Astria Therapeutics Inc (ATXS) 2023 Q3 法說會逐字稿

Good morning. And welcome to the Astria Therapeutics quarter three 2023 corporate update. (Operator Instructions) As a reminder, this call is being recorded. And a replay will be made available on the Astria website following the conclusion of the event. I'd now like to turn the call over to Liz Higgins, Director of Communications and Investor Relations at Astria Therapeutics. Please go ahead, Liz.

早安.歡迎來到 Astria Therapeutics 2023 年第三季公司更新。 （操作員說明）謹此提醒，此通話正在錄音。活動結束後，Astria 網站將提供重播。我現在想將電話轉給 Astria Therapeutics 的傳播和投資者關係總監 Liz Higgins。請繼續，莉茲。

Thank you, Tara. Welcome to today's Astria Therapeutics Q3 2023 conference call. With me today are Jill Milne, Chief Executive Officer; Christopher Morabito, Chief Medical Officer; Andrew Komjathy, Chief Commercial Officer; Andrea Matthews, Chief Business Officer; and Noah Clauser, Chief Financial Officer.

謝謝你，塔拉。歡迎參加今天的 Astria Therapeutics 2023 年第三季電話會議。今天與我在一起的有執行長吉爾‧米爾恩 (Jill Milne)；克里斯多福‧莫拉比托，首席醫療官；安德魯‧科姆賈西 (Andrew Komjathy)，首席商務長；安德里亞·馬修斯，首席商務官；和財務長諾亞·克勞瑟。

We issued a press release this morning summarizing our corporate update and third quarter financial results, which we will reference on today's call and is available on our website. We are also using slides during today's call that are available within the Events and Presentations section in 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情況和第三季度財務業績，我們將在今天的電話會議上引用該新聞稿，並可在我們的網站上查看。我們也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簡報部分中找到。

I would like to note, during today's event, as mentioned on slide 2, we will be making forward-looking statements relating to our business based on current and future expectations. Actual results may differ materially from those indicated by these statements as a result of a variety of risks and uncertainties, including those discussed in our most recent Form 10-K and our subsequent SEC filings.

我想指出，在今天的活動中，正如幻燈片 2 中所提到的，我們將根據當前和未來的預期做出與我們業務相關的前瞻性聲明。由於各種風險和不確定性，包括我們最近的 10-K 表格和隨後的 SEC 文件中討論的風險和不確定性，實際結果可能與這些聲明所示的結果有重大差異。

Such statements represent our judgment as of today. And we undertake no obligation to publicly update any forward-looking statements except as required by law. I will now pass the call over to Jill Milne, Chief Executive Officer. Jill.

這些陳述代表了我們今天的判斷。除法律要求外，我們不承擔公開更新任何前瞻性聲明的義務。我現在將把電話轉給執行長吉爾·米爾恩 (Jill Milne)。吉爾.

Good morning. And thank you for joining our earnings call. We've had an exciting few months at Astria and are in a strong position to close out the year. Just a few days ago at ACAAI Annual Meeting, we shared positive Phase 1a data for STAR-0215, our lead program, that supports our vision for STAR-0215 to be the first choice preventative treatment for hereditary angioedema or HAE.

早安.感謝您參加我們的財報電話會議。我們在 Astria 度過了激動人心的幾個月，並且處於有利地位來結束這一年。就在幾天前的ACAAI 年會上，我們分享了我們的主導項目STAR-0215 的1a 期積極數據，這支持了我們的願景：STAR-0215 成為遺傳性血管性水腫或HAE 的首選預防性治療藥物。

The data confirmed the potential for STAR-0215 to prevent HAE attacks with dosing two or four times per year. We aim to provide patients the option to choose a dosing regimen that works best for their lives, which we will review more on the coming slides.

數據證實了 STAR-0215 每年給藥兩到四次即可預防 HAE 發作。我們的目標是為患者提供選擇最適合其生活的給藥方案的選擇，我們將在接下來的幻燈片中對此進行更多回顧。

Last month, we also announced the expansion of our pipeline with STAR-0310. We plan to present a preclinical profile for this program next year with a planned IND submission by the end of 2024 and Phase 1a initiation expected in Q1 2025.

上個月，我們也宣布擴大 STAR-0310 的產品線。我們計劃明年提供該計畫的臨床前概況，計劃於 2024 年底提交 IND，並預計於 2025 年第一季啟動 1a 期。

Our focus for Astria is to develop first-choice products that improve the health outcomes of patients with allergic and immunological diseases. First-choice to us means patients and treating physicians would choose our products because of their strong competitive efficacy, low treatment burden, and favorable safety and tolerability profile.

我們對 Astria 的重點是開發改善過敏性和免疫性疾病患者健康結果的首選產品。對我們來說，首選意味著患者和治療醫生會選擇我們的產品，因為我們的產品具有強大的競爭功效、低的治療負擔以及良好的安全性和耐受性。

Our initial pipeline is focused on well-established mechanisms, mechanisms that are clinically validated where we believe we can advance ultimately best-in-class programs. Very much in line with this strategy is our STAR-0215 program.

