Amylyx Pharmaceuticals Inc (AMLX) 2024 Q2 法說會逐字稿

Good morning. My name is Camille, and I will be your conference operator for today. At this time, I would like to welcome everyone to the Amylyx Pharmaceuticals' Second Quarter 2024 Earnings Conference Call. All participants will be on a listen-only mode. After today's presentation, there will be an opportunity to ask questions. (Operator Instructions) Please be advised that this call is being recorded at the company's request.

早安.我叫卡米爾，今天我將擔任你們的會議操作員。現在，我歡迎大家參加 Amylyx Pharmaceuticals 2024 年第二季財報電話會議。所有參與者將處於僅聽模式。今天的演講結束後，將有機會提問。（操作員說明）請注意，本次通話是應公司要求進行錄音的。

I would now like to turn the call over to Lindsey Allen, Head Investor Relations and Communications. Please proceed.

我現在想將電話轉給投資者關係和通訊主管林賽艾倫 (Lindsey Allen)。請繼續。

Good morning and thank you all for joining us today to discuss our second quarter 2024 financial results. With me on the call today are Joshua Cohen and Justin Klee, our co-CEOs, Dr. Camille Bedrosian, our Chief Medical Officer, and James Frates, our Chief Financial Officer.

早安，感謝大家今天加入我們討論我們 2024 年第二季的財務表現。今天與我一起參加電話會議的有我們的聯合執行長 Joshua Cohen 和 Justin Klee、我們的醫療長 Camille Bedrosian 博士以及我們的財務長 James Frates。

Before we begin, I would like to remind everyone that any statements we make or information presented on this call that are not historical facts are forward-looking statements that are based on our current beliefs, plans, and expectations and are made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.

在我們開始之前，我想提醒大家，我們在本次電話會議中所做的任何非歷史事實的陳述或提供的資訊都是前瞻性陳述，這些陳述基於我們當前的信念、計劃和期望，並根據安全資訊做出。

These statements include, but are not limited to, our expectations with respect to Avexitide, AMX0035 and AMX0114, statements regarding regulatory and clinical developments and the impact thereof and the expected timing thereof, and statements regarding our cash runway.

這些聲明包括但不限於我們對 Avexitide、AMX0035 和 AMX0114 的預期、有關監管和臨床開發及其影響及其預期時間的聲明，以及有關我們現金跑道的聲明。

Actual events and results could differ materially from those expressed or implied by any forward-looking statements. You are cautioned not to place any undue reliance on these forward-looking statements, and Amylyx disclaims any obligation to update such statements unless required by law.

實際事件和結果可能與任何前瞻性陳述明示或暗示的事件和結果有重大差異。請您注意不要過度依賴這些前瞻性陳述，除非法律要求，Amylyx 不承擔任何更新此類陳述的義務。

Now, I will turn the call over to Justin.

現在，我將把電話轉給賈斯汀。

Good morning and thank you all for joining us today. As an organization, we have made significant progress over the past few months as part of our continued mission and our goal to deliver important treatment options to the neurodegenerative, neuroendocrine, and endocrine communities we serve.

早安，感謝大家今天加入我們。作為一個組織，我們在過去幾個月中取得了重大進展，這是我們持續使命和目標的一部分，即為我們服務的神經退化性疾病、神經內分泌和內分泌社區提供重要的治療選擇。

Most notably, last month, we expanded our late-stage pipeline with our acquisition of Avexitide and now have three assets targeting orphan indications. Avexitide is a Phase 3 ready asset with FDA breakthrough therapy designation in diseases with no approved treatment options.

最值得注意的是，上個月，我們透過收購 Avexitide 擴大了後期產品線，現在擁有三項針對孤兒適應症的資產。Avexitide 是一種已進入第 3 階段的資產，具有 FDA 突破性療法指定，用於治療尚未批准治療方案的疾病。

Avexitide is a GLP-1 receptor antagonist with orphan drug designation in hyperinfluenemic hypoglycemia. The GLP-1 receptor is one of the key regulators of the glucose insulin response, and an imbalance in this response leads to hyperinfluenemic hypoglycemia, which underlies several conditions and diseases.

Avexitide 是一種 GLP-1 受體拮抗劑，具有治療高流感性低血糖的孤兒藥資格。GLP-1 受體是葡萄糖胰島素反應的關鍵調節因子之一，這種反應的不平衡會導致高流感性低血糖，這是多種病症和疾病的基礎。

So far, Avexitide has been studied in two indications characterized by hyperinfluenemic hypoglycemia, post-bariatric hypoglycemia, or PBH, and congenital hyperinfluenism. The first indication, PBH, is a significant but orphan condition that affects the subpopulation of people who have undergone bariatric surgery.

