Rhythm Pharmaceuticals Inc (RYTM) 2025 Q1 法說會逐字稿

Good day and thank you for standing by welcome to the Rhythm Pharmaceuticals first quarter 2025 earnings conference call. (Operator's Instruction). I would not like to hand a conference over to your speaker today, David Connolly, Investor Relations at Rhythm.

大家好，感謝您的到來，歡迎參加 Rhythm Pharmaceuticals 2025 年第一季財報電話會議。（操作員指令）。今天我不想把會議交給你們的發言人，Rhythm 投資者關係部的 David Connolly。

Thank you, Josh. I'm David 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 of our website ir.rhythmtx.com. This morning, we issued our press release that provides our Q1 2025 financial results.

謝謝你，喬希。我是Rhythm Pharmaceuticals的David Connolly，對於參加電話會議的各位，您可以訪問我們網站ir.rhythmtx.com的投資者專區訪問和查看我們的幻燈片。今天上午，我們發布了2025年第一季財務業績的新聞稿。

And a business update, and that press release is available on our website. Our agenda is listed on slide two on the call today are David Meeker, our Chairman, Chief Executive Officer and President. Jennifer Lee, Executive Vice President, Head of North America. Hunter Smith, Chief Financial Officer, and Yann Mazabraud, Executive Vice President, Head of International, is on the line and joining us from Europe.

以及業務更新，新聞稿可在我們的網站上查閱。我們的議程列在今天電話會議的第二張幻燈片上，與會者包括我們的董事長、執行長兼總裁大衛·米克 (David Meeker)。Jennifer Lee，執行副總裁、北美地區負責人。財務長 Hunter Smith 和執行副總裁、國際業務主管 Yann Mazabraud 正在從歐洲與我們通話。

On slide three, I'll remind you that 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 on our most recent annual or quarterly reports on file with the SEC.

在第三張投影片上，我要提醒您，本次電話會議包含有關未來預期、計劃和前景的評論，這些評論構成了前瞻性陳述。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所討論的因素，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 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. With that, I'll turn the call over to David Meeker, who'll begin on slide five.

此外，任何前瞻性陳述均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。我們明確否認有更新此類聲明的義務。接下來，我將把電話交給 David Meeker，他從第五張投影片開始發言。

Thank you, Dave. So good morning and thank you for joining. So we're about one month since our call highlighting the top line results from phase 3 trial on acquired hypothalamic obesity. We remain on track for Q3 filing, including having an in-person Type D meeting scheduled with the FDA. I will say the FDA is responsive, and I would characterize our interactions as completely normal.

謝謝你，戴夫。早安，感謝您的加入。距離我們召開電話會議強調獲得性下丘腦肥胖症第 3 階段試驗的最終結果已經過去了一個月。我們仍在按計劃進行第三季的備案，包括與 FDA 安排面對面的 D 類會議。我想說的是，FDA 反應迅速，我認為我們的互動完全正常。

We have reviewed all of the data which we will present at upcoming meetings. The more we dig into the data, the more convinced we and I are that [eplannotite] has the potential to transform the life of both the patient and their families. I will remind you of the top line data with a little additional colour in the next few slides. Commercially with BBS, we had a very good first quarter.

我們已經審查了所有數據並將在即將舉行的會議上展示。我們對資料探勘得越多，我們和我就越相信 [eplannotite] 有潛力改變患者及其家人的生活。在接下來的幾張投影片中，我將用一些額外的顏色來提醒您頂線資料。從 BBS 商業角度來看，我們第一季表現非常好。

In the US, demand, as reflected in Biles dispense to patients, continues to grow. The team, as Jennifer will describe, is making good progress on multiple fronts addressing the challenges of this complex disease. The growth in demand is obscured this quarter by the inventory shifts which Hunter will walk you through. The international team continues to execute on its country-by-country BBS launch strategy.

在美國，對膽汁的需求（體現在向患者分發的膽汁中）持續成長。正如詹妮弗所描述的，該團隊在應對這種複雜疾病的挑戰的多個方面取得了良好進展。本季需求的成長被庫存變化所掩蓋，亨特將向您介紹這一點。國際團隊繼續執行其逐國 BBS 發布策略。

And the HO contribution to revenues predominantly from France and Italy continues to grow, supporting our view of the unmet need and the level of interest in Setmelanotide. As we have highlighted, we're looking forward to the Bivi Meigon phase 2 readout in Q3 and having something to say about the ongoing DWS study Prader-Willi and the 718-weekly study NHO by the end of the year.

而且，HO 對主要來自法國和義大利的收入貢獻持續增長，支持了我們對未滿足需求的看法以及對 Setmelanotide 的興趣程度。正如我們所強調的，我們期待在第三季度獲得 Bivi Meigon 第 2 階段的讀數，並對正在進行的 DWS 研究 Prader-Willi 和年底前 718 週的研究 NHO 發表一些看法。

And we remain well capitalized with a projected cash runway in 2027. On slide six, this is data from a publication by Professor Mueller from Germany, a renowned expert in the field of hypothalamic obesity. It provides some numbers behind what we are learning as we get to know this community and review the data from this trial.

我們的資本充足，預計 2027 年仍有足夠的現金流。第六張幻燈片是來自德國下丘腦肥胖領域著名專家穆勒教授的出版物的數據。它為我們在了解這個社區和審查這次試驗的數據時所學到的知識提供了一些數字。

The medical complexity and severity that these patients and their families are dealing with is unlike any disease I have worked on in my industry career. There are diseases with higher mortality rates, but very few with higher medical complexity. And you can see that from the numbers on the slide 3.7 hospitalizations in the first two years after the injury, of which 23% required an ICU admission.

這些患者及其家人所面對的醫療複雜性和嚴重性與我職業生涯中所治療過的任何疾病都不同。有些疾病的死亡率較高，但很少有疾病的醫學複雜性較高。從投影片上的數字可以看出，受傷後的頭兩年內有 3.7 人次住院，其中 23％ 需要入住 ICU。

12 visits to the general practitioner, and on average 20 visits to a specialist. And even more strikingly, the average number of prescriptions written per month is 5.5. The average number of unique medications prescribed in the first two years is 22, and 89% of these patients require three or more therapies for neuroendocrine dysfunction.

平均看全科醫生 12 次，看專科醫生 20 次。更令人吃驚的是，平均每月開出的處方數量為5.5張。前兩年平均開立的獨特藥物數量為22種，其中89%的患者需要三種或三種以上的神經內分泌功能障礙治療。

As the data from this trial shows us, including the exit interviews with patients and caregivers, the untreated hypothalamic obesity with its associated hyperphasia and fatigue represent a significant part of the medical burden they are dealing with. The fact that patients were willing to commit to this 52-week placebo-controlled trial, given the incremental burden of testing and clinic visits, which are part of any trial.

正如本試驗的數據（包括對患者和照護者的離院訪談）向我們展示的那樣，未經治療的下丘腦肥胖及其相關的多語症和疲勞佔了他們所面臨的醫療負擔的很大一部分。事實是，考慮到檢測和門診就診的負擔不斷增加（這是任何試驗的一部分），患者願意參加這項為期 52 週的安慰劑對照試驗。

Speaks to the motivation of this community to find solutions. We at Rhythm are highly motivated. On slide seven, I'll provide you a little additional colour on the results of the phase 3 study. First, the top line and it is worth showing again with a 16.5% reduction in BMI in the Setmelanotide cohort as opposed to a 3.3% increase in BMI in the placebo group.

講述了這個社區尋找解決方案的動機。我們 Rhythm 的員工積極性很高。在第七張投影片上，我將為大家提供一些有關第三階段研究結果的額外資訊。首先，值得再次顯示的是，Setmelanotide 組的 BMI 降低了 16.5%，而安慰劑組的 BMI 增加了 3.3%。

For a placebo adjusted difference of 19.8%. As we showed you last time to slide eight, there was no difference in effect between patients under 18 and those over 18. Well we have broken this out further. So on slide nine, we did stratify patients between three age groups breaking out the under 18 to those between 12 and 18 and those less than 12.

安慰劑調整後的差異為 19.8%。正如我們上次在第八張幻燈片中展示的那樣，18 歲以下患者和 18 歲以上患者的效果沒有差異。好吧，我們對這一點進行了進一步的分解。因此，在第九張投影片上，我們將患者分為三個年齡組，分別為 18 歲以下、12 至 18 歲之間和 12 歲以下。

Adults may be a relatively homogeneous population, but there's a big difference between a 4-year-old and a 17-year-old. Here you can see the three age cohorts, and remarkably they are similar again with placebo adjusted BMI percent changes ranging from 19.2% to 21%. And slide 10 hallmark of the trials of Setmelanotide in this disease has been the consistency of response, and as we showed you last call.

成年人可能是相對同質的群體，但 4 歲和 17 歲之間存在很大差異。在這裡您可以看到三個年齡組，令人驚訝的是，它們再次相似，安慰劑調整後的 BMI 百分比變化範圍從 19.2% 到 21%。第 10 張投影片展示了 Setmelanotide 在該疾病中的試驗特點，即反應的一致性，正如我們上次向您展示的那樣。

80% of the patients lost more than 5%, suggesting some response. As always, the patients of greatest interest, at least to me, are the apparent non-responders, and I gave three patient examples last call of patients who did not reach the 5% but had other data suggesting a response to drug a more complete summary of that analysis is as follows.

80%的患者體重減輕超過5%，顯示有一定療效。像往常一樣，至少對我來說，最受關注的患者是明顯無反應的患者，我最後一次給出了三個患者示例，這些患者未達到 5%，但有其他數據表明對藥物有反應，該分析的更完整總結如下。

There were 17 out of 81 Setmelanotide treated patients who were not considered responders by virtue of reaching 5% or more in this analysis eight of these patients discontinued treatment prematurely and had their data imputed. Three of these eight patients actually had reductions in BMI greater than equal to 5% at their last time point assessed.

在本次分析中，81 名接受 Setmelanotide 治療的患者中，有 17 名未達 5% 或以上，因此不被視為有反應，其中 8 名患者提前停止治療並將其數據估算出來。這八名患者中有三名在上次評估時 BMI 下降幅度實際上大於 5%。

But were counted as non-responders due to the conservative nature of the multiple imputation method which uses the placebo patient data to generate the imputation values of the nine non-responders who did complete the trial, six of the nine patients either had a response greater than 5% at some point during the trial, and or for the pediatric patients had a BMI score decrease greater than equal to 0.2.

但由於多重插補法的保守性質，他們被計為無反應者，該方法使用安慰劑患者數據來產生完成試驗的 9 名無反應者的插補值，9 名患者中有 6 名在試驗期間的某個時間點的反應大於 5%，或者兒科患者的 BMI 評分下降大於等於 0.2。

Which is clinically significant. Two of the three patients with no response and no other explanation had drug blood levels consistent with significant noncompliance. So in summary, the consistency we saw in the phase 2 trial and the consistency response we're seeing in the real world French experience is evident here.

這具有臨床意義。三名對治療沒有反應且沒有其他解釋的患者中，有兩名患者的血液藥物濃度與嚴重的不依從性相符。總而言之，我們在第二階段試驗中看到的一致性以及我們在現實世界法國經驗中看到的一致性反應在這裡顯而易見。

This further analysis sports the thesis that the biology in this disease is driven by impaired signaling through the MC4R pathway with a consequent deficit in alpha melanocyte stimulating hormone. The consistency of the response to Setmelanotide we see across this highly heterogeneous and medically complex patient populations suggesting suggests we are helping to correct a fundamental biologic deficit.