我們最初的管道專注於完善的機制，這些機制經過臨床驗證，我們相信我們可以推進最終一流的專案。我們的 STAR-0215 計劃非常符合此策略。

We think that STAR-0215 is very well positioned to be the first-choice preventative treatments to help normalize the lives of patients living with HAE, a rare, life-changing, and, at times, life-threatening disease. STAR-0310 is an anti-OX40 antibody, also aligns with this strategy that we plan to develop as a potential best-in-class therapeutic for atopic dermatitis and potentially other indications.

我們認為 STAR-0215 非常適合成為首選預防性治療藥物，幫助 HAE 患者的生活正常化，HAE 是一種罕見的、改變生活的、有時甚至危及生命的疾病。 STAR-0310 是一種抗 OX40 抗體，也符合我們計劃開發的此策略，作為治療異位性皮膚炎和潛在其他適應症的潛在最佳療法。

The next slide is an overview of our expected milestones for the integrated pipeline with both programs. We just shared additional Phase 1a results at ACAAI this weekend, which further support STAR-0215 best-in-class PK profile and the options for Q3 and Q6 month dosing as a potential HAE preventative therapy with robust attack suppression and low treatment burden.

下一張投影片概述了我們對這兩個項目的整合管道的預期里程碑。本週末我們剛剛在ACAAI 上分享了額外的1a 期結果，這進一步支持了STAR-0215 一流的PK 特性以及第三季度和第六季度的給藥選擇，作為潛在的HAE 預防療法，具有強大的發作抑製作用和低治療負擔。

Our ALPHA-STAR trial in HAE patients is progressing very well. We are now planning to share meaningful initial proof-of-concept results in Q1 of 2024. Assuming positive results from this trial, we plan to initiate a pivotal Phase 3 trial in Q1 of 2025 and are looking at ways to accelerate this timeline.

我們針對 HAE 患者的 ALPHA-STAR 試驗進展順利。我們現在計劃在2024 年第一季分享有意義的初步概念驗證結果。假設此次試驗取得積極成果，我們計劃在2025 年第一季啟動關鍵的第3 階段試驗，並正在尋找加快這一時間表的方法。

We are actively working on the design of our Phase 3 trial. With STAR-0310, we expect to submit an IND by year-end 2024 and to share the preclinical profile in 2024 at a scientific conference. We anticipate early proof-of-concept results from a Phase 1a trial in Q3 of 2025, which we believe will be an important milestone for the program.

我們正積極設計第三階段試驗。對於 STAR-0310，我們預計在 2024 年底之前提交 IND，並於 2024 年在科學會議上分享臨床前資料。我們預計 2025 年第三季的 1a 期試驗將獲得早期概念驗證結果，我們相信這將是該計劃的一個重要里程碑。

Next, assuming positive results in the Phase 1a trial, we anticipate initiating a Phase 1b clinical trial in atopic dermatitis patients in the second half of 2025. I will now turn it over to Chris Morabito, our Chief Medical Officer, who will review the new data we have seen for STAR-0215. Chris.

接下來，假設1a 期試驗取得積極結果，我們預計將於2025 年下半年在異位性皮膚炎患者中啟動1b 期臨床試驗。我現在將其交給我們的首席醫療官Chris Morabito，他將審查新的我們已經看到了 STAR-0215 的數據。克里斯。

Thanks, Jill. STAR-0215 is a potential first-choice treatment for the prevention of attacks in hereditary angioedema. HAE is a rare, life-threatening, and life-changing disease characterized by severe, unpredictable, painful, and sometimes life-threatening oedema in the skin, the abdomen, and the airway.

謝謝，吉爾。 STAR-0215 是預防遺傳性血管水腫發作的潛在首選治療方法。 HAE 是一種罕見、危及生命、改變生命的疾病，其特徵是皮膚、腹部和氣道嚴重、不可預測、疼痛，有時甚至危及生命的水腫。

Patients with HAE live in fear of having an attack that could be immensely painful or leave them disfigured for several days, or worse, could be fatal. For most patients, it's caused by a deficiency in a protein called C1-inhibitor, which is an important component of the body's complement system.

HAE 患者生活在恐懼之中，擔心發作可能會帶來極大的痛苦或導致他們在幾天內毀容，或更糟的是可能致命。對於大多數患者來說，這是由 C1 抑制劑蛋白質缺乏引起的，C1 抑制劑是人體補體系統的重要組成部分。

Deficiency in C1-inhibitor may lead to runaway plasma kallikrein activity producing bradykinin that causes painful swelling attacks that characterize HAE. STAR-0215 inhibits plasma kallikrein in order to prevent bradykinin release and subsequent swelling, the same mechanism as market leader Takhzyro.

C1 抑制劑的缺乏可能會導致血漿激肽釋放酶活性失控，產生緩激肽，導致 HAE 特有的疼痛性腫脹發作。 STAR-0215 抑制血漿激肽釋放酶，以防止緩激肽釋放和隨後的腫脹，其機制與市場領導者 Takhzyro 相同。

We believe that 0215 has the potential to differentiate from currently available therapies. And our goal is to reduce the disease and treatment burden for people living with HAE and help to normalize their lives.

我們相信 0215 有潛力區別於目前可用的療法。我們的目標是減輕 HAE 患者的疾病和治療負擔，幫助他們恢復正常生活。

STAR-0215 is a YTE-modified extended half-life monoclonal antibody, which is a trusted modality in HAE. STAR-0215 has the potential to support dosing every three and every six months. And we have formulated it to be high concentration and citrate-free for self-administration that may be less painful.

