Astria Therapeutics Inc (ATXS) 2022 Q4 法說會逐字稿

Good morning and welcome to the Astria Therapeutics 2022 quarter four and full-year financial results and business update conference call. (Operator Instructions) As a reminder, this call is being recorded and a replay will be made available on the Astria Therapeutics website for 90 days following the conclusion of the event.

早上好，歡迎參加 Astria Therapeutics 2022 年第四季度和全年財務業績和業務更新電話會議。 （操作員說明）謹此提醒，本次通話將會被錄音，並會在活動結束後 90 天內在 Astria Therapeutics 網站上提供重播。

I'd now like to turn the call over to Andrea Matthews, Senior Vice President of Corporate Affairs at Astria Therapeutics. Please go ahead, Andrea.

我現在想將電話轉給 Astria Therapeutics 公司事務高級副總裁 Andrea Matthews。請繼續，安德里亞。

Thank you, operator. Welcome to today's Astria Therapeutics conference call, where we will provide a corporate update and review our fourth quarter and full-year 2022 financial results. With me today are Jill Milne, Chief Executive Officer; Andy Nichols, Chief Scientific Officer; Andrew Komjathy, Chief Commercial Officer; Chris Morabito, Chief Medical Officer; and Noah Clauser, Chief Financial Officer.

謝謝你，接線員。歡迎參加今天的 Astria Therapeutics 電話會議，我們將在會上提供公司最新情況並回顧我們第四季度和 2022 年全年的財務業績。今天與我在一起的有首席執行官吉爾·米爾恩 (Jill Milne)；安迪·尼科爾斯，首席科學官；安德魯·科姆賈西 (Andrew Komjathy)，首席商務官；克里斯·莫拉比托 (Chris Morabito)，首席醫療官；和首席財務官諾亞·克勞瑟。

We issued a press release this morning summarizing our corporate update and our Q4 and full-year 2022 financial results, which we'll reference on today's call. It is available on our website. We are also using slides during today's call that are available within the events and presentations section of the investors part of our website.

我們今天早上發布了一份新聞稿，總結了我們的公司最新動態以及第四季度和 2022 年全年財務業績，我們將在今天的電話會議上參考。它可以在我們的網站上找到。我們還在今天的電話會議中使用幻燈片，這些幻燈片可在我們網站投資者部分的活動和演示部分中找到。

I would like to note that during today's call, as mentioned on slide 2, we will make forward-looking statements related to our business based on current and future expectations that may be considered -- actual results may differ from those indicated, including those discussed in our most recent annual report on Form 10-K, as well as discussions of potential risks, uncertainties, and other important factors in subsequent SEC filings, which will be available on our website. Such statements represent our judgment as of today, and Astria undertakes no obligation to publicly update any forward-looking statements except as required by law.

我想指出的是，在今天的電話會議中，正如幻燈片 2 中提到的，我們將根據可能考慮的當前和未來預期，做出與我們業務相關的前瞻性陳述——實際結果可能與所示結果不同，包括討論的結果我們最新的 10-K 表格年度報告，以及後續向 SEC 提交的文件中對潛在風險、不確定性和其他重要因素的討論，這些內容將在我們的網站上提供。此類陳述代表我們截至今天的判斷，除法律要求外，Astria 不承擔公開更新任何前瞻性陳述的義務。

With that, let me pass the call over to Jill, who will provide a corporate update. Andrew will discuss the HAE market opportunity. Chris will go through the Phase 1a safety and PK results, and the ALPHA-STAR trial; and Andy will discuss the PD data. Noah will follow with the financial update. Jill will then wrap things up. Jill?

接下來，讓我將電話轉接給吉爾，她將提供公司最新情況。 Andrew 將討論 HAE 市場機會。 Chris 將完成 1a 階段安全性和 PK 結果以及 ALPHA-STAR 試驗； Andy 將討論 PD 數據。諾亞將隨後發布財務更新。然後吉爾會把事情包起來。吉爾？

Thank you, Andrea. Good morning, everyone, and thank you for joining us on today's call. Starting on slide 3, Astria, patients are our guiding stars. We're fortunate to be able to hear firsthand from patients living with HAE about their experiences with disease and their hopes for the future during our first-ever STAR-0215 Day last month. As you might expect, on February 15. Jasmine shown here, shared with us her hope to live a life without the burden of frequently administered treatment. Our goal is to fulfill her vision with a product like STAR-0215.

謝謝你，安德里亞。大家早上好，感謝您參加今天的電話會議。從幻燈片 3 開始，Astria，患者是我們的指路明燈。在上個月舉辦的首個 STAR-0215 Day 活動中，我們很幸運能夠直接聽到 HAE 患者講述他們的疾病經歷以及他們對未來的希望。正如您所料，2 月 15 日。這裡展示的 Jasmine 與我們分享了她希望過上沒有頻繁治療負擔的生活。我們的目標是通過 STAR-0215 這樣的產品實現她的願景。

Moving to slide 4, Jasmine helps echo what we have heard from the HAE community. The desire to live without limitations from their symptoms and treatments. Our vision for STAR-0215 is to become the first-choice preventative treatment for HAE with administration every three or six months, with the goal of normalizing the lives of people living with HAE like Jasmine. We believe that by reducing both treatment and disease burden, we can allow patients to focus their time and energy on what matters most to them.

轉到幻燈片 4，Jasmine 幫助回應了我們從 HAE 社區聽到的內容。渴望生活不受症狀和治療的限制。我們對 STAR-0215 的願景是成為 HAE 的首選預防性治療藥物，每三到六個月給藥一次，目標是讓像 Jasmine 這樣的 HAE 患者的生活正常化。我們相信，通過減少治療和疾病負擔，我們可以讓患者將時間和精力集中在對他們最重要的事情上。

Turning to slide 5, here's our planned STAR-0215 early development strategy to execute on this vision. We believe that the HAE treatment paradigm can be transformed with a highly effective every-three-month preventative treatment, like our target profile for STAR-0215. We were able to check the first box here regarding safety, PK, and PD in healthy subjects with the positive results from the Phase 1a trial. We will go into more detail about these results today.

轉向幻燈片 5，這是我們計劃的 STAR-0215 早期開發戰略，以實現這一願景。我們相信，每三個月一次的高效預防性治療可以改變 HAE 治療模式，就像我們 STAR-0215 的目標概況一樣。我們能夠在健康受試者中勾選第一個框，了解 1a 期試驗的積極結果，了解健康受試者的安全性、PK 和 PD。今天我們將更詳細地討論這些結果。

We also see strong interest in the treatment with this profile from both patients and physicians. Currently, we are evaluating the safety and efficacy of STAR-0215 in HAE patients with our ongoing Phase 1b/2 ALPHA-STAR trial. And expect proof-of-concept results in mid-2024. Chris will discuss this trial in more detail.

我們還看到患者和醫生對這種治療方法表現出濃厚的興趣。目前，我們正在通過正在進行的 1b/2 期 ALPHA-STAR 試驗評估 STAR-0215 在 HAE 患者中的安全性和有效性。預計概念驗證結果將在 2024 年中期公佈。克里斯將更詳細地討論這次試驗。

Turning to the right-hand side of this slide, we are also exploring a six-month dosing interval for STAR-0215 as a potential additional option for patients. Additional cohorts in the Phase 1a trial are assessing six-month dosing. Initial results are expected in the fourth quarter of this year. The ALPHA-STAR trial design includes the opportunity to gain initial information on six-month safety and efficacy in HAE patients, and we are learning more about patient and physician interest in a product with this potential profile.