迄今為止，Avexitide 已在兩種適應症中進行了研究，其特徵是高流感性低血糖、減肥後低血糖或 PBH 以及先天性高流感症。第一個適應症，PBH，是一種重要但罕見的疾病，影響接受過減重手術的人。

Now, let me elaborate a little further on the market opportunity ahead. Despite the introduction of GLP-1 receptor agonists for weight loss, more than 200,000 new bariatric procedures are performed every year, and this number has continued to grow on an annual basis.

現在，讓我進一步詳細闡述未來的市場機會。儘管引入了 GLP-1 受體激動劑來減肥，但每年仍有超過 200,000 例新的減肥手術被實施，並且這個數字每年都在持續增長。

Over the past 10 years, approximately two million people in the United States have undergone the two most common types for weight loss, Roux-en-Y gastric bypass and sleeve gastrectomy. Experts expect surgery to remain a cornerstone of weight loss therapy given the procedure is highly effective and results in substantial and sustained weight loss, particularly for people with higher BMIs. Evidence also suggests that bariatric surgery reduces the risk of cardiovascular events and the severity of metabolic dysfunction associated liver disease.

在過去的 10 年裡，美國大約有 200 萬人接受了兩種最常見的減肥方法：Roux-en-Y 胃繞道術和袖狀胃切除術。專家預計手術仍將是減肥療法的基石，因為手術非常有效，並能實現大幅、持續的體重減輕，特別是對於體重指數較高的人。有證據也表明，減重手術可以降低心血管事件的風險以及與肝病相關的代謝功能障礙的嚴重程度。

Turning to PBH, this persistent condition can develop in people who had received bariatric surgery one to three years prior, and in some cases, even longer post-surgery. We estimate that approximately 8% of the two million people I referenced, or 160,000 people in the US today, have symptomatic PBH.

就PBH而言，這種持續的病症可能發生在那些在一到三年前接受過減肥手術的人身上，在某些情況下，甚至在手術後更長時間。我們估計，在我提到的 200 萬人中，即當今美國的 16 萬人中，約有 8% 患有有症狀的 PBH。

Symptomatic PBH is characterized by hypoglycemic events associated with brain glucose starvation, known as neuroglycopenia, including impaired cognition, loss of consciousness and seizures, as well as activation of the autonomic nervous system, presenting as hunger, sweating, tingling, tremors, palpitations, and anxiety.

有症狀的PBH 的特徵是與腦葡萄糖飢餓相關的低血糖事件，稱為神經血糖減少症，包括認知受損、意識喪失和癲癇發作，以及自主神經系統激活，表現為飢餓、出汗、刺痛、震顫、心悸和焦慮。

People living with PBH could benefit from a treatment that helps stabilize glucose levels, particularly the dangerously low crashes in blood glucose associated with PBH. Camille will discuss our plans for the Phase 3 development program for Avexitide, which we expect to initiate in the first quarter of next year.

患有 PBH 的人可以從有助於穩定血糖水平的治療中受益，特別是與 PBH 相關的危險的低血糖崩潰。卡米爾將討論我們的 Avexitide 第三階段開發計劃，我們預計該計劃將於明年第一季啟動。

There is agreement with FDA on the primary outcome for the pivotal Phase 3 study for PBH. The outcome, reduction in the composite of level two and level three hypoglycemia events is clearly linked to GLP-1 receptor antagonism, and was already met in the Phase 2 and Phase 2B clinical trials of Avexitide and PBH with high significance.

與 FDA 就 PBH 關鍵 3 期研究的主要結果達成協議。結果是，二級和三級低血糖事件的複合減少與 GLP-1 受體拮抗作用明顯相關，並且已經在 Avexitide 和 PBH 的 2 期和 2B 期臨床試驗中得到滿足，具有高度意義。

Camille will also recap the key data, including the statistically significant and clinically meaningful reductions in hypoglycemic events. We are highly encouraged by the greater than 50% reductions in level one, two, and three hypoglycemic events that have been demonstrated by Avexitide. Avexitide has the potential to be the first-in-class GLP-1 receptor antagonist.

卡米爾也將回顧關鍵數據，包括低血糖事件的統計顯著性和臨床意義的減少。Avexitide 所證明的一級、二級和三級低血糖事件減少了 50% 以上，這讓我們深受鼓舞。Avexitide 有潛力成為一流的 GLP-1 受體拮抗劑。

Before I turn it over to Camille, I would like to quickly touch on our cash runway. In the second quarter, we largely completed our restructuring. We expect our cash runway to take us into 2026. Jim will provide additional context.

在將其交給卡米爾之前，我想快速談談我們的現金跑道。第二季度，我們基本上完成了重組。我們預計我們的現金跑道將帶我們進入 2026 年。吉姆將提供更多背景資訊。

I will now turn the call over to Camille.

我現在將把電話轉給卡米爾。

Thanks, Justin. Now I will briefly review each of our four programs, Avexitide and hyperinsulinemic hypoglycemia, including post-bariatric hypoglycemia or PBH, AMX0035 in Wolfram syndrome, and in progressive supranuclear palsy or PSP, and AMX0114 in ALS.