STAR-0215 是一種經過 YTE 修飾的延長半衰期的單株抗體，是 HAE 中值得信賴的治療方式。 STAR-0215 有可能支持每三個月和每六個月給藥一次。我們將其配製為高濃度且不含檸檬酸鹽，以便自我給藥，可能不會那麼痛苦。

As Jill mentioned, we have now shared the results of our Phase 1 healthy subject trial up through day 224 days. And these data support our vision for the program. I will now review them in more detail in the coming slides.

正如 Jill 所提到的，我們現在已經分享了截至 224 天的第一階段健康受試者試驗的結果。這些數據支持了我們對該計劃的願景。我現在將在接下來的幻燈片中更詳細地回顧它們。

The Phase 1a trial of 0215 is a randomized, double-blind, placebo-controlled trial conducted in 41 healthy subjects. Shown here are the five single-dose cohorts. The results that we'll share over the next few slides include safety, tolerability, PK, and PD data through the full follow-up period for cohorts 1 through 3, and the initial results for cohorts 4 and 5. Ultimately, we are very pleased to see that these results support both every three and every six month dosing strategies for a potential HAE-preventative therapy with robust attack suppression and low treatment burden.

0215的1a期試驗是一項在41名健康受試者中進行的隨機、雙盲、安慰劑對照試驗。這裡顯示的是五個單一劑量組。我們將在接下來的幾張投影片中分享的結果包括隊列 1 至隊列 3 整個隨訪期間的安全性、耐受性、PK 和 PD 數據，以及隊列 4 和 5 的初步結果。最終，我們非常非常高興看到這些結果支持每三個月和每六個月的劑量策略，用於潛在的HAE 預防療法，具有強大的發作抑制和低治療負擔。

On slide 8, we turn to the pharmacokinetic results. In the graph, you can see the rapid and sustained increases in 0215. In the 600-milligram dose, for example, concentration's above 12 micrograms per mL. This threshold we believe is associated with clinical benefit were achieved at about 11 hours after the dose was administered.

在投影片 8 上，我們轉向藥物動力學結果。在圖中，您可以看到 0215 的快速且持續的增加。例如，在 600 毫克劑量中，濃度高於每毫升 12 微克。我們認為該閾值與給藥後約 11 小時實現的臨床益處有關。

For all the doses above 100 milligrams, concentrations remained above the threshold for clinical benefit for more than 84 days or 3 months. Based on these data, we estimate the half-life of 0215 to be up to 127 days. We also saw favorable safety and tolerability with 215 and no serious adverse events or discontinuations due to an adverse event.

對於所有超過 100 毫克的劑量，濃度在超過 84 天或 3 個月內保持在臨床獲益閾值以上。根據這些數據，我們估計0215的半衰期長達127天。我們還發現 215 具有良好的安全性和耐受性，沒有發生嚴重不良事件或因不良事件而停藥。

The most common treatment-emergent adverse events observed were associated with injection site reactions of erythema, pruritus, and swelling. Here we see our modeling for potential three- and six-month dosing regimens updated with these newest data.

觀察到的最常見的治療中出現的不良事件與紅斑、搔癢和腫脹等注射部位反應有關。在這裡，我們看到了使用這些最新數據更新的潛在三個月和六個月給藥方案的模型。

As we've seen, these results confirm our approach to evaluate administration of 2.5 every three and every six months. On the left side, we have a stimulated three-month dosing regimen that begins with the 600-milligram loading dose on day zero and then follows it up with a 300-milligram dose given then every three months. We are pleased to see that this dosing regimen can maintain Ctrough levels at about 25 micrograms per mL, well above the 12 microgram per mL threshold associated with the prevention of HAE attacks.

正如我們所看到的，這些結果證實了我們每三個月和每六個月評估 2.5 次給藥的方法。在左側，我們有一個為期三個月的刺激給藥方案，從第 0 天的 600 毫克負荷劑量開始，然後每三個月給予 300 毫克劑量。我們很高興地看到這種給藥方案可以將 Ctrough 水平維持在約 25 微克/毫升，遠高於與預防 HAE 發作相關的 12 微克/毫升閾值。

On the graph on the right, we have a simulated six month-dosing regimen, which begins with the 600 milligram loading dose and then 600 milligrams every six months starting 28 days later. Again, we see Ctrough levels that stay well above the 12 microgram per mL threshold, this time at 27 micrograms per mL.

在右圖中，我們模擬了六個月的給藥方案，從 600 毫克負荷劑量開始，然後從 28 天後開始每六個月服用 600 毫克。我們再次看到 Ctrough 水平遠高於每毫升 12 微克閾值，這次為每毫升 27 微克。

Based on these results, we believe that both of these regimens could be successful in preventing HAE attacks. We will talk more about our dosing strategy on upcoming slides.

基於這些結果，我們相信這兩種方案都可以成功預防 HAE 發作。我們將在接下來的幻燈片中更多地討論我們的劑量策略。

On slide 10, we turn to the pharmacodynamic results. The graph shows the reporter-substrate assay in healthy subjects and include STAR-0215 data, as well as lanadelumab data, acknowledging that these are data from two different healthy subjects, single-dose clinical trials.