轉向這張幻燈片的右側，我們還在探索 STAR-0215 六個月的給藥間隔，作為患者的潛在額外選擇。 1a 期試驗的其他隊列正在評估六個月的給藥方案。初步結果預計將在今年第四季度公佈。 ALPHA-STAR 試驗設計包括獲得 HAE 患者六個月安全性和療效的初步信息的機會，我們正在更多地了解患者和醫生對具有這種潛在特徵的產品的興趣。

Moving on to slide 6, 2022 was a pivotal year for Astria as we progressed our mission to bring life-changing therapies to patients and families impacted by HAE and rare and niche allergic immunological diseases. Here are the three main points that I would like to emphasize for today's call, we brought STAR-0215 into the clinic and shared positive results from our Phase 1a clinical trial in December. The Phase 1b/2 ALPHA-STAR trial in people living with HAE is underway with initial proof-of-concept results expected in mid-2024.

繼續看幻燈片 6，2022 年對 Astria 來說是關鍵的一年，我們不斷推進我們的使命，為受 HAE 和罕見和小眾過敏性免疫疾病影響的患者和家庭提供改變生活的治療方法。以下是我想在今天的電話會議中強調的三個要點，我們將 STAR-0215 引入臨床，並分享了 12 月份 1a 期臨床試驗的積極結果。針對 HAE 患者的 1b/2 期 ALPHA-STAR 試驗正在進行中，初步概念驗證結果預計將於 2024 年中期得出。

Additionally, we are well-funded to achieve our goals with the closing of an underwritten offering of common stock with gross proceeds of approximately $115 million in December, bringing our expected cash runway through the first half of 2025 based on our current operating plan.

此外，我們有充足的資金來實現我們的目標，12 月完成了普通股承銷發行，收益總額約為 1.15 億美元，根據我們當前的運營計劃，我們的預期現金跑道將持續到 2025 年上半年。

I will now turn the call over to Andrew to talk about the market opportunity. Andrew?

我現在將把電話轉給安德魯，討論市場機會。安德魯？

Thanks, Jill. So as shown on slide 7, the HAE treatment market is substantial and it's growing. The global HAE market was well over $2 billion in 2022 and is expected to grow to $4.2 billion by 2028. This growth is expected to be driven by patients being diagnosed earlier, more patients opting for treatments to prevent HAE attacks, and the expansion of available therapies in more geographic regions. While there are several preventative treatments currently available and in development, we believe that the profile of STAR-0215 as an effective monoclonal antibody plasma kallikrein inhibitor, dosed every three months or less frequently, can address the unmet need in this market and become a leading treatment option for HAE patients.

謝謝，吉爾。正如幻燈片 7 所示，HAE 治療市場規模巨大，而且還在不斷增長。 2022 年，全球 HAE 市場遠超 20 億美元，預計到 2028 年將增長至 42 億美元。這一增長預計將由患者更早診斷、更多患者選擇預防 HAE 發作的治療以及可用治療方案的擴大所推動。更多地理區域的治療。雖然目前有幾種預防性治療方法可供使用和正在開發中，但我們相信 STAR-0215 作為一種有效的單克隆抗體血漿激肽釋放酶抑製劑，每三個月或更少的頻率給藥一次，可以解決該市場未滿足的需求，並成為領先的治療藥物HAE 患者的治療選擇。

Turning to Slide 8. We recently completed a quantitative market research study with over 100 HAE patients where we ask them their willingness to try our product profile, like STAR-0215. As you can see on the graph to the left, all surveyed patients indicated that they were willing to try our product with this profile, and close to 70% being very willing to either start or switch to a product with this profile. These results include patients either on Orladeyo, the only current oral treatment available; and those on the monthly dosing regimen of Takhzyro, also known as lanadelumab, and a current market leader. Although most patients are on the every-two-week regimen.

轉向幻燈片 8。我們最近完成了一項針對 100 多名 HAE 患者的定量市場研究，我們詢問他們是否願意嘗試我們的產品簡介，例如 STAR-0215。正如您在左圖上看到的，所有接受調查的患者都表示他們願意嘗試我們具有此配置文件的產品，並且接近 70% 的患者非常願意開始或切換到具有此配置文件的產品。這些結果包括接受 Orladeyo（目前唯一可用的口服治療）的患者；以及每月服用 Takhzyro（也稱為 lanadelumab）的患者，該藥物是目前的市場領導者。儘管大多數患者採用每兩週一次的治療方案。

We've also been conducting research with HAE prescribers who also expressed a very strong willingness to prescribe treatment with STAR-0215 potential profile, and suggested STAR-0215 would gain strong patient share in a future HAE market; and that's what really excites us with bringing this treatment to the HAE community.

我們還一直在與 HAE 處方醫生進行研究，他們也表示非常願意開具 STAR-0215 潛力的治療處方，並建議 STAR-0215 將在未來的 HAE 市場中獲得強大的患者份額；這正是我們將這種治療方法引入 HAE 社區的真正令人興奮的地方。

I'll now hand it over to Andy to speak about STAR-021's profile. Andy?

現在我將把它交給安迪來談談 STAR-021 的簡介。安迪？

Thanks, Andrew, and good morning, everyone. So turning to slide 9. STAR-0215 was designed with the vision of normalizing the lives of people living with HAE. The goals in our program are twofold: first, to generate a high-potent antibody that could inhibit plasma kallikrein to the same levels as lanadelumab; and second, to engineer an antibody with this long circulating half-life with the potential to prevent HAE attacks with dosing once every three months or even less frequently.

謝謝安德魯，大家早上好。請看幻燈片 9。STAR-0215 的設計初衷是讓 HAE 患者的生活正常化。我們項目的目標有兩個：首先，產生一種高效抗體，可以將血漿激肽釋放酶抑制至與lanadelumab相同的水平；其次，設計一種具有長循環半衰期的抗體，每三個月甚至更低的劑量給藥一次，有可能預防 HAE 發作。

We've demonstrated that STAR-0215 allosterically binds to a unique site on plasma kallikrein to produce potent and selective inhibition of plasma kallikrein activity. STAR-0215 includes weighted-in modifications in the Fc domain, specifically to extend its half-life. The high concentration of our formulation and lack of citric acid enables patient-friendly subcutaneous dosing of STAR-0215, with the goal of significantly less injection-site pain to patients compared with lanadelumab.

我們已經證明，STAR-0215 以變構方式結合到血漿激肽釋放酶上的獨特位點，從而對血漿激肽釋放酶活性產生有效和選擇性的抑制。 STAR-0215 在 Fc 結構域中進行了加權修飾，特別是為了延長其半衰期。我們的配方濃度高且不含檸檬酸，使得 STAR-0215 能夠以患者友好的方式進行皮下給藥，與 Lanadelumab 相比，其目標是顯著減輕患者的注射部位疼痛。

I'll now hand it over to Chris to go through the Phase 1a clinical trial. Chris?

我現在將其交給 Chris 進行 1a 期臨床試驗。克里斯？

Thanks, Andy, and good morning, everyone. Moving to slide 10, we are pleased to review initial data from the Phase 1a trial of STAR-0215 that were recently presented at the AAAAI meeting in February of this year. This is a randomized, double-blind, placebo-controlled trial of single-ascending doses in healthy adult subjects.

謝謝安迪，大家早上好。轉到幻燈片 10，我們很高興回顧 STAR-0215 1a 期試驗的初始數據，這些數據最近在今年 2 月的 AAAAI 會議上公佈。這是一項在健康成年受試者中進行的單次遞增劑量的隨機、雙盲、安慰劑對照試驗。

We have results from the first three cohorts through three months of the approximately eight months total follow-up. We have added two additional cohorts to the Phase 1a trial in healthy subjects to explore the potential of administering STAR-0215 every six months. Cohorts four and five have single doses of 1,200 milligrams subcutaneous, and 600 milligrams IV, respectively. Initial results from these additional cohorts and final results from the first three cohorts are expected in fourth quarter of this year.