進一步的分析表明，這種疾病的生物學特性是由 MC4R 路徑信號傳導受損引起的，從而導致 α 黑素細胞刺激激素缺乏。我們看到，在這些高度異質且醫學複雜的患者群體中，對 Setmelanotide 的反應具有一致性，這表明我們正在幫助糾正根本的生物學缺陷。

On slide 11, I remind you of the disposition in this trial, the vast majority of the 143 patients enrolled, consisting of 120 in the pivotal cohort, 11 supplemental, and 12 in the Japanese cohort have moved to the open label extension trial. A total of 120 patients remain on treatment. That's 108 patients who transitioned to the open label extension and the 12 Japanese patients who remain in the blinded portion of the study.

在第 11 張投影片上，我提醒您本次試驗的安排，在入選的 143 名患者中，絕大多數（包括關鍵隊列中的 120 名、補充隊列中的 11 名和日本隊列中的 12 名）已轉入開放標籤擴展試驗。共有120名患者仍在接受治療。其中 108 名患者轉入開放標籤擴展研究，12 名日本患者仍留在研究的盲法部分。

And importantly, there were no new safety signals related to Setmelanotide observed, which of course is in line with tides well established and well understood safety profile. Consistent with prior experience, Setmelanotide is also generally well tolerated.

重要的是，沒有觀察到與 Setmelanotide 相關的新的安全訊號，這當然符合其完善和充分理解的安全概況。與先前的經驗一致，Setmelanotide 通常也具有良好的耐受性。

And on slide 12, which you've seen before, to remind you of the very significant opportunity in acquired HO. The unmet need is there. These patients are accessible, they're diagnosed, and this Setmelanotide data looks extremely promising. We believe we can make a significant difference in this disease. So that'll turn the call over to Jennifer.

在第 12 張投影片上，您之前已經看過，它提醒您收購 HO 所帶來的非常重要的機會。存在未滿足的需求。這些患者很容易接觸，他們也得到了診斷，而 Setmelanotide 的數據看起來非常有希望。我們相信我們能夠對這種疾病產生重大影響。因此，我們將把電話轉給詹妮弗。

Thank you, David. Beginning on slide 14, we are pleased to report that the demand for IMCIVREE as the only treatment that addresses the root cause of hyperphagia and obesity associated with Bardet-Biedl syndrome remains strong in the first quarter of 2025.

謝謝你，大衛。從第 14 張幻燈片開始，我們很高興地報告，作為唯一能夠解決與 Bardet-Biedl 綜合徵相關的暴食症和肥胖症根本原因的治療方法，IMCIVREE 的需求在 2025 年第一季度依然強勁。

Overall, we have seen continued increasing demand from IMCIVREE, with a consistent number of new prescriptions received over the past several quarters, resulting in ongoing growth in patients on reimbursed therapy. During the first quarter, we did see an increase in the number of patients that transition to new insurance plans, which happens at the beginning of every year.

總體而言，我們看到 IMCIVREE 的需求持續增長，過去幾個季度收到的新處方數量保持穩定，導致報銷治療的患者數量持續增長。在第一季度，我們確實看到轉向新保險計劃的患者數量增加，這種情況在每年年初都會發生。

This resulted in an increase in the number of patients that temporarily transitioned from receiving commercial drugs to receiving free drugs from our bridge program. I am pleased to report that we secured access for the vast majority of these patients and exited Q1 with the overall percentage of bridge patients back to normal levels experienced at the end of 2024.

這導致暫時從接受商業藥物過渡到從我們的橋樑計劃中接受免費藥物的患者數量增加。我很高興地報告，我們確保了絕大多數患者能夠獲得治療，並且在第一季結束時，過渡期患者的整體比例已恢復到 2024 年底的正常水平。

On the next slides, I will update you on two additional positive trends relating to improved Medicaid coverage and improvements in the breadth and depth of prescribers. Next slide. We continue to see increased breadth and depth of prescribers.

在下一張投影片中，我將向您介紹另外兩個正面趨勢，即改善醫療補助覆蓋範圍以及提高處方廣度和深度。下一張投影片。我們持續看到處方人員的廣度和深度不斷增加。

In Q1, we saw the highest number of total prescribers within the quarter since the launch of IMCIVREE and saw a 13% growth in the total number of prescribers this quarter compared to Q4 of 2024. This growth was driven by an increase in new prescribers, which is an important driver of the business. Since launch to date, approximately 33% of new prescribers become repeat prescribers.

在第一季度，我們看到了自 IMCIVREE 推出以來本季度的總處方數量最高，與 2024 年第四季度相比，本季度的總處方數量增加了 13%。這一增長是由新處方人員的增加所推動的，這是業務的重要驅動力。自推出至今，約有 33% 的新處方者成為重複處方者。

This demonstrates that when a physician is educated to look for the clinical manifestations of BBS in their patients, they begin to find more BBS patients. Second positive trend is Medicaid access on the next slide. The last time we shared this metric was a year ago when the breakdown between states with positive coverage from IMCIVREE versus no coverage was approximately 85 to 15.

這表明，當醫生接受培訓在患者身上尋找 BBS 的臨床表現時，他們會開始發現更多的 BBS 患者。第二個正面趨勢是下一張投影片中的醫療補助服務。我們上次分享這項指標是在一年前，當時獲得 IMCIVREE 積極覆蓋的州與未獲得覆蓋的州之間的比例約為 85 比 15。

We continue to work persistently to expand access, and in recent months we have secured in specific policies in 3 additional states. We now have IMCIVREE specific policies or positive coverage decisions from IMCIVREE in states that account for greater than 95% of covered Medicaid lives, leaving less than 5% in states with no positive coverage from IMCIVREE to date.

我們將繼續堅持不懈地努力擴大准入，近幾個月來，我們已在另外 3 個州獲得了具體政策。目前，在佔醫療補助覆蓋人口 95% 以上的州，我們擁有 IMCIVREE 的具體政策或來自 IMCIVREE 的積極覆蓋決定，而迄今為止尚未獲得 IMCIVREE 積極覆蓋的州則不到 5%。

This success in securing access for IMCIVREE from Medicaid as well as commercial payers will serve as a strong foundation for our next potential launch in acquired hypothalamic obesity. We are excited by the potential to bring in IMCIVREE to HO patients since our market research, both with physicians and patients and caregivers, points to a significant need for a therapy for this devastating disease. Next slide.

成功確保醫療補助計劃和商業付款人能夠獲得 IMCIVREE，將為我們下一步在獲得性下丘腦肥胖症領域的潛在推出奠定堅實的基礎。我們對將 IMCIVREE 引入 HO 患者的潛力感到非常興奮，因為我們對醫生、患者和照護者進行的市場調查都表明，對這種毀滅性疾病的治療有巨大的需求。下一張投影片。

We know endocrinologists remain critical for patients with hypothalamic obesity, enabling us to focus our efforts on this one specialty, which is the same specialty that accounts for about 50% of prescribers for BBS. Weight gain, lack of energy, and hyperphagia were outlined by EOS to have a significant negative impact on patients' day to day lives, with current treatment options insufficient in addressing these symptoms for patients.

我們知道，內分泌科醫生對於下丘腦肥胖患者仍然至關重要，這使我們能夠將精力集中在這一專業上，該專業佔 BBS 處方者的 50% 左右。EOS 指出，體重增加、精力不足和暴飲暴食會對患者的日常生活產生嚴重的負面影響，目前的治療方案不足以解決患者的這些症狀。

As expressed by one endo, we need a treatment that is going to be more effective, well tolerated, and safe to continue long term because this problem is not going to go away. These patients are going to be on this treatment for their lifetime. Once you withdraw the treatment, they will regain the weight and more. When shared a blinded target product profile, all physicians outlined they would prescribe Setmelanotide for HO.

正如一位內分泌科醫生所表達的，我們需要一種更有效、耐受性更好、可以長期安全進行的治療方法，因為這個問題不會消失。這些患者將終生接受這種治療。一旦停止治療，他們的體重就會反彈，甚至更重。當共享盲法目標產品概況時，所有醫生都表示他們會為 HO 開出 Setmelanotide。

On my next and my last slide, our research with patients and caregivers illustrates just how significant the impact of hunger and hyperphagia, decreased energy or fatigue, and weight gain are for patients. As seen in the first quote, I was just feeling like a different person after the tumor, and the hunger rules your life.

在我的下一張也是最後一張投影片中，我們對患者和照護者的研究說明了飢餓和暴飲暴食、精力下降或疲勞以及體重增加對患者的影響有多嚴重。如第一句引言所述，罹患腫瘤後，我感覺自己就像變了一個人，飢餓感主宰著我的生活。

These patients know what life was before the onset of these symptoms associated with HO, and they want their lives back. With that, let me hand it over to Jann.

這些患者知道在出現與 HO 相關的症狀之前的生活是怎樣的，他們希望恢復正常生活。說完這些，讓我把它交給 Jann。

Thank you, Jennifer. We be very available to reimburse taxes, and patients or access programs now in more than 15 countries outside the United States. We are seeing steady global growth in the number of on pa therapy patients on treatment to the patient identified in Europe than remain an important contributor in the BBS. (Inaudible)

謝謝你，詹妮弗。我們非常樂意報銷稅款，並且目前在美國以外的 15 多個國家/地區為患者提供或訪問計劃。我們看到，全球接受 PA 治療的患者數量穩定成長，而歐洲的患者仍是 BBS 的重要貢獻者。（聽不清楚）

However, the main driver of revenue outside the United States with steady growth in BBS and reimburse in Germany and France it also, more patients with hypothalamic obesity through early access programs and also of course, we are being of course with the paid EME approval for both acquired and congenital. But the early access for narrating. We are now seeing in Spain and even if we our first.

然而，美國以外收入的主要驅動力是 BBS 的穩定增長以及德國和法國的報銷，還有更多的下丘腦肥胖患者通過早期訪問計劃獲得治療，當然，我們也獲得了針對後天性和先天性疾病的付費 EME 批准。但早期的敘述方式是這樣的。我們現在在西班牙看到，即使這是我們的第一次。

I started next slide we are looking forward to major European week at which we have 10%. Including 5 (Inaudible). The first ever joint conference of the European. [The and the European I The 30]. In Madagascar We are particularly looking forward to presenting of real-world data from the French but (Inaudible). Recall in the fall of 2024 presented data demonstrating the potential efficacy of in patients with acquired hypothalamic obesity (Inaudible)[12 and 21 B].

我在下一張投影片開始我們期待歐洲主要週，屆時我們將有 10% 的成長。包括 5（聽不清楚）。歐洲首次聯合會議。[和歐洲 I 30]。在馬達加斯加，我們特別期待展示來自法國的真實世界數據，但（聽不清楚）。2024 年秋季的回顧性研究提供了數據，證明了獲得性下丘腦肥胖患者的潛在療效（聽不清楚）[12 和 21 B]。

Next week we will set up. Or more also the with the presentation of word for German BDS which points of the as well as detect [on how our the in So Vity Corre. In the daybreak. As represents] (Inaudible). HIP Altogether we have 10 presentations at these two conferences plus 2 [spo]. This level of activity. Okay, this is the level of support and a very strong interest from experts. (Inaudible)No, I would. (Inaudible)

下週我們將開始設定。或更多也與德國 BDS 的介紹詞，其中的點以及檢測[關於我們在 So Vity Corre 的情況。在黎明時分。如所代表的]（聽不清楚）。 HIP 總共在這兩個會議上有 10 場演講，外加 2 場 [spo]。這種程度的活動。好的，這是專家們的支持程度和濃厚興趣。（聽不清楚）不，我會的。（聽不清楚）

Yeah, I, so Yann, you were breaking up a little bit there. I think we lost some of your communication there. I'm just going to read briefly from your script just so everybody has the last part. I think I'll summarize briefly, things are going incredibly well in Europe, as Yann highlighted. Hopefully people got that and the BBS launch is progressing across countries.