在投影片 10 上，我們轉向藥效學結果。該圖顯示了健康受試者中的報告基因-底物測定，包括 STAR-0215 數據以及 lanadelumab 數據，承認這些數據來自兩個不同的健康受試者的單劑量臨床試驗。

With 0215, we saw statistically significant inhibition of plasma kallikrein activity observed through day 140 after single doses of 300 and 600 milligrams and through day 224 after single doses of 1,200 milligrams subcu. The percent inhibition of plasma kallikrein is maintained through D84 for after single doses at levels greater than or similar to those achieved by lanadelumab at peak.

對於 0215，我們觀察到單劑量 300 和 600 毫克後第 140 天以及單劑量 1,200 毫克 subcu 後第 224 天觀察到血漿激肽釋放酶活性具有統計學顯著抑製作用。單次劑量後，血漿激肽釋放酶的抑制百分比在 D84 期間維持在高於或類似 lanadelumab 在峰值時達到的水平。

Given the promising healthy subjects results, we are excited to be studying STAR-0215 in HAE patients. Here's an outline of our ALPHA-STAR trial, which is currently evaluating STAR-0215 in HAE patients. We are pleased to share that this trial is progressing well. And we are currently enrolling into the third cohort.

鑑於健康受試者的良好結果，我們很高興能夠在 HAE 患者中研究 STAR-0215。以下是我們的 ALPHA-STAR 試驗的概述，該試驗目前正在 HAE 患者中評估 STAR-0215。我們很高興地告訴大家，這項試驗進展順利。我們目前正在招收第三批學生。

We are now planning to share initial proof-of-concept results in HAE patients in the first quarter of 2024. Assuming positive results from this trial, we expect to initiate pivotal Phase 3 trial in Q1 2025. And we are looking at strategies to accelerate this timeline.

我們現在計劃在 2024 年第一季分享 HAE 患者的初步概念驗證結果。假設這項試驗取得積極結果，我們預計將在 2025 年第一季啟動關鍵的 3 期試驗。我們正在尋找加速的策略這個時間線。

The ALPHA-SOLAR long term open label trial is open. Now there are data accruing of participants who have received multiple doses of STAR-0215. I will now turn it over to Andrew Komjathy, our Chief Commercial Officer, who will review the results of some new market research. Andrew.

ALPHA-SOLAR 長期開放標籤試驗現已開放。現在已經收集了接受多劑 STAR-0215 的參與者的數據。我現在將把它交給我們的首席商務官安德魯·科姆賈西（Andrew Komjathy），他將審查一些新的市場研究的結果。安德魯。

Thank you, Chris. And good morning, everyone. Our vision for STAR-0215 is to develop a treatment option that can help normalize the lives of patients with HAE.

謝謝你，克里斯。大家早安。我們對 STAR-0215 的願景是開發一種治療方案，幫助 HAE 患者恢復正常生活。

As Chris mentioned, we've recently completed or conducted some additional market research with both patients and physicians to get a better understanding of the level of interest and enthusiasm around every three and every six month dosing options for STAR-0215. We presented STAR-0215 profile with both three- and six-month dosing options to 92 HAE patients and caregivers and 16 HAE treatment providers.

正如 Chris 所提到的，我們最近與患者和醫生完成或進行了一些額外的市場研究，以更好地了解人們對 STAR-0215 每三個月和每六個月給藥方案的興趣和熱情程度。我們向 92 名 HAE 患者和照護者以及 16 名 HAE 治療提供者介紹了 STAR-0215 概況，包括三個月和六個月的劑量選擇。

From the left graph, you can see that 90% of patients are likely to ask their HCPs about our product with STAR-0215's profile with every three month dosing. And 97% of HCPs are likely to prescribe it.

從左圖可以看出，90% 的患者可能會向他們的 HCP 詢問我們的產品以及 STAR-0215 每三個月給藥一次的資料。 97% 的 HCP 可能會開這種藥。

On the right, you see that 76% of patients are likely to ask their prescribers about the profile with every six-month dosing. And 93% of prescribers are likely to prescribe it.

在右側，您可以看到 76% 的患者可能會詢問他們的處方醫生每六個月的用藥情況。 93% 的處方醫生可能會開這種藥。

While the patients and caregivers indicated a slightly higher preference for the three-month dosing regimen, both options indicated a high level of interest from both patients and from prescribers. Given the faster development timeline for a three-month dosing regimen, we intend to prioritize clinical development for every three-month administration, followed by a six-month dosing option, enabling patients to choose a regimen that works best for them.

雖然患者和照護者對三個月的給藥方案表現出稍高的偏好，但這兩種選擇都表明患者和處方者都高度感興趣。鑑於三個月給藥方案的開發時間表較快，我們打算優先考慮每三個月給藥的臨床開發，然後是六個月的給藥方案，使患者能夠選擇最適合他們的方案。

So in summary, we're excited about the potential of STAR-0215 becoming the first-choice preventative treatment for HAE patients for the following reasons. One, as Chris shared earlier, we have compelling data from our 1a trial that supports its potential best-in-class profile. Two, STAR-0215's mechanism of action and modality are proven safe and effective in HAE, as demonstrated by the current market leader. Three, STAR-0215 has the potential to provide rapid and durable protection against HAE attacks. Four, STAR-0215's citric acid-free formulation is expected to reduce injection site pain associated with formulations that contain citrate buffers.