我們得到了前三組到大約八個月的總隨訪中三個月的結果。我們在健康受試者的 1a 期試驗中增加了兩個額外隊列，以探索每六個月施用 STAR-0215 的潛力。第四組和第五組的單劑量分別為 1,200 毫克皮下注射和 600 毫克靜脈注射。這些額外隊列的初步結果和前三個隊列的最終結果預計將於今年第四季度公佈。

Turning to Slide 11. These initial data suggest that STAR-0215 is well tolerated and has a favorable safety profile. In total, there were eight subjects with related treatment-emergent adverse events, seven receiving STAR-0215, and one receiving placebo. All treatment-emergent adverse events were mild and resolved. There were no moderate, severe, or serious adverse events. There were six subjects with injection-site reactions, all in subjects receiving STAR-0215. The most common injection-site reaction was injection-site redness. There were no reports of injection-associated pain. As noted, these were all mild and resolved without sequelae.

轉向幻燈片 11。這些初始數據表明 STAR-0215 具有良好的耐受性並具有良好的安全性。總共有 8 名受試者出現了相關的治療相關不良事件，其中 7 名接受 STAR-0215 治療，1 名接受安慰劑治療。所有治療引起的不良事件都很輕微並且已得到解決。沒有出現中度、重度或嚴重不良事件。有六名受試者出現注射部位反應，全部是接受 STAR-0215 的受試者。最常見的注射部位反應是注射部位發紅。沒有註射相關疼痛的報告。如前所述，這些症狀都很輕微並且已得到解決，沒有留下後遺症。

For perspective, the most commonly reported adverse reactions associated with lanadelumab are injection-site reactions; most commonly pain, upper respiratory tract infection, and headache. More than half of lanadelumab-treated subjects reported injection-site reactions with administrations during the Phase 3 trial. Lastly, no treatment-emergent antidrug antibodies were detected with STAR-0215.

從長遠來看，最常見的與lanadelumab相關的不良反應是注射部位反應。最常見的是疼痛、上呼吸道感染和頭痛。超過一半的接受 lanadelumab 治療的受試者在 3 期試驗期間報告了注射部位反應。最後，STAR-0215 沒有檢測到治療引起的抗藥物抗體。

Let's move on now to pharmacokinetic data. Shown on slide 12 are the initial STAR-0215 concentrations over 84 days for the first three cohorts: 100 milligram, 300 milligram, and 600 milligram, given one-time subcutaneously. Note that the profile shows rapid and sustained concentrations over time after a single subcutaneous doses, and that the concentrations are proportional to dose.

現在讓我們繼續討論藥代動力學數據。第 12 張幻燈片顯示了前三組在 84 天內的 STAR-0215 初始濃度：100 毫克、300 毫克和 600 毫克，一次性皮下注射。請注意，該曲線顯示單次皮下給藥後隨時間的推移快速且持續的濃度，並且濃度與劑量成正比。

We can see visually that the elimination phase is long. This long elimination phase as a result of the YTE modification, which is designed to prolong half-life by slowing down drug clearance. Based on these data, the estimated half-life of STAR-0215 is up to 117 days. Importantly, the 300 milligram and 600 milligram profiles showed durable concentration at and above levels, we believe to be consistent with clinical benefit for at least three months.

我們直觀地看到淘汰階段很長。這種長消除期是 YTE 修飾的結果，其目的是通過減慢藥物清除來延長半衰期。根據這些數據，STAR-0215的估計半衰期長達117天。重要的是，300 毫克和 600 毫克的曲線顯示出持久濃度等於或高於水平，我們相信這與至少三個月的臨床益處一致。

Andy will now walk through our pharmacodynamic data that support this, with results consistent with levels associated with clinical benefit. Andy?

安迪現在將介紹支持這一點的藥效學數據，其結果與臨床獲益相關的水平一致。安迪？

Thanks, Chris.

謝謝，克里斯。

So on slide 13, you can see that we assess the pharmacodynamic activity of STAR-0215 and measuring the functional inhibition of plasma kallikrein using assays that are similar to those used by Dyax in a Phase 1 trial of lanadelumab in healthy volunteers. And which allowed them to predict doses that would be effective in reducing HAE attacks.

因此，在幻燈片 13 上，您可以看到我們評估了 STAR-0215 的藥效活性，並使用類似於 Dyax 在健康志願者中進行的 lanadelumab 1 期試驗中使用的檢測方法來測量血漿激肽釋放酶的功能抑制。這使他們能夠預測有效減少 HAE 發作的劑量。

In healthy adult subjects, plasma kallikrein levels are very well. So in order to mimic what happens during an HAE attack, we stimulated the production of plasma kallikrein ex vivo by adding factor XIIa to samples taken from the subjects before at various time points after dosing. The plasma kallikrein that is produced cleaves its natural substrate, high-molecular-weight kininogen that is present in the plasma. And the use the western blot assay technique to measure this cleavage of high-molecular-weight kininogen. As a reminder, using this technique, lanadelumab at 3 milligrams per kilogram or approximately 250 milligrams produced about a 50% reduction in factor XIIa activated cleavage -- high-molecular-weight kininogen in healthy volunteers.

在健康成人受試者中，血漿激肽釋放酶水平非常好。因此，為了模擬 HAE 發作期間發生的情況，我們通過在給藥後不同時間點從受試者採集的樣本中添加因子 XIIa 來刺激離體血漿激肽釋放酶的產生。產生的血漿激肽釋放酶會裂解其天然底物，即血漿中存在的高分子量激肽原。並使用蛋白質印跡測定技術來測量高分子量激肽原的這種裂解。提醒一下，使用這種技術，每公斤 3 毫克或大約 250 毫克的 lanadelumab 可使健康志願者中因子 XIIa 激活的裂解（高分子量激肽原）減少約 50%。

In addition, we've also assessed the inhibition of plasma kallikrein activity using a peptide substrate reporter assay, in which we look at the cleavage of a small three-amino-acid peptide that we add to the plasma. Using this assay format, lanadelumab had the approximately 250-milligram dose in healthy volunteers inhibited factor-XIIa-activated plasma kallikrein activity by about 40%, and this effect was lost 40 days after dosing.

此外，我們還使用肽底物報告測定法評估了血漿激肽釋放酶活性的抑制，其中我們觀察了添加到血漿中的小三氨基酸肽的裂解。使用這種檢測形式，lanadelumab 在健康志願者中的約 250 毫克劑量可將因子 XIIa 激活的血漿激肽釋放酶活性抑制約 40%，並且這種效果在給藥後 40 天消失。

On slide 14, we show that STAR-0215 inhibited plasma kallikrein activity by 40% to 60% in both assay formats out through day 84 for the 300- and 600-milligram doses. The magnitude of this effect in both assays is similar to that produced by lanadelumab in healthy subjects; but consistent with STAR-0215's long half-life, the effect is sustained for a substantially longer period of time compared with lanadelumab. Importantly, the level of activity observed to STAR-0215 is consistent with the level of inhibition of plasma kallikrein shown to prevent HAE attacks with lanadelumab.

在幻燈片 14 上，我們顯示，在第 84 天，300 毫克和 600 毫克劑量的 STAR-0215 在兩種檢測形式中均將血漿激肽釋放酶活性抑制了 40% 至 60%。兩種檢測中這種效應的程度與 lanadelumab 在健康受試者中產生的效應相似；但與 STAR-0215 的長半衰期一致，與 lanadelumab 相比，該效應的持續時間要長得多。重要的是，觀察到的 STAR-0215 活性水平與 lanadelumab 預防 HAE 發作的血漿激肽釋放酶抑制水平一致。

I'll now hand it back to Chris to review the design of our ongoing clinical trial in HAE patients. Chris?