是的，我，所以 Yann，你在那裡有點崩潰了。我想我們失去了你們的部分通訊。我只是想簡單讀一下你的劇本，以便每個人都能看到最後一部分。我想我會簡單總結一下，正如 Yann 所強調的那樣，歐洲的情況進展得非常好。希望人們能夠理解這一點，並且 BBS 的推出正在各個國家推進。

The EOSD meeting, which is coming up, and this is what he was speaking to at the end, is we're excited about that, and we have, multiple. Abstracts that are being presented there and just to summarize what he said and make sure everybody heard it. So we've previously presented data on the data from the initial 8 patients in the French real-world experience, and next week we'll see data.

即將召開的 EOSD 會議，這是他在會議結束時所講的內容，我們對此感到非常興奮，而且我們已經有多個這樣的會議。那裡展示的摘要只是為了總結他所說的內容並確保每個人都聽到了。因此，我們之前已經展示了法國現實世界經驗中最初 8 名患者的數據，下週我們將看到數據。

From 24 patients with acquired congenital obesity who have reached at least three months or more in Setmelanotide. And then there'll also be a presentation of real-world evidence of IMCIVREE for German BDS patients, which will point to the benefit of reducing hyperphagia and obesity, as well as details on how this specialized nursing support program contributes to patient and caregiver satisfaction.

來自 24 名患有先天性肥胖症且使用 Setmelanotide 至少三個月或更長時間的患者。然後還將展示針對德國 BDS 患者 IMCIVREE 的真實世界證據，指出減少暴食症和肥胖的好處，並詳細介紹這項專門的護理支援計劃如何提高患者和照護者的滿意度。

And then there'll be a publication or an abstract on the genetic rare MC4 pathway indication studied in daybreak, including representing findings on patients with this PHIP variant, which is one of the variants which had particularly strong results in our initial phase 2 daybreak study, and we look forward to doing more work there so that'll be there.

然後，將會有一篇關於在黎明研究中遺傳罕見 MC4 通路適應症的出版物或摘要，包括代表對患有這種 PHIP 變體的患者的發現，這是我們在初始第 2 階段黎明研究中結果特別強勁的變體之一，我們期待在那裡做更多的工作。

And I think I'll just comment that on the HO data, the 24 patients you're going to see, we're embargoed now, so we can't present that data, but you won't be surprised. There's nothing about that data set that's inconsistent with what we've seen so far. So with that, I'll turn it over to Hunter.

我想我只想評論一下 HO 數據，您將要看到的 24 名患者，我們現在處於禁運狀態，因此我們無法提供該數據，但您不會感到驚訝。該資料集與我們目前所見的並無任何不一致之處。因此，我將把發言權交給亨特。

Thank you, David. Thank you, Yann. Rhythm had a very good first quarter. Let me walk you through the components on slide 23. Revenue from global sales of IMCIVREE was $37.7 million in the first quarter of '25. The number of patients on reimbursed therapy increased 14% globally during the quarter.

謝謝你，大衛。謝謝你，Yann。Rhythm 第一季表現非常好。讓我帶您了解第 23 張投影片上的各個組成部分。25 年第一季度，IMCIVREE 全球銷售收入為 3,770 萬美元。本季度，全球接受報銷治療的患者數量增加了 14%。

The bigger, the biggest driver of the Q4 to Q1 change in revenue was an inventory swing of $8.3 million at the specialty pharmacy that dispenses sever to patients in the US. As we discussed in our Q4 call, the specialty pharmacy had purchased approximately $4.1 million more than it dispensed to patients in that quarter.

第四季與第一季收入變化的最大驅動因素是向美國患者提供藥物的專業藥房的 830 萬美元庫存波動。正如我們在第四季度電話會議上所討論的那樣，該專業藥房在該季度的採購量比其向患者發放的藥品多出約 410 萬美元。

This resulted in an increase in the specialty pharmacy's inventory to more than 22 days on hand, effectively pulling forward orders from Q1 into Q4. In the first quarter of 2025, this ordering and shipment pattern more than reversed itself. The specialty pharmacy ordered $4.2 million less than it dispensed to patients, reducing inventory days on hand to less than nine.

這導致專業藥房的庫存增加到 22 天以上，有效地將訂單從第一季提前到第四季度。2025年第一季度，這種訂購和出貨模式發生了逆轉。該專科藥房的訂購金額比其發放給患者的金額少了 420 萬美元，導致庫存天數減少到不到 9 天。

Typically, the specialty pharmacy inventory runs between 10 days and 15 days on hand. The value of IMCIVREE dispensed to patients in the US. The best measure of demand for IMCIVREE increased $1.1 million sequentially over Q4. Major drivers of this included a 4% price increase taken in January, an increase in the number of reimbursed BBS patients on therapy.

通常，專業藥局的庫存量為 10 天至 15 天。向美國患者分發的 IMCIVREE 的價值。IMCIVREE 需求的最佳衡量指標比第四季度連續增加了 110 萬美元。主要驅動因素包括 1 月價格上漲 4% 以及接受治療的 BBS 患者報銷數量的增加。

An increase in the number of patients on bridge therapy at the start of the quarter, as Jennifer described earlier, that resolved itself by the end of the quarter, and a modest decrease in patient compliance. Outside the United States, sequential revenue growth was strong at $3.1 million, primarily driven by France, Germany, and Italy.

正如詹妮弗之前所述，本季度初接受橋接療法的患者數量有所增加，但到本季度末這一問題已得到解決，同時患者的依從性略有下降。在美國以外，營收連續成長強勁，達到 310 萬美元，主要受法國、德國和義大利的推動。

Taken together, the $8.3 million inventory swing, the increase of $1.1 million in product dispensed to patients in the US, and the $3.1 million increase ex US resulted in a net revenue decrease of $4.1 million compared to the fourth quarter of 2024, reflecting timing difference from inventory shipment patterns in what was an otherwise strong period of growth.

綜合起來，830 萬美元的庫存波動、分配給美國患者的產品增加 110 萬美元以及美國以外地區增加 310 萬美元，導致淨收入與 2024 年第四季度相比減少 410 萬美元，這反映了原本強勁的增長時期與庫存發貨模式的時間差異。

Looking ahead, we don't expect such significant swings in inventory at the specialty pharmacy as we experienced in the last two quarters, but if we do experience them, we will continue to highlight any significant impacts as we have done in the past. Now move to slide 24 with our financial snapshot in Q1 2025.

展望未來，我們預計專業藥房的庫存不會像過去兩個季度那樣大幅波動，但如果確實出現這種情況，我們將繼續像過去一樣強調任何重大影響。現在轉到投影片 24，其中顯示了我們 2025 年第一季的財務快照。

In comparison to Q1 2024, net product revenues increased $11.7 million, or 45% over the first quarter of 2024. For some additional colour on the P&L, gross to net for US sales was 84.2%, generally in line with the 85% GTM we've reported previous quarters.

與 2024 年第一季相比，淨產品收入增加了 1,170 萬美元，比 2024 年第一季增加了 45%。為了讓損益表增添一些色彩，美國銷售額的毛利與淨利比為 84.2%，與我們前幾季報告的 85% GTM 基本一致。

R&D expenses were $37 million for Q1 2025 compared to $128.7 million during the first quarter of last year when we incurred R&D costs of $92.4 million associated with the acquisition of Bivi Meigon from LG Camp. On a sequential basis, R&D expenses are down by approximately 10% from the $41.2 million we reported in the fourth quarter of '24.

2025 年第一季的研發費用為 3,700 萬美元，而去年第一季為 1.287 億美元，當時我們從 LG Camp 收購 Bivi Meigon 時產生的研發成本為 9,240 萬美元。與上一季相比，研發費用較 2024 年第四季報告的 4,120 萬美元下降了約 10%。

Due to decreased spending on the pediatric phase 3 trial, daybreak and emanate trials, and decreased costs associated with the RM 718 Phase 1 trial. Also, we are seeing lower costs related to post-trial access due to a more efficient design for our open label extensions. SG&A expenses were $39.1 million for the first quarter of 2025 as compared to $34.4 million for the first quarter of 2024.

由於兒科 3 期試驗、Daybreak 和 Emate 試驗的支出減少，以及 RM 718 1 期試驗相關成本減少。此外，由於我們的開放標籤擴展設計更加高效，我們看到與試驗後訪問相關的成本降低。2025 年第一季的銷售、一般及行政費用為 3,910 萬美元，而 2024 年第一季為 3,440 萬美元。

Sequentially, SG&A expenses increased modestly by less than 3% compared to Q4. For the first quarter of '25, the weighted average common shares outstanding were $63.1 million compared to $60.1 million for the first quarter of '24. And $61.6 million weighted average common shares outstanding in Q4.

與第四季相比，銷售、一般及行政費用 (SG&A) 較上季小幅成長不到 3%。25 年第一季，加權平均流通普通股為 6,310 萬美元，而 24 年第一季為 6,010 萬美元。第四季流通普通股加權平均金額為 6,160 萬美元。

The increase quarter over quarter primarily reflects the approximately 1.3 million shares sold under the ATM program in December and January, which we announced in conjunction with our Q4 earnings. Cash used in operations was approximately $40.4 million compared to $19 million in the fourth quarter.

環比增長主要反映了 12 月和 1 月根據 ATM 計劃出售的約 130 萬股股票，我們在第四季度收益中宣布了這一消息。營運現金使用量約為 4,040 萬美元，而第四季為 1,900 萬美元。

This change represents an expected seasonal increase that occurs in the first quarter each year with the payment of annual bonuses company-wide. In addition, the $6.3 million in cash consideration paid to reacquire the rights to ins in China was recorded this quarter. Looking at cash flow going forward, the final 4 going forward into Q2.

這項變更代表著每年第一季隨著全公司發放年度獎金而出現的預期季節性成長。此外，本季還記錄了為重新收購中國境內權利而支付的 630 萬美元現金對價。看看未來的現金流，最後 4 個將進入第二季。

Just to remind everyone, the final $40 million portfolio, final $40 million portion of the license fee payable to LG as part of that Bivi Meigon transaction will be paid during the coming quarter. It was extended in the first quarter of 2024 as previously mentioned. On slide 25, we ended the quarter with $314.5 million in cash on hand, which we believe will be sufficient to cover all planned operations into 2027.

需要提醒大家的是，作為 Bivi Meigon 交易的一部分，最後的 4000 萬美元投資組合、支付給 LG 的許可費的最後一部分 4000 萬美元將在下個季度支付。如前所述，該協議將於 2024 年第一季延長。在第 25 張投影片上，我們在本季結束時持有 3.145 億美元現金，我們相信這筆錢足以支付到 2027 年的所有計畫營運費用。

As we touched on earlier, US revenues were affected by an inventory swing from Q4 to Q1, which decreased the the US percentage of overall product revenue to 65% in Q1 from 74% in Q4. OpEx for Q1 2025 includes $20.9 million in stock-based compensation. We noted previously about reacquiring our rights in China for $6.3 million during Q1.