總而言之，我們對 STAR-0215 成為 HAE 患者首選預防性治療的潛力感到興奮，原因如下。第一，正如 Chris 之前分享的那樣，我們從 1a 試驗中獲得了令人信服的數據，這些數據支持其潛在的同類最佳特徵。第二，正如當前市場領導者所證明的那樣，STAR-0215 的作用機制和模式在 HAE 中被證明是安全有效的。第三，STAR-0215 有潛力針對 HAE 攻擊提供快速、持久的保護。第四，STAR-0215 的無檸檬酸配方可望減少與含有檸檬酸鹽緩衝劑的配方相關的注射部位疼痛。

Finally, we plan to develop STAR-0215 in options that support patient choice by prioritizing development on a three-month dosing option first, followed by a six-month dosing regimen. We see a very bright future for STAR-0215 as the potential first-choice preventative HAE therapy. And we look forward to providing you additional updates on our progress next quarter. I'll now turn it over to Andrea Matthews, our Chief Business Officer, who will introduce our STAR-0310 program. Andrea.

最後，我們計劃開發 STAR-0215，以支持患者選擇，首先優先開發三個月的給藥方案，然後是六個月的給藥方案。我們認為 STAR-0215 作為潛在的首選預防性 HAE 療法有著非常光明的前景。我們期待為您提供有關下季度進展的更多最新資訊。現在我將把它交給我們的首席商務官 Andrea Matthews，他將介紹我們的 STAR-0310 計劃。安德里亞.

Thanks, Andrew. Let's turn to our second program, STAR-0310 in atopic dermatitis. Atopic dermatitis is an immune disorder associated with loss of skin barrier function and itching. It is driven by diverse mechanisms which span the spectrum of T cell-driven pathology. And it affects approximately 5% of the US population.

謝謝，安德魯。讓我們轉向我們的第二個項目，即治療異位性皮膚炎的 STAR-0310。異位性皮膚炎是一種與皮膚屏障功能喪失和搔癢相關的免疫性疾病。它由跨越 T 細胞驅動病理學範圍的多種機制所驅動。它影響了大約 5% 的美國人口。

Half of these cases are reported to be moderate to severe. The burden experienced by moderate to severe atopic dermatitis patients can be significant and can include intense itch, inflamed skin, sleep disruption, depression, and infections.

據報道，其中一半病例為中度至重度。中度至重度異位性皮膚炎患者所承受的負擔可能很大，包括劇烈搔癢、皮膚發炎、睡眠中斷、憂鬱和感染。

Here you see, psoriasis demonstrates precedent for market growth and evolution for targeted therapies in dermatology. US sales for targeted therapies for psoriasis were approximately $1 billion in 2010. And that's with over two drug classes approved compared to more than [17 million] in 2022, with 15 approved therapies across four major drug classes.

在這裡您可以看到，牛皮癬展現了皮膚科標靶治療市場成長與演變的先例。 2010 年，美國銀屑病標靶治療藥物的銷售額約為10 億美元。其中批准了兩種以上的藥物類別，而2022 年將有超過[1,700 萬] 種藥物獲得批准，其中四個主要藥物類別中有15 種藥物獲得批准。

In atopic dermatitis, there are currently only two approved drug classes for biologic therapies. Given the higher prevalence of atopic dermatitis than psoriasis, we and others see the atopic dermatitis market has even greater potential. We think that the moderate to severe atopic dermatitis treatment market could reach $26 billion by 2030.

對於異位性皮膚炎，目前只有兩種核准的生物療法藥物類別。鑑於異位性皮膚炎的盛行率高於牛皮癬，我們和其他人認為異位性皮膚炎市場具有更大的潛力。我們認為，到 2030 年，中度至重度異位性皮膚炎治療市場可能達到 260 億美元。

Currently, Dupixent is the market leader for targeted atopic dermatitis treatments. And our base case assumption is that OX40 treatments will be after Dupixent in the treatment regimen for atopic dermatitis. However, there's good rationale for this to evolve prior to the potential launch of our program.

目前，Dupixent 是異位性皮膚炎標靶治療的市場領導者。我們的基本案例假設是，在異位性皮膚炎的治療方案中，OX40 治療將在 Dupixent 之後進行。然而，在我們的計劃可能啟動之前，這種發展是有充分理由的。

In both scenarios, we believe that there's substantial opportunity for STAR-0310. I'll now hand the presentation over to Chris, who will review the disease pathology of atopic dermatitis and also our mission for STAR-0310. Chris.

在這兩種情況下，我們相信 STAR-0310 都有很大的機會。我現在將演講交給 Chris，他將回顧異位性皮膚炎的疾病病理學以及我們 STAR-0310 的任務。克里斯。

Thank you, Andrea. Here you can see the immune dysregulation in atopic dermatitis can be complex. Current approved biologics and other late stage non-OX40 biologics target only the Type 2 pathway, hitting downstream cytokine from Th2 cells.

