Rhythm Pharmaceuticals Inc (RYTM) 2024 Q4 法說會逐字稿

Good day and welcome to Rhythm Pharmaceuticals fourth quarter and fiscal year 2024 earnings conference call. [Operator Instructions] I would like to turn the call over to David Connolly, IR and corporate communications. Please go ahead.

大家好，歡迎參加 Rhythm Pharmaceuticals 2024 財年第四季和收益電話會議。[操作員指示] 我想將電話轉給 IR 和公司通訊部門的 David Connolly。請繼續。

Thank you, Michel. 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 2024 and full year 2024 financial results and a business update, and that press release is available on our website.

謝謝你，米歇爾。我是 Rhythm Pharmaceuticals 的 David Connolly，對於參加電話會議的人來說，可以透過造訪我們網站 ir.rhythmtx.com/ 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，提供了 2024 年和 2024 年全年的財務業績和業務，該新聞稿可在我們的網站上查閱。

Our agenda is listed on slide 2. 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 joining us from Europe. On slide 3, 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 in our most recent.

我們的議程列在第二張投影片。參加今天電話會議的有我們的董事長、執行長兼總裁 David Meeker、執行副總裁兼北美地區負責人 Jennifer Lee、財務長 Hunter Smith 和執行副總裁 Yann Mazabraud。國際業務主管正在從歐洲連線我們。在投影片 3 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（包括我們最近討論的因素），實際結果可能與這些前瞻性陳述所示的結果有重大差異。

Annual or quarterly reports on file with the SEC. In addition, any forward-looking statements represents our views 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 will begin on slide 5.

向美國證券交易委員會提交的年度或季度報告。此外，任何前瞻性陳述均代表我們今天的觀點，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。說完這些，我將把電話轉給 David Meeker，他將從第 5 張投影片開始發言。

Thank you, Dave. Good morning, everybody. thank you for joining. so we pre-announced strong fourth quarter earnings in advance of the JPM conference. We are entering 2025 well capitalized, having recently raised $75 million in gross proceeds from our ATM program, which extends our cash run rate into 2027 through multiple inflection points, and we have completed enrollment in our phase 2daily oral Maigon study.

謝謝你，戴夫。大家早安。感謝您的加入。因此我們在摩根大通會議召開之前預先宣布了強勁的第四季度收益。我們將以充足的資本邁入 2025 年，最近我們從 ATM 計劃中籌集了 7500 萬美元的總收益，這將通過多個轉折點將我們的現金運行率延長至 2027 年，並且我們已經完成了第 2 階段每日口服 Maigon 研究的招募。

We feel incredibly positive about how the opportunity in genetically driven impairments to the MC4R pathway signaling is evolving. As we have highlighted many times, ultra rare disease opportunities like BBS, where there is a significant unmet medical need, a high percentage of undiagnosed patients, and where the availability of a precision therapy can accelerate the number of patients getting to a diagnosis, these opportunities will continue to grow at a steady pace for a decade or longer.

我們對 MC4R 路徑訊號傳導中由基因驅動的損傷機會的演變感到無比樂觀。正如我們多次強調的那樣，像 BBS 這樣的極度罕見疾病存在著巨大的未滿足的醫療需求、大量未確診的患者，而精準治療可以加速患者數量的確診，這些機會將在未來十年或更長時間內繼續以穩定的速度增長。

The US opportunity is taking shape, and we will continue to expand internationally. We could build a business around the BBS Opportunity alone. we are excited about the progress we are making with our next generation compounds, bivialigon, a once daily oral pill, and the weekly sub-Q injection RM-718.

美國機會正在形成，我們將繼續進行國際擴張。我們可以單獨圍繞 BBS 機會建立業務。我們對下一代化合物藥物 bivialigon（每日一次的口服藥）和每週一次的皮下注射 RM-718 所取得的進展感到非常興奮。

Now our goal with the next generation opportunities is not just to extend patent life, but to actually make a better drug. Both products have robust robust activity in preclinical models and have no cardiovascular activity in the appropriate models. Both are MC1R sparing, so no hyperpigmentation, and significantly more convenient.

現在，我們在下一代機會上的目標不僅是延長專利期，而是真正製造出更好的藥物。兩種產品在臨床前模型中均表現出強勁的活性，在適當的模型中則不具有心血管活性。兩者都保留了 MC1R，因此不會造成色素沉著，而且更加方便。

Whether there is an opportunity to improve on efficacy remains to be seen. The Bivi Meigon Phase 2 study is fully enrolled this quarter and we'll read out in the third quarter, and the 718 program is beginning to enroll this quarter.

是否有機會提高療效還有待觀察。Bivi Meigon 第 2 階段研究本季已全面招募患者，我們將在第三季讀完，718 計畫也將於本季開始招募患者。

So slide 7 is the now familiar design slide for a phase 3 trial of Semelannoide and acquired HO, and we continue to receive the majority of our questions here. What is the timing of the readout and what is the expected percent change in BMI? We have guided to the trial reading out in the first half, and we can now be more specific that it will be a second quarter readout.

因此，幻燈片 7 是現在熟悉的 Semelannoide 和獲得性 HO 的 3 期試驗的設計幻燈片，我們繼續在這裡收到大部分問題。讀數的時間是什麼時候？我們已經指導了上半年的試讀，現在我們可以更具體地說，這將是第二季的讀出。

Our updates remain consistent with what we have said. Our dropout rate remains below 10%, which I think is incredibly strong metric. Patients are rolling over into the open label extension. They do remain blinded to their original assignment, and only one patient has not rolled over and because that patient wanted to start a family.

我們的更新與我們所說的內容保持一致。我們的退學率仍然低於 10%，我認為這是一個非常強烈的指標。患者正在轉向開放標籤擴展。他們確實仍然不知道自己原來的任務，只有一名病人沒有轉任，因為該病人想要建立家庭。

With regard to the percent change in BMI, it is a blinded phase 3 clinical trial. We have, however, reminded people that the current fervor around percent change comes out of the many trials being run in a general obesity space with some version of a GLP-1. These trials have similar designs, so comparisons can be made across trials, although this is always imperfect.

對於BMI的百分比變化，這是一項盲法3期臨床試驗。然而，我們已經提醒人們，目前對百分比變化的熱情來自於在一般肥胖領域使用某些版本的 GLP-1 進行的許多試驗。這些試驗具有相似的設計，因此可以跨試驗進行比較，儘管這總是不完美的。

When we look at ce melannoide in HO, it is an apples and oranges comparison. The biology is fundamentally different. We are replacing a deficit in the hormone alpha melanocyte stimulating hormone. The GOP one approach is to provide pharmacologic doses on top of intact physiology.

當我們觀察 HO 中的 ce melannoide 時，這是一個蘋果和橘​​子之間的比較。生物學有著根本的不同。我們正在彌補α-黑素細胞刺激激素的缺陷。GOP 的一種方法是在完整的生理基礎上提供藥理劑量。

Our trial enrolls 4-year-old patients and 60-year-old patients, and we measure the same endpoint, the percentage change in BMI of 52 weeks. In our phase 2 trial, the youngest patient, aged six, lost approximately 35% of their BMI at 16 weeks, whereas the oldest patient, 24 years old, lost 14%. Now the 24 year old patient actually lost more weight, but on a percent basis it was a smaller change. So these are variables which will impact the final numbers.

我們的試驗招募了 4 歲患者和 60 歲患者，我們測量相同的終點，即 52 週的 BMI 百分比變化。在我們的第二階段試驗中，最小的患者（6 歲）在 16 週時 BMI 下降了約 35%，而最年長的患者（24 歲）則下降了 14%。現在這位 24 歲的患者實際上減掉了更多的體重，但從百分比來看，變化較小。因此這些變數將會影響最終數字。

That said, all of our data to date, the phase 2 study, which was predominant in pediatric patients, and the French pre-approval early access data, which was all adults, suggests we will do well on the primary. the secondaries will break out the pediatric and adult patients so the full story can be clearly understood. The Japanese cohort of 12 patients, for which we recently completed enrollment, will read out independently from the pivotal cohort, so there's no impact on timing of top line data and subsequent regulatory filings in the United States and Europe.

儘管如此，我們迄今為止的所有數據、主要針對兒科患者的第 2 階段研究以及法國上市前早期使用數據（全部為成人）都表明，我們將在主要研究方面取得良好的結果。次要研究將把兒科患者和成人患者分開，以便清楚地了解整個故事。我們最近完成招募的 12 名日本患者隊列將獨立於關鍵隊列讀取，因此不會對頂線數據的時間和隨後在美國和歐洲的監管備案產生影響。

We expect the Japanese cohort will read out in the first half of 6. If successful, these data will enable us to seek marketing authorization in Japan, where there is a higher prevalence of certain brain tumors and hypothalamic obesity than in the US or Europe.

我們預計日本代表團將在 6 月上半年宣讀該報告。如果成功，這些數據將使我們能夠在日本尋求行銷授權，日本某些腦腫瘤和下丘腦肥胖的盛行率高於美國或歐洲。

A reminder on slide 8 that the opportunity in the HO is significant, and we continue to learn more. We affirm our original estimates, which we believe were appropriately conservative. The populations reflected on the slides with 5,000 to 10,000 patients in the US and a similar range in Europe, and 500 to 8,000 patients in Japan, represent a pool of patients who may be largely diagnosed and concentrated in the endocrinology specialty call point.

第 8 頁的投影片提醒我們，HO 中的機會非常重要，我們將繼續了解更多資訊。我們確認我們最初的估計，我們認為該估計是適當保守的。幻燈片上顯示的人群為美國 5,000 至 10,000 名患者、歐洲類似範圍的患者以及日本 500 至 8,000 名患者，這代表了可能主要在內分泌專科呼叫點進行診斷和集中的患者群體。

There's an additional pool of patients with injury to the hypothalamus where the diagnosis is not so clear and they are likely to remain undiagnosed. We look forward to expanding our understanding of this patient population.