正如我們先前所提到的，美國營收受到第四季至第一季庫存波動的影響，導緻美國在整體產品收入中的佔比從第四季的 74% 下降至第一季的 65%。2025 年第一季的營運支出包括 2,090 萬美元的股票薪酬。我們之前曾提到，我們在第一季以 630 萬美元的價格重新獲得了在中國的權利。

This transaction was recorded as a reduction of license revenue of $5 million due to the termination of our licensing agreement with Rare stone and a reduction of deferred revenue on our balance sheet of $1.3 million. Our GAAP EPS for the first quarter of 2025 was a net loss per basic and diluted share of $0.81.

由於我們與 Rare stone 的授權協議終止，該交易被記錄為授權收入減少 500 萬美元，並且我們的資產負債表上的遞延收入減少 130 萬美元。我們 2025 年第一季的 GAAP EPS 為每股基本和稀釋淨虧損 0.81 美元。

This includes $0.08 per share for the Rare stone repayment and $0.02 per share for accrued dividends on convertible preferred stock of $1.3 billion. Lastly on slide 26, our opEx guidance remains unchanged. We anticipate approximately 285 to $315 million in non-gap OpEx comprised of non-gap SGNA expenses of $135 million to $145 million and non-gap R&D expenses of $150 million to $170 million.

其中包括每股 0.08 美元的 Rare Stone 償還款和每股 0.02 美元的 13 億美元可轉換優先股應計股息。最後，在第 26 張投影片上，我們的營運支出指引保持不變。我們預計非差距營運支出約為 2.85 億至 3.15 億美元，其中包括 1.35 億至 1.45 億美元的非差距 SGNA 費用和 1.5 億至 1.7 億美元的非差距研發費用。

With that, I'll turn the call back over to David for Q&A.

說完這些，我將把電話轉回給大衛進行問答。

Thanks, Hunter. So in summary again hopefully what you're hearing, Rhythm continues to grow and by all metrics I'll give you one additional metric. We're about 300 people now employed at Rhythm to manage the diverse set of activities we have going on. And as I look across everything, our commercial efforts, as you've heard.

謝謝，亨特。所以，總而言之，希望您所聽到的，節奏正在繼續增長，並且根據所有指標，我將為您提供一個額外的指標。目前，Rhythm 約有 300 名員工，負責管理我們正在進行的各種活動。正如你所聽到的，當我回顧一切時，我們發現了我們的商業努力。

BBS launching progressively around the world, global expansion efforts and then our development efforts, we're in a really good place. And I've been in this industry again, as you all know, for a very long time, much of that time spent in clinical development, and I have to say, I don't know if I've had another phase 3 set of data that has been more rewarding in terms of the fun you have analyzing that data set.

BBS 正在全球逐步推出，全球擴張努力以及我們的開發努力，我們處於一個非常好的位置。眾所周知，我又進入這個行業很長時間了，大部分時間都花在了臨床開發上，我不得不說，我不知道我是否擁有過另一組 3 期數據，從分析該數據集的樂趣來看，這組數據能給我帶來更多回報。

And realizing the impact that it is having and will have hopefully for a much larger number of patients going forward. So we feel good about where we are. Look forward to your questions, and that we'll turn it over to Q&A.

並意識到它正在產生的影響，並希望未來能對更多的患者產生影響。因此我們對目前的狀況感到滿意。期待您的提問，我們將進入問答環節。

Thank you. (Operator's Instructions). Our first question comes from John Woods with Citizens, you may proceed.

謝謝。（操作員指示）。我們的第一個問題來自公民的約翰·伍茲，你可以繼續。

Hey thanks for taking the question and congrats on the update. David, I hope you could talk a little bit more about those non-responders you highlighted. It sounded like several of them were having good responses but dropped out. So what were the reasons for those discontinuations?

嘿，感謝您提出這個問題，並祝賀更新。大衛，我希望你能多談談你強調的那些無反應者。聽起來他們中有幾個人的反應很好但卻退出了。那麼這些停產的原因是什麼呢？

Yeah, I mean, again there were variety, and they were cost both placebo and treated. They mixed from just, patients withdrawing because they couldn't keep up with the clinical trial, either themselves or the family managing it, so that was about half of the group. And then the other, including some in the small number of the placebo group, were due to reactions. So GI injection site overall.

是的，我的意思是，它們又有多種多樣，而且它們的成本既有安慰劑成本，也有治療成本。他們來自不同的群體，有的患者因為無法跟上臨床試驗而退出，無論是他們自己還是管理它的家人，所以這大約佔了該組的一半。而其他人，包括少數安慰劑組的人，則是由於反應。所以胃腸道注射部位整體來說。

The patient who had the seizure disorder preexisting had uncontrolled seizures during the trial and ended up actually dying of uncontrolled seizures at the end of the trial. That patient did not complete, so that's a dropout. I think as I've explained what I was trying to explain with when patients drop out, their data does get imputed and the way companies are guided to handle that is done in the most conservative way.

患有癲癇症的患者在試驗期間出現無法控制的癲癇發作，並最終在試驗結束時死於無法控制的癲癇發作。該患者未完成治療，因此屬於退學。我想，正如我所解釋的那樣，當患者退出時，他們的數據確實會被估算，而公司處理這種情況的方式是最保守的。

Which is not surprising the FDA wants to make sure that they're not in any way getting to a robust result here. So the imputation is done by using data from the placebo group in terms of their trajectory over the course of the trial, and that value is used to create or generate the imputation values and obviously the placebo patient group here gained weight.

這並不奇怪，FDA 希望確保他們不會以任何方式獲得可靠的結果。因此，估計是使用安慰劑組在試驗過程中的軌跡數據進行的，並且該值用於創建或生成估算值，顯然這裡的安慰劑患者組體重增加了。

So if you're using data from that data set, it's going in the opposite direction of what might support evidence of an effect. So that's why I was just highlighting that three of the patients out of the eight who dropped out had already reached a point of response at the point they dropped out, but the imputation then, took them down below that 5% level.

因此，如果您使用該資料集中的數據，其方向將與支持影響證據的方向相反。所以這就是為什麼我剛才要強調，八名退出的患者中有三名在退出時已經達到了反應點，但當時的估算結果卻將他們的反應率降到了 5% 以下。

Can you talk just a minute about real world persistence, and, understanding of, expectations for adverse events and how that understanding keeps patients on drugs or not, like, what's the real world experience and how does that translate from the clinical data?

您能否花一點時間談談現實世界的持久性，以及對不良事件的預期的理解，以及這種理解如何讓患者繼續服用藥物，例如，現實世界的經驗是什麼以及如何從臨床數據中轉化出來？

Yeah, I mean, we can talk this more. I mean, what we talked about generally across all of our patient populations treated our commercial experiences, we're, globally with a number around 30% of patients who discontinue in the HO. And we've gotten this question, are we going to see fewer discounts there and the numbers still relatively small, but I think the answer is yes.

是的，我的意思是我們可以進一步討論這個問題。我的意思是，我們一般談論的是針對所有患者群體的治療，根據我們的商業經驗，在全球範圍內，約有 30％ 的患者在 HO 中停藥。我們遇到了這個問題，我們是否會看到更少的折扣並且數量仍然相對較少，但我認為答案是肯定的。

I mean the discontinuation rate in this trial again was a little less than 10% of the total of 143 patients that were enrolled. Compliance looks like it was extremely high overall and so part of my goal in giving you the background around the medical complexity is, yeah, that's the world they're living in, but despite all of that, the importance of continuing Setmelanotide and the relief they're getting from that.

我的意思是，這次試驗的退出率再次略低於總共 143 名患者中的 10%。總體而言，依從性看起來非常高，因此，我向您介紹醫療複雜性的背景部分目的是，是的，這就是他們生活的世界，但儘管如此，繼續使用 Setmelanotide 的重要性以及他們從中獲得的緩解。

It seems to be incredibly high. So I think we're going to do better, maybe quite well in the HO population with regard to both discounts and compliance.

它看起來高得令人難以置信。因此我認為我們會做得更好，在折扣和合規性方面，我們在 HO 人群中可能會做得相當好。

That's helpful. Thanks for the colour.

這很有幫助。謝謝你的顏色。

Thanks.

謝謝。

Thank you. Our next question comes from Derek Archila with Wells Fargo. You may proceed.

謝謝。我們的下一個問題來自富國銀行的 Derek Archila。您可以繼續。

Hey, good morning, and thanks for taking the questions. Congrats on the progress here. Just two quick ones from us just for Part C, for RM 718. I know you highlighted enrollment will complete by the end of the year, but we just wanted to confirm whether you actually plan to share any efficacy data for patients reaching 16 weeks before the end of the year.

嘿，早上好，感謝您回答問題。恭喜你在這裡的進展。我們只需提供兩個 C 部分的報價，價格為 RM 718。我知道您強調了招募將在年底前完成，但我們只是想確認您是否真的計劃分享年底前達到 16 週的患者的任何療效數據。

And then the second question for Hunter, you noticed some changes on compliance during the quarter, so I was wondering if you could just elaborate on that and I guess how we should be thinking about that trending for the rest of the year. Thanks.

然後第二個問題是針對亨特的，您注意到本季度合規性方面發生了一些變化，所以我想知道您是否可以詳細說明這一點，以及我們應該如何看待今年剩餘時間的趨勢。謝謝。

Yeah, I'll take the first one and turn over Hunter. So yeah, Part C is just getting underway as it's, as we say, it's true, obviously it's hard to guide until, the trial's really up and running and you're enrolling at a more consistent rate here, so we're just at the beginning. The reason we're guiding to hopefully being able to say something by the end of the year is that we're not targeting necessarily a specific number of patients.

是的，我會選擇第一個，然後把 Hunter 交給他。是的，C 部分才剛剛開始，正如我們所說，這確實很難指導，直到試驗真正啟動並運行，並且您在這裡以更穩定的速度註冊，所以我們才剛剛開始。我們之所以希望在年底前能做出一些決定，是因為我們的目標患者數量不一定是特定的。

So for example, for the Bivi Meigon trial, that's a blinded forearm trial, 28 patients. You've got to enroll 28 and get them to the end. But in the open label effort here for 718, it's also true for Prader-Willi. With the open label, we just want to get to a robust number, which is why my hope and expectation is that we will have enough patients treated for a long enough period of time that we will have something to say by the end of the year.

例如，對於 Bivi Meigon 試驗，這是一項盲法前臂試驗，有 28 名患者參與。你必須招收 28 名學生並讓他們堅持到最後。但在 718 的開放標籤努力中，這對 Prader-Willi 來說也是如此。對於開放標籤，我們只是希望獲得一個穩健的數字，這就是為什麼我希望和期望是，我們將有足夠多的患者接受足夠長時間的治療，以便我們在今年年底前能夠得到一些結果。

Derek, on compliance, we generally have seen compliance sort of in the low 80%, 80% zip code, and we had a very strong compliance rate in Q4, which was a bit of a tailwind in Q4, and it returned to a more normalized level in Q1.

德里克，關於合規性，我們通常看到合規性在 80% 到 80% 的低郵政編碼地區，並且我們在第四季度的合規率非常高，這在第四季度有點順風，並且在第一季度恢復到了更正常的水平。

Understood. Okay thank you.

明白了。好的，謝謝。

Thank you. Our next question comes from Tanzina Ahmed with Bank of America. He may proceed.

謝謝。我們的下一個問題來自美國銀行的 Tanzina Ahmed。他可以繼續。

Hi, good morning. Thanks for taking my question. I'm sorry if this was part of Yann's comments. I couldn't hear him clearly, but can you just talk to us about the importance of these continual data updates that you're expecting to make now at conferences going forward? It's our understanding from companies that we've spoken to or doctors that we've spoken to that they think that the data is pretty much perfect.

