和拆分，您現在也將擁有兩個團隊來真正幫助 BBS 正在進行的工作以及任何未來的發布。我認為就我們如何適應而言，這是一個很好的學習和實施。

I would say similarly in terms of, for the prescriber base, of course, we have not really been talking about HO, in terms of our field organizations today, just simply because of the state we're in, in terms of not having approval yet. But there -- these patients are being seen by endocrinologists and folks who are the obesity specialists. So those are directly our targets, just in terms of our field efforts, in terms of educating just even for BBS. So I do imagine that there is going to be a higher level of overlap in terms of targets as we move forward in BBS and future potential indications.

我想說的是，對於處方者基礎而言，當然，就我們今天的現場組織而言，我們並沒有真正談論 HO，只是因為我們所處的狀態，就沒有批准而言然而。但在那裡，內分泌科醫生和肥胖專家正在給這些患者看診。因此，這些直接是我們的目標，就我們的現場努力而言，甚至就 BBS 的教育而言。因此，我確實認為，隨著我們在 BBS 和未來潛在跡象方面的進展，目標方面將會有更高程度的重疊。

Tazeen Ahmad, BofA Securities.

塔津‧艾哈邁德 (Tazeen Ahmad)，美國銀行證券公司。

I maybe wanted to go back and ask about the Basket Study. You talked earlier about the potential of finding a few more amenable mutations. But do you have a sense on how big the opportunities of the mutations could be in general if we wanted to frame it size wise, let's say between BBS and HO, we'd love to know if you have any idea of how big those to be. And then secondly, as you advance in the launch of the product in Europe, can you talk about how we should think about pricing as more and more countries start selling products and you move away from the high compensation countries like Germany, what should we be assuming for modeling purposes?

我也許想回去問籃子研究的狀況。您之前談到了發現一些更適合的突變的潛力。但是，如果我們想明智地確定其大小，那麼您是否知道突變的機會一般有多大，比方說在 BBS 和 HO 之間，我們很想知道您是否知道這些機會有多大。其次，隨著您在歐洲推出該產品，您能否談談我們應該如何考慮定價，因為越來越多的國家開始銷售產品，並且您遠離德國等高補償國家，我們應該做什麼假設用於建模目的？

Yeah. So Yann, I'll let you take the pricing question in Europe. First, the Basket DAYBREAK study, as we said, in terms of the size of the population, again, there's a wide range of genes, and some of the genes we discontinued, if you remember, because we were just having trouble enrolling. And that was consistent with our screening numbers, of course, extremely rare diseases.

是的。 Yann，我將讓你回答歐洲的定價問題。首先，籃子黎明研究，正如我們所說，就人口規模而言，再次，有各種各樣的基因，如果你還記得的話，我們終止了一些基因，因為我們只是在招募方面遇到了困難。當然，這與我們的篩檢數字一致，是極為罕見的疾病。

We're still hopeful down the line that there'll be a way to access some of those incredibly rare genes and a more efficient development program. So we don't necessarily have to study them all independently, but that's not in the near-term of the genes we might be interested in. By definition, they need to be large enough to study. And so that range will be, I would say, is a way to think about it. It will be between BBS and HO. There'll be some that will be sort of at the BBS end of the extension, if you will, and then there are some that are more frequent for sure. Sorry, Yann, yes, sorry.

我們仍然希望將來能夠找到一種方法來獲取其中一些極其罕見的基因和更有效的開發計劃。所以我們不一定要獨立地研究它們，但這不是我們可能感興趣的近期基因。所以我想說，這個範圍是一種思考方式。它將在 BBS 和 HO 之間進行。如果您願意的話，會有一些在擴展的 BBS 端，然後肯定會有一些更頻繁。對不起，Yann，是的，對不起。

Yes. David, it was breaking on my side. Can you -- sorry, repeat the question?

是的。大衛，我這邊已經壞了。抱歉，你能重複這個問題嗎？

Yes. The question was just around pricing in Europe as we go to other countries should they just seen and others think differently about pricing as we get into some of these smaller markets, if you will?

是的。問題在於歐洲的定價，當我們進入其他國家時，當我們進入一些較小的市場時，他們是否會看到和其他人對定價有不同的看法，如果你願意的話？

Sorry. It was breaking again. So your question is difference between prices in the key European countries and the smallest countries?