還有一部分下視丘損傷患者，其診斷不那麼明確，很可能無法得到診斷。我們期待進一步加深對這群患者的了解。

Now the path to building the future of rhythm is clear. We have opportunities to further explore genetically driven impairments in the MC4R pathway. The M&A trial is enrolled and we'll read out in the first half of 2026. There are genes coming out of the daybreak trial which with a little more work can also be targeted. Prader-Willi syndrome is a challenging disease, but there's a sound biologic rationale as to why an MC4R agonist can work in that disease. This quarter we have initiated, as a new 26 week open label phase 2 trial to evaluate cemelannoide and Prater-Willi syndrome.

現在，建構節奏未來的道路已經清晰起來。我們有機會進一步探討 MC4R 路徑中由基因驅動的缺陷。併購案審理正在進行中，我們將在 2026 年上半年宣讀結果。黎明試驗中產生的一些基因，只要再做一些工作就可以成為目標。普拉德-威利症候群是一種很難治療的疾病，但有合理的生物學原理可以解釋 MC4R 激動劑為什麼能夠治療疾病。本季度，我們啟動了一項新的為期 26 週的開放標籤 2 期試驗，以評估 cemelannoide 和 Prater-Willi 症候群。

We plan to Up to 20 patients, 6 to 65 years old in the signal finding study, and patients will be dose escalated to 5 mg a day, which is significantly higher than the dose we used in the first attempt at Prader-Wiling, and they'll be dose escalated to that 5 mg as tolerated.

我們計劃在訊號發現研究中招募多達 20 名年齡在 6 至 65 歲之間的患者，並且患者的劑量將增加到每天 5 毫克，這明顯高於我們在第一次嘗試 Prader-Wiling 時使用的劑量，並且他們將根據耐受情況將劑量增加到 5 毫克。

So we are conducting this trial at a single US site under an investigator with deep experience in Prader-Willi syndrome, and we look forward to updating you on that progress. The other pillar which is emerging as an incredibly exciting opportunity is that related to injury to the hypothalamus or failure of the hypothalamus to develop.

因此，我們正在一位對普拉德-威利症候群有著豐富經驗的研究人員的指導下，在美國的一個地點進行這項試驗，我們期待向您通報進展。另一個正在興起並成為令人難以置信的機會的支柱是與下丘腦損傷或下丘腦發育失敗有關的支柱。

We have focused on tumors and their associated treatment, which may lead to injury, but there are clearly many more ways the hypothalamus may be injured, leaving the patient with acquired HO. We look forward to learning more about semelannoized activity in patients with developmental abnormalities related to congenital syndromes involving this area of the brain, and we are on track to enroll the first patients with congenital HO in an independent 39 patient 34 week substudy in the first quarter of 2025.

我們一直專注於腫瘤及其相關治療，這些治療可能會導致損傷，但顯然下丘腦受傷的方式還有很多，導致患者出現後天性 HO。我們期待更多地了解與涉及大腦該區域的先天性綜合症相關的發育異常患者的半黑素化活動，並且我們預計在 2025 年第一季度招募首批先天性 HO 患者，進行一項獨立的 39 名患者 34 週的子研究。

Finally, we anticipate doing much, if not all, of the supplemental indication expansion work with one or both for our next generation compounds with patent lines which extend past 2040. We have completed enrollment in the phase 2 Bivvaaligon trial and acquired HO this quarter, and we anticipate the data readout to me in the second half of 2025. Also, we will begin enrolling patients with acquired HO in Part C of the Phase 1 trial of RM 718 this quarter and are aiming for a data readout before the end of the year.

最後，我們預計將對下一代化合物進行大部分（如果不是全部的話）補充適應症擴展工作，這些化合物的專利線將延長到 2040 年以後。我們已經完成了第二階段 Bivvaaligon 試驗的招募，並於本季度獲得了 HO，我們預計在 2025 年下半年向我提供數據。此外，我們將於本季開始在 RM 718 第 1 階段試驗的 C 部分招募患有獲得性 HO 的患者，併計劃在年底前讀取數據。

So, in summary, 2024 was a year of execution, and 2025 is the year of readouts, which could prove to be transformative for rhythm in addition to some critical trial initiations. I will now turn the call over to Jennifer.

因此，總而言之，2024 年是執行之年，而 2025 年是宣讀之年，除了一些關鍵的試驗啟動之外，這可能會對節奏產生變革性的影響。現在我將把電話轉給珍妮佛。

Thank you, David. so 2024 was a solid year for every sales in the US with consistent growth throughout the year. Over the years we have fine-tuned our process to find patients, get them to an accurate diagnosis, and ensure access to therapy. Once on therapy, we work with patients and their healthcare providers to support maintenance on therapy. more than 2 years and from launch, the system we have put in place is working and will also help future potential launches.

謝謝你，大衛。因此，2024 年對於美國的各項銷售來說都是穩健的一年，全年都將持續成長。多年來，我們不斷優化流程，以尋找患者、讓他們得到準確的診斷並確保他們能夠接受治療。一旦開始治療，我們將與患者及其醫療保健提供者合作，以支持維持治療。從發佈到現在已經兩年多了，我們建立的系統一直運作良好並且將有助於未來的潛在發布。

New prescriptions received in the fourth quarter were consistent quarter over quarter. We are seeing continued success in approvals and reauthorizations, and our tailored support to patients and families are enabling patients to receive the long-term benefits of maintaining on therapy.

第四季收到的新處方數量與上一季持平。我們在批准和重新授權方面不斷取得成功，我們為患者和家屬提供的客製化支援使患者能夠獲得維持治療的長期益處。

Within the fourth quarter, the increase in the number of patients on reimbursed therapy was attributable to a number of incrementally positive trends that when combined, added up to a strong growth. For example, in addition to the steady level of approvals for reimbursement from scripts received, we saw fewer discontinuations for patients who are on reimbursed therapy.

第四季度，接受報銷治療的患者數量的增加歸因於一系列逐漸積極的趨勢，這些趨勢結合起來形成了強勁的增長。例如，除了收到的處方報銷批准水準穩定外，我們還發現接受報銷治療的患者中止治療的情況減少了。

Several switches from our free drug program to reimburse therapy and some later stage appeal wins during the quarter. while none of the quarterly metrics in each of these categories would stand out as a significant change on their own, when taken together, it resulted in a strong quarter.

本季度，我們的免費藥物計劃有數項轉變為報銷治療，並且一些後期上訴也獲得勝利。雖然每個類別的季度指標本身都不會出現重大變化，但綜合起來看，這是一個強勁的季度。

Turning to slide 12. In December, the FDA approved a label expansion for Miri to include children as young as 2 years of age with obesity due to BBS or POMC PCSK1 or leper deficiency. This approval sends a strong message that helps us differentiate the root cause and impact of these rare MC4R pathway diseases.

翻到第 12 張投影片。12 月，FDA 批准擴大 Miri 的標籤範圍，將因 BBS 或 POMC PCSK1 或麻風病缺陷導致肥胖的 2 歲以下兒童也納入其中。此批准發出了強烈的訊息，有助於我們區分這些罕見的 MC4R 路徑疾病的根本原因和影響。

With this insatiable hunger, most patients develop early onset obesity before the age of 5. Obesity in childhood, if left untreated, may lead to severe and long-term health complications. Intervention at a young age can be critical, as treating obesity early can lead to better health outcomes. We are excited about what this label expansion means for patients like Ben and their families.

由於這種無法滿足的飢餓感，大多數患者在 5 歲之前就會出現早發性肥胖症。兒童肥胖如果不加以治療，可能會導致嚴重的長期健康併發症。年輕時介入至關重要，因為早期治療肥胖可以帶來更好的健康結果。我們很高興知道這個標籤擴展對像本這樣的患者及其家人意味著什麼。

Ben was diagnosed with bioluli leper deficiency when he was 2 years old, and up until then, he was seen by approximately 20 different doctors. His mother outlined Ben was constantly crying for food, even when he had a snack in his hand.

本在 2 歲時被診斷出患有 bioluli 麻風病缺乏症，在此之前，他已經看過大約 20 位不同的醫生。他的母親說，本經常哭著要食物，即使手裡拿著零食。

Even though the doctors did not know it, she knew something was not right. Ben enrolled in our phase 3 pediatric trial when he was 3.5 years old, and his BMI went from 36.8 to 30. Ben, who is now on commercial therapy, and his entire family have more freedom now that their lives do not revolve around food. This story is one example of Mire making a positive impact on a young child and his family.

儘管醫生不知道，但她知道有些不對勁。本在 3.5 歲時參加了我們的 3 期兒科試驗，他的 BMI 從 36.8 降至 30。本現在正在接受商業治療，他和他的家人現在的生活不再圍繞著食物，因此擁有了更多的自由。這個故事是米爾對一個小孩和他的家庭產生積極影響的一個例子。

Moving to slide 13. our teams are preparing for a positive outcome in our phase 3 trial in acquired hyperbolic obesity and the next potential launch. Market research to gain insights from physicians, payers, and patients and families is ongoing. We're actively engaging with patient advocacy groups, and our teams are executing physician engagement efforts in 2025. We look forward to sharing more details with you as we progress with potential SDA submission and launch. Now I'll turn the call over to Yann.