嗨，早安。感謝您回答我的問題。如果這是 Yann 的評論的一部分，我感到很抱歉。我聽不清楚，但您能否跟我們談談您希望在未來的會議上進行的這些持續資料更新的重要性？據我們了解，從我們接觸過的公司或醫生那裡了解到，他們認為這些數據非常完美。

So what additional data do you think is necessary?

那麼您認為還需要哪些額外的數據呢？

Yeah, that's right. I'll take that one also, I'm not sure if your connection back solid. Yeah, no, it's a fair question. I think, my view of particularly the rare disease world is every patient is incremental in news in a sense, particularly when you're early on. So the French patient data that we presented last fall, it was only 8 patients.

是的，沒錯。我也會選擇那個，我不確定你的連接是否穩定。是的，不，這是一個公平的問題。我認為，我對罕見疾病領域的看法是，從某種意義上說，每個患者都會收到越來越多的消息，尤其是在早期階段。因此，我們去年秋天提供的法國患者數據只有 8 名患者。

But it was incredibly important data as we all realized because it highlighted a group that we hadn't studied in our phase two, meaning. These are all adults and with the mean age of 30 and you know they were also out about 11 years from the time of their insults. So it addressed based on small numbers an important question there which now this phase 3 trial is also highlighted or answered.

但我們都意識到，這是非常重要的數據，因為它突顯了我們在第二階段尚未研究過的群體。這些都是成年人，平均年齡為 30 歲，而且從他們受到侮辱到現在已經過了 11 年左右。因此，它根據小數字解決了一個重要問題，現在這個第三階段試驗也得到了強調或解答。

I think, which is it doesn't matter whether you're an adult or a pediatric patient, you're going to respond well. What is the value of now having a 24-patient update as opposed to an 8? Again, it's just, it's, 24 is a lot more than 8. It's still a small number of patients.

我認為，無論您是成人還是兒科患者，您都會有良好的反應。現在有 24 名患者的更新資訊（相對於 8 名患者）有什麼價值？再說一遍，24 比 8 多得多。患者人數仍然很少。

So it's not that we're going to have every quarter an update on how many patients are treated in France and Italy and some of these other countries which you may have missed. I mean, we do have, individual patients and sort of named patient settings and a few other countries as well treated for HO. So we'll do that for a little while but not endlessly. So I don't know if that answers your question.

因此，我們不會每季更新法國、義大利和其他一些國家接受治療的患者數量（您可能錯過了）。我的意思是，我們確實有個別患者和指定患者環境，而且其他一些國家也對 HO 進行治療。因此我們會這樣做一段時間，但不會無止盡地這樣做。所以我不知道這是否回答了你的問題。

Yeah, and then just on questions around seasonality, I just want to clarify, are you expecting to see any seasonality for the remaining quarters of the year?

是的，然後關於季節性的問題，我只想澄清一下，您是否預計今年剩餘幾季會出現季節性？

Mean Jennifer, you want to take that?

意思是詹妮弗，你想接受這個嗎？

Yeah, I think like overall like Q1 is probably the biggest impact based off of, what we outlined in terms of those insurance changes that happened just across the board for any patient population and the ability for us to work through with the new payer to regain insurance, that that is what really hit us from Q1 perspective. I think Q4, we don't have a real control in terms of what the special.

是的，我認為總體而言，第一季可能是最大的影響，基於我們概述的針對所有患者群體的保險變化以及我們與新付款人合作重新獲得保險的能力，這才是從第一季度的角度來看真正對我們造成打擊的。我認為，對於第四季的特殊情況，我們並沒有真正的控制權。

Pharmacy orders, so that may be something that happens in the very last couple of orders of the month in December. But beyond that, we haven't really experienced a lot of other seasonality throughout the year.

藥房訂單，所以這可能是 12 月最後幾個訂單中發生的事情。但除此之外，我們全年其實並沒有經歷過很多其他季節性變化。

Just to add to that, if we look at our pattern of a prescriptions written and approvals for reimbursement received with the exception of the impact on, change in the calendar year, we don't see a significant difference between the quarters.

補充一點，如果我們看一下開出的處方和收到的報銷批准的模式，除了對日曆年變化的影響之外，我們沒有看到各個季度之間有顯著的差異。

Okay, thank you.

好的，謝謝。

Thank you. Our next question comes from Phil Nadeau with TD Cowen, you may proceed.

謝謝。我們的下一個問題來自 TD Cowen 的 Phil Nadeau，您可以繼續。

Good morning. Congrats on progress and thanks for taking our questions. A few from us first, David, you mentioned in your prepared remarks that you have an FDA meeting scheduled. Can you discuss what elements of the filing need to be out with the FDA at this point? Any uncertainties or is the meeting more a formality?

早安.恭喜您取得進展並感謝您回答我們的問題。首先我們來談談幾點，大衛，你在準備好的發言中提到你已經安排了一次 FDA 會議。您能否討論一下目前需要向 FDA 提交哪些文件內容？有任何不確定性嗎？或者這次會議只是一種形式？

It's, I can just say probably for the past five years I'm thrilled anytime we can get more meaningful interactions with the FDA, meaning just they're busy and have a lot to do. What I was excited about here is we've got an in-person meeting and this will be my first in-person meeting in about five years, so looking forward to that in terms of why the meeting this is a you invariably have they get called different things.

我可以說，在過去的五年裡，每當我們能夠與 FDA 進行更有意義的互動時，我都感到非常興奮，這意味著他們很忙，有很多事情要做。讓我興奮的是，我們將舉行一次面對面的會議，這將是我大約五年來的第一次面對面的會議，所以我很期待這次會議，至於為什麼這次會議，你總是會叫他們不同的東西。

But a meeting before a filing and it is to clarify. What we're presenting in the filing, how we look to present the data, and make sure they're all aligned with how that's going to come through so that's it.

但在提交文件之前要召開一次會議，以澄清情況。我們在文件中呈現的內容、我們如何呈現數據，並確保它們都與最終呈現的方式保持一致，就是這樣。

Got it the second question is on the Q4. Hunter, you noted that there was somewhat of an impact because of the time to get insurance reauthorizations and the bridging of patients on for drugs. Could you quantify that impact in the quarter? Do you have a sense of how much revenue was hit by that in particular?

明白了，第二個問題是關於 Q4 的。亨特，您指出，由於獲得保險重新授權和為患者提供藥物銜接的時間較長，因此產生了一定的影響。您能量化本季的影響嗎？您是否知道這具體對收入造成了多大的衝擊？

That was about a $700,000.

那大約是70萬美元。

Perfect and then, last question is on the payer mix. Can you remind us what the payer mix is for BBS between Medicare and Medicaid and private pay, and where do you expect that to go for the HO population?

完美，最後一個問題是關於付款人組合。您能否提醒我們，醫療保險、醫療補助和私人支付之間的 BBS 付款人組合是什麼，以及您預計 HO 人群將如何受益？

Yeah. So, the commercial as well as the Medicaid population accounts for about like 80% with approximate equal split between the two, with Medicare being a smaller portion in terms of the impact of the BBS patient population, and we are currently still evaluating the HO opportunity to better understand what that payer looks like.

是的。因此，商業和醫療補助人口約佔 80%，兩者之間大致相等，而就 BBS 患者群體的影響而言，醫療保險所佔比例較小，我們目前仍在評估 HO 機會，以更好地了解付款人的情況。

Great, thanks for taking our questions.

太好了，感謝您回答我們的問題。

You Our next question comes from Seamus Fernandez with Guggenheim Securities. He may proceed.

我們的下一個問題來自古根漢證券公司的 Seamus Fernandez。他可以繼續。

Great, thanks for the question. So, to really kind of focused in on the Bivi Meigon opportunity and how you see this advancing in the pace at which you can kind of bring that product forward should the phase two program deliver the profile that you anticipate, which again if you could just remind us, the profile that you're expecting, I recall David you saying that.

太好了，謝謝你的提問。因此，真正關注 Bivi Meigon 的機會，以及如果第二階段計劃能夠提供您預期的概況，您如何看待這一進展，您可以以何種速度推出該產品，如果您能再次提醒我們，您所期望的概況，我記得大衛您說過。

Your hope for that product is that it would deliver efficacy comparable to what we've seen in HO, with setmelanotide, but excluding the impacts of MCR1 and the hyperpigmentation. So that's my first question.

您希望該產品能夠提供與我們在 HO 中看到的 setmelanotide 相當的功效，但不包括 MCR1 和色素沉著的影響。這是我的第一個問題。

Yeah, so you put the right emphasis on my hope, see what the data shows the way of, now answering that question and these answers evolve a little bit, but they've evolved since I've seen the phase 3 data. I think given the efficacy of setmelanotide.

是的，所以你正確地強調了我的希望，看看數據顯示了什麼，現在回答這個問題，這些答案有所演變，但自從我看到第三階段的數據以來，它們已經發生了變化。我認為考慮到 setmelanotide 的功效。

Shown in phase three, the threshold here is really to be better than 10%. So I was, what's clinically meaningful, that's certainly clinically meaningful. Does it have to be the same as what we saw with A setmelanotide, meaning if we ended up short of the 16.5% without the placebo correction part, does that mean you don't have a drug?

第三階段顯示，這裡的門檻確實要優於 10%。所以我想，什麼具有臨床意義，這肯定具有臨床意義。它是否必須與我們在 A setmelanotide 中看到的情況相同，這意味著如果沒有安慰劑校正部分，我們最終未達到 16.5%，這是否意味著您沒有藥物？

I say no. I mean, I think you can have different formulations oral versus a sub Q. Many patients might prefer an oral. I think, the GLP1 world is a good example of where, everybody's getting tied up in knots about two or three differences in GLP-1 outcomes when clinically makes absolutely no difference at all. I mean they're all robust, results to responses to that drug.

我說不。我的意思是，我認為口服和皮下注射可以有不同的配方。許多患者可能更喜歡口服。我認為，GLP1 世界就是一個很好的例子，每個人都對 GLP-1 結果的兩三個差異感到困惑，但從臨床上看，這些差異根本沒有任何區別。我的意思是，它們都是對該藥物反應的有力證據。

So internally I think our threshold would be we're looking for something north of 10%. I think if we get that we have a drug and then how quickly we can develop it we are developing new formulations which are going to be critical, most specifically for the pediatric population. We'll have both a liquid and a chewable tablet, so that's going to be a little bit gating in terms of getting forward.

因此，我認為從內部來看，我們的門檻是尋求 10% 以上的數字。我認為，如果我們有了這種藥物，那麼我們就能快速開發它，我們正在開發新的配方，這將是至關重要的，特別是對於兒科人群而言。我們將同時提供液體和咀嚼片兩種產品，因此這對於前進來說會有點限制。

I can't put quite a timeline on that, but what I will say is if we have positive data, we will move aggressively. To get into a phase 3 effort specifically in HO and in parallel we will look at our strategies for doing BBS and Palm C, but we will certainly move quickly to get into HO and maybe we have to stagger it a little bit in terms of you know how peeds come into that, depending on availability of product.

我無法為此設定一個具體的時間表，但我要說的是，如果我們有積極的數據，我們就會積極採取行動。為了進入 HO 領域的第三階段工作，我們將同時研究 BBS 和 Palm C 的策略，但我們肯定會迅速進入 HO 領域，也許我們必須稍微錯開速度，這取決於產品的可用性。

Great, and a follow up to kind of pipeline opportunity and and questions there, and the PWS opportunity, can you talk a little bit more about how you see that opportunity potentially emerging?