謝謝，賈斯汀。現在我將簡要回顧我們的四個項目，Avexitide 和高胰島素性低血糖，包括減肥後低血糖或PBH、Wolfram 綜合徵中的AMX0035、進行性核上性麻痺或PSP 中的AMX0035，以及ALS 中的AMX0114。

Avexitide is designed to bond to the GLP-1 receptor on pancreatic islet beta cells and block the effect of GLP-1 to mitigate hypoglycemia by decreasing insulin secretion and stabilizing glucose levels. Avexitide has been studied in five clinical trials in PBH.

Avexitide 旨在與胰島β細胞上的 GLP-1 受體結合，並阻斷 GLP-1 的作用，透過減少胰島素分泌和穩定血糖水平來減輕低血糖。Avexitide 已在 PBH 中進行了五項臨床試驗的研究。

Data from these trials demonstrated highly significant reductions in hypoglycemic events. Most notably, the 90 milligram dose, which we intend to study in Phase 3, showed a 66% reduction in level three hypoglycemic events in a Phase 2B trial with a P value of 0.0003 and a 53% reduction in level two hypoglycemic events with a P value of 0.004.

這些試驗的數據顯示低血糖事件顯著減少。最值得注意的是，我們打算在3 期研究的90 毫克劑量顯示，在2B 期試驗中，三級低血糖事件減少了66%，P 值為0.0003，二級低血糖事件減少了53%，P值為0.0003。

The primary efficacy outcome of our Phase 3 program will be the reduction in the composite of level two and level three hypoglycemic events. The FDA has agreed on this primary efficacy outcome.

我們第三階段計畫的主要療效結果將是減少二級和三級低血糖事件的複合。FDA 已就這項主要療效結果達成協議。

Furthermore, these data were achieved while demonstrating a favorable safety profile. The benefit of Avexitide is further supported by four additional trials in PBH, which reproducibly showed glucose stabilization and decreased insulin levels with statistically significant P values.

此外，這些數據是在展示良好的安全性的同時獲得的。Avexitide 的益處得到了 PBH 中另外四項試驗的進一步支持，這些試驗可重複地顯示血糖穩定和胰島素水平降低，且 P 值具有統計意義。

We reviewed these data in-depth during our conference call last month. Based on these data, we are actively planning and are on track to initiate a pivotal Phase 3 program in PBH in Q1 of next year. For those of you who are not familiar with PBH, the condition affects people who have undergone bariatric surgery.

我們在上個月的電話會議上深入審查了這些數據。根據這些數據，我們正在積極規劃，並預計在明年第一季在 PBH 啟動關鍵的第三階段計劃。對於不熟悉 PBH 的人來說，這種情況會影響接受過減肥手術的人。

Symptomatic PBH can have disabling effects on quality of life and ability to live independently, especially the neuroglycopenic symptoms. Imagine you are driving and your blood sugar drops without you realizing it and you have a seizure. As a result, your license could be suspended. Or because you could potentially faint and lose consciousness at any time, you have to move in with a friend or relatives so they can provide immediate assistance or call 911 if you fall and injure yourself.

有症狀的 PBH 會對生活品質和獨立生活能力產生不良影響，尤其是神經低血糖症狀。想像一下，您正在開車，您的血糖在您沒有意識到的情況下下降，並且您癲癇發作。因此，您的執照可能會被暫停。或者，由於您隨時可能暈倒並失去知覺，因此您必須搬去與朋友或親戚住在一起，以便他們可以立即提供幫助，或者在您摔倒並受傷時撥打 911。

Imagine being forced to retire mid-career because you have impaired cognition due to sustained low glucose. These examples are experiences that individuals living with PBH have shared. This is the reality for the 160,000 people that we estimate are currently living with symptomatic PBH.

想像一下，由於持續的低血糖導致認知能力受損，你被迫在職業生涯中期退休。這些例子是 PBH 患者分享的經驗。我們估計目前有 16 萬人患有有症狀的 PBH，這就是現實。

These individuals could benefit from a therapy that might mitigate unexpected or current drops in blood glucose, which can create very problematic health, social and economic issues, despite their best efforts with dietary modifications and off-label use of other medications.

這些人可以從可能緩解意外或當前血糖下降的治療中受益，儘管他們盡了最大努力調整飲食和超說明書使用其他藥物，但血糖下降可能會造成非常嚴重的健康、社會和經濟問題。

We believe the significant unmet need coupled with the robust of Avexitide clinical data in PBH contribute to the excitement about our PBH program among endocrinologists. We will work to enroll participants in our Phase 3 program as promptly as possible, such that we will be in a position to share top line data from the program in 2026.