轉到投影片 13。正在進行市場研究以獲得醫生、付款人、患者和家屬的見解。我們正在積極與患者權益團體合作，我們的團隊正在 2025 年進行醫生參與工作。我們期待在 SDA 提交和發布方面取得進展，與您分享更多細節。現在我將電話轉給 Yann。

Thank you Jennifer. we are pleased with the growth in the international region for the fourth quarter of 2024 and for the year of 2024. we have achieved access for MCV in more than 15 countries outside the US for patients with POMCLA, BBS, and HO through either reimbursed access or inpatient cells.

謝謝你，詹妮弗。我們對 2024 年第四季和 2024 年國際地區的成長感到滿意。

Germany, with the BBS launch now well established, and France with paid early access programs for BDS and HO remain the main drivers for the region. in Germany, our BBS launch is steady and mirrors the consistent growth pattern of the US, and we continue to expand the number of centers treating BBS patients.

德國的 BBS 推出已非常成熟，而法國則推出了 BDS 和 HO 的付費早期訪問計劃，它們仍然是該地區的主要推動力。在德國，我們的 BBS 推廣工作穩步推進，反映了美國持續的成長模式，並且我們繼續擴大治療 BBS 患者的中心數量。

France is also contributing with both the pre-EA approval paid early access program for HO and the paid early access programs for DBS. We continue to receive positive feedback from the physicians treating patients in France under these programs, specifically, patients with either acquired or congenital hypothalamic obesity are responding well to.

法國也為 HO 的 EA 批准前付費早期訪問計劃和 DBS 的付費早期訪問計劃做出了貢獻。我們不斷收到來自法國透過這些計畫治療患者的醫生的正面回饋，具體來說，患有後天性或先天性下丘腦肥胖的患者反應良好。

Also, like in the US, the marketing authorization for pediatric patients has led to reimbursement for patients as young as 2 years old in many countries, including the UK, Spain, and Italy. today we announced a new strategic partnership in Turkey where there is a significant unmet need. The prevalence rates for rare diseases in general and C and DDS in our case are greater than the rest of Europe, providing us an incremental growth opportunity. Our partner is Tripera Pharma Solutions, an entity very well known to us. We began working with them as a consultancy further back. And recently formalized the new partnership.

此外，與美國一樣，英國、西班牙、義大利等許多國家都已獲得了兒科患者的上市許可，年僅 2 歲的患者也可以獲得報銷。今天，我們宣布與土耳其建立新的戰略合作夥伴關係，該地區存在大量未滿足的需求。罕見疾病的盛行率總體上以及在我們這裡C類和DDS的盛行率都高於歐洲其他地區，這為我們提供了增量機會。我們的合作夥伴是 Tripera Pharma Solutions，一家我們非常熟悉的公司。我們很早就開始以諮詢顧問的身份與他們合作。並最近正式確立了新的合作關係。

Trispera has deep experience in relationship with rare disease community and MC4Rathway disease experts and centers of excellence in Turkey.

Trispera 在與土耳其罕見疾病社群和 MC4Rathway 疾病專家及卓越中心的關係方面擁有豐富的經驗。

Last but not least, in Japan, we are beginning to build out operations in anticipation of success in acquired hypothalamic obesity, with a significant unmet need and a prevalence per capita greater than in the US or in Europe. Japan represents a major opportunity for reason.

最後但同樣重要的一點是，在日本，我們開始開展業務，以期成功治療獲得性下丘腦肥胖症，該疾病存在巨大的未滿足需求，且人均患病率高於美國或歐洲。日本為理性提供了重大機會。

Overall, 2024 has served a foundational year in expanding access to MII across the international region, met with enthusiasm among scientific and medical experts, clinicians, and patient advocacy groups, and recognized MIV as a precision medicine for certain rare neuroendocrine diseases.

總體而言，2024 年是擴大國際地區 MII 覆蓋範圍的基礎之年，受到了科學和醫學專家、臨床醫生和患者權益團體的熱烈歡迎，並被公認為某些罕見神經內分泌疾病的精準醫療。

Thank you Yann. before getting into Q4 and the year end financial results, I want to start with our balance sheet beginning on slide 17. rhythm ended 2024 with $320.6 million in cash and cash equivalents.

謝謝你，Yann。在介紹第四季和年終財務業績之前，我想先從第 17 張投影片開始介紹我們的資產負債表。

We raised gross proceeds of $75 million through the sale of approximately $1.3 million shares of common stock at a weighted average price of $56.30 under our at the market or ATM equity offering program during the fourth quarter of 2024 and continuing into January of 2025. the $320.6 million of cash on hand includes about $40 million of gross proceeds raised in Q4, but not the additional gross proceeds of $35 million raised in January.

我們在 2024 年第四季至 2025 年 1 月期間根據市場或 ATM 股票發行計畫以 56.30 美元的加權平均價格出售了約 130 萬股普通股，籌集了 7,500 萬美元的總收益。

We expect this level of cash to be sufficient to fund planned operations into 2027, well past several meaningful milestones and data readouts, including the pivotal phase 3 data readout and acquired hypothalamic obesity, as well as the data readouts for both the Phase 2 trial of Bivvo Meigon and HO and the Phase 1 Part C study of RM 7,718 and HO. We also anticipate data from the single single site Protter-Willy trial, as well as data from the Phase 3 Eate trial within this time frame.

我們預計這一現金水準足以資助到 2027 年的計劃運營，遠遠超過幾個有意義的里程碑和數據讀數，包括關鍵的 3 期數據讀數和獲得性下丘腦肥胖，以及 Bivvo Meigon 和 HO 的 2 期試驗和 RM 7,718 和 HO 的 1 期 C 部分研究的數據讀數。我們也預計在此時間範圍內獲得單一單點 Protter-Willy 試驗的數據以及第 3 階段 Eate 試驗的數據。

Let's now review the snapshot of the Q4 and full year P&L on slide 18. we pre-announced preliminary un audited revenue from global sales of Osivry in January reporting that net revenue from global sales of Osivy came in at $41.8 million in Q4 and $130.1 million for the full year 2024 as compared to $24.2 million and $77.4 million for the fourth quarter and full year 2023.

現在讓我們回顧一下幻燈片 18 上的第四季度和全年損益表快照。

Gross net in the US remained consistent at about 85% for both the third and fourth quarters of 2024. Cost of sales during the fourth quarter was $3.8 million, or approximately 9% of net product revenue versus 11.5% of net product revenue in the third quarter of 24 and 13. 4% in the fourth quarter of 2023. COGS as a percentage of revenues decreased in part due to capitalized costs associated with higher inventory produced versus products sold in the quarter. The largest component of COGS remains the 5% royalty on Msiri which we paid at IPs. R&D expenses were $41.2 million for the fourth quarter compared to $29.9 million in the fourth quarter of 2023.

2024 年第三季和第四季，美國的毛淨值都維持穩定在 85% 左右。第四季的銷售成本為 380 萬美元，約佔淨產品收入的 9%，而 2024 年第三季為淨產品收入的 11.5%，2023 年第四季為 13.4%。銷貨成本佔收入的百分比下降，部分原因是本季生產的庫存高於銷售的產品，導致資本化成本增加。銷貨成本中最大的部分仍然是我們在 IP 上支付的 Msiri 5% 的特許權使用費。第四季研發費用為 4,120 萬美元，而 2023 年第四季為 2,990 萬美元。

Sequentially quarter over quarter, we experienced a 9% increase in R&D expenses due to increased costs associated with the ongoing trials of Biv Meigon and RM 718 and the new phase two Semelannoide trial in Prader-Willi, which began this quarter. The year over year increase was primarily due to acquisition costs related to biva Meigon.

與上一季相比，我們的研發費用增加了 9%，這歸因於正在進行的 Biv Meigon 和 RM 718 試驗以及本季開始的 Prader-Willi 新第二階段 Semelannoide 試驗相關成本的增加。年成長主要歸因於與 biva Meigon 相關的收購成本。

That G&A expenses were $38.1 million for the fourth quarter of 24 as compared to $32.4 million for the fourth quarter of 23. sequentially, SG&A expenses increased by almost 8% compared to Q3, primarily driven by increased headcount and marketing costs.

24 年第四季的 G&A 費用為 3,810 萬美元，而 23 年第四季的 G&A 費用為 3,240 萬美元。

For the fourth quarter of 2024, weighted average common shares outstanding were $61.6 million almost $61 million for the full year of 2024. cash used in operations was approximately $19 million for in Q4 and has averaged approximately $28.5 million in the last four quarters.

2024 年第四季，加權平均流通在外普通股為 6,160 萬美元，2024 年全年接近 6,100 萬美元。

Fourth quarter operating expenses included. total stock-based compensation of $10.6 million for the quarter compared to $11 million in the prior quarter. reported GAAP EPS for the fourth quarter was a net loss for basic and diluted share of $0.72, and this includes $0.02 per share from accrued dividends on convertible preferred stock of $1.3 million. As a reminder, this ongoing accrual will be $1.3 million per quarter.

包括第四季的營運費用。本季股票薪酬總額為 1,060 萬美元，上一季為 1,100 萬美元。第四季報告的 GAAP EPS 為基本和稀釋每股淨虧損 0.72 美元，其中包括 130 萬美元可轉換優先股應計股息每股 0.02 美元。提醒一下，該持續應計費用每季將達到 130 萬美元。

Some highlights from the quarter and the year are broken out on slide 19. as mentioned, Q4 revenue from global sales of Miv was $41.8 million. US revenue in the fourth quarter was $31.7 million of that, accounting for 76% of revenue during the quarter.

投影片 19 列出了本季和本年度的一些亮點。我們其中第四季營收為3,170萬美元，佔本季營收的76%。

For the year, US sales accounted for 74% of revenue. as we detailed in January, the sequential quarter over quarter revenue growth of greater than $8 million was evenly split by an increase in the number of US patients on reimbursed therapy, which Jennifer spoke to, and increased inventory stocking during the fourth quarter by our specialty pharmacy. Such inventory moves are not unusual in the fourth quarter of a calendar year.