現在我將把它交還給 Chris 來審查我們正在進行的 HAE 患者臨床試驗的設計。克里斯？

Outlined on slide 15, ALPHA-STAR is a dose-ranging, proof-of-concept trial assessing the potential effectiveness of STAR-0215 in long-term prevention of HAE attacks. This trial is assessing the effects of single and multiple doses of STAR-0215 in people living with HAE due to C1-inhibitor deficiency. As a dose-ranging, proof-of-concept trial, the results, if positive, would show robust and durable protection against HAE attacks and inform on dose regimens that may be tested in future trials. All qualifying participants will receive STAR-0215. Initial proof-of-concept data are expected in late 2024.

如幻燈片 15 所示，ALPHA-STAR 是一項劑量範圍概念驗證試驗，評估 STAR-0215 在長期預防 HAE 發作方面的潛在有效性。該試驗正在評估單劑量和多劑量 STAR-0215 對因 C1 抑製劑缺乏而患有 HAE 的患者的影響。作為一項劑量範圍的概念驗證試驗，結果如果是積極的，將顯示出針對 HAE 攻擊的強大而持久的保護作用，並為未來試驗中可能測試的劑量方案提供信息。所有符合資格的參與者都將收到 STAR-0215。預計將於 2024 年底獲得初步概念驗證數據。

As shown here, we are planning to amend the trial to add a new cohort, labeled here as cohort three. That would assess the effects of a subcutaneous dose regimen that targets high initial concentrations to STAR-0215; and that we anticipate would maintain plasma kallikrein inhibitory concentrations consistent with clinical benefit for six months. Results from this cohort, if positive, would assist in dose selection of STAR-0215 for a potential administration every six months.

如圖所示，我們計劃修改試驗以添加一個新隊列，此處標記為第三隊列。這將評估針對 STAR-0215 的高初始濃度的皮下給藥方案的效果；我們預計血漿激肽釋放酶抑制濃度將在六個月內保持與臨床獲益一致。該隊列的結果如果呈陽性，將有助於每六個月潛在給藥一次的 STAR-0215 劑量選擇。

The other two cohorts will remain the same, with the exception that part of the sample size from cohort two would be reallocated to cohort three. While we continue to target enrolling up to 18 subjects, we plan to add flexibility to enroll more participants to cohorts if needed. Cohort one remains a single-dose cohort, administering 450 milligrams once in people with HAE and following for clinical effects out through six months. Cohort two is a multiple-dose cohort, testing a loading dose of 600 milligrams followed by a maintenance dose of 300 milligrams given three months later, and participants will follow through six months after the 300-milligram dose. We anticipate that the effects on HAE attack reduction and people enrolled in these first two cohorts may last for three months or longer.

其他兩個隊列將保持不變，但第二組的部分樣本量將重新分配給第三組。雖然我們繼續以招募最多 18 名受試者為目標，但我們計劃增加靈活性，以便在需要時招募更多參與者。第一組仍然是單劑量組，HAE 患者一次服用 450 毫克，並在六個月內觀察臨床效果。第二組是多劑量組，測試 600 毫克的負荷劑量，然後在三個月後給予 300 毫克的維持劑量，參與者將在 300 毫克劑量後繼續服用 6 個月。我們預計，HAE 發作減少以及參加前兩個隊列的患者的影響可能會持續三個月或更長時間。

The cohort three has two initial 600-milligram doses given one month apart, with participants and follow up for six months after the second dose. Given the PK and PD profile demonstrated in healthy human subjects, it's possible that the clinical results from a dose regimen that targets these anticipated concentrations may endure for six months. The endpoints for the trial including safety, attack rate changes, PK, and PD remain the same.

第三組初始注射兩次 600 毫克劑量，間隔一個月，參與者在第二次注射後隨訪六個月。鑑於在健康人類受試者中展示的 PK 和 PD 特徵，針對這些預期濃度的劑量方案的臨床結果可能會持續六個月。試驗終點包括安全性、發病率變化、PK 和 PD 保持不變。

So far, the trial has initiated in the US and Canada, and we're actively bringing patients into the trial. And we're on track to initiate in Europe, including UK midyear, assuming we seek for regulatory approvals. Data are expected in mid-2024 and are anticipated to include initial results from all three cohorts. The goal is to show significant reduction in HAE attacks following STAR-0215 treatment. We expect these data, if positive, will help us refine our approach to establishing the effectiveness of STAR-0215 as a long-term preventative against HAE attacks, will bring us towards our goal of normalizing the lives of people living with HAE.

到目前為止，該試驗已在美國和加拿大啟動，我們正在積極讓患者參與試驗。假設我們尋求監管部門的批准，我們有望於年中在歐洲（包括英國）啟動。數據預計將於 2024 年中期公佈，預計將包括所有三個隊列的初步結果。目標是顯示 STAR-0215 治療後 HAE 發作顯著減少。我們預計，如果這些數據是積極的，將有助於我們完善方法，確定 STAR-0215 作為長期預防 HAE 攻擊的有效性，使我們實現讓 HAE 患者生活正常化的目標。

Finally, we show on this slide the planned long-term open-label trial. This trial is anticipated to enroll participants from ALPHA-STAR and is expected to start later this year in time for the initial completers of the ALPHA-STAR trial to enroll. We expect this trial to evaluate primarily safety, as well as effects on HAE attack and quality of life.

最後，我們在這張幻燈片上展示了計劃的長期開放標籤試驗。該試驗預計將招募 ALPHA-STAR 的參與者，並預計於今年晚些時候開始，以便 ALPHA-STAR 試驗的最初完成者能夠註冊。我們預計該試驗主要評估安全性以及對 HAE 發作和生活質量的影響。

I will now turn it over to Noah to provide a financial update. Noah?

我現在將其轉交給諾亞，以提供最新的財務信息。諾亞？

Thanks, Chris, and good morning, everyone. Turning to slide 6, patient, I'll provide a brief summary of important financial information.

謝謝克里斯，大家早上好。請耐心閱讀第 6 張幻燈片，我將提供重要財務信息的簡要摘要。

In December 2022, we closed a $115 million underwritten offering of common stock. As of December 31, 2022, we had cash, cash equivalents, and short-term investments of $226.4 million compared to $116.6 million as of September 30. We expect that our cash, cash equivalents, and short-term investments are sufficient to fund our current operating plan through the first half of 2025.

2022 年 12 月，我們完成了 1.15 億美元的普通股承銷發行。截至 2022 年 12 月 31 日，我們的現金、現金等價物和短期投資為 2.264 億美元，而截至 9 月 30 日為 1.166 億美元。我們預計我們的現金、現金等價物和短期投資足以為我們的目前的運營計劃截至 2025 年上半年。

Our net loss was $13.3 million for the fourth quarter of 2022 or $0.72 per share, and $51.8 million for the full-year 2022 or $3.55 per share. As of December 31, we had approximately 27.5 million common shares outstanding, and approximately 33.2 million common equivalent shares outstanding when including our outstanding convertible preferred shares on an as-converted basis. For additional financial information, please see our earnings press release and our 10-K, which we plan to file with the SEC after market today.

2022 年第四季度我們的淨虧損為 1,330 萬美元，即每股 0.72 美元，2022 年全年淨虧損為 5,180 萬美元，即每股 3.55 美元。截至 12 月 31 日，我們已發行約 2,750 萬股普通股，若包括按轉換後的已發行可轉換優先股，則約 3,320 萬股已發行普通股。有關更多財務信息，請參閱我們的收益新聞稿和 10-K，我們計劃今天在盤後向 SEC 提交。

Jill will now review our upcoming milestones and then open the call for questions. Jill?