我們相信，大量未滿足的需求加上 Avexitide 在 PBH 中的可靠臨床數據，使得內分泌學家對我們的 PBH 計畫感到興奮。我們將努力盡快讓參與者加入我們的第 3 階段計劃，以便我們能夠在 2026 年分享該計劃的頂線數據。

Now, turning to the Wolfram syndrome program. We look forward to presenting the top line data for all 12 participants in the Helios trial at week 24, including longer term data available for participants who have reached their week 36 or week 48 visit at that time at the International Society for Pediatric and Adolescent Diabetes Conference this fall. We are engaging with stakeholders, including the FDA and planning for a single Phase 3 clinical trial and we'll provide more details once finalized.

現在，轉向沃爾夫勒姆綜合症計劃。我們期待在第 24 週公佈 Helios 試驗中所有 12 名參與者的主要數據，包括國際兒科和青少年糖尿病協會當時已達到第 36 週或第 48 週就診的參與者的長期數據今年秋天舉行的會議。我們正在與包括 FDA 在內的利害關係人合作，並計劃進行一項 3 期臨床試驗，一旦最終確定，我們將提供更多細節。

As a reminder, AMX0035 has shown highly significant benefits in glycemic control in the in-vivo WSS1 knockout mouse model of Wolfram syndrome. These glycemic results were recapitulated and extended in our clinical trial of Wolfram, including promising data on glycemic, as well as optic and global impressions of change outcomes presented in April.

需要提醒的是，AMX0035 在 Wolfram 症候群體內 WSS1 敲除小鼠模型中顯示出對血糖控制非常顯著的益處。這些血糖結果在我們的 Wolfram 臨床試驗中得到了概括和擴展，包括有希望的血糖數據，以及 4 月提出的變化結果的視覺和整體印象。

Recall the Wolfram syndrome is a progressive neurodegenerative disease. While we had anticipated slowing of this progression, in fact, the data suggested stabilization or even improvement across these outcomes.

回想一下，沃爾夫勒姆症候群是一種進行性神經退化性疾病。雖然我們預期這項進展會放緩，但事實上，數據顯示這些結果趨於穩定甚至有所改善。

Now turning to the Orion PSP program, enrollment in the study is going well. As we have described previously, we intend to conduct an interim analysis of Orion and share data in mid 2025.

現在轉向 Orion PSP 項目，研究的註冊進展順利。正如我們之前所描述的，我們打算在 2025 年中期對 Orion 進行中期分析並共享資料。

I would like to describe the planned analysis in a bit more detail. We have introduced an operationally seamless Phase 2B3 study design. The first part will include approximately 100 people living with PSP. Mid 2025, we plan to conduct an unblinded analysis of top line data through week-24 for these participants. In addition, the available data on participants who have proceeded beyond 24 weeks also will be analyzed.

我想更詳細地描述計劃的分析。我們引入了可操作的無縫 2B3 期研究設計。第一部分將包括大約 100 名 PSP 患者。2025 年中期，我們計劃對這些參與者截至第 24 週的頂線資料進行非盲分析。此外，還將分析 24 週以上參與者的可用數據。

The goal of this analysis is to inform a go no go decision. Strong data will encourage us to move seamlessly into the second portion of the study, whereas mixed or negative data will allow us to reprioritize our resources.

此分析的目的是為「繼續」決策提供資訊。強有力的數據將鼓勵我們無縫地進入研究的第二部分，而混合或負面的數據將使我們能夠重新確定資源的優先順序。

As a reminder, AMX0035 has shown highly significant reductions of tau and CSF in a randomized placebo controlled study in Alzheimer's disease. As we have previously discussed, PSP is a tauopathy with a highly significant genetic link between variance in tau and the disease and with clear tau pathology in human samples. AMX0035 is believed to affect intracellular tau and we believe it is the first agent to be studied in a large trial with the potential to impact intracellular tau pathology.

提醒一下，在一項針對阿茲海默症的隨機安慰劑對照研究中，AMX0035 顯示出 tau 蛋白和 CSF 的顯著減少。正如我們之前討論的，PSP 是一種 tau 蛋白病，tau 蛋白變異與疾病之間存在高度顯著的遺傳聯繫，並且在人類樣本中具有明確的 tau 蛋白病理學。AMX0035被認為會影響細胞內tau蛋白，我們相信它是第一個在大型試驗中進行研究的藥物，有可能影響細胞內tau蛋白病理學。

Finally, our AMX0114 program remains on track. We plan to begin clinical testing before the end of the year. AMX0114 is an antisense oligonucleotide, or ASO, designed specifically to inhibit Calpain-2, a protein involved in axonal degeneration and neurofilament biology.

最後，我們的 AMX0114 專案仍然步入正軌。我們計劃在今年年底前開始臨床測試。AMX0114 是一種反義寡核苷酸 (ASO)，專門設計用於抑制 Calpain-2（一種參與軸突變性和​​神經絲生物學的蛋白質）。

We are planning to study this agent in a multiple ascending dose placebo controlled study in ALF to evaluate the safety and the biological activity of AMX0114. At AMLX, our goal is to significantly impact diseases of unmet need and with these four programs, we believe we are on track to do so.