太好了，接下來是關於管道機會和問題，以及 PWS 機會，您能否再多談談您如何看待這種機會的潛在出現？

For MC4R specifically targeted agents, largely because we know that the first effort, kind of missed the mark, but I know you're testing higher doses, so. Trying to get a better sense of the PWS opportunity that you see for the product and if there are additional learnings that have kind of brought you forward to the willingness to kind of pursue a higher dose here. Thanks.

對於 MC4R 專門針對的藥物，主要是因為我們知道第一次嘗試有點偏離目標，但我知道你正在測試更高的劑量，所以。試著更了解您在產品中看到的 PWS 機會，以及是否有其他學習成果讓您願意在此追求更高的劑量。謝謝。

Yeah, so let me just remind you a bit on the original study. So yes, I think we used too low a dose, but it wasn't just dosing in that first trial. It was too short a trial and it was a complicated design with crossover and the like. So as we've said and I've said, I I don't think we learned much of anything from that original effort, one, two.

是的，那麼讓我稍微提醒一下你最初的研究。所以是的，我認為我們使用的劑量太低了，但這不僅僅是第一次試驗中的劑量問題。試驗時間太短，而且設計很複雜，有交叉之類的。所以正如我們和我所說的，我認為我們沒有從最初的努力中學到任何東西，一，二。

I think we maybe have some increased level of confidence in the biology here. I mean, this pathway is absolutely part of what is impaired in patients with paraor welling. Now that's a very complex disease. There's a lot of other things going on, other. Genes which are deleted and maybe impacting things like behavior and the like, which makes it more challenging to study.

我想我們可能對這裡的生物學更有信心了。我的意思是，這種通路絕對是喉嚨腫脹患者受損的一部分。這是一種非常複雜的疾病。還有很多其他的事情正在發生。被刪除的基因可能會影響行為等，這使得研究變得更具挑戰性。

So with the context that you know this is a tough disease and I've always thought, you could have a drug which works and maybe your trial fails just because the disease in the background is so challenging. That said, yeah, I, I've put our sort of general probability of success here, which is kind of a non-answer, sort of the 50/50 range, but it's a legitimate 50/50 and I have to say, so what are we looking for?

因此，在你知道這是一種很難治療的疾病的情況下，我一直認為，你可能有一種有效的藥物，但你的試驗可能會失敗，只是因為這種疾病太難治療了。話雖如此，是的，我，我在這裡提出了我們成功的總體機率，這有點像非答案，有點像 50/50 的範圍，但這是一個合法的 50/50，我不得不說，那麼我們在尋找什麼呢？

The bar is lower in Prader-Willi, so I think, HO, we came in and you know we have the phase 2 data we're looking for something north of 10. We ended up with 16, placebo adjusted of almost 20. That's not what we're looking for in Prader-Willi. Prader-Willi nothing helps those patients lose weight.

普拉德-威利症候群的標準較低，所以我認為，HO，我們參與進來，你知道我們擁有第 2 階段的數據，我們正在尋找 10 以北的某個值。我們最終得到 16 個，安慰劑調整後接近 20 個。這並不是我們在普拉德-威利症候群中所尋找的。普拉德威利症候群沒有任何東西可以幫助這些患者減重。

Solano's drug just got approved for, decreasing their hunger. But there's a big unmet medical need which remains there. So anything that moves the needle there, that's going to be interesting and something I think we'll seriously look forward to take forward.

索拉諾的藥物剛剛獲得批准，可以減少他們的飢餓感。但仍存在大量未滿足的醫療需求。因此，任何能夠推動這一進程的事情都會很有趣，我認為我們會認真期待並推進它。

Great, thanks so much.

太好了，非常感謝。

Thank you.Our next question comes from Whitney Ijem with Canaccord Genuity. You may proceed.

謝謝。我們的下一個問題來自 Canaccord Genuity 的 Whitney Ijem。您可以繼續。

Hey, thanks for taking the question. Just wanted to follow up on HO and kind of the launch trajectory versus BBS. I know you've talked a lot about the specifics of the HO patient population that should that hopefully will lead to kind of faster uptake or a different launch trajectory. I think most of those comments have been thinking about the US or contemplating the US.

嘿，謝謝你回答這個問題。只是想跟進 HO 和與 BBS 相比的發射軌跡。我知道您已經談論了很多有關 HO 患者群體的具體情況，希望這能夠帶來更快的吸收或不同的啟動軌跡。我認為大多數評論都是在思考或考慮美國。

But it seems those same things should be the case in Europe with potential for maybe even. More momentum just given some of the early access progress that's been made on the HO front there. So just curious if you can talk a little bit more about how to think about HO uptake in Europe specifically relative to what we've seen in BBS so far.

但似乎歐洲也會出現同樣的情況，甚至可能出現。鑑於 HO 方面取得的一些早期進展，我們將獲得更大的動力。所以我很好奇您是否可以再多談談如何看待歐洲的 HO 吸收，特別是相對於我們迄今為止在 BBS 上看到的情況。

Yeah, Yann, do you want to give it another shot and we'll just see how your connection is. If not, I'll take it back.

是的，Yann，你想再試一次嗎，我們看看你的連接情況如何。如果沒有的話，我就收回它。

Yeah, I, it was quite. So, the first As I've said the engagement with the (Inaudible).

是的，我，確實如此。因此，正如我所說，與（聽不清楚）。

Yann Yann. I'm going to stop you just because you're, we're losing too much of what you said there, so I'll give you my answer, Whitney. There's a lot of things about Europe rare diseases in general, HO specifically, which are of course advantageous from a launch standpoint and that, the centers of excellence aspect of this patients tend to be more concentrated.

鄢鄢。我要阻止你，只是因為我們失去了你所說的太多內容，所以我會給你我的答案，惠特尼。歐洲在罕見疾病領域，特別是 HO 領域，有許多優勢，從推出的角度來看當然是有利的，而且針對這類患者的卓越中心往往更加集中。

That said, I think the dynamic in Europe, which is going to be similar to the US, is Heavily concentrated in the endocrinologists, these patients, they have, a very high percentage of them have pituitary insufficiency, and they are chronically managed by endocrinologists. And so to that extent it will be very similar between the US and Europe in terms of our approach to that market and then you know the rate at which they come on.

話雖如此，我認為歐洲的情況與美國類似，主要集中在內分泌科醫生身上，這些患者中很大一部分患有腦下垂體功能不全，需要長期接受內分泌科醫生的治療。因此從某種程度上來說，美國和歐洲對該市場的態度非常相似，然後你就知道他們進入的速度了。

I don't know if it's going to be different. I mean they have different reasons for you. Why it may go faster or slow and slower either in the US or Europe, and I think you know what we've seen, BBS, for example, it's not been so different, and I think that may be the case here. I do think, as we've said and we'll continue to say, HO is a very different opportunity than BBS. So some of that will be reflected in our launch trajectory, of course.

我不知道情況是否會有所不同。我的意思是他們對你有不同的理由。為什麼它在美國或歐洲可能會更快或更慢，我想你知道我們已經看到了什麼，例如 BBS，它並沒有那麼不同，我認為這裡可能就是這種情況。我確實認為，正如我們已經說過並將繼續說的那樣，HO 與 BBS 是一個非常不同的機會。當然，其中一些將反映在我們的發射軌跡中。

Got it. That's helpful. And then thinking about the label, can you just remind us how you are thinking about that currently? I know I think we're expecting an acquired HO specific label, but should we be thinking about BMI requirements or age or time from injury, any other kind of parameters that we should be thinking about?

知道了。這很有幫助。然後考慮標籤，您能否提醒我們目前是如何考慮的？我知道我們期待獲得一個 HO 特定標籤，但是我們是否應該考慮 BMI 要求或年齡或受傷時間，或者我們應該考慮的任何其他類型的參數？

So don't know. We have had zero interaction around the label to date, so I don't have any insight there. In general, FDA labels your drug based on how your inclusion exclusion criteria are written in the trial. The BMI criteria FDA is moving away from that, so I'm actually not expecting that to be part of it, meaning this threshold of, 30 being a magical number whereby, above and below it you're obese or not obese.

所以不知道。到目前為止，我們還沒有就該標籤進行過任何互動，所以我對此沒有任何見解。一般來說，FDA 會根據試驗中納入排除標準的方式對您的藥物進行標記。FDA 的 BMI 標準正在逐漸放棄這一標準，所以我實際上並不期望它成為其中的一部分，這意味著 30 這個閾值是一個神奇的數字，高於或低於這個數字，你就是肥胖或不肥胖。

So I don't expect hopefully that that will not be a bit because it's not helpful. And the other thing for which I think they will understand this is about the change in trajectory. It's not about an absolute level of weight or BMI. It's about you were at a level of quote unquote relative normality before you had your injury or your insult, and then following the injury, then you have a rapid acceleration.

所以我不希望這有一點幫助，因為它沒有幫助。我認為他們會理解的另一件事是軌跡的改變。這與體重或 BMI 的絕對水平無關。也就是說，在你受傷或受到侮辱之前，你的狀態處於相對正常的水平，而在受傷之後，你的狀態就會迅速加速。

Of your weight gain increasing your BMI. So long story short, I don't think it's going to be there age wise we went down to four. We've gone down to we're approved for two and above for BBS in Palm C. I think, this trial only studied four, so four and above, and we had a four-year-old in the trial.

您的體重增加會增加您的 BMI。長話短說，我認為從年齡上來說我們不會再有這樣的情況了，我們已經把年齡降到了四個。我們已經批准在 Palm C 上使用 2 歲以上的 BBS。我認為，這次試驗只研究了 4 歲及以上的兒童，而且我們在試驗中有一個 4 歲的兒童。

So I would expect minimally we'll get a four and above in terms of age, so not really an age restriction on what we're seeing here. And then, we have hunger in the label in Europe. We have tried to get it in here that we have the ability to promote. We have data on hunger in the label. We'd like to get it in the indication statement.

因此，我預計我們至少會得到 4 歲以上的人，所以我們在這裡看到的並不是年齡限制。然後，我們在歐洲的標籤上看到了飢餓感。我們已盡力將其推廣到這裡，以證明我們有能力推廣它。標籤中有關於飢餓的數據。我們希望將其納入指示聲明中。

To me, that's been more about our inclusion and exclusion criteria. It's a key secondary in this trial. We hit hunger. We're going to go back and try again, and I think that's, it's an important part of the indication statement, so we'll work hard to get it, but, to be seen.

對我來說，這更多的是關於我們的納入和排除標準。這是本次試驗中關鍵的次要部分。我們感到飢餓。我們將回去再試一次，我認為這是指示聲明的重要組成部分，所以我們會努力實現它，但還有待觀察。

Awesome, thanks so much.

太棒了，非常感謝。

Great, thank you. Our next question comes from Dennis Ding with Jefferies, you may proceed.

太好了，謝謝。我們的下一個問題來自 Jefferies 的 Dennis Ding，您可以繼續。

Hi, good morning. Thanks for taking the question. Just one for me. So consensus has HO revenue ramping from around $55 million to $60 million in 2026 to a billion plus in 2030. So there's quite a steep ramp in just four or five years of launch. Can you talk about your level of confidence that the launch will be solid and what are the different moving parts that could drive revenue higher or lower than consensus? Thank you.

嗨，早安。感謝您回答這個問題。對我來說只有一個。因此，人們一致認為，HO 收入將從 2026 年的約 5,500 萬美元增加到 6,000 萬美元，到 2030 年將達到 10 億美元以上。因此，在推出後的短短四、五年內，成長速度就相當快。您能否談談您對此次發表會順利進行的信心程度，以及哪些不同的因素可能導致收入高於或低於預期？謝謝。

Yeah, Dennis, thanks. So I think consensus and ourselves, we're all continuing to work a problem. None of us, of course, know exactly, so I'm not going to guide on the on the revenue piece of it specifically. I'll reinforce some of the elements, try to answer the other parts of your question.