吉爾現在將回顧我們即將到來的里程碑，然後開始提問。吉爾？

Thank you, Noah.

謝謝你，諾亞。

In summary on slide 17, we were thrilled that STAR-0215 has shown early proof of concept to the Phase 1a trial for its target profiles: a long-acting preventative therapy for HAE, a best-in-class PK profile, and dosing every three months or less frequently. We also believe there could be an opportunity to dose STAR-0215 every six months, and we are evaluating this with cohorts added to our ongoing Phase 1a in ALPHA-STAR trials. Looking to our upcoming milestones, we expect preliminary results from the additional cohorts in healthy subjects, as well as the final results from cohorts one through three in the fourth quarter of this year.

總結幻燈片 17，我們很高興 STAR-0215 已在 1a 期試驗中展示了其目標特徵的早期概念證明：針對 HAE 的長效預防性治療、一流的 PK 特徵以及每個劑量的劑量。三個月或更短的頻率。我們還相信，可能有機會每六個月注射一次 STAR-0215，我們正在對 ALPHA-STAR 試驗中添加到我們正在進行的 1a 期試驗中的隊列進行評估。展望即將到來的里程碑，我們預計健康受試者的其他隊列的初步結果以及今年第四季度第一至第三隊列的最終結果。

As Chris reviewed, the ALPHA-STAR trial in HAE patients is underway with initial results expected in mid-2024 from single and multiple dose cohorts, including the planned third cohort. Additionally, we will plan to initiate a long-term open-label trial in the second half of this year. As we think about the future, we are excited about the potential for STAR-0215 to provide long-acting effective attack prevention for people living with HAE.

正如 Chris 所評論的，針對 HAE 患者的 ALPHA-STAR 試驗正在進行中，單劑量和多劑量隊列（包括計劃的第三隊列）預計將於 2024 年中期獲得初步結果。此外，我們計劃在今年下半年啟動長期開放標籤試驗。當我們思考未來時，我們對 STAR-0215 為 HAE 患者提供長效有效攻擊預防的潛力感到興奮。

Turning to slide 18. Here, we see Jasmine again, this time with Kim, Melissa; and Melissa's daughter, Hannah, all living with HAE, from when they joined us at our offices last month. Speaking with the HAE patient community to better understand their lives and needs guides all that we do at Astria, and we are so thankful to Jasmine, Kim, Melissa, and Hannah, for sharing their experiences with us. We are turning a new path for HAE patients, one that envisions an opportunity for a better quality of life with a long-acting preventative therapy that has meaningful efficacy with infrequent dosing and could fulfill the vision of normalcy that these for patients express.

轉向幻燈片 18。在這裡，我們再次看到 Jasmine，這次是 Kim、Melissa；梅麗莎 (Melissa) 的女兒漢娜 (Hannah) 自從上個月來到我們的辦公室以來，都與 HAE 住在一起。與 HAE 患者社區交談，更好地了解他們的生活和需求，指導我們在 Astria 所做的一切，我們非常感謝 Jasmine、Kim、Melissa 和 Hannah 與我們分享他們的經驗。我們正在為 HAE 患者開闢一條新的道路，即通過長效預防性治療提供更好的生活質量的機會，這種治療在不頻繁給藥的情況下具有有意義的療效，並且可以實現這些患者所表達的正常願景。

Lastly, on slide 19. To recap, 2022 was a pivotal year for Astria as we progressed STAR-0215 into the clinic and share the positive results from our Phase 1a clinical trial in December. The Phase 1b/2 ALPHA-STAR trial is enrolling HAE patients, and we anticipate proof-of-concept results in mid-2024. We are well-funded to achieve our goals with anticipated cash runway through the first half of 2025 based on our current operating plan. We are well positioned to execute on our development plans for STAR-0215 as we aim to allow patients to focus their time and energy on what matters most to them.

最後，在幻燈片 19 上。回顧一下，2022 年對 Astria 來說是關鍵的一年，我們將 STAR-0215 推進到臨床，並分享了 12 月 1a 期臨床試驗的積極結果。 1b/2 期 ALPHA-STAR 試驗正在招募 HAE 患者，我們預計將於 2024 年中期獲得概念驗證結果。根據我們目前的運營計劃，我們資金充足，可以在 2025 年上半年實現預期的現金跑道，實現我們的目標。我們有能力執行 STAR-0215 的開發計劃，因為我們的目標是讓患者將時間和精力集中在對他們最重要的事情上。

With that, I'll ask the operator to open up the call for your questions. Operator, can you please repeat the instructions and poll for questions? Thank you.

之後，我將要求接線員接通您的電話以解答您的問題。接線員，您可以重複一下說明並投票回答問題嗎？謝謝。

(Operator Instructions) Hartaj Singh, Oppenheimer.

（操作員說明）Hartaj Singh，Oppenheimer。

Great. Thank you. I've got a couple of questions. So I'll just ask one -- they're a little different. So I'll just ask one and then follow-up with the second one. You talked about the YTE modification to the antibody and then lack of citrate -- so there is kind of getting into extended follow-up with patients. So just want to ask Andy about, historically, we have YTE modifications over the long term -- produce some side effects you're watching out for -- just anything untoward or not. And again, great presentation on all the data, which I didn't see earlier. So thank you.

偉大的。謝謝。我有幾個問題。所以我只想問一個——他們有點不同。所以我只會問一個，然後跟進第二個。您談到了抗體的 YTE 修飾以及檸檬酸鹽的缺乏——因此需要對患者進行長期隨訪。所以我只想問安迪，從歷史上看，我們對 YTE 進行了長期的修改——會產生一些你需要注意的副作用——是否有任何不良反應。再說一遍，我之前沒有看到過所有數據的精彩演示。所以謝謝。

And thanks Hartaj. So all of the YTE-modified antibodies that have been studied in the clinic, there have been no specific (technical difficulty) of any safety issues associated with the YTE. I recall, it has actually been studied quite extensively in the context of Nirsevimab , the anti-RSV antibody that is used in neonates for the prevention of RSV infection during the RSV season. So nonetheless, to provide six months of coverage. And also in the Evusheld product, which contains two YTE-modified antibodies that for prevention of COVID-19 in high-risk individuals. And there has been no reported safety issues associated with those antibodies. That would lead us to have any concerns about the way to ease specifically.

感謝哈塔傑。因此，所有經過臨床研究的 YTE 修飾抗體，均不存在與 YTE 相關的任何特定（技術難度）安全問題。我記得，實際上已經在 Nirsevimab 的背景下進行了相當廣泛的研究，Nirsevimab 是一種抗 RSV 抗體，用於新生兒在 RSV 季節預防 RSV 感染。儘管如此，還是要提供六個月的保險。 Evusheld 產品中也包含兩種經過 YTE 修飾的抗體，可用於預防高危人群中的 COVID-19。目前還沒有與這些抗體相關的安全問題的報導。這會讓我們對具體的放鬆方式產生任何擔憂。

Great. Thank you, Andy, and then I got a question on just on the commercial side. What we're hearing from companies that we cover and just others is that, suddenly the HAE market is kind of shifting over to a prophylaxis market. Used to be less than 50% prophylaxis and now it's getting close to sort of two-thirds prophylaxis and could increase even to maybe 80%. And then with the orals being introduced, there are more and more patients potentially taking -- being on medication. How do you see in the future -- 215? I know it's early days. Do you really think it's more -- competes against other injectables, or do you think the orals -- which are still looks like once a day and probably will stay there, that they will be fair games also assuming that three-month profile maybe even up to six months? Thank you for the questions.