我們計劃在 ALF 的多劑量遞增安慰劑對照研究中研究該藥物，以評估 AMX0114 的安全性和生物活性。在 AMLX，我們的目標是顯著影響未滿足需求的疾病，透過這四個項目，我們相信我們正在實現這一目標。

I will now turn over the call to Jim. Jim?

我現在將把電話轉給吉姆。吉姆？

Thanks, Camille. Following Phoenix topline results, we restructured quickly, which placed us in a strong cash position and enabled us to focus on our meaningful near-term clinical milestones. We ended Q2 with $309.8 million in cash and investments. As a reminder, we acquired Avexitide in early Q3 for a purchase price of $35.1 million.

謝謝，卡米爾。在鳳凰城的營收結果之後，我們迅速進行了重組，這使我們擁有強大的現金狀況，並使我們能夠專注於有意義的近期臨床里程碑。第二季末，我們擁有 3.098 億美元的現金和投資。提醒一下，我們在第三季初以 3510 萬美元的價格收購了 Avexitide。

As a result of this work, we believe our cash will take us into 2026 and we will work to manage the company through meaningful clinical data readouts, namely the data readout from our Phase 2 Helio, the interim readout from our PSP program, interim clinical data from our AMX0114 program and the readout of top line data from the Avexitide Phase 3 program.

透過這項工作，我們相信我們的現金將帶我們進入2026 年，我們將努力透過有意義的臨床數據讀出來管理公司，即我們的2 期Helio 的數據讀出、我們的PSP 項目的臨時讀出、臨時臨床數據讀出來自我們的 AMX0114 程序的數據以及來自 Avexitide Phase 3 程序的頂線數據的讀出。

Now, turn into other details of our financial results. Net product revenue was negative $1 million for the second quarter due to adjustments to our gross to net revenue reserve estimates. This was mainly driven by adjustments to our estimates for returns once we stopped our sales. Cost of sales were $7.4 million for Q2 compared to $5.6 million for the same period in 2023.

現在，讓我們來看看我們財務表現的其他細節。由於我們對總收入儲備金預測的調整，第二季產品淨收入為負 100 萬美元。這主要是由於我們停止銷售後對退貨估計的調整。第二季的銷售成本為 740 萬美元，而 2023 年同期為 560 萬美元。

Cost of sales this quarter were primarily related to estimated losses on firm commitments under commercial manufacturing and supply agreements for RELYVRIO and ALBRIOZA that were established for future production prior to the results from Phoenix. We do not expect any material COGS moving forward.

本季的銷售成本主要與 RELYVRIO 和 ALBRIOZA 的商業製造和供應協議下的堅定承諾的估計損失有關，這些協議是在 Phoenix 公佈業績之前為未來生產而製定的。我們預計不會有任何實質的銷貨成本。

Research and development expenses were $23.3 million for the quarter compared to $29 million for the same period in 2023. The decrease was primarily due to a decline in payroll and personnel related costs as a result of our restructuring and a decrease in clinical expense due to the outcome of the Phoenix trial.

該季度的研發費用為 2,330 萬美元，而 2023 年同期的研發費用為 2,900 萬美元。減少的主要原因是我們的重組導致工資和人員相關成本下降，以及鳳凰試驗結果導致臨床費用減少。

Selling general and administrative expenses were $21.6 million for Q2 compared to $43.4 million for the same period in 2023. The decrease was primarily due to a decline in payroll and personnel related costs and a decrease in consulting and professional services following our decision to voluntarily discontinue the marketing of RELYVRIO and ALBRIOZA.

第二季的銷售一般和管理費用為 2,160 萬美元，而 2023 年同期為 4,340 萬美元。減少的主要原因是在我們決定自願停止 RELYVRIO 和 ALBRIOZA 的行銷後，薪資和人事相關成本下降以及諮詢和專業服務減少。

Restructuring expense was $22.9 million in the quarter compared to zero for the same period in 2023. The majority of this charge is related to employee severance and termination related benefits that were paid in Q2, and our restructuring plan was largely completed this quarter. Consistent with our prior expectations as we move into 2025, we expect total combined spend on R&D and SG&A will be in the range of $30 million to $40 million in cash per quarter.

本季重組費用為 2,290 萬美元，而 2023 年同期重組費用為零。這筆費用大部分與第二季支付的員工遣散費和解僱相關福利有關，我們的重組計畫已在本季基本完成。進入 2025 年，我們預計研發和銷售及管理費用 (SG&A) 的總合併支出將在每季 3,000 萬美元至 4,000 萬美元的現金範圍內，這與我們先前預期的一致。

Finally, in the second quarter, we recorded a net loss of $72.7 million or $1.7 per share, including the restructuring charges. Overall, we're in a solid financial position and believe in our ability to deliver on the clinical milestones that we outlined today.

最後，在第二季度，我們錄得淨虧損 7,270 萬美元，即每股 1.7 美元，其中包括重組費用。總體而言，我們的財務狀況穩健，並相信我們有能力實現我們今天概述的臨床里程碑。

I'll now turn the call over to Josh to provide some closing remarks.