是的，丹尼斯，謝謝。所以我認為，共識和我們自己，我們都在繼續努力解決問題。當然，我們誰也不知道確切情況，所以我不會具體指導收入部分。我會強化其中的一些要素，並嘗試回答你問題的其他部分。

Fundamentally different and you know I've talked before the numbers here 5,000 to 10,000 in the US or numbers in Europe. Aren't arguably that much larger than BBS, right, 4,000 to 5,000 in BBS, but of that 5,000 to 10,000, a much higher percentage of those patients are diagnosed. They're visible. They have complex, and they're actively being managed by specialists, and that specialist is endocrinologists.

根本上是不同的，你知道我之前談過，美國的數字是 5,000 到 10,000，歐洲的數字是。可以說並不比 BBS 大很多，對吧，BBS 中有 4,000 到 5,000 人，但在這 5,000 到 10,000 人中，確診患者的比例要高得多。它們是可見的。他們的情況很複雜，需要由專家積極治療，而這些專家就是內分泌學家。

And about 50% of the patients of the writers, scriptwriters in the US for BBS who happen to be endocrinologists. So this is a world we're in. HO will be even more concentrated in the endocrinology world and as Jennifer and her team, continue to work to develop the plans for launch, we will approach this in a different way than we did. In a rare disease world where the majority of patients are not diagnosed.

而美國BBS的作家、編劇的病人中大約有50%是內分泌學家。這就是我們所處的世界。HO 將更加專注於內分泌學領域，隨著 Jennifer 和她的團隊繼續努力製定發布計劃，我們將以不同於以往的方式來實現這一目標。在罕見疾病的世界裡，大多數患者都無法得到診斷。

You're trying to build a system that helps them get to a diagnosis. You don't find the patients by knocking on doors. You really find it by working with a system, and then a patient gets to the diagnosis, and often they find us, some of them, we find them.

您正在嘗試建立一個幫助他們做出診斷的系統。你不可能透過敲門來找到病人。你確實可以透過一個系統找到它，然後病人就會得到診斷，通常他們會找到我們，其中一些人，我們會找到他們。

In this, which is much more special like. If they're concentrated in a specialty, you can cover that specially, and our goal will be in a tiered way to cover certainly those endocrinologists, which is a significant number, where the majority of these patients sit. So all that says it should be a different ramp than we're seeing with BBS. Now that said, it's still a $375,000 a year price point. There'll be no change in price.

在這其中，哪一點比較特別呢。如果他們專注於某個專業，那麼您可以專門覆蓋該專業，我們的目標是以分層的方式覆蓋那些內分泌科醫生，這是一個相當大的數字，大多數患者都在那裡。所以，所有這些都表明它應該與我們在 BBS 上看到的坡道不同。話雖如此，每年的價格仍為 375,000 美元。價格不會有變動。

That puts a natural drag on any launch. You have a prior authorization as you go through and so. There'll be a balance between some of this. We have a huge advantage of having been out there around BBS. It's not like we're new to this community. They know us. Increasingly people know the drug and increasingly people are seeing the importance of MC4 our pathway as being a, this is a critical fundamental underlying biology.

這自然會給任何發布會帶來阻礙。您在通過時已經獲得了事先授權。這其中的一些將會保持平衡。我們在 BBS 方面擁有巨大的優勢。我們並不是這個社區的新成員。他們認識我們。越來越多的人了解這種藥物，也越來越多的人認識到 MC4 路徑的重要性，因為它是一種關鍵的基礎生物學。

So all of that, how that nets out, I don't know, but I'll summarize and leave it with, yes, it's going to be a different trajectory. I can't comment on, whether that those numbers and consensus are going to be the ones we're going to hit.

所以所有這些，其結果如何，我不知道，但我會總結並說，是的，這將是一條不同的軌跡。我無法評論我們是否會達到這些數字和共識。

Great, thanks for the call.

太好了，謝謝您的來電。

Thank you. Our next question comes from Leland Gershell with Oppenheimer. You may proceed.

謝謝。我們的下一個問題來自 Oppenheimer 的 Leland Gershell。您可以繼續。

Hi, good morning. Great to see the consistency across the age subgroups in the HO study. A couple of questions from us first, question for Hunter, apologies if I if I missed it in the discussion about inventories, but should we expect lumpiness this year as we model quarterly revenue? Should we think about another fourth quarter kind of inventory stocking?

嗨，早安。很高興看到 HO 研究中各個年齡亞組的一致性。首先我們想問幾個問題，關於 Hunter 的問題，如果我在討論庫存時遺漏了這個問題，請見諒，但是當我們對季度收入進行建模時，我們是否應該預期今年會出現波動？我們是否應該考慮在第四季度進行另一種庫存補充？

And also a question for Jennifer, just on your comments about the about a third of first-time prescribers, turning to repeat prescribers, is that particularly limited by the number of patients who fall under in current indications or are there other factors that may be limiting the a prescribers becoming repeat prescribers. Thank you.

另外想問 Jennifer 一個問題，關於您提到的大約三分之一的首次開處方者變成了重複開處方者，這是否特別受到符合當前適應症的患者數量的限制，或者是否存在其他因素可能限制了首次開處方者成為重複開處方者。謝謝。

So on the lumpiness there are factors that are that are a normal pattern, SPs do tend to do a little bit of stocking during the fourth quarter. It's a way they try to manage their, we believe it's a way they try to manage their gross margins because they think there may be price increases coming in the new year. It's not isolated to Rhythm. Obviously, it's a very common factor across the industry.

因此，在不均勻性方面，存在一些因素，這些因素是正常模式，SP 確實傾向於在第四季度進行少量備貨。這是他們試圖管理的一種方式，我們相信這是他們試圖管理毛利率的一種方式，因為他們認為新的一年可能會出現價格上漲。它並不孤立於節奏。顯然，這是整個產業非常普遍的因素。

Some of the lumpiness occurs by things as arcane as the fact that the quarter ended on a Monday, which is the day, Monday March 31, which is the day when SPs usually place their order but they don't receive it until the next day. So that type of thing, if you would like to try and forecast that level of minutiae, I wish you luck.

一些不一致性是由一些神秘的事情引起的，例如該季度結束於星期一，即 3 月 31 日星期一，這是 SP 通常下訂單的日子，但他們直到第二天才能收到訂單。所以，如果你想嘗試預測這種程度的細節，我祝你好運。

I can't do it, but again, overall, we don't think the moves in days on hand are going to be this significant. We think in general they will sit in sort of the 10 day to 15 day range on average. And the rest around that will just be the vagaries of timing and to some extent ways they may try to manage their own gross margin.

我做不到，但總的來說，我們認為未來幾天的舉措不會這麼重大。我們認為，總體而言，它們的平均停留時間將在 10 天到 15 天之間。其餘的只是時間的變化，在某種程度上，他們可能會嘗試管理自己的毛利率。

And to the other question just regarding the repeat prescribers, I think in a disease like BBS, and if I compare BBS to HO and what a follow on to what David has been outlining, I think for an indication like BBS, we sort of have smaller little breadcrumbs where the teams are really scouring to get to a physician who may have this type of patient population and educating them so that they are aware so that.

至於關於重複開處方者的另一個問題，我認為對於像 BBS 這樣的疾病，如果我將 BBS 與 HO 進行比較，並延續 David 所概述的內容，我認為對於像 BBS 這樣的適應症，我們的病例就像是更小的“麵包屑”，團隊正在努力尋找可能有這種類型患者群體的醫生，並對他們進行教育，使他們意識到這一點。

When that patient comes to them, they are able to get that patient to a diagnosis. For HO in contrast, I think the bread crumbs are much larger that will lead us to the right physician more quickly in terms of being able to educate and engage with that physician population a once a physician actually gets a patient to a diagnosis.

當病人來找他們時，他們就能對病人進行診斷。相比之下，對於 HO，我認為麵包屑要大得多，這將使我們更快找到合適的醫生，因為一旦醫生真正為患者做出診斷，我們就能夠對醫生群體進行教育和互動。

Then they realize that this is something that they should be aware of as this patient with all these different symptoms comes to them, and it just becomes more of a piece of these patients could be anywhere and sometimes they go to a physician who has already had experience with a BBS patient and other times they're in the has of someone who that is the first patient diagnosed.

然後他們意識到這是他們應該注意的事情，因為這個具有各種不同症狀的患者來找他們，而且這些患者可能在任何地方，有時他們會去找已經有過 BBS 患者治療經驗的醫生，其他時候他們會去找第一個被診斷出患有 BBS 的患者。

I will say that once that physician diagnoses and has a great experience on IMCIVREE, then they are more likely to also prescribe this drug for those particular patient populations. So it's a bit of a mix of that in terms of where the patients land in terms of care and also the positive experience after touching and seeing what else can we do for the BBS population that results in a repeat prescriber.

我想說的是，一旦醫生做出診斷並且對 IMCIVREE 有了豐富的經驗，那麼他們就更有可能為特定的患者群體開出這種藥物。因此，就患者在護理方面所獲得的結果以及接觸後的積極體驗而言，這有點混合，並且可以看到我們還能為 BBS 人群做些什麼，從而重複開處方。

And so Leland, just to reinforce again what Jennifer said that, why don't the 1/3 of patients all prescribe another drug as a rule, she said, if you get one patient on, you have that experience, you're a believer, then it's more a question of do you have other patients.

因此，Leland，只是為了再次強調 Jennifer 所說的話，為什麼 1/3 的病人不都開另一種藥作為規則，她說，如果你有一個病人，你有那種體驗，你是一個信徒，那麼更多的問題是你是否有其他病人。

That's very helpful. Thanks very much.

這非常有幫助。非常感謝。

Thank you. Our next question comes from Michael Occi with Morgan Stanley. He may proceed.

謝謝。我們的下一個問題來自摩根士丹利的 Michael Occi。他可以繼續。

Hello, this is Selena on for Mike. Thanks for taking our question. For the congenital HO substudy, could you describe the patient mix that you're seeing among the different pituitary deficiency disorders included and any learnings on reliably diagnosing congenital HO? Thank you.

大家好，我是 Selena，為 Mike 播報。感謝您回答我們的問題。對於先天性 HO 子研究，您能否描述一下您在所見的不同腦下垂體缺陷症患者組合中的情況，以及對可靠地診斷先天性 HO 的任何經驗教訓？謝謝。

Yeah, I know, we're I don't know, way too early to answer that in any kind of meaningful way. I mean, I think the list we've talked about of, SOD, cephaloptic dysplasia, pituitary stock interruption syndrome, multiple pituitary deficiency.

是的，我知道，我們現在還不知道，現在以任何有意義的方式回答這個問題還為時過早。我的意思是，我認為我們已經討論過的清單包括 SOD、頭顱發育不良、腦下垂體庫存中斷症候群、多垂體功能低下。

I mean we're going to see all of those right now. I would say the SOD pituitary stock maybe interruption, maybe two of the more common, but we're so early. I just can't answer that in a meaningful way about how it will break out across the different quote unquote categories.

我的意思是我們現在就可以看到這些。我想說 SOD 垂體庫存可能會中斷，也許是兩種更常見的情況，但我們還為時過早。我只是無法以有意義的方式回答它將如何在不同的“引號”類別中脫穎而出。

Okay. Thank you.

好的。謝謝。

Our next question comes from Joseph Stringer with Needham & Company. You may proceed.