偉大的。謝謝你，安迪，然後我有一個關於商業方面的問題。我們從我們所報導的公司和其他公司那裡聽到的是，HAE 市場突然轉變為預防市場。過去預防率不到 50%，現在已經接近三分之二的預防率，甚至可能增加到 80%。隨著口服療法的推出，越來越多的患者可能正在接受藥物治療。您如何看待未來——215？我知道現在還為時過早。你真的認為它更多 - 與其他注射劑競爭，或者你認為口服 - 看起來仍然每天一次，並且可能會留在那裡，它們將是公平的遊戲，也假設三個月的概況可能甚至最長六個月？謝謝你的提問。

I can take that. Good morning. So a couple of comments. So you're absolutely right, the preventative market in the US, about two thirds of patients are on a preventative treatment. That percentage is slightly lower or lower in Europe, closer to 40% and 45%. So we do believe that the market will continue to grow with the emergence of new treatments.

我可以接受。早上好。所以有幾點評論。所以你說得完全正確，在美國的預防市場，大約三分之二的患者正在接受預防性治療。歐洲的這一比例略低或更低，接近 40% 和 45%。因此，我們確實相信，隨著新療法的出現，市場將繼續增長。

However, as I mentioned earlier in the presentation, we're really excited about the profile of STAR-0215 -- the potential of being an effective treatment, but also one that reduces the burden of treatment. And 100% of the patients that we surveyed expressed a willingness to either try the product -- so those were patients that were currently not on treatment, or switch to that treatment. And then the subgroups of patients, those that were on either ORLADEYO, or those that were on a monthly treatment of TAKHZYRO, 100% of those patients have expressed an interest in switching to those treatments.

然而，正如我在演講中前面提到的，我們對 STAR-0215 的概況感到非常興奮——它不僅有潛力成為一種有效的治療方法，而且還能減輕治療負擔。我們調查的 100% 患者表示願意嘗試該產品——也就是說，這些患者目前沒有接受治療，或者轉而接受該治療。然後是接受 ORLADEYO 治療或每月接受 TAKHZYRO 治療的患者亞組，其中 100% 的患者表示有興趣改用這些治療方法。

So we do believe that the market will continue to grow. But also, we believe that given the profile of STAR-0215 that we'll be able to successfully switch -- transition patients from either orals or other injectables on to STAR-0215.

因此，我們確實相信市場將繼續增長。而且，我們相信，鑑於 STAR-0215 的特點，我們將能夠成功地將患者從口服或其他注射劑過渡到 STAR-0215。

Great. And you had actually -- I'm sorry, I apologize. I have one follow-up question and I apologize for this. Maybe just a little bit of a shout out to know -- we noticed that your fourth quarter spend was lower than what we expected. And we've been kind of being more cautious in outlook for spend by small-cap biotechs. If you can just talk a little bit about how you see the progression of your OpEx through the rest of the year. And again, thank you for all the questions.

偉大的。而你實際上——對不起，我道歉。我有一個後續問題，對此我深表歉意。也許只是想知道一下——我們注意到你們第四季度的支出低於我們的預期。我們對小型生物技術公司的支出前景更加謹慎。您能簡單談談您如何看待今年剩餘時間內運營支出的進展嗎？再次感謝您提出的所有問題。

Hartaj, I think I point you to our runway guidance, which is that our current cash supports us through all of the first half of 2025, with the understanding that we do expect to have sort of a gradual ramp along the way. So I think without getting into too many specifics about quarter-over-quarter expense, I think a gradual ramp as we ramp up clinical activities is the right way to think about it.

Hartaj，我想我向您指出了我們的跑道指導，即我們當前的現金支持我們度過 2025 年上半年，但我們確實預計在此過程中會有逐步的增長。因此，我認為，在不涉及太多有關季度環比費用的細節的情況下，我認為隨著臨床活動的增加而逐步增加是考慮這個問題的正確方法。

Great. Thank you, Noah. Thanks, everyone.

偉大的。謝謝你，諾亞。感謝大家。

Oliver McCammon, LifeSci Capital.

奧利弗·麥卡蒙，生命科學資本。

Hi, this is Oliver McCammon filling in for Sam Slutsky.

大家好，我是奧利弗·麥卡蒙 (Oliver McCammon) 接替薩姆·斯盧茨基 (Sam Slutsky)。

Just one question from me. For the ongoing Phase 1 study in healthy volunteers, how might the data from the 1,200-milligram subcutaneous and 600-milligram IV cohorts impact your strategy on the future clinical development of 215 versus what is already known from the prior cohorts? Thanks so much for taking my question.

我只想問一個問題。對於正在進行的健康志願者 1 期研究，與先前隊列中已知的數據相比，來自 1,200 毫克皮下注射和 600 毫克 IV 隊列的數據會如何影響您對 215 未來臨床開發的策略？非常感謝您提出我的問題。

Hi, Oliver. This is Chris. Thanks for the question, and it's an important one. The data that we've obtained so far are compelling and suggest that we have the capability with this molecule to achieve a profile that could target of six months administration to people; sufficient enough to prevent attacks in a meaningful way. We have a half-life now that's about four months long and we have no evidence so far of safety signals that would give us pause.

嗨，奧利弗。這是克里斯。感謝您提出這個問題，這是一個重要的問題。迄今為止，我們獲得的數據令人信服，表明我們有能力利用該分子實現對人進行六個月給藥的目標；足以以有意義的方式防止攻擊。我們現在的半衰期大約有四個月長，到目前為止，我們還沒有證據表明安全信號會讓我們停下來。

What we are doing with these additional cohorts is asking the question, can higher concentrations maintain STAR-0215 -- higher initial concentration has maintained STAR-0215 over six months above that critical threshold, which we think at 12 micrograms per mil -- or 80 mil or -- associated with robust target engagement and strong pharmacodynamic activity. We're also asking the question, how well tolerated is administrations of STAR-0215 to achieve these kinds of concentrations.

我們對這些額外隊列所做的事情是提出一個問題，更高的濃度能否維持 STAR-0215——更高的初始濃度使 STAR-0215 在六個月內維持在臨界閾值以上，我們認為該臨界閾值為 12 微克/密耳——或 80 mil 或 - 與強大的目標參與和強大的藥效活性相關。我們還想問一個問題，STAR-0215 達到這些濃度的耐受性如何。

Based on what we've seen so far, I believe we do not need to go up to 1,200 milligrams to achieve a profile that would allow for six-month administration, but the subject in healthy volunteers will give us the upper limit that we can stretch to as we think about how to do so.

根據我們迄今為止所看到的情況，我相信我們不需要達到 1,200 毫克的劑量來達到允許六個月給藥的水平，但健康志願者的受試者將為我們提供上限。當我們思考如何做到這一點時，就會延伸到。

Thank you very much.

非常感謝。

Joe Pantginis, H.C. Wainwright.

喬·潘吉尼斯，H.C.溫賴特。

Hi, everybody, good morning. Thanks for the questions, and thanks for a very efficient call. So just a couple of questions on ALPHA-STAR. So first, as the HAE market grows and getting a little more crowded slowly with the new therapies and therapies that are growing, how do you view -- I mean, it's not a big study, but how do you view additional trials and competition for patients to start with?