謝謝你，安德里亞。在這裡您可以看到異位性皮膚炎的免疫失調可能很複雜。目前核准的生物製劑和其他後期非 OX40 生物製劑僅針對 2 型途徑，攻擊 Th2 細胞的下游細胞激素。

But AD is more complicated than this. Type 1 and Type 3 pathways also contribute to this disease. STAR-0310 is an OX40 inhibitor, which targets multiple effector T cell pathways. It aims to reduce the activity of a broader group of Th cells that are known to contribute to the disease and has the potential to induce higher rates of clinical responses in more patients than currently available biologics, and may be disease-modifying

但 AD 比這更複雜。 1 型和 3 型途徑也導致這種疾病。 STAR-0310 是 OX40 抑制劑，針對多種效應 T 細胞路徑。它的目的是減少更廣泛的 Th 細胞群的活性，這些細胞已知會導致疾病，並且有可能比目前可用的生物製劑在更多患者中誘導更高的臨床反應率，並且可能會改善疾病

Here, we do a deeper dive on the OX40 pathway programs. There are three programs that have achieved clinical proof of concept: amlitelimab from Sanofi, which targets OX40 ligand, rocatinlimab from Amgen and, telazorlimab, which is the parent program for STAR-0310, both of which target OX40 on activated T cells.

在這裡，我們對 OX40 途徑計畫進行了更深入的研究。有三個項目已經實現了臨床概念驗證：賽諾菲的 amlitelimab，靶向 OX40 配體；安進的 rocatinlimab；以及 STAR-0310 的母體項目 telazorlimab，這兩個項目都靶向活化 T 細胞上的 OX40。

All three of these programs have seen promising clinical efficacy results through Phase 2b in atopic dermatitis. Amlitelimab targets OX40 ligand, which is expressed on a wider array of cell types, which could lead to increased risk for respiratory and vascular adverse events.

這三個項目都在 2b 期治療異位性皮膚炎中取得了有希望的臨床療效結果。 Amlitelimab 靶向 OX40 配體，該配體在更廣泛的細胞類型中表達，這可能導致呼吸和血管不良事件的風險增加。

Rocatinlimab is an afucosylated anti-OX40, which is selective for T cells, but depletes T cells via enhanced ADCC. T cell depletion leads to cytokine release and potential increased risk of infection.

Rocatinlimab 是一種無岩藻糖基化抗 OX40，對 T 細胞具有選擇性，但透過增強 ADCC 來消耗 T 細胞。 T 細胞耗竭會導致細胞激素釋放並潛在增加感染風險。

0310 is a next generation of telazorlimab. 0310 is designed to have higher affinity, greater potency, and YTE half-life extension technology. We believe that 0310 has the potential to be the first-choice OX40 for moderate to severe in atopic dermatitis.

0310 是下一代 Telazorlimab。 0310被設計為具有更高的親和力、更強的效力以及YTE半衰期延長技術。我們相信0310有潛力成為中度至重度異位性皮膚炎的首選OX40。

As mentioned on the previous slide, it is designed for a high affinity with selective potency. And we believe that it can match or beat the efficacy seen in other OX40 programs. The half-life of 0310 is extended with YTE technology, with the goal of reducing the time between doses. And we also believe that we have the potential to administer 0310 with subcutaneous delivery.

如上一張投影片中所提到的，它的設計具有高親和力和選擇性效力。我們相信它可以達到或超過其他 OX40 項目的功效。 YTE 技術延長了 0310 的半衰期，目的是縮短給藥間隔。我們也相信我們有潛力透過皮下給藥方式施用 0310。

And given that 0310 is designed to be T cell preserving with low ADCC, we think it has the potential to have the best-in-class safety profile. We have filed a provisional patent application for STAR-0310 that if converted, granted, and nationalized, would provide patent term extension through 2044 before taking into consideration any potential patent term extensions.

鑑於 0310 被設計為以低 ADCC 保存 T 細胞，我們認為它有可能擁有一流的安全性。我們已經提交了 STAR-0310 的臨時專利申請，如果轉換、授予並國有化，將在考慮任何潛在的專利期限延長之前將專利期限延長至 2044 年。

As noted, we believe that 0310 could be a best-in-class and first-choice treatment for atopic dermatitis. Starting first with common factors for OX40 pathway monoclonal antibodies, targeting this pathway has the ability to have disease-modifying impacts. The OX40 pathway has potential for effectiveness across AD, driven by multiple effector T cell types, not just Th2.

如前所述，我們相信 0310 可能是治療異位性皮膚炎的最佳首選藥物。首先從 OX40 途徑單株抗體的共同因素開始，針對此途徑能夠產生緩解疾病的影響。 OX40 途徑在多種效應 T 細胞類型（而不僅僅是 Th2）的驅動下，具有跨 AD 的有效性潛力​​。

The potential benefit here is robust and sustained responses across a broad range of AD. We also believe that due to the YTE modification, long acting 0310 has the potential to be administered four to six times per year compared to the anticipated 12 times per year for amlitelimab and rocatinlimab. We believe the safety profile of 0310 will differentiate from both rocatinlimab and amlitelimab as 0310 has a potential for reduced T cell depletion due to ADCC and limited potential for AEs due to off-target binding.

這裡的潛在好處是在廣泛的 AD 範圍內做出強烈和持續的反應。我們也相信，由於 YTE 的修改，長效 0310 有可能每年給藥 4 至 6 次，而 amlitelimab 和 rocatinlimab 預計每年給藥 12 次。我們相信 0310 的安全性將不同於 rocatinlimab 和 amlitelimab，因為 0310 有可能減少 ADCC 導致的 T 細胞耗竭，並且由於脫靶結合而導致 AE 的可能性有限。

Beyond atopic dermatitis, we believe that targeting the OX40 has strong potential in a broad range of additional indications. Nova Clauser, our Chief Financial Officer, will now review our financial information and upcoming milestones. Noah.