該年度，美國銷售額佔總收入的 74%。正如我們在一月份詳細說明的那樣，季度環比收入增長超過 800 萬美元，這主要得益於美國接受報銷治療的患者數量的增加（Jennifer 談到了這一點），以及我們專科藥房在第四季度增加的庫存。在一年的第四季度，這樣的庫存變動並不罕見。

Our USA op for 2024 totaled $382.3 million, and that included $39.7 million in stock-based compensation as well as $92.4 million in consideration for the acquisition of the global rights to Dialigon from LGM. for the year, non-gap OpEx came in at $250.2 million, which is at the low end of our $250 million to $270 million guidance range.

我們在 2024 年在美國營運總額為 3.823 億美元，其中包括 3,970 萬美元的股票薪酬以及從 LGM 收購 Dialigon 全球權利的 9,240 萬美元對價。全年非差距營運支出為 2.502 億美元，位於我們 2.5 億至 2.7 億美元指引範圍的低端。

Consistent with years past, we are not giving revenue guidance, but we are offering guidance on non-gap operating expenses. for 2025 we anticipate approximately $285 million to $315 million in non-gap OpEx comprised of non-gap SGNA expenses of $135 to $145 million and non-gap R&D expenses of $150 to $170 million. The overall increase in expected non-gap OpEx for 2025 is due to anticipated increase in the GNA as we grow our organization in preparation for launching in Siri for the treatment of hypothalamic obesity in the United States and subsequently in Europe and Japan.

與過去幾年一致，我們沒有提供收入指導，但提供了非缺口營運費用指導。到 2025 年，我們預計非缺口營運支出約為 2.85 億至 3.15 億美元，其中包括 1.35 億至 1.45 億美元的非缺口 SGNA 費用和 1.5 億至 1.7 億美元的非缺口研發費用。2025 年預期非缺口營運支出整體增加是由於隨著我們組織的發展，為在美國以及隨後在歐洲和日本推出 Siri 治療下丘腦肥胖症做準備，GNA 預計會增加。

Increased R&D spending is anticipated due to ongoing trials and development of Meigon and RM 718 NHO set melanotide in the new Prader-Willy trial and expansion of our medical affairs programs. We believe this increased level of investment in our business will drive long-term growth and shareholder value.

由於在新的 Prader-Willy 試驗中正在進行 Meigon 和 RM 718 NHO 組黑素勝肽的試驗和開發以及我們醫療事務項目的擴展，預計研發支出將增加。我們相信，對我們業務的投資增加將推動長期成長和股東價值。

One final point, we will pay $40 million in cash to LG1 in July 2025. This is the second and final tranche of the license fee for Bivvi Meigon. This payment is included in our cash out guidance, but not our 2025 OpEx guidance, as this amount was recognized as R&D expense in 2024. with that, I'll hand the call back over to David. Thank You.

最後一點，我們將在 2025 年 7 月向 LG1 支付 4,000 萬美元現金。這是 Bivvi Meigon 的第二筆也是最後一筆授權費。這筆款項包含在我們的現金支出指引中，但不包含我們的 2025 年營運支出指引中，因為這筆金額在 2024 年被確認為研發費用。謝謝。

Thanks, Hunter. So hopefully what you've heard is rhythm's in a really good place. We're established commercially and we're growing. We've got exciting developmental programs which all potentially open up significant opportunities for us, and we've significantly strengthen our balance sheet, putting us in a really strong position to execute on what's in front of us. So we feel good about where we are. But that will open it up to Q&A.

謝謝，亨特。所以希望您聽到的是節奏非常好的聲音。我們已經在商業上站穩腳跟，並且正在不斷發展。我們擁有令人興奮的發展計劃，這些計劃都可能為我們帶來重大機遇，並且我們大大加強了我們的資產負債表，使我們能夠真正處於有利地位來實現我們面前的目標。我們對目前的狀況感到很滿意。但這將會引發問答。

Thank you [Operator Instructions] Derek Archila with Wells Fargo. Your line is open.

感謝[操作員指示]富國銀行的 Derek Archila。您的線路已開通。

Hey, good morning and congrats on the progress. Just two questions from us. Just first, could you comment on whether you're going to share the sad mad portion of the RM 718 study separately or will that kind of be wrapped into the second half 25 update with part C? And then just on in Siri's phase 3 trial on HO, I was wondering if you could just remind us the mix of adults and pediatric patients you expect and ultimately will the split be the same in the Japanese cohort. Thanks.

嘿，早上好，祝賀你取得的進展。我們只想問兩個問題。首先，您能否評論一下您是否會單獨分享 RM 718 研究中悲傷瘋狂的部分，或者將其與 C 部分一起包含在下半年 25 更新中？然後就在 Siri 對 HO 的 3 期試驗中，我想知道您是否可以提醒我們您預期的成人和兒科患者的組合，以及最終在日本隊列中的比例是否相同。謝謝。

Yeah, so for the sad, mad piece of it, I think it is likely we will, we don't have specific plans to present that as an independent breakout, so you're right, we'll probably do that in concert with the Part C of that trial. but what I will say about that is it's a little bit of no news for sad mad opportunities, as long as you're progressing, you can assume that things are going well there. So we're we're feel good about where we are with the data that's coming out so far on 718.

是的，所以對於悲傷、瘋狂的部分，我認為我們很可能會這樣做，我們沒有具體的計劃將其作為獨立的突破來呈現，所以你是對的，我們可能會與該試驗的 C 部分一起做這件事。但我要說的是，對於悲傷的瘋狂機會來說，這並不是什麼新聞，只要你在進步，你就可以假設事情進展順利。因此，我們對目前 718 發布的數據感到很滿意。

For phase 3, the HO adult peed split, we did not, the regulators wanted more adults in the trial, so we were very focused on that and we got multiple additional adult centers to participate. We're about 50/50, but like I said, we did not cap the number of pes or adults to lock the number to have it be exactly the same. The split's going to be roughly even 500. next question.

對於第 3 階段，HO 成人小便分組，我們沒有，監管機構希望更多的成年人參與試驗，因此我們非常專注於此，並讓多個額外的成人中心參與。我們的比例大約是 50/50，但就像我說的，我們沒有限制兒童或成年人的數量，而是將數字鎖定為完全相同。分割將大致為 500。

Thank you. Our next question comes from Seamus Fernandez with Guggenheim Securities. Your line is open.

謝謝。下一個問題來自古根漢證券公司的 Seamus Fernandez。您的線路已開通。

Oh, thanks so much for the question. So, David, you're emphasizing a lot the market opportunity NHO being quite firm at the, sort of 5,000 to 10,000 patient range, interested to get a sense of, with success, how you would see uptake in that population just more identifiable.

哦，非常感謝您的提問。所以，大衛，你強調了 NHO 的市場機會，它在 5,000 到 10,000 名患者範圍內相當穩固，你感興趣的是了解，如果成功的話，你如何看到該人群的接受度更加明顯。

Than the BBS patient population or perhaps even the genetic population, so interested to just get a better understanding there. And then as we've spoken with some thought leaders in the space, there's a little bit of a discussion around sort of the pre-existing obesity set point.

比 BBS 患者群體或甚至遺傳群體更感興趣，只是想在那裡獲得更好的了解。然後，當我們與該領域的一些思想領袖進行交談時，他們會圍繞預先存在的肥胖設定點進行一些討論。

As a, potential contributor because of the hormone replacement dynamics of treatment with selannoide. Just interested to know, if you feel like that could have an impact on the phase 3 HO trial results in any direction given the mix of patients that you just talked about in the phase 3 study. Thanks.

由於使用 selannoide 治療的荷爾蒙替代動力學，因此成為潛在的貢獻者。我只是感興趣地想知道，考慮到您剛才談到的第三階段研究中的患者組合，您是否覺得這可能會對第三階段 HO 試驗結果產生任何影響。謝謝。

Sorry, I didn't quite understand the second question there. So you're saying that the variations in endocrine replacement impact their outcomes.

抱歉，我不太明白第二個問題。所以您的意思是內分泌替代的變化會影響他們的結果。

More than that there was a pre-existing set point prior to the injury and that, it could sort of limit the magnitude of benefits depending on the timing of that injury.

不僅如此，在受傷之前還存在一個預先存在的設定點，並且它可能會根據受傷的時間來限制福利的幅度。

Yeah, let me take that question first. I mean, that's a really interesting question. I think the way, again we're learning, right? When we entered into HO, nothing really worked. Nobody really understood what the underlying biology was, and then, we have this result where essentially every patient who took the drug, a small number of patients, took an MC4 agonist, had a response which suggests that the problem in HO is in fact signaling through this minor cord 4 pathway.

是的，讓我先回答這個問題。我的意思是，這是一個非常有趣的問題。我想，我們又在學習了，對吧？當我們進入 HO 時，什麼都沒有起作用。沒有人真正了解背後的生物學原理，然後，我們得到了這樣的結果：基本上每個服用該藥物的患者，少數服用 MC4 激動劑的患者，都產生了反應，這表明 HO 的問題實際上是通過這條次要的索 4 通路發出信號。

And what I highlighted in my, prepared remarks was, one major difference between the GOP ones and ourselves is we're replacing a deficit. So in a sense, in theory restoring normal physiology, and you know we have examples of that which is, our lean mass, particularly in, teenage boys where you'd expect them to be gaining, muscle mass, they did, they gained well and so I think there's some Support for the idea that we're going to restore your normal physiology and then you are who you are.