現在我將把電話轉給喬希，他將發表一些結束語。

Thank you, Jim. In closing, we are excited about our four pipeline programs, upcoming milestones and path ahead. Avexitide has both FDA breakthrough therapy designation and orphan drug designation, and is poised to advance into Phase 3 development in PBH beginning in the first quarter of 2025.

謝謝你，吉姆。最後，我們對我們的四個管道項目、即將到來的里程碑和未來的道路感到興奮。Avexitide 擁有 FDA 突破性療法認定和孤兒藥認定，並準備於 2025 年第一季開始進入 PBH 的 3 期開發。

In Wolfram syndrome, we expect the top line data from Helios in the fall for all 12 participants at week 24, including longer term data available for participants who have reached their week-36 or 48 visits at that time. We are engaging the FDA and other stakeholders and planning for a single Phase 3 clinical trial. We will provide more details on the trial once the design is finalized.

在 Wolfram 症候群中，我們預計秋季 Helios 在第 24 週提供所有 12 名參與者的頂線數據，包括當時已達到第 36 週或第 48 週就診的參與者的長期數據。我們正在與 FDA 和其他利害關係人合作，並計劃進行 3 期臨床試驗。設計完成後，我們將提供有關試驗的更多詳細資訊。

The Orion trial of AMX0035 and PSP is recruiting well, and we continue to expect data from interim analysis mid next year. AMX0114 is on track to be studied in people living with ALS later this year. And we believe we have the team and resources in place to deliver on four meaningful clinical data readouts ahead. We look forward to keeping you updated as we build upon our critical work in orphan neurodegenerative, neuroendocrine and endocrine diseases of high unmet need.

AMX0035 和 PSP 的 Orion 試驗招募情況良好，我們繼續期待明年中期中期分析的數據。AMX0114 預計將在今年稍後在 ALS 患者中進行研究。我們相信，我們擁有適當的團隊和資源，可以在未來提供四個有意義的臨床數據讀數。當我們在孤兒神經退化性疾病、神經內分泌和高度未滿足需求的內分泌疾病方面開展關鍵工作時，我們期待為您提供最新資訊。

Now I would like to open the call up for Q&A.

現在我想開啟問答環節。

(Operator Instructions). Charlie Yang, Bank of America.

（操作員說明）。查理楊，美國銀行。

Great. Thanks for taking my questions. I just wanted to ask about the PSP data in mid next year in terms of the county expectation over there. And then, I was assuming if there's a signal observed -- is there -- I guess, is there a path to make an adjustment to a number of pages as needed to further kind of amplify the potential success of this trial at the final readout?

偉大的。感謝您回答我的問題。我只是想問明年年中的PSP數據，那邊縣的預期是怎麼樣的。然後，我假設是否觀察到一個訊號——是否存在——我猜，是否有一種方法可以根據需要對多個頁面進行調整，以進一步放大最終讀數時該試驗的潛在成功率？

Yeah, thank you, Charlie. This is Camille. As we indicated in our prepared remarks, we will -- the first part of the study is the Phase 2B where we will analyze about 100 participants, unblinded, AMX0035 versus placebo, and do a full-on analysis at 24 weeks. And for those who have gone beyond 24 weeks to look at their longer-term data as well. And based on that result, we will then, if positive and strong, we will proceed seamlessly into the Phase 3 portion of the study. And based on those data, the final sample size will be determined.

是的，謝謝你，查理。這是卡米爾。正如我們在準備好的發言中指出的，我們將——研究的第一部分是2B 階段，我們將分析大約100 名參與者，非盲法，AMX0035 與安慰劑相比，並在24 週時進行全面分析。對於那些已經超過 24 週的人來說，也可以查看他們的長期數據。基於該結果，如果積極且有力，我們將無縫地進入研究的第三階段部分。根據這些數據，將確定最終的樣本量。

Great, thanks. And maybe just one quick follow-up, just in terms of the Wolfram opportunity in Europe, how does that kind of compare to the US? Thank you.

太好了，謝謝。也許只是一個快速的後續行動，就 Wolfram 在歐洲的機會而言，與美國相比如何？謝謝。

Yeah. So we are certainly aware of endocrinologists who are familiar with Wolfram and have a large, relatively speaking, Wolfram population. So -- but right now we are focusing on the US and though we do -- yeah, so more to come on that as we do more research.

是的。因此，我們當然知道熟悉 Wolfram 的內分泌學家，並且相對而言擁有大量 Wolfram 人群。所以——但現在我們關注的是美國，儘管我們確實——是的，隨著我們做更多的研究，還會有更多的關注。

But I would add that, Wolfram being a monogenic disease, we do see people with Wolfram syndrome all around the world. So it is very much a global unmet need.

但我想補充一點，Wolfram 是一種單基因疾病，我們確實在世界各地看到患有 Wolfram 綜合徵的人。因此，這在很大程度上是一個全球性的未滿足的需求。

Gavin Johnson, Goldman.