嗨，大家早上好。感謝您提出問題，也感謝您的高效通話。我想問幾個關於 ALPHA-STAR 的問題。首先，隨著 HAE 市場的增長，隨著新療法和療法的不斷增長，HAE 市場變得越來越擁擠，您如何看待——我的意思是，這不是一項大型研究，但您如何看待額外的試驗和競爭患者從何入手？

So what we thought deeply about this as we designed ALPHA-STAR -- the operational risk, I think is an important one that we've considered as we thought about the design, obviously about how we're executing the trial. One important element that we consider when talking to physicians and patients is that there is no wide access to medicines that have the potential to be effective. There's also access to additional trials. How can we design this in a way that would allow patients to feel comfort that they're going to get something out of it? So we eliminated the placebo group -- and we've done so using strong science to support the data integrity that we'll get from this.

因此，我們在設計 ALPHA-STAR 時對此進行了深入思考——我認為操作風險是我們在考慮設計時考慮的一個重要因素，顯然是我們如何執行試驗的風險。在與醫生和患者交談時，我們考慮的一個重要因素是，無法廣泛獲得可能有效的藥物。還可以獲得額外的試驗。我們如何設計才能讓患者感到舒適，因為他們將從中得到一些東西？因此，我們消除了安慰劑組，並且我們使用強大的科學來支持我們從中獲得的數據完整性。

And that simple act of eliminating the placebo group has resounded favorably in the community. And optimistically, it will allow for some people who were hesitant to enter a trial, and wait for up to nine months, they would not receive anything but their on-demand therapy, are now thinking about this trial. We've also been working incredibly closely with the HAE physician and patient community. This space is fortunate. And that the advocacy organization that is based in the US with outreaches throughout the world, so the HAEI, is very strong, has an active community, works well with us as a partner; and is helping us think about how to operationalize the study in a way that makes sense for people living with this disease. We've been working with the physician community to understand how to talk with the community about their potential participation.

消除安慰劑組的簡單行為在社區中引起了良好的反響。樂觀的是，這將使一些猶豫是否參加試驗並等待長達九個月的人開始考慮這項試驗，他們除了按需治療外不會接受任何治療。我們還一直與 HAE 醫生和患者群體密切合作。這個空間是幸運的。總部位於美國、業務遍及世界各地的倡導組織 HAEI 非常強大，擁有活躍的社區，作為合作夥伴與我們合作良好；並幫助我們思考如何以對患有這種疾病的人有意義的方式實施這項研究。我們一直在與醫生社區合作，以了解如何與社區討論他們的潛在參與。

And the final point is that it's a global trial with a big footprint. We have -- I think we've now been pretty open about this. We have lots of sites that we're targeting to participate in this trial. And we hope that even if sites find just one patient to potentially participate, that will be able to resolve this in a way that meets our operational guidelines.

最後一點是，這是一項全球性的試驗，影響範圍很大。我認為我們現在對此持相當開放的態度。我們有很多目標網站要參與此試驗。我們希望，即使網站只發現一名患者可能參與，也能夠以符合我們操作指南的方式解決這個問題。

That's very helpful. Thanks. And I guess when you look at these the data you have and the plan that you have for ALPHA-STAR in the long-term dosing intervals, how do you look to present the data and also the potential impact on any statistics you're looking at with the potential or anticipated, albeit small, anticipated needs for the rescue meds?

這非常有幫助。謝謝。我想當您查看這些數據以及長期給藥間隔中 ALPHA-STAR 的計劃時，您會如何呈現這些數據以及對您正在查看的任何統計數據的潛在影響是否滿足對救援藥物的潛在或預期（儘管很小）的需求？

Yes. So what we anticipate is that we'll have proof-of-concept data in mid-2024. And that will include the initial data from all three of these cohorts. So those initial data would be able to communicate what we think would be meaningful for the community. And what we would like to be able to show is that the profile from a safety perspective is favorable that there aren't any additional or unexpected safety findings; that we have robust durable reduction in attacks -- in this case, measured from baseline and change from baseline and attack frequency; that we have PK and PD that's supportive of the clinical and safety findings that we have been describing; and that we have a meaningful and positive impact on quality of life.

是的。因此，我們預計我們將在 2024 年中期獲得概念驗證數據。這將包括所有這三個群體的初始數據。因此，這些初始數據將能夠傳達我們認為對社區有意義的信息。我們希望能夠證明的是，從安全角度來看，情況是有利的，沒有任何額外或意外的安全發現；我們的攻擊持續強勁減少——在本例中，是根據基線以及相對於基線和攻擊頻率的變化來衡量的；我們的 PK 和 PD 支持我們所描述的臨床和安全性發現；我們對生活質量產生了有意義和積極的影響。

This is a disease -- as you know, from other trials. So this is a disease that in proof-of-concept trials using a small sample size allows for a demonstrably meaningful representation of data, typically in Phase 1b/2 trials in this space, cohorts are about four to seven subjects, and that's exactly where we anticipate being here with the option to add more if we need to. The reason for that is that we anticipate a very large effect size. Lanadelumab, [pertuzumab] -- in Phase 3, we're showing about 85% reduction compared to placebo. That size, in terms of change from baseline, allows for a smaller overall sample size. So even with these fewer number of subjects in each cohort, we anticipate being able to demonstrate that this has the potential for meaningful effect for the patients.

正如你從其他試驗中了解到的，這是一種疾病。因此，這種疾病在使用小樣本量的概念驗證試驗中可以得到明顯有意義的數據表示，通常在該領域的 1b/2 期試驗中，隊列大約有四到七名受試者，而這正是如果需要的話，我們預計可以選擇添加更多內容。原因是我們預計效果會非常大。 Lanadelumab，[pertuzumab]——在第 3 階段，我們顯示與安慰劑相比減少了約 85%。就相對於基線的變化而言，該大小允許較小的總體樣本量。因此，即使每個隊列中的受試者數量較少，我們預計也能夠證明這有可能對患者產生有意義的影響。

Thank you.

謝謝。

Eun Yang, Jefferies.

楊恩，杰弗里斯。

The proof-of-concept data that we are expecting mid next year. So you mentioned, over 30 cohort. So how many months of follow up are we expecting when we see the data? And the second question is the -- you mentioned its safety tolerability, PK/PD changes in attack rate. Because it's a single dose -- so we are not going to see -- certainly, we are not going to see attack-free rating in this study, correct?

我們預計明年年中會得到概念驗證數據。所以你提到了，超過 30 個隊列。那麼，當我們看到這些數據時，我們期望進行多少個月的跟進？第二個問題是——你提到了它的安全耐受性、攻擊率中的 PK/PD 變化。因為它是單劑量的——所以我們不會看到——當然，我們不會在這項研究中看到無攻擊評級，對嗎？

Thanks for the question. So in terms of data, we are anticipating proof-of-concept data in mid-2024. Our proof-of-concept data should be able to demonstrate that we are entitled to achieve our target profile, which as you know, is a reducing effects when given every three months or potentially every six months. So while I can't guide you today to what we anticipate showing in mid '24, I could tell you that we're looking to be able to show data that would support that kind of profile.

謝謝你的提問。因此，就數據而言，我們預計 2024 年中期會出現概念驗證數據。我們的概念驗證數據應該能夠證明我們有權實現我們的目標概況，正如您所知，如果每三個月或可能每六個月給予一次，就會減少影響。因此，雖然我今天無法引導您了解我們預計在 24 年中期顯示的內容，但我可以告訴您，我們希望能夠顯示支持此類配置文件的數據。

Regarding your question about endpoints. The proportion of people who were attack-free is a meaningful, important endpoint. It is possible that with this profile, given its PK curve and as you know, now the PD effects out through at least 84 days, that we can show a substantial people -- number of people that have no attacks compared to baseline. And if we do have compelling data -- meaning high-integrity data that are capable of showing that, we would be pleased to be able to show that.