我在準備好的發言中強調的是，我們和共和黨之間的一個主要區別是，我們正在彌補赤字。因此從某種意義上說，從理論上講，恢復正常生理機能，你知道我們有這樣的例子，那就是我們的瘦體重，特別是十幾歲的男孩，你期望他們增加肌肉質量，他們也確實增加了，所以我認為有證據支持我們將恢復你的正常生理機能，然後你就是你了。

So back to your question of if you were obese prior to getting your tumor and enveloping your insult, in theory we could get you back to where you were before, but our drug is not a drug for general obesity, so that underlying deficit or your underlying normal physiology aren't likely to be impacted. So I think that is true. And I think what we've talked about internally and with experts and the like is our hope, and we have some anecdotal evidence of this is we'd like to get you back to where you were before your injury.

所以回到你的問題，如果你在患有腫瘤和包裹性損傷之前就已經很肥胖，理論上我們可以讓你恢復到以前的狀態，但我們的藥物不是針對一般肥胖的藥物，所以潛在的缺陷或你潛在的正常生理機能不太可能受到影響。所以我認為這是真的。我認為我們內部以及與專家等人討論的是我們的希望，我們有一些軼事證據證明這一點，我們希望讓您恢復到受傷前的狀態。

I think that's a very reasonable expectation, and that would be a huge restoration of health. So hopefully that answered the question okay. And then on the uptake side of this, yeah, we're not guiding and also I mean as Jennifer said we're early here.

我認為這是非常合理的期望，這將是一次巨大的健康恢復。希望這能回答這個問題。然後就這個方面的吸收而言，是的，我們沒有指導，而且我的意思是，正如珍妮佛所說，我們在這裡還為時過早。

We're learning along with all of you, as we do our own research and the like. What we can say is this is fundamentally different than BBS, meaning, so yes, we expect a different uptake than we saw with BBS. These patients as we've highlighted are We know concentrated in an endocrino point.

我們和大家一起學習，做自己的研究等等。我們可以說的是，這與 BBS 有著根本的不同，也就是說，是的，我們預期其吸收量與 BBS 不同。正如我們所強調的，這些患者集中在內分泌點。

The reason they're concentrated in the endocrinologicol point is because the vast majority, 80-85% of these patients have pituitary insufficiency, and they need to be managed by an endocrinologist to make sure that that aspect of their health is being appropriately managed.

他們之所以集中在內分泌科，是因為絕大多數（80-85％）的患者患有腦下垂體功能不全，需要由內分泌科醫生進行管理，以確保他們的健康狀況得到適當的管理。

And that's also especially where they recognize this entity. So concentrated, larger number of patients, higher percentage diagnosed. All of that will lead to a faster uptake. Now that said, counterbalancing that, which is always true, this isn't you write a script and you go to your local pharmacy. So it's not going to launch like some drugs do.

這也是他們特別認可這個實體的地方。如此集中，患者數越多，診斷比例就越高。所有這些都將促進更快的吸收。話雖如此，但要平衡這一點，這始終是正確的，這不是你寫一個腳本然後去你當地的藥房。因此它不會像某些藥物那樣上市。

We'll have prior authorization. We'll still have to go through, the reimbursement challenges that we have. It's a, we're not changing the price, so it's still going to be, priced at a level where, payers are going to be looking at it carefully. That said, we've been encouraged by the feedback from payers initially, and so we expect that to go well, but those are balancing factors that are, what causes us to be a little bit different from maybe a more easily accessible specialty opportunity. great, thanks so much.

我們將獲得事先授權。我們仍需要克服報銷方面的挑戰。我們不會改變價格，因此價格仍將維持在付款人會仔細查看的水平。也就是說，我們最初受到付款人的回饋的鼓舞，因此我們預計一切都會順利，但這些都是平衡因素，導致我們與更容易獲得的專業機會略有不同。太好了，非常感謝。

Thank you. Our next question comes from Phil Nadeau with TD Cowen, your line is open.

謝謝。我們的下一個問題來自 TD Cowen 的 Phil Nadeau，您的電話線暢通無阻。

Good morning. Thanks for taking our questions too from us as well, diving into the HO pivotal data a bit more deeply in your prepared remarks, you said you expect Se Melannoide to do well on the primary point. I'm sure the question we're going to get from investors is what does management think well is, I guess, in the spectrum of 5% weight loss.

早安.也感謝您回答我們的問題，在您準備好的發言中更深入地探討了 HO 關鍵數據，您說您希望 Se Melannoide 在主要觀點上表現出色。我確信投資人會問我們這樣的問題：管理層認為在 5% 的減重範圍內，減重效果會如何？

which is the regulatory hurdle to 25% BMI reduction, which is what you saw in the The long term extension kind of where in that in that spectrum is quote well. That's the first question then second one for Hunter in terms of Q1 trends, just trying to assemble all the data points you gave us it sounds like there was $4 million of inventory bill in Q4. Is that likely to be destocked in Q1 and therefore is a modestly down quarter of a quarter possible or is that going to be absorbed in the channel and bled out more slowly?

這是將 BMI 降低 25% 的監管障礙，這也是您在長期延伸中看到的，在那個範圍內引用得很好。這是第一個問題，然後是第二個問題，關於 Hunter 就第一季的趨勢而言，只是試圖匯總您提供給我們的所有數據點，聽起來第四季度的庫存賬單為 400 萬美元。是否有可能在第一季去庫存，因此可能出現季度小幅下滑，還是會被通路吸收，流失得更慢？

Thanks. So I'll take the second question first, and I would say yes, we absolutely anticipate the destocking to occur in this quarter. so, you know how it is, Phil. I mean, one for all companies like us, especially when you have a single specialty pharmacy, can always be a little wonky.

謝謝。所以我先回答第二個問題，我的回答是，是的，我們絕對預期本季將出現去庫存現象。所以，你知道情況是怎麼樣的，菲爾。我的意思是，像我們這樣的眾包公司，特別是當你只有一家專科藥局時，總是會有點不穩定。

Yeah, got it. thank you., and, so the question of what does management think our percent change? I mean, the reason, and as I highlighted, we've had this question in a sense endlessly, and it's understandable, and I tried to highlight that I think it's coming to a large extent out of how we've all been conditioned by the GOP-1 world and you know this world's fundamentally different and TRY to give you some examples as to why. Those comparisons are challenging.

嗯，明白了。謝謝。我的意思是，原因正如我所強調的，我們在某種意義上一直在問這個問題，這是可以理解的，我試圖強調的是，我認為這在很大程度上源於我們都受到了 GOP-1 世界的影響，而你知道這個世界從根本上是不同的，我試著給你一些例子來解釋原因。這些比較具有挑戰性。

So that said, what do we know? We know that in a small number of patients in phase two and then the, this early experience in France and France, essentially everybody's taken the drug has responded well. And we know that the average numbers are 20% less at one year and for both of those groups.

那麼，我們知道什麼呢？我們知道，在第二階段的少數患者中，以及在法國和法國的早期經驗中，基本上每個服用該藥物的患者都反應良好。我們知道，一年後這兩個群體的平均數字都會減少 20%。

We also know that we have patients who I gave you the example of the 24-year-old who at 16 weeks, right, he lost more subsequently, but at 16 weeks, had lost less on a% basis than a very light, a much lighter individual who lost a larger percent of his BMI, but, a smaller overall absolute amount. So those are just variables that are really hard to predict.

我們也知道，我之前給你們舉的一個例子就是一個 24 歲的患者，在 16 週時，他隨後減掉了更多體重，但是 16 週時，其減重百分比比一個非常輕的人要少，這個體重輕得多的人雖然 BMI 減重的百分比更大，但是總體絕對量較小。所以這些只是很難預測的變數。

We have a larger number of adults in this trial now. I have no fear, and the adults look like they respond well. I think that was an incredibly powerful part coming out of HO. So this long answer to your question is, I mean what we've said is, 5%'s the regulatory hurdle. We'd be incredibly disappointed if for less than 10%. I feel incredibly good about, I know this drug works. I have, the ability to project, what percent change, we're likely to see becomes much more difficult beyond that.

目前，我們有更多的成年人參與這項試驗。我並不害怕，大人看起來反應也很好。我認為這是 HO 中非常強大的部分。所以對於你的問題的長答案是，我的意思是我們說過 5% 是監管障礙。如果低於 10%，我們會非常失望。我感覺非常好，我知道這種藥有效。我有能力預測我們可能會看到的變化百分比，但這變得更加困難。

Thank you. Our next question comes from Whitney Ijem with Canaccord Genuity, your line is open.

謝謝。我們的下一個問題來自 Canaccord Genuity 的 Whitney Ijem，您的電話是開放的。

Hey guys, thanks for taking the question. I just wanted to follow up on Seamus's question around prevalence in HO and I guess some of the commentary earlier on the call, just around the prevalence numbers that have been quoted, I think largely being based on cranial pharyngioma data. So is there any work that, I mean, I know there's work, so can you speak to any of the work ongoing, in terms of the prevalence that might come from other ideologies including the congenital form?

嘿夥計們，謝謝你們回答這個問題。我只是想跟進 Seamus 關於 HO 患病率的問題，我想早些時候在電話會議上發表的一些評論，只是圍繞所引用的患病率數字，我認為主要是基於顱咽管瘤數據。那麼，有沒有什麼工作，我的意思是，我知道有工作，所以你能談談正在進行的任何工作嗎，就可能來自其他意識形態（包括先天形式）的流行程度而言？

So it's a work in progress, you're hearing increased confidence around those numbers that we put out because, this work is supporting the fact that, we're at least that good we believe, early things which we can highlight, I will say that or aspects of that initial modeling we're looking at we Entered with the assumption that cranial pharyngioma was going to be the majority of cases.