加文·約翰遜，高盛。

Hey, good morning. This is [Palak] on for Gavin. Two from us on the PSP front, the first being what do prior studies in PSP suggest for placebo and natural history population at the 24-week time point? And then the second was, what are you thinking about in terms of the threshold for futility at the 24-week end point in the interim analysis? Thank you.

嘿，早安。這是加文的[Palak]。我們在 PSP 方面提出了兩個建議，第一個是 PSP 的先前研究對 24 週時間點的安慰劑和自然史人群有何建議？第二個問題是，您對中期分析中 24 週終點無效的閾值有何看法？謝謝。

Yeah. So as you are alluding, in fact, the progression of the disease is actually quite reproducible. There were three relatively large Phase 3 studies in PSP, unfortunately, none of which were showed a benefit of the active ingredient -- active drug, but it did show that there was reproducible deterioration at a relatively similar rate. So we do use that as a basis for understanding and looking at the data coming up.

是的。正如您所提到的，事實上，這種疾病的進展實際上是相當可重複的。不幸的是，PSP 中有三項相對較大的 3 期研究，沒有一項研究顯示出活性成分（活性藥物）的益處，但它確實表明存在以相對相似的速率可重複惡化的情況。因此，我們確實將其用作理解和查看即將出現的數據的基礎。

And as your other question too, on the threshold for futility, this is not a formal futility analysis. We're doing a full evaluation of the data. So we'll be looking at kind of a full top line release, essentially a Phase 2B release when we do that interim analysis.

正如你的另一個問題一樣，關於無效性的門檻，這不是正式的無效性分析。我們正在對數據進行全面評估。因此，當我們進行中期分析時，我們將專注於完整的頂線版本，本質上是 2B 階段版本。

And just highlighting Camille's point as well, when you look at the past larger randomized placebo controlled studies that have been conducted in PSP, the placebo rate is actually quite strikingly consistent, usually at just under a point a month.

也要強調卡米爾的觀點，當你查看過去在 PSP 中進行的更大規模的隨機安慰劑對照研究時，你會發現安慰劑率實際上非常驚人地一致，通常每月不到一個點。

Understood. Thank you.

明白了。謝謝。

Umer Raffat, Evercore.

烏默·拉法特，Evercore。

Hi, good morning. This is [Chinchanau] on for Umer. Thanks for taking our questions. Firstly, for Wolfram syndrome Phase 3 trial, does it need to be placebo controlled? And secondly, for 0114, are you planning to give incremental data update as it progresses? Maybe the timing between Phase 2 Wolfram trial data this fall and the Phase 3 PSP interim next year?

嗨，早安。這是 Umer 的 [Chinchanau]。感謝您回答我們的問題。首先，對於Wolfram症候群3期試驗，是否需要安慰劑對照？其次，對於0114，你們是否計劃在進展過程中進行增量資料更新？也許是今年秋天第二階段 Wolfram 試驗數據與明年第三階段 PSP 中期數據之間的時間安排？

Right. So thank you for the question. This is Camille. Regarding Wolfram, as we indicated in our prepared remarks, we are engaging with stakeholders that include of course the FDA. And once our plans are finalized, we'll share those with you. Just as a reminder, later this fall, we will share data on all 12 participants to 24 weeks and additional longer term data for those individuals who have gone through week-36 and 48.

正確的。謝謝你的提問。這是卡米爾。關於 Wolfram，正如我們在準備好的演講中指出的那樣，我們正在與利益相關者接觸，其中當然包括 FDA。一旦我們的計劃最終確定，我們將與您分享。提醒一下，今年秋天晚些時候，我們將分享所有 12 名參與者至 24 週的數據，以及已經歷第 36 週和第 48 週的個人的其他長期數據。

So we're looking forward to those readouts as well. And then regarding 0114, as we indicated, we are planning to initiate our multiple ascending dose study in individuals with ALS by the end of the year. And as the study progresses, we'll be able to provide more detailed timing and types of data we'll be sharing through 2025.

因此，我們也期待這些讀數。然後，關於 0114，正如我們所指出的，我們計劃在今年年底前針對 ALS 患者啟動多次劑量遞增研究。隨著研究的進展，我們將能夠提供到 2025 年共享的更詳細的時間表和資料類型。

Thank you.

謝謝。

Graig Suvannavejh, Mizuho Financial Group.

Graig Suvannavejh，瑞穗金融集團。

Good morning, everyone. This is Charles [Wayne] for Graig. Thanks for taking our question. We were wondering what type of data will you present at the updated data presentation for Helios? Should we expect it to be similar to the interim readout earlier this year? Thanks.