關於你關於端點的問題。未受攻擊的人數比例是一個有意義且重要的終點。有了這個概況，鑑於其 PK 曲線，並且如您所知，現在 PD 效果至少持續 84 天，我們可以向大量人員展示——與基線相比沒有受到攻擊的人數。如果我們確實擁有令人信服的數據——意味著能夠證明這一點的高完整性數據，我們將很高興能夠證明這一點。

I got one more follow up. So clinical sites in the US and Canada are up and running and sounds like the patients are being enrolled as we speak. And then, European sites to open later this year. When you enroll patient, do you have to enroll is sequential from quarter one to three? Or can you actually enroll patients simultaneously, of course, accordingly to cohort?

我又收到了一份跟進報告。因此，美國和加拿大的臨床中心已經建立並運行，聽起來就像我們說話時正在招募患者一樣。然後，歐洲站點將於今年晚些時候開放。當您登記患者時，是否必須按第一季度到第三季度的順序登記？或者，當然，您實際上可以根據隊列同時招募患者嗎？

Right. So the protocol as written calls for safety check before we start cohort two. That's the one requirement that's in the protocol so far. Beyond that, it is possible that we could enroll one and not completely fill up before we start the other. At this point, we anticipate not enrolling all three at the same time for a variety of reasons, the most important being just the accumulation of data. So the answer to your question is mixed. We don't have to go exactly through each one to start the next, but if we are staggering the start of the quarter.

正確的。因此，書面協議要求在我們開始第二組之前進行安全檢查。這是迄今為止協議中的一項要求。除此之外，我們有可能在註冊其中一個後，在開始另一個之前尚未完全填滿。目前，由於各種原因，我們預計不會同時註冊這三個人，最重要的是數據的積累。所以你的問題的答案是複雜的。我們不必精確地完成每一項才能開始下一項，但如果我們錯開本季度的開始時間。

Do you have a kind of a ratio in terms of number of patients being enrolled in the US/Canada versus Europe?

您是否有美國/加拿大與歐洲入組患者人數的比例？

I don't.

我不。

Thank you very much.

非常感謝。

Michael Higgins, Ladenburg.

邁克爾·希金斯，拉登堡。

Hi, guys. Thanks for taking the questions. The question on the cohorts in Phase 1a. Are there triggers for adding cohorts in ALPHA-STAR? If you could share those with us, we'd appreciate it. Thanks.

嗨，大家好。感謝您提出問題。關於階段 1a 中的隊列的問題。在 ALPHA-STAR 中添加群組是否有觸發器？如果您能與我們分享這些內容，我們將不勝感激。謝謝。

Michael, could you maybe clarify your question. The Phase 1a data to trigger ALPHA-STAR?

邁克爾，你能澄清一下你的問題嗎？觸發 ALPHA-STAR 的 Phase 1a 數據？

No, in Phase 1a, there were additional cohorts obviously from the first three to the next two. I'm wondering if there are any triggers to add additional cohorts in ALPHA-STAR.

不，在第 1a 階段，從前三個到後兩個顯然還有其他群組。我想知道是否有任何觸發因素可以在 ALPHA-STAR 中添加額外的群組。

So we have added the possibility to add cohorts to ALPHA-STAR -- actually, that's been sort of in our mind from the beginning. We've done that now with adding cohort three to test the feasibility of a regimen that could achieve the potential for every-six-month dosing. There aren't any priority-defined triggers for additional cohorts. However, if evolving data from our trial or from the Phase 1 show that there might be additional questions to ask, we do have that possibility.

因此，我們增加了向 ALPHA-STAR 添加群組的可能性——實際上，我們從一開始就想到了這一點。我們現在已經做到了這一點，添加了第三組來測試一種方案的可行性，該方案可以實現每六個月一次給藥的潛力。對於其他群組，沒有任何優先級定義的觸發器。然而，如果我們的試驗或第一階段的不斷發展的數據表明可能還有其他問題需要問，我們確實有這種可能性。

Okay. And then one follow up. Are you doing anything in the current trials or potentially future trials to reduce injection-site reactions? Hasn't been a major issue so far, but curious your thoughts there.

好的。然後是一個跟進。您在當前的試驗或未來可能的試驗中是否正在採取任何措施來減少注射部位反應？到目前為止還不是一個大問題，但很好奇你的想法。

Yeah. So we're fortunate that the injection-site reaction data are very reassuring so far. We've had a few, they've been mild. The most common one is just redness, which is fairly common when you inject anything under your skin. So far, it is comforting to know that there's nothing here that makes us concerned about moving forward. The formulation right now is 150 milligrams per mil, which is standard for a subcutaneously administered monoclonal antibody. There may be opportunities to concentrate that a bit more to allow for less volume that could potentially decrease the frequency of injection-site reactions. And that's work that's ongoing, and we'll certainly be able to fill you and the community in about that as those efforts continue.

是的。因此，我們很幸運，到目前為止，注射部位反應數據非常令人放心。我們吃過一些，它們都很溫和。最常見的就是發紅，當您在皮下注射任何東西時，這種情況相當常見。到目前為止，令人欣慰的是，我們沒有任何事情讓我們擔心繼續前進。目前的配方為每密耳 150 毫克，這是皮下注射單克隆抗體的標準。可能有機會集中更多一點，以減少注射量，這可能會降低注射部位反應的頻率。這項工作正在進行中，隨著這些努力的繼續，我們一定能夠向您和社區通報這一情況。

I think I have one more in here. Question on the IV. If you could review for us your rationale for testing in IV, the 600 milligrams in the Phase 1 again. Thanks.

我想我這裡還有一個。關於IV的問題。如果您能為我們回顧一下您在 IV 中進行測試的理由，即在第一階段再次測試 600 毫克。謝謝。

Sure. So there's two main: one is that 600 milligrams IV will provide a very high concentration. And what we're more concerned about in the Phase 1a data is the effect of the concentration than anything else. And that will allow us to -- the ability to get to a high concentration to watch the PK profile -- PD profile, ultimately safety profile over time -- over the full eight months of follow up.

當然。所以主要有兩個：一是600毫克IV會提供非常高的濃度。在 1a 階段的數據中，我們更關心的是濃度的影響。這將使我們能夠在整個八個月的隨訪期間高度集中精力觀察 PK 概況、PD 概況以及最終的安全概況。

The second is to say, we have some additional questions regarding bioavailability and absorption that comparing the IV -- 600 milligrams IV to the 600-milligram subcutaneous dose would help us answer.

第二個意思是，我們還有一些關於生物利用度和吸收的其他問題，比較 IV - 600 毫克 IV 和 600 毫克皮下劑量將有助於我們回答。

Appreciate that. Thanks, guys.

感謝。多謝你們。

Thank you for the questions, Michael. This concludes our question-and-answer session. I'll now turn the call back over to Jill.

謝謝你的提問，邁克爾。我們的問答環節到此結束。我現在將把電話轉回給吉爾。

Thank you, Operator. Thank you all for joining our call this morning and for your continued support of Astria. We'll keep you updated as we execute on our STAR-0215 program, the ALPHA-STAR trial, and share other areas of progress of the company. We look forward to speaking with you again. Andrea?

謝謝你，接線員。感謝大家今天早上加入我們的電話會議以及對 Astria 的持續支持。我們將在執行 STAR-0215 計劃（即 ALPHA-STAR 試驗）時隨時向您通報最新情況，並分享公司其他領域的進展。我們期待再次與您交談。安德里亞？

That concludes today's call. A webcast replay will be available for 90 days via the investor relations page on our website at www.astriatx.com. Thank you.

今天的電話會議到此結束。通過我們網站 www.astriatx.com 上的投資者關係頁面將提供為期 90 天的網絡廣播重播。謝謝。