所以這是一項正在進行的工作，您會聽到對我們發布的這些數字越來越有信心，因為這項工作支持了這樣一個事實，即我們至少相信這一點，我們可以強調的早期事情，我想說的是，我們正在研究的初始模型的某些方面，我們假設顱咽管瘤佔大多數病例。

That's not necessarily true. There's clearly many more tumors which are contributing significantly to this population, and so that's coming out of some of this early claims work, which, we'll see where that takes the ultimate numbers.

但事實不一定如此。顯然，還有更多的腫瘤對這一人群的貢獻很大，這是從一些早期索賠工作中得出的結論，我們將拭​​目以待最終的數字。

The other thing was we We did our initial calculation with taking a 20 year period post injury. We know these patients live longer, so if you have your tumor at age 15, you don't die at 35, you tend to live a much longer life.

另一件事是，我們最初的計算是以受傷後 20 年為時段的。我們知道這些病人的壽命更長，所以如果你在 15 歲時患有腫瘤，你不會在 35 歲時死去，你往往會活得更長。

And then seeing that the adults respond well also I think there's, that part of the model we may have been conservative on. So those are things we'll continue to look at and we will come out and update these numbers as we get more confidence there. And the last thing I will say, which I again highlighted briefly in prepared marks, was we're measuring what we can see, what the system can see.

然後看到成年人的反應也很好，我認為，我們可能會對模型的這一部分持保守態度。因此，我們會繼續關注這些事情，並在信心增強後更新這些數字。我要說的最後一件事，我在準備好的標記中再次簡要強調過，就是我們正在測量我們可以看到的東西，系統可以看到的東西。

There's clearly an undiagnosed pool here and you know we talked about injury and it's still way. I mean that's a case report in the world today, and it's way too early to say, maybe it's nothing more than a case report, but I am quite confident that if you have a head injury and you suddenly start gaining weight, nobody's thinking you have acquired hypothalamic obesity. So that's a population that is likely undiagnosed today. that helpful things.

這裡顯然有一個未確診的病例，你知道我們談論過傷病，但情況仍然如此。我的意思是，這是當今世界上的病例報告，現在說還為時過早，也許它只不過是一個病例報告，但我很有信心，如果你頭部受傷並且突然開始體重增加，沒有人會認為你已經患上了下丘腦肥胖症。因此，目前這群人很可能尚未得到診斷。那些有用的東西。

Thank you. Our next question comes from Tazeen Ahmad with Bank of America, your line is open.

謝謝。我們的下一個問題來自美國銀行的 Tazeen Ahmad，您的電話是開放的。

Hi, good morning. Thanks for taking my questions. David, I wanted to ask a little bit more detail about, I know what you said about your thoughts but not really, being able to project. What results you'll get other than knowing that this is an active drug and that it works over time.

嗨，早安。感謝您回答我的問題。大衛，我想問得更詳細一些，我知道你所說的想法，但實際上無法投射。除了知道這是一種活性藥物並且會長期起作用之外，您還會獲得什麼結果？

But what have doctors told you about what they'd like to see in terms of weight loss in order for them to want to be using it right away in HO patients? And then my second is more of a financial one. You completed your ATM, but you do have this HO data set readout coming up very soon. would you rule out doing a cash raise after that data set reads out, assuming that it's positive? Thanks.

但是，醫生告訴您他們希望看到什麼樣的減肥效果，以便他們願意立即在 HO 患者身上使用它？我的第二個問題更多的是與財務有關。您已完成 ATM，但很快就會出現此 HO 資料集讀數。假設該資料集為正值，您是否會排除在現金增加之後進行現金增加的可能性？謝謝。

Yeah, thanks. and can answer that question, of course, but to be H first, we're not asking the doctors that very direct question. Would you use it if we, had a 12% or not use it if it was 12% and you would use it if it was 15% or 18%.

是的，謝謝。當然可以回答這個問題，但首先要說的是 H，我們不會向醫生提出這個非常直接的問題。如果我們有 12%，你會使用它嗎？

What the doctors are telling us is nothing in general works in this. Now we all know there's case reports out there and small series with GLP-1s, and we quoted, I've quoted what some of the doctors have said that you know about 20% of the HO patients will have some response to a GLP-1, and that response tends to be less than 10%,

醫生告訴我們，一般來說，這種病沒有什麼療效。現在我們都知道，目前有關於 GLP-1 的病例報告和小系列研究，我們引用了一些醫生的說法，你知道大約 20% 的 HO 患者會對 GLP-1 產生反應，而這種反應往往不到 10%，

So. I think where the doctors are certainly the doctors who are knowledgeable and, actively understand this problem and following them is if this is approved, labeled, and indicated for this indication, and is anything like our experience to date, it will be an amazing.

所以。我認為，這些醫生肯定是知識淵博、積極理解這個問題並遵循他們的做法的醫生，如果這種藥物得到批准、貼上標籤並表明可用於這種適應症，並且與我們迄今為止的經驗相似，那將是一件了不起的事情。

Difference for these patients today in terms of what they're experiencing experiencing. So I just can't give, I have no idea why, projecting a percent outcome in a clinical trials, of course, incredibly difficult, but I really think it's the wrong question and I think it's not what the majority of doctors who are treating these patients are focused on. They want to know, does it work consistently and does it work better than what they've had in the past.

就今天這些病人所經歷的情況而言，情況有所不同。所以我無法給出答案，我不知道為什麼，預測臨床試驗的百分比結果當然非常困難，但我真的認為這是一個錯誤的問題，而且我認為這不是治療這些患者的大多數醫生所關注的。他們想知道，它是否能持續發揮作用，並且是否比過去的方法更好。

And Tazine, to your second question, and thank you very much for the question. First of all, I'm I'm sure you're hearing and I want to reiterate that we have very high confidence in this data readout that's coming up. And we're at the same time, given the uncertainty of the broader market conditions as well as the vagaries of market reactions to data, we thought it prudent to take, to extend the runway to a period where we didn't absolutely have to do a raise following the data, and we're now in that position and we're very happy to be here and we think it benefits, our overall operational flexibility.

Tazine，關於您的第二個問題，非常感謝您的提問。首先，我相信你們已經聽說了，我想重申一下，我們對即將公佈的數據非常有信心。同時，考慮到更廣泛的市場狀況的不確定性以及市場對數據的反應變化，我們認為明智的做法是，將跑道延長到一個我們不必根據數據絕對加薪的時期，我們現在處於這個位置，我們很高興能在這裡，我們認為這有利於我們的整體運營靈活性。

Our investment program for the coming years is generally associated with Bivvi Meigon and RM 718 and indication expansion, so the need to invest more and the need to raise more will be driven largely by success in those programs, which is exciting. And so we're not in a position today where we would say no, we're done raising money or anything like that.

我們未來幾年的投資計劃通常與 Bivvi Meigon 和 RM 718 以及適應症擴張有關，因此更多投資和更多融資的需求將在很大程度上取決於這些計劃的成功，這是令人興奮的。因此，我們今天還不能說「我們已經籌集了資金」或諸如此類的話。

Having said that, we want to be in a position which we are in where we don't have to do a raise following the rehab.

話雖如此，我們希望在康復之後不必加薪。

Thank you. Our next question comes from Joseph Stringer with Needham & Company, your line is open.

謝謝。我們的下一個問題來自 Needham & Company 的約瑟夫·斯特林格，您的電話線是開放的。

Hi, good morning. Thanks for taking our question. Just on the phase 3 HO trial, the inclusion criteria.

嗨，早安。感謝您回答我們的問題。僅限第 3 階段 HO 試驗，納入標準。

Has slightly different age groups compared to the open label phase 2 where phase 3, it's including 4 to 6 year olds and then also patients older than 40. So, can you describe what impact the inclusion of each of these groups of patients could have on the phase 3 be my primary endpoint both in terms of magnitude of effect and overall data variability.

與開放標籤第 2 階段相比，年齡組略有不同，第 3 階段包括 4 至 6 歲的兒童，也包括 40 歲以上的患者。那麼，您能否描述一下將這些患者分組會對第 3 階段的主要終點產生什麼影響，包括影響程度和整體數據變異性。

Thanks. yeah, no thanks. I none again, and I say that cautiously, meaning that we had patients down to 6. I think the difference between 4 and 6 is negligible. I think, the 4 year old will do as well as the 6-year-old. the French data was incredibly helpful. hese were the 8 adult patients we reported out at Toss. They had, if you tremember, they had a mean age of 30, so some were significantly older than 30, and on average they were 11 years out from their insults. So that provided.

謝謝。是的，不用了，謝謝。我再也沒有說過，而且我謹慎地說，這意味著我們的病人減少到 6 人了。我認為 4 和 6 之間的差異可以忽略不計。我認為，4 歲的孩子會做得和 6 歲的孩子一樣好。法國的數據非常有用。這些就是我們在托斯報告的8名成年患者。如果你還記得的話，他們的平均年齡為 30 歲，有些人的年齡明顯超過 30 歲，而且平均而言，他們受到侮辱後已 11 年。所以提供了。

Strong support for this concept that it isn't a problem that only works if you can, get it in in the first one to two years post-injury. It really looks like, it doesn't matter how far out you are. Once you've injured your hypothalamus, you're living with impaired signaling to the MC4R, you're living with it. And if we can intervene with an MC4 hour agonist, then we've got a good chance of helping those people. So I don't think either end of the spectrum is going to have any impact on how we're going to do.