除了異位性皮膚炎之外，我們相信靶向 OX40 在廣泛的其他適應症中具有強大的潛力。我們的財務長 Nova Clauser 現在將審查我們的財務資訊和即將到來的里程碑。諾亞。

Thank you, Chris. On this slide, I'll provide a brief summary of important financial information. As of September 30, 2023, we had $188.8 million in cash, cash equivalents, and short-term investments.

謝謝你，克里斯。在這張投影片上，我將提供重要財務資訊的簡短摘要。截至 2023 年 9 月 30 日，我們擁有 1.888 億美元的現金、現金等價物和短期投資。

In October 2023, we closed a $64 million underwritten offer. Following the October financing, we expect our cash to support our current operating plan into 2026. Our current operating plan includes the development of STAR-0215 and STAR-0310, including, for STAR-0215, support for all program activities up to the initiation of the planned pivotal Phase 3 trial, and for STAR-0310, the anticipated submission of an IND, the planned Phase 1a clinical trial in healthy subjects, and any related anticipated milestone payments.

2023 年 10 月，我們完成了 6,400 萬美元的承銷要約。在10 月融資之後，我們預計我們的現金將支持我們目前的營運計畫到2026 年。我們目前的營運計畫包括STAR-0215 和STAR-0310 的開發，其中包括對STAR-0215 啟動前所有專案活動的支持計劃的關鍵 3 期試驗，對於 STAR-0310，預計提交 IND、計劃在健康受試者中進行的 1a 期臨床試驗以及任何相關的預期里程碑付款。

Also illustrated here is a summary of our outstanding equity. In addition to our 36.3 million outstanding common shares, we now have 1.6 million prefunded warrants and 5.2 million as converted preferred shares. So in total, we have 43.1 million outstanding common equivalent shares.

這裡也展示了我們未償權益的摘要。除了 3,630 萬股已發行普通股外，我們現在還擁有 160 萬股預融資認股權證和 520 萬股轉換優先股。因此，我們總共擁有 4,310 萬股已發行普通等價股。

For additional financial information, please see our earnings press release issued earlier this morning and our 10-K, which we plan to file with the SEC after market today. I will now touch on our key upcoming milestones. And then we will open up for questions.

有關更多財務信息，請參閱我們今天上午早些時候發布的收益新聞稿以及我們計劃在今天盤後向 SEC 提交的 10-K 報表。我現在將談談我們即將到來的關鍵里程碑。然後我們將開放提問。

On this slide, you can see the cadence of anticipated milestones as well as our future development goals for our combined pipeline with at least one clinical milestone each year in the coming years. Next year's a big year as we expect to report proof-of-concept results for STAR-0215 in patients in Q1. And for STAR-0310, we plan to submit an IND by year end.

在這張投影片上，您可以看到預期里程碑的節奏以及我們組合管道的未來發展目標，未來幾年每年至少有一個臨床里程碑。明年是重要的一年，我們預計在第一季報告 STAR-0215 在患者中的概念驗證結果。對於 STAR-0310，我們計劃在年底前提交 IND。

Our ultimate goal is to bring first-choice therapies to patients. And we are looking forward to executing on that goal in the years to come. I will now ask the operator to open up the line for questions. Thank you.

我們的最終目標是為患者提供首選療法。我們期待在未來幾年實現這一目標。我現在請接線生開通電話詢問問題。謝謝。

(Operator Instructions) Eun Yang, Jefferies. Eun, you might be on mute.

（操作員指令）Eun Yang，Jefferies。恩，你可能處於靜音狀態。

Oh. yes. Can you hear me okay?

哦。是的。你聽得到我說話嗎？

Yes, we can.

我們可以。

Okay, great. Thank you very much. So Phase 1b data in HAE patients who have been accelerated, can you talk about what has caused the accelerated timeline for the data readout. And second question is on Phase 3. I think Jill mentioned that it's going to start in first quarter 2025. But you are looking into expediting the timeline. So, Phase 3, do you think the design would be similar to ASO-targeting kallikrein from Ionis? Or do you think that you may add on active competitor, as such as Takhzyro, efficacy comparison. Thank you.

好的，太好了。非常感謝。那麼HAE患者的1b期數據已經被加速了，您能談談是什麼導致了數據讀出時間軸的加速。第二個問題是關於第三階段的。我認為吉爾提到它將在 2025 年第一季開始。但您正在考慮加快時間表。那麼，第三階段，您認為該設計是否類似於 Ionis 的 ASO 靶向激肽釋放酶？或者您認為您可以添加活躍的競爭對手，例如 Takhzyro，進行功效比較。謝謝。

Great, thanks, Eun. And Chris will address those questions.