大家早安。這是格雷格的查爾斯[韋恩]。感謝您提出我們的問題。我們想知道您將在 Helios 的更新資料示範中呈現什麼類型的資料？我們是否應該期望它與今年早些時候的臨時數據類似？謝謝。

Yeah, thank you. This is Camille again. Indeed, so we do intend to provide longer term data for those individuals about whom we reported in April of this year, as well as data through 24 weeks for all 12 participants. Its top line data, primary endpoint and key secondary endpoints. And we look forward to sharing those details with you at the upcoming international meeting.

是的，謝謝。這又是卡米爾。事實上，我們確實打算提供我們在今年 4 月報告的個人的長期數據，以及所有 12 名參與者的 24 週數據。其頂線資料、主要終點和關鍵次要終點。我們期待在即將舉行的國際會議上與您分享這些細節。

Thank you, Graig. Marc Goodman, Leerink Partners.

謝謝你，格雷格。馬克古德曼，Leerink Partners。

Hi, thanks for taking my question. This is [Jujudi] on line for Marc. Can you talk about R&D expenses moving into 2025? What is your strategy to build the pipeline going forward with both internal and external assets? Thanks.

您好，感謝您提出我的問題。我是 Marc 的 [Jujudi]。能談談進入 2025 年的研發費用嗎？您利用內部和外部資產建立未來管道的策略是什麼？謝謝。

Yeah, thank you. It's Jim, good morning. I think one of the things that is happening on our R&D line, right? As our restructuring has occurred and as the large Phoenix Phase 3 winds down, and you can find some detail on those expenses historically in our Qs, that really opens up room for some of the new spending that we have going on. And currently the Wolfram study is ongoing.

是的，謝謝。我是吉姆，早安。我認為我們研發線上正在發生的事情之一，對吧？隨著我們的重組已經發生，隨著大型鳳凰城第三階段的結束，你可以在我們的 Q 中找到歷史上這些支出的一些細節，這確實為我們正在進行的一些新支出開闢了空間。目前 Wolfram 研究正在進行中。

The PSP study is starting to move up into a range where that's going to be consistent as opposed to really growing. And so that leaves us room as we move forward to spend on the 114 study and the new of Avexitide program. And then just overall, as we outlined, we expect cash expense, now that's excluding non-cash comp, to be in the range of $30 million to $40 million a quarter for both R&D and SG&A. So that's how some of the moving parts are going into 2025.

PSP 研究開始進入一個範圍，該範圍將保持一致，而不是真正成長。因此，這為我們在 114 研究和新的 Avexitide 項目上投入資金留下了空間。總體而言，正如我們所概述的，我們預計研發和銷售管理費用每季的現金支出（不包括非現金補償）將在 3,000 萬美元至 4,000 萬美元之間。這就是 2025 年一些變化的情況。

Very helpful. Thanks.

非常有幫助。謝謝。

You're welcome.

不客氣。

Joel Beatty, Baird.

喬爾·比蒂，貝爾德。

Hi, thanks for taking the questions. For the PSP interim analysis to get data around mid 2025, does that mean completing enrollment around the end of this year? And what gives you confidence on the trial completing enrollment around that timeframe?

您好，感謝您提出問題。PSP 中期分析要在 2025 年中期左右獲得數據，這是否意味著在今年年底左右完成註冊？是什麼讓您對試驗在該時間範圍內完成註冊充滿信心？

Yeah, hi Joel, this is Camille. We are enrolling quite well, as I indicated in our prepared remarks, and we're tracking toward having data mid 2025. We'll give more information as we march toward that timeframe.

是的，嗨喬爾，我是卡米爾。正如我在準備好的發言中指出的那樣，我們的註冊情況非常好，我們正在努力爭取在 2025 年中期獲得數據。當我們朝著這個時間表邁進時，我們將提供更多資訊。

Great. And then as a follow-up, do you anticipate any more acquisitions after the recent acquisition of Avexitide?

偉大的。接下來，您預計在最近收購 Avexitide 後還會有更多收購嗎？

Yeah, I'll say we wouldn't -- we've had a process ongoing for some time where we're evaluating many assets for whether they fit well into our pipeline and have the requisite scientific and clinical and commercial path forward. Today, we're very excited about the assets we have today and that's our focus, but we're always looking and I'd say we wouldn't rule out adding additional things to that.

是的，我會說我們不會——我們已經進行了一段時間的流程，我們正在評估許多資產，看看它們是否適合我們的管道，並擁有必要的科學、臨床和商業路徑。今天，我們對我們今天擁有的資產感到非常興奮，這是我們的重點，但我們一直在尋找，我想說我們不會排除添加額外的東西。

Thank you.

謝謝。

Thank you. There are no further questions at this time. I'll turn the call back to Mr. Klee.

謝謝。目前沒有其他問題。我會把電話轉回給克利先生。

Thank you for joining us today on today's call to discuss our second quarter 2024 financial results. Have a great day.

感謝您今天參加我們今天的電話會議，討論我們 2024 年第二季的財務表現。祝你有美好的一天。

Thank you for joining today's call. Please disconnect your line. Thank you.

感謝您參加今天的電話會議。請斷開您的線路。謝謝。