對不起。它又壞了。那麼您的問題是歐洲主要國家和最小國家的價格有何差異？

Yes, so, exactly. So the question is, as they develop their models, should we think differently as we move from the Germany's and France's to some of the smaller markets in terms of what the pricing we might expect to get?

是的，確實如此。所以問題是，當他們開發自己的模型時，當我們從德國和法國轉向一些較小的市場時，我們是否應該以不同的方式思考我們可能獲得的定價？

Okay. Okay. So yes, no, so it's an interesting question, because, in fact, sometimes we have higher price where we don't expect them, and we end with lower prices when we were expecting maybe medium type of prices. So I would say first that there is not a rule, especially in the last years, where there have been a lot of changes in terms of negotiation dynamics, et cetera.

好的。好的。所以是的，不，所以這是一個有趣的問題，因為事實上，有時我們的價格比我們預期的要高，而當我們預期的價格可能是中等類型時，我們最終會得到較低的價格。所以我首先要說的是，沒有規則，特別是在過去幾年，談判動態等方面發生了很多變化。

So I would say that, as usual, we know that there are some countries with higher prices and this has not changed. This has not changed, and Germany is one of them. There are some countries with prices that are a bit lower, Spain is one example. But I mean, yes, we've had good surprises with other countries. So I cannot really precisely answer this question. It's really country by country.

所以我想說，像往常一樣，我們知道有些國家的價格較高，這一點沒有改變。這一點沒有改變，德國就是其中之一。有些國家的價格略低，西班牙就是一個例子。但我的意思是，是的，我們與其他國家的合作給我們帶來了驚喜。所以我無法真正準確地回答這個問題。確實是一個國家一個國家。

What I can say in general about pricing in Europe, or with our pricing in Europe is that we are pleased with where we are. And I think it's really because PPL and BBS have been recognized as rare disease, distinct from general obesity, and priced as such. So I cannot answer country by country, but for sure, we are in the same range as other more typical rare disease therapies.

關於歐洲的定價，或者我​​們在歐洲的定價，我可以說的是，我們對目前的情況感到滿意。我認為這實際上是因為 PPL 和 BBS 已被認為是罕見疾病，與一般肥胖不同，並且定價如此。所以我無法逐個國家回答，但可以肯定的是，我們與其他更典型的罕見疾病療法處於同一範圍。

And Tazeen, I realize this isn't necessarily so helpful, but our original guidance, if you will, that the discount on a country by country basis was somewhere between zero and 50%, not zero, not 50%, I mean it still basically holds.

Tazeen，我意識到這不一定那麼有幫助，但如果您願意的話，我們最初的指導意見是，各國的折扣在零到50% 之間，而不是零，也不是50%，我的意思仍然是基本成立。

Joseph Stringer, Needham & Company.

約瑟夫‧斯金格，李約瑟公司。

Just wondering if you could remind us of the two to six-year-old addressable BBS patient population, assuming label expansion, US approval by year-end, how soon should we expect an impact to sales, and how much of an impact do you think this will have?

只是想知道您是否可以提醒我們兩到六歲的可尋址 BBS 患者群體，假設標籤擴展，美國在年底前獲得批准，我們預計多久會對銷售產生影響，以及您會產生多大的影響覺得這個會有嗎？

So I characterize it as modest. Jennifer is going to provide some more color.

所以我把它形容為謙虛。珍妮佛將提供更多的色彩。

In terms of the label expansion, I think one of the best benefits, honestly is just the ability to outline, the approval in this patient population, which further distinguishes, our population and the need versus that of the patient population with general obesity. We have not once again talked about this piece, but just in terms of numbers, what we do know is that approximately less than 10% of the patients represented in the CRIBBS registry are younger than seven years of age. And there are patients that are young that are being treated by some of our prescribers. So there may be some, but I would not say that it's a significant number at this point of time.

就標籤擴展而言，老實說，我認為最好的好處之一就是能夠概述該患者群體的批准，這進一步區分了我們的人群和需求與一般肥胖患者群體的需求。我們沒有再次討論過這件事，但就數字而言，我們確實知道 CRIBBS 登記中大約不到 10% 的患者年齡低於 7 歲。有些年輕患者正在接受我們的一些處方醫生的治療。所以可能會有一些，但我不會說目前這個數字很大。

Michael Higgins, Ladenburg Thalmann.