強烈支持這個概念，即這不是一個只有你能解決的問題，在受傷後的一到兩年內解決它。看起來，無論你離得有多遠都並不重要。一旦下丘腦受傷，您向 MC4R 發送的信號就會受損，您必須忍受它。如果我們可以使用 MC4 小時激動劑進行幹預，那麼我們就有很大的機會幫助這些人。因此我認為，無論是哪一種情況，都不會對我們的工作產生任何影響。

And one other thing I'm just going to offer up because I know people are appropriately focused on sort of what could the percent change be. Another thing to remember is in that phase 2 trial, the patient who did least well at 16 weeks, meaning they had about a 4% decrease in their BMI, that was the only patient who took the drug who did not lose 10% or more was on track to lose 10% or more by 16 weeks.

我還要提供另外一件事，因為我知道人們非常關注百分比變化可能是多少。還有一件需要記住的事情是，在第 2 階段試驗中，第 16 週時表現最差的患者，即他們的 BMI 下降了約 4%，也是唯一一位服用該藥物且體重沒有減輕 10% 或更多的患者，預計在 16 週時減輕 10% 或更多。

That patient, when you looked like they were the least good responder, when you looked at the DEXA scan, they had like a 20+% increase in their lean body mass and a 15% decrease in their fat mass. So from a health response standpoint, arguably that was one of our best responders. So again, back to this idea that we're replacing a deficit, restoring more normal physiology, and allowing you to, do what you should do. So teenage boys should put on lean muscle mass. Other groups will behave differently. That help, Joey? thank you.

那個病人，當你看起來他們的反應最差時，當你查看 DEXA 掃描時，他們的瘦體重增加了 20% 以上，而脂肪量減少了 15%。因此，從健康反應的角度來看，可以說這是我們最好的反應之一。所以，再次回到這個想法：我們正在彌補缺陷，恢復更正常的生理機能，並允許你做你應該做的事情。因此，青少年男孩應該增加肌肉質量。其他團體則會有不同的表現。這樣有幫助嗎，喬伊？謝謝。

Our next question comes from Leland Gershell with Oppenheimer, your line is open.

我們的下一個問題來自 Oppenheimer 的 Leland Gershell，您的電話線是開放的。

Hey, good morning. Thanks for the update, and we have two questions. First, I just want to ask, it's early days, but since the label expansion to younger just want to see to what extent expansion of the younger ages is becoming a component of commercial uptake and then also want to ask as you look to enroll patients with Congenital, HO if you could just review with us kind of maybe the similarity in governs in the way those patients are identified, versus your other historical congenital, genetic therapy.

嘿，早安。感謝您的更新，我們有兩個問題。首先，我想問一下，現在還為時過早，但是由於標籤擴展到更年輕，我只是想看看擴大年輕化在多大程度上成為商業應用的一個組成部分，然後還想問一下，當您尋求招募先天性 HO 患者時，您是否可以與我們一起回顧一下這些患者在識別方式上的相似性，與您歷史上的其他先天性基因治療相比。

Yeah, let me take a second person and then Jennifer can comment on the 26 year old opportunity. So we're learning about the congenital HO opportunity and again this was brought to us by doctors who are following large populations here and what they observed is, patients with this area of the brain not developing appropriately and there's a variety of different syndromes, quote unquote, depending on how they present. But it's clear that there is some percentage of these patients who have obesity, and the very early data in France suggests that some of those patients respond to an MC4R agonist.

是的，讓我換一個人來，然後珍妮佛可以對這個 26 歲的機會發表評論。因此，我們正在了解先天性 HO 的機會，這也是由追蹤大量人群的醫生帶給我們的，他們觀察到，患者的這個大腦區域沒有正常發育，並且有各種不同的綜合症，這取決於他們的表現方式。但很明顯，這些患者中有一定比例患有肥胖症，法國早期的數據表明，其中一些患者對 MC4R 激動劑有反應。

So our challenge, and the literature just is not very helpful here yet, understanding the percent of patients with one of these congenital syndromes who have obesity and then one step further, which is that that obesity is related to hypothalamic impairment.

因此，我們面臨的挑戰以及現有的文獻目前還不是很有幫助，即了解患有這些先天性綜合症的患者中肥胖症患者的百分比，然後再進一步了解，即肥胖與下丘腦功能障礙有關。

And I think the challenge here is unlike an injury setting where you have it before and after, these of course are congenital, they start at birth and they emerge over time. Their pituitary insufficiencies emerge over time. It's not like they're born with a full blown picture. So as obesity might emerge, you can imagine that a doctor looking at that patient wouldn't necessarily connect with you that you have genital syndrome and all your obesity is related.

我認為這裡的挑戰不同於受傷前後都會出現的傷害，這些當然是先天性的，從出生時就開始，並隨著時間的推移而出現。他們的腦下垂體功能不全隨著時間的推移而顯現出來。他們並不是生來就擁有完整的形象。因此，當肥胖症出現時，你可以想像，看著那個病人的醫生不一定會認為你患有生殖器綜合症並且與你所有的肥胖症有關。

In today's world it's equally likely they just think you have obesity on top. So that's our challenge. I think we're going to learn a lot over the next year. like I said, there's a lot of enthusiasm around this as we talk to physicians again, it's a little bit like HO. yes, I have these patients, and yes, I would love to have something to do for them, so very early as you said.

在今天的世界裡，他們同樣可能只是認為你只是肥胖而已。這就是我們的挑戰。我認為我們明年將會學到很多東西。就像我說的，當我們再次與醫生交談時，他們對此表現出很大的熱情，這有點像 HO。是的，我有這些病人，是的，我很樂意為他們做點什麼，所以正如你說的，很早就開始了。

The point about the the potential opportunity for the pediatric expansion. one, I would say that in Q4, really the indication came quite late in the year, so it didn't have an impact in terms of the outline of the revenue that we, released.

關於兒科擴展的潛在機會的要點。首先，我想說的是，在第四季度，這個跡象確實來得相當晚，所以對於我們發布的收入摘要沒有產生影響。

A moving forward, we are very happy to have this as an option for patients who are 2 years of age, and as I outlined during my story around Ben's background, the impact can be significant for these patients. however, we don't feel like it's going to be a significant market opportunity just in terms of significant increase or impact on revenue.

展望未來，我們很高興能為 2 歲的患者提供這一選擇，正如我在講述本的背景故事中所概述的那樣，這對這些患者的影響可能是巨大的。然而，我們認為，僅從收入的大幅增加或影響來看，這不會是一個重大的市場機會。

We are more happy to have this as an additional piece of information that really further differentiates our patient population in terms of the need to be which is shown by the ability to actually get approval for 2 year odds plus so that consistency and differentiation of our patient population and it is what we're really focused on moving forward.

我們更高興有這條額外的訊息，它確實進一步根據需要區分了我們的患者群體，這體現在實際獲得 2 年期批准的能力上，從而保證了我們患者群體的一致性和差異化，這也是我們真正關注的重點。

Great, thank you. next question.

太好了，謝謝。下一個問題。

Thank you. Our next question comes from Dennis Ding with Jefferies, your line is open.

謝謝。我們的下一個問題來自 Jefferies 的 Dennis Ding，您的電話是開放的。

Good morning. This is Anthea on for Dennis. thank you for taking our questions. 2 from us on the upcoming PAHO trial, could you talk a little bit about glip one use at baseline and if drop-ins are allowed throughout the trial and how you anticipate that to impact efficacy? And then on the bio phase two, do you see any read-throughs from the Seaha trial in terms of efficacy as well as enrollment and the adult pediatric fix? thank you very much.

早安.這是丹尼斯的安西婭。感謝您回答我們的問題。 2 關於即將進行的 PAHO 試驗，您能否談談基線時使用 glip one 的情況，以及在整個試驗過程中是否允許隨時使用，以及您預計這會對療效產生什麼影響？那麼在第二階段的生物研究中，您是否看到 Seaha 試驗在療效以及招募和成人兒科修復方面的任何解釋？非常感謝。

Sorry, which phase two trial? Oh, for biva. read through in terms, say it again. What's the question about the day of the trial?

抱歉，哪個第二階段試驗？噢，為了 biva。讀一遍，再說一遍。關於審判當天有什麼問題？

Yes, do you see any read throughs from the seminatlannoide trial in terms of efficacy and then also in terms of enrollment and the adult pediatrics.

是的，您是否看到 seminatlannoide 試驗在療效、入組和成人兒科方面的任何評論？

Yeah, so that's a 28 patient for arms, so seven patients for arm, blinded trial. So no, we have obviously no insight into the efficacy at this point. We didn't restrict it. It's 12 and older, so it's a slightly older population. We need to, we're still developing the pediatric formulation for BIA, which we're making great progress on, and that will be part of our next trial, but we don't have that part of the population. So that's all I can say now about the mix of patients.

是的，這是一項有 28 名患者參與的試驗，每組有 7 名患者參與，是盲法試驗。所以不，我們目前顯然還不了解其功效。我們沒有限制它。年齡為 12 歲及以上，因此人口年齡稍大。我們需要，我們仍在開發 BIA 的兒科配方，我們在這方面取得了很大進展，這將是我們下一次試驗的一部分，但我們還沒有那部分人群。關於病人的混合情況我現在能說的就這麼多。

With regard to GLPs in the phase 3 trials, so about 25% of the patients had previously been on a GLI and or were continuing a gli. If they continued a GLP, they could not have had weight loss of 2% or greater in the prior three months. And so you had to be stable on it and you cannot add a new weight loss medication during the trial, and that didn't happen, but that was excluded by protocol.

關於第 3 期試驗中的 GLP，大約 25% 的患者之前曾接受 GLI 治療或正在繼續接受 gli 治療。如果他們繼續進行 GLP，那麼在過去三個月內他們的體重減輕不可能達到 2% 或更多。所以你必須保持穩定，並且在試驗期間不能添加新的減肥藥，而這並沒有發生，但這已被協議排除在外。

Got it thank you.