我們的下一個問題來自 Needham & Company 的 Joseph Stringer。您可以繼續。

Hi, thanks for taking our questions. For the instant relaunch of BBS, can you disclose the number of written TRX and reimbursed TRX in the US in the first quarter?

您好，感謝您回答我們的問題。對於BBS的即時重啟，能否透露第一季美國TRX的掛單量和還款量是多少？

Yeah, we're not breaking those out, Joe. I mean, we did in the beginning just to give everybody a sense because we didn't have revenues that spoke meaningfully to where we are. I think now we're very much relying on the revenues which are a more holistic view of how the market's doing. That's right. So when we gave you colour around it, by the way, we're not going to break out the exact numbers.

是的，喬，我們不會把這些數字單獨列出來。我的意思是，我們一開始就這麼做了，只是為了讓大家有個大概的了解，因為我們的收入不足以說明我們目前的狀況。我認為現在我們非常依賴收入，這是對市場表現的更全面的了解。這是正確的。因此，當我們給你周圍顏色時，順便說一句，我們不會透露確切的數字。

Okay, thank you.

好的，謝謝。

Yeah, thanks.

是的，謝謝。

Thank you. (Operator Instructions). Our next question comes from Raghuram Selvaraju with H.C. Wainwright. You may proceed.

謝謝。（操作員指令）。下一個問題來自 H.C. Wainwright 的 Raghuram Selvaraju。您可以繼續。

Thanks very much for taking our questions. Firstly, I was wondering if you could comment on any qualitative differences that you expect to see and implement in the context of the commercial rollout in hypothalamic obesity relative to the other indications for which is already approved. I'm just trying to look here for, any changes in broader marketing and promotional strategy that you might utilize in this specific indication.

非常感謝您回答我們的問題。首先，我想知道您是否可以評論一下，相對於已經獲得批准的其他適應症，在下丘腦肥胖症的商業推廣背景下，您預計會看到和實施的任何品質差異。我只是想在這裡尋找您可能在此特定適應症中利用的更廣泛的營銷和促銷策略的任何變化。

I think, there are similar aspects in terms of any rare disease where the trajectory is really based off of how quickly you can identify the patients because usually, and it's the case here for both BBS and HO, there was a need for an additional therapy. We have done market research.

我認為，任何罕見疾病都有類似的方面，其發展軌跡實際上取決於識別患者的速度，因為通常情況下，對於 BBS 和 HO 來說，都需要額外的治療。我們已經做過市場調查。

We've gathered feedback from our field teams who have started engaging with physicians just around better understanding the HO market. The pieces that, make us feel very positive about the opportunity is that consistently the the The comments expressed about the unmet need in this particular population is so incredibly high.

我們收集了現場團隊的回饋，他們已經開始與醫生接觸，以便更好地了解 HO 市場。讓我們對這個機會感到非常樂觀的是，關於這一特定人群未滿足需求的評論一直非常高。

We hear that from patients and caregivers as well, as I outlined just in terms of our blinded TPP, which we went out with slightly less efficacy. Then what we actually saw from a top line data perspective, the reaction to IMCIVREE efficacy as well as overall profile has been very overwhelming in terms of, positive feedback from the physician population.

我們也從患者和照護者那裡聽說了這一點，正如我剛才就我們的盲法 TPP 所概述的那樣，我們的療效略低。然後，我們從頂線數據角度實際看到的是，對 IMCIVREE 療效以及整體概況的反應非常強烈，來自醫生群體的積極反饋也十分積極。

And so those two pieces are, sort of right in terms of the need that exists and the other comment that David had outlined, for HO, these patients, because of all of the other clinical manifestations due to what they went through from a treatment perspective. They are in the hands of these endocrinologists, the vast majority of them, like it could be 80% of them, are still seeing endocrinologists.

因此，從存在的需求和 David 概述的另一條評論來看，這兩點是正確的，對於 HO 患者來說，由於從治療角度來看他們所經歷的所有其他臨床表現，這些患者都有這樣的情況。他們由內分泌科醫生負責治療，其中絕大多數人，大約 80% 的人，仍在看內分泌科醫生。

So that specialty call and that ability to go to that particular physician set with the data that we have to be able to H1 us down to which of those even within. Specialty is much higher than, like I said, the breadcrumbs that we started with in BBS where there was no ICD 10 code. They are scattered amongst various different physicians. So I think those dynamics make it a more interesting and exciting potential launch for us.

因此，透過專業呼叫和根據數據聯繫特定醫生的能力，我們必須能夠將 H1 精確到其中哪一個。正如我所說，專業性比我們在沒有 ICD 10 代碼的 BBS 中開始使用的麵包屑要高得多。他們分散在不同的醫生那裡。所以我認為這些動態會讓它成為我們更有趣、更令人興奮的潛在發布。

Great. And then secondly, very quickly, in the wake of the rare stone termination, I was just wondering in the context of the broader international strategy, how you intend to go forward in China if you are looking at the possibility of bringing in a replacement partner or if your assessment of the China commercial opportunity you know has kind of signaled an evolution in your thinking about how best to penetrate that opportunity. Thanks.

偉大的。其次，在稀有寶石交易終止之後，我很想知道，在更廣泛的國際戰略背景下，如果您正在考慮引入替代合作夥伴的可能性，或者您對中國商業機會的評估是否表明了您對如何最好地抓住這一機會的想法的轉變，那麼您打算如何在中國繼續前進。謝謝。

Yeah, no thanks. So when we're thrilled to have that, the rights to China back. I feel good about having global rights here number one. Number two, we absolutely are expanding globally. We're really excited about the Japan opportunity. I talked about that on this fall, but that's going to be a very meaningful opportunity. HO China itself, we Learned a lot in our partnership with the rare stone and it was incredibly helpful.

是的，不用了，謝謝。因此，我們很高興能夠將版權歸還給中國。我很高興在這裡擁有全球權利。第二，我們絕對正在全球擴張。我們對日本的機會感到非常興奮。我在今年秋天談到了這一點，但這將是一個非常有意義的機會。對於中國本身來說，我們在與稀有寶石的合作中學到了很多東西，這非常有幫助。

In that sense and that, they did some good work. Other work had been done. The genetic side of this opportunity is probably less in China, not that it's not there, but HO is absolutely there and I don't have numbers for you today, but we know it's there, so. We will have a China strategy today. I wouldn't say we're committed to any particular course of action, meaning, would we go alone.

從這個意義上來說，他們做了一些很好的工作。其他工作已經完成。在中國，這種機會的遺傳方面可能較少，並不是說它不存在，而是 HO 絕對存在，我今天沒有提供具體數字，但我們知道它存在，所以。今天我們將有一個中國戰略。我不會說我們致力於採取任何特定的行動方針，也就是說，我們會單獨行動。

Which I think is it's, we can go alone in Japan, much more challenging perhaps to go alone in China. So that would suggest we'd need a partner, but all that's to come. But I think, China and Asia, in a larger sense, Taiwan, South Korea. Those are meaningful opportunities, and we'll work our way through that and keep thinking about what's the right strategy for China.

我認為，我們可以獨自前往日本，但獨自前往中國可能更具挑戰性。所以這表明我們需要一個合作夥伴，但這一切都還不算太晚。但我認為，中國和亞洲，從更廣泛的意義上來說，還有台灣、韓國。這些都是很有意義的機會，我們會努力把握這些機會，並不斷思考什麼才是適合中國的正確策略。

Thank you.

謝謝。

Thank you. Our next question comes from [Patis with people], you may proceed.

謝謝。我們的下一個問題來自 [Patis 與人們]，你可以繼續。

Hey, sorry about that. I think I saw you earlier. I appreciate you putting me in. Just going back to Balon really quickly, anything you guys can say about safety, from the study, given that it's pretty far along now, anything just on the idiosyncratic safety side related to live.

嘿，很抱歉。我想我早些時候見過你。我很感激你讓我加入。讓我們很快回到 Balon 的話題，考慮到這項研究已經進行了很長時間，從安全性方面來說，你們能說說任何與生活相關的特殊安全方面的事情嗎？

Or anything else that kind of you're seeing that would give you more comfort in the molecule and then I just wanted to clarify David on the bar, I mean 10% makes sense, but this study is meaningfully shorter than the setmelanotide phase 3. So how do you think about the bar for the shorter phase 2.

或者您看到的任何其他東西都會讓您對分子更加放心，然後我只想澄清一下 David 的說法，我的意思是 10% 是有道理的，但這項研究比 setmelanotide 第 3 階段要短得多。那麼您如何看待較短的第二階段的標準呢？

Yeah, that's a great question, Paul. Thank you. So on the safety side, again, it's blinded, but obviously you follow the safety in a blinded sense and. All I will say there's no significant safety signals here that we're concerned about, I don't have fine detail in terms of looking at individual patients' LFT data, but if there was a serious adverse event related to LFTs, we would see that.

是的，保羅，這個問題問得很好。謝謝。因此，從安全性來看，這又是盲目的，但顯然你是在盲目的意義上遵循安全的。我想說的是，這裡沒有我們擔心的重大安全信號，我沒有詳細查看個別患者的 LFT 數據，但如果發生與 LFT 相關的嚴重不良事件，我們就會發現。

So we're not seeing any of that. So I would categorize our blinded view of all that is quite reassuring, number one. And then two, your question on the bar, it's a good one which I why I always. Don't, I don't like being boxed in, particularly around data. There's always context around data and particularly in a rare disease. I mean, the means are, I'm not at all interested in the mean value so much.

所以我們沒有看到任何這些。因此，我認為我們對所有令人放心的事情的盲目看法是第一類。其次，你關於酒吧的問題很好，這也是我一直問的問題。不要，我不喜歡被束縛，特別是在數據方面。數據總是有背景資訊的，特別是對於罕見疾病而言。我的意思是，我對平均值根本就不太感興趣。

I'm very much interested in patient by patient and if the mean doesn't get to 10%, but you can explain a couple of patients that were dragging the mean down, then okay, you've still got a drug. So we'll look at the data that way. One way of looking at this is our phase two data, if you remember, with set melanotide was 16 weeks and they did hit, almost all of those patients had 10% or greater or were on track to lose 10% or greater.

我對每個病人的情況非常感興趣，如果平均值沒有達到 10%，但你可以解釋幾個拉低平均值的病人，那麼好吧，你仍然有一種藥物。所以我們會以這種方式來看待數據。觀察這一情況的一種方式是我們的第二階段數據，如果您還記得的話，設定的黑素肽治療時間為 16 週，並且確實達到了效果，幾乎所有患者的病情都減輕了 10% 或更多，或者預計會減輕 10% 或更多。

So I think 10%'s not an unreasonable target here in terms of using set as the bar, setmelanotide as the bar, but there'll be contexts that we'll have to take into consideration, and 16 weeks is relatively short.

因此，我認為，就使用 set 作為標準、以 setmelanotide 作為標準而言，10% 並不是一個不合理的目標，但我們必須考慮一些背景，而 16 週相對較短。

Makes sense. Thanks a Lot

有道理。多謝

Thank you. I would not like to turn the call back over to David Meeker for any closing remarks.

謝謝。我不想將電話轉回給戴維·米克爾 (David Meeker) 來做任何結束語。

Okay, well, thanks everybody. A long call this morning, a lot of questions. I appreciate that and we look forward to our next update.

好的，謝謝大家。今天早上的通話很長，有很多問題。我對此表示感謝，我們期待下次更新。

Thank you. This concludes the conference. Thank you for your participation. You may now disconnect now.

謝謝。會議到此結束。感謝您的參與。您現在可以斷開連線。