麥可希金斯，拉登堡塔爾曼。

All right, guys. Congrats on the strong results. Looking forward to seeing pivotal HO data first half of 2025. In regards to IMCIVREE, earlier this year, you had an issue with one of your Medicaid state programs and reimbursement. Any update for us on the progress in getting that business to return?

好吧，夥計們。祝賀取得強勁的成果。期待在 2025 年上半年看到關鍵的 HO 數據。關於讓該業務恢復的進展有什麼最新消息嗎？

Yes. Jennifer?

是的。詹妮弗？

Yes. So one thing that I will reiterate in terms of that particular state is that they were one of the first to come on Board with a specific policy for IMCIVREE. They still remain in terms of having an IMCIVREE policy in place. We do have patients that are being covered under this particular Medicaid state, and we are still working through, trying to regain approvals for patients. They do have a much more stringent requirement in terms of the amount of information. So it is a slow ongoing process.

是的。因此，就該特定州而言，我要重申的一件事是，他們是第一批為 IMCIVREE 制定具體政策的國家之一。他們仍然保留 IMCIVREE 政策。我們確實有患者受到這種特定醫療補助狀態的覆蓋，我們仍在努力，試圖重新獲得對患者的批准。他們對資訊量確實有更嚴格的要求。所以這是一個緩慢持續的過程。

But I think the other piece that I will also iterate is that while those are all positive and still work in progress, this has had absolutely no read through in terms of any other state or policy that we have seen, and even the new policies that we have also been able to put directly in place have been much more consistent with our label.

但我認為我還要重申的另一件事是，雖然這些都是積極的並且仍在進行中，但就我們所看到的任何其他國家或政策而言，這絕對沒有通讀，甚至是新政策我們也能夠直接放置，與我們的標籤更加一致。

And just wanted to follow-up on it. Based on your working through the more stringent requirements, do you think you'll ever get back to that prior level and the growth that you had prior to that decision earlier this year?

只是想跟進一下。根據您對更嚴格要求的處理，您認為您會恢復到今年早些時候做出決定之前的水平和增長嗎？

So the guidance in the past had been that for us, we really didn't put in our forecast that we were going to regain all of those patients back. And that was also our guidance for others just in terms of considerations. We still do get prescriptions from that state. And like I said, it may be a slow process, but our teams are very actively working through to try to gain approvals for these patients.

因此，過去對我們的指導是，我們確實沒有預測我們將重新獲得所有這些患者。這也是我們對其他人的指導，只是出於考慮。我們仍然從該州獲得處方。正如我所說，這可能是一個緩慢的過程，但我們的團隊正在非常積極地爭取這些患者的批准。

Michael, I think that's the key -- this state is working. It's just in the beginning with one of the more -- perhaps more liberal policies. Clearly, there were more patients going through, but it is working, and we're continuing to get patients through. So we're feeling good about that.

邁克爾，我認為這是關鍵——這種狀態正在發揮作用。其中一項更自由的政策才剛開始。顯然，有更多的患者正在經歷這個過程，但它正在發揮作用，我們將繼續幫助患者度過難關。所以我們對此感覺良好。

Thank you. And I'm showing no further questions at this time. And I would like to turn the conference back over to David Meeker for any further remarks.

謝謝。目前我不會再提出任何問題。我想將會議轉回給大衛·米克（David Meeker），以便他發表進一步的評論。

Okay. Well, thanks, everybody, for tuning in this morning. As you can hear, 2024 has been a year of execution, and we feel really good about how we're executing to-date. So look forward to updating you at the next quarter.

好的。好的，謝謝大家今天早上的收聽。正如您所聽到的，2024 年是執行的一年，我們對迄今為止的執行情況感到非常滿意。因此，期待在下個季度為您提供最新資訊。

This concludes today's conference call. Thank you for participating, and you may now disconnect. Everyone, have a great day.

今天的電話會議到此結束。感謝您的參與，您現在可以斷開連接。大家，祝你有美好的一天。