明白了，謝謝。

Thank you our next question comes from Ram Selvaraju with H.C. Wainwright and Company, your line is open.

謝謝。溫賴特公司，您的路線已開通。

So much for taking my questions and congrats on all the progress recently. I just wanted to ask if You could comment a little bit more on the recent impact of the label expansion for ivy and what specific dynamics you're seeing in the US market regarding patient acquisition, patient adherence, and how that compares to the ex-S experience that you've had since that label has been in place for longer outside of the US. And the second question is, if we think about The Trispera relationship that you have announced.

謝謝您回答我的問題，並祝賀您最近的所有進展。我只是想問一下，您是否可以再多評論一下 Ivy 標籤擴展的近期影響，以及您在美國市場看到的患者獲取、患者依從性方面的具體動態，以及與您在美國以外地區實施時間較長的 ex-S 經驗相比如何。第二個問題是，如果我們考慮您所宣布的 Trispera 關係。

To what extent is this likely to be a template or a model for future relationships in ex-S territories? Is this likely to inform to a significant extent your future ex-USBD activities, or is it very much kind of individualized to the Turkish context? thank you.

這在多大程度上可能成為未來前南地區關係的模板或典範？這是否會對您未來在前 USBD 成員中的活動產生重大影響，還是說這是否很大程度上針對土耳其的具體情況而製定？謝謝。

Yeah, so Jan, can you comment on the your experience, international experience here with 2 to 6? Jennifer just commented on the US and how you see that impacting the overall opportunity and then of course how we think about distributorships and partnerships.

是的，那麼 Jan，您能評論一下您的經驗，2 到 6 歲的國際經驗嗎？珍妮佛剛才評論了美國，以及您認為這對整體機會有何影響，當然還有我們如何看待分銷和合作夥伴關係。

So, yes, thank you. So, pediatric in Europe, so we are now treated patients. younger than 16 in a few countries in France, in Germany, in the UK, and Spain, and we'll continue to see more more of that. As Jennifer said previously, the impact on revenues will not be significant, but the impact for the patients and for the caregivers and also for the the clinicians is is a significant one. So in a nutshell, that's what I can say about the pediatric indication in Europe.

是的，謝謝。所以，在歐洲，我們現在正在治療兒科患者。在法國、德國、英國和西班牙等幾個國家，這一數字已低於 16 歲，我們將繼續看到越來越多的這種情況。正如珍妮佛之前所說，對收入的影響不會很大，但對病人、照護人員以及臨床醫生的影響卻是巨大的。簡而言之，這就是我對歐洲兒科適應症的看法。

And then maybe you can build on this and so the way we think about dishiership, it is country by country. I mean our general approach is to go direct where we can and then be practical and smart about where we need to leverage additional help. So maybe you know I'm just a little bit of thinking behind, the decision to use that distributor in Turkey and how that might, represent or be indicative of our thinking going forward.

然後也許你可以以此為基礎，我們思考菜式的方式是因國而異的。我的意思是，我們的一般方法是盡可能直接地提供幫助，然後採取切實可行的方法並明智地選擇需要額外幫助的地方。所以也許你知道我只是在思考，決定使用土耳其的經銷商，以及這可能如何代表或表明我們未來的想法。

Yes, exactly as you say, David. So I think we choose our approach country by country. Of course, in the main European countries we are direct for some specific territories where we believe that the expertise in the ground is better with partners than what we do and we have done such with medicine in Israel, with joint farm in the Middle East, and now with Tripea in Turkey, and we have I have to say that we have been very happy with these. It was three but no ships.

是的，正如你所說，大衛。所以我認為我們會根據每個國家的具體情況來選擇我們的方法。當然，在歐洲主要國家，我們直接針對一些特定地區，我們認為這些地區的合作夥伴在當地擁有比我們更好的專業知識，我們已經在以色列的醫藥領域、在中東的聯合農場以及現在在土耳其的 Tripea 開展了合作，我不得不說，我們對這些合作感到非常滿意。有三艘，但沒有船。

Great

偉大的

Thank you. Our next question comes from [John Wallabin] with Citizens JMP. Your line is open.

謝謝。我們的下一個問題來自 Citizens JMP 的 [John Wallabin]。您的線路已開通。

Hey, thanks for taking the question. Just wondering, in the phase.

嘿，謝謝你回答這個問題。只是好奇，處於這個階段。

Two.

二。

We did see some patients who dose reduced due to AEs, see a regain of BMI, which, gives us confidence in the drug effect, but wondering in the phase 3 protocol if you're allowing dose reductions for AEs during the 52 week period or if everyone's set after the dose titration period.

我們確實看到一些由於不良反應而減少劑量的患者，BMI 有所恢復，這使我們對藥物效果充滿信心，但我們想知道在第 3 階段方案中是否允許在 52 週期間因不良反應減少劑量，或者每個人在劑量滴定期後是否都已設定。

Yeah, no, good question. I think so the protocol is set so everybody dose escalates to three as tolerated.

是的，不，好問題。我認為協議已經設定好，因此每個人的劑量都會增加到可以耐受的三劑量。

If you can't tolerate it, then you stay a little longer at that dose to hopefully acclimate. Most patients do, and then dose escalate again and or if you truly are having trouble, you can dose decrease. So it's a dosing paradigm that does allow titration to tolerance. Now the vast majority of patients get to the, desired dose at three not everybody's, needed to go to three , and I know this has been a question out there. I do think the HO world's going to end up somewhere between two and three.

如果您無法忍受，那麼您可以繼續服用該劑量一段時間以期適應。大多數患者都會這樣，然後再次增加劑量，或者如果您確實遇到困難，可以減少劑量。因此，這是一種允許滴定至耐受性的劑量範例。現在，絕大多數患者在三天內就能達到所需劑量，但並不是每個人都需要三天，我知道這一直是個疑問。我確實認為 HO 世界最終會處於二和三之間的某個位置。

BBS weighs a little heavier to the three . I think HO will be more firmly in the two to three range, but individual patients, and we had one in the trial who just couldn't tolerate it and ended up stopping the drug, yeah, we may lose some like that, but that's quite uncommon. And again, I'll remind you we've only had, we've had fewer than 10% dropouts in the trials so far, so that. It doesn't seem to be an issue in the phase 3.

BBS 比這三者重一點。我認為 HO 將更穩定地處於兩到三種範圍內，但個別患者，我們在試驗中有一個患者無法耐受該藥並最終停止使用藥物，是的，我們可能會失去一些這樣的患者，但這種情況很罕見。我再次提醒大家，到目前為止，我們在試驗中的退出率不到 10％。這似乎不是第三階段的問題。

Okay, and one more if I may. You talked a little bit about the Vivimegaon and 718 being having less activity at MC1, wondering, can you talk about the relative activity at MC4 between the next gens and Semiennoide? You say, efficacy is kind of TBD if there's going to be a difference there, but you talk about the specificity of the MC4R receptor between those three candidates.

好的，如果可以的話我再說一個。您談到了 Vivimegaon 和 718 在 MC1 上的活動較少，想知道您能談談下一代和 Semiennoide 在 MC4 上的相對活動嗎？您說，如果存在差異，那麼療效還有待確定，但您討論了這三種候選藥物之間 MC4R 受體的特異性。

Yeah, so we, the 718 and set melanitide and in vitro assay is functional looking at, potency are highly similar. We are the potency as it was assessed for vivialigon was done in a different assay. It wasn't done head to head. We're actually running that now. I don't have those full results now, but so I can't comment on that, within the same assay comparison.

是的，所以我們，718 和設定的黑素勝肽以及體外測定功能從功效來看，效力非常相似。我們對 vivialigon 的效力進行了評估，這是透過不同的分析完成的。這並不是面對面的較量。我們實際上現在正在運行它。我現在還沒有完整的結果，但是我無法在相同的分析比較中對此發表評論。

What I can say is the preclinical data, and again it's on a milligram per milligram base, obviously an oral drug, you've got bioabsorption and availability and the like, so a lot of factors. So your dosing is much higher on a milligram basis, obviously, but we can get or they got in an extensive set of models similar results using the dose of biblailigon as we saw with cemlanotide and with, and the doses that are being used in the trial were built off of that understanding. So I think we are likely to be in a therapeutic range, and I'm expecting that we're going to get adequate MC4 agonism across each one of these.

我可以說的是臨床前數據，而且它是以毫克為單位的，顯然是一種口服藥物，有生物吸收和利用度等，所以有很多因素。因此，以毫克為基礎，您的劑量顯然要高得多，但我們可以得到，或者他們在廣泛的模型中使用 biblailigon 的劑量得到類似的結果，就像我們在 cemlanotide 中看到的那樣，並且試驗中使用的劑量是基於這種理解而建立的。因此我認為我們很可能處於治療範圍內，我期望我們將在每一個中獲得足夠的 MC4 激動劑。

Got it. Alright, thanks.

知道了。好的，謝謝。

David. That's helpful. Thank you. I'm sure no further questions at this time. I'd like to turn the call back over to David Meeker when the close your remarks.

大衛。這很有幫助。謝謝。我確信現在沒有其他問題了。當您結束演講時，我想將電話轉回給戴維·米克爾 (David Meeker)。

Okay, well, great, thanks again for tuning in this morning, as you heard, we're excited about where we are and we look forward to our next calls which we'll be updating you on some exciting information.

好的，太好了，再次感謝您今天早上的收聽，正如您所聽到的，我們對目前的狀況感到非常興奮，我們期待著下一次電話會議，我們將向您更新一些令人興奮的信息。

Thanks Pa.

謝謝爸爸。

Thank you for your participation. You may now disconnect. Everyone, have a great day.

感謝您的參與。您現在可以斷開連線。祝大家有個愉快的一天。