太好了，謝謝，恩。克里斯將回答這些問題。

Yeah, thanks, Eun. Yeah, we're very excited about the ability to demonstrate some initial proof-of-concept data in patients and even more excited that the timeline for that has been accelerated and now into Q1. And the reason for that is because we've now achieved target enrollment in cohorts 1 and 2, and are enrolling into cohort 3, and anticipate that we will achieve a planned interim analysis trigger earlier than anticipated. So the data that we plan to share in Q1 will be based on the interim analysis that we'll trigger in Q1 and, as mentioned during the call, aim to provide meaningful POC data demonstrating that whether STAR-0215 may be effective when given every three months and every six months to patients.

是的，謝謝，恩。是的，我們對能夠在患者中展示一些初步概念驗證數據感到非常興奮，更令人興奮的是，這一過程的時間表已經加快，現在已進入第一季。原因是我們現在已經實現了隊列 1 和隊列 2 的註冊目標，並且正在註冊隊列 3，並且預計我們將比預期更早實現計劃的中期分析觸發。因此，我們計劃在第一季分享的數據將基於我們將在第一季度觸發的中期分析，並且正如電話會議中提到的，旨在提供有意義的POC 數據，證明STAR-0215 在每次給予時是否有效。三個月和每六個月向患者提供一次。

The second question about the Phase 3 design, yes, we are anticipating that the Phase 3 is in Q1. But we're looking at every opportunity to potentially accelerate that. We've been doing a lot of work thinking about the design of the Phase 3 study.

關於第三階段設計的第二個問題，是的，我們預期第三階段是在第一季。但我們正在尋找一切可能加速這一進程的機會。我們一直在思考第三階段研究的設計。

Our current assumption is that it will be a placebo-controlled trial, that we will not be versus an active comparator. We also assume that we would have similar treatment period as other Phase 3 trials, which specifically is about six months of treatment period, and that the primary endpoint would be a similar to what's been used also in Phase 3 studies, which is essentially change from baseline or versus placebo and monthly attack rates.

我們目前的假設是，這將是一項安慰劑對照試驗，我們不會與積極的比較者進行比較。我們也假設我們將有與其他 3 期試驗類似的治療期，具體來說是大約六個月的治療期，並且主要終點將與 3 期研究中使用的類似，這本質上是從基線或與安慰劑相較以及每月的發生率。

Thank you.

謝謝。

Sam Slutsky, LifeSci Capital.

薩姆‧斯盧茨基 (Sam Slutsky)，LifeSci Capital。

Hey, good morning, everyone. Thanks for the questions. And congrats on the updates. Just two for me, I guess for the upcoming ALPHA-STAR interim analysis, given that there's no placebo arm, what data are you looking for that you would consider, when before moving to Phase 3, as you think about the different dosing regimens that you might take forward.

嘿，大家早安。感謝您的提問。並祝賀更新。對我來說只有兩個，我想對於即將到來的 ALPHA-STAR 中期分析，考慮到沒有安慰劑組，在進入第 3 階段之前，當你考慮不同的給藥方案時，你會考慮哪些數據？你可能會繼續前進。

Yeah, Chris?

是啊，克里斯？

Yeah, sure. Hi, Sam. So right, we don't have a placebo. But we've built into this a robust run-in period in which we collect important baseline information on all of our participants. The planned efficacy analysis is change from baseline on various efficacy parameters to inform the effectiveness of this drug in HAE, specifically whether a dose could prevent for three months and a dose could prevent for six months.

好，當然。你好山姆。是的，我們沒有安慰劑。但我們已經建立了一個強大的磨合期，在此期間我們收集所有參與者的重要基線資訊。該計劃的功效分析是各種功效參數相對於基線的變化，以告知該藥物在 HAE 中的有效性，特別是一個劑量是否可以預防三個月，一個劑量是否可以預防六個月。

Perfect. And then just as you think about the quicker enrollment you saw in ALPHA-STAR and read through to Phase 3, anything that stands out, whether it be certain sites you may be reuse or just patient feedback in terms of your dosing regimen, et cetera, as we think about timelines for Phase 3?

完美的。然後，正如您想到在ALPHA-STAR 中看到的更快註冊並通讀第3 階段一樣，任何突出的內容，無論是您可能重複使用的某些網站，還是只是患者在劑量方案方面的反饋，等等等，當我們考慮第三階段的時間表時？

Sure. So I think two key things have contributed to the accelerated timelines here. One is the profile. I think that when we talk with physicians, the community, the patients are working with our advocacy organizations.

當然。所以我認為有兩個關鍵因素促成了這裡的時間表的加快。一是簡介。我認為，當我們與醫生、社區、病人交談時，他們正在與我們的倡議組織合作。

We get a lot of, frankly, positive feedback that the profile is something that is meaningful to patients with this disease, specifically the ability to administer in such a way that has the potential to potentially normalize the lives of people living with this disease appears to be very attractive. And there is interest among sites and potential participants in joining or development program.

坦白說，我們得到了很多積極的回饋，表明該概況對患有這種疾病的患者有意義，特別是能夠以有可能使患有這種疾病的人的生活正常化的方式進行管理。非常有吸引力。網站和潛在參與者對加入或開發計劃有興趣。

And the second is the trial design. I think we found a lot of -- we've put a lot of effort into thinking about a clinical trial that would provide meaningful data in a timely fashion. And you pointed out one in question one, which is the lack of a placebo group, which for many is a detriment, so eliminating the placebo group and thinking about dosing regimens that could provide important data with limited resource utilization, i.e. sample size, again appears to be attractive to sites and also to patients.

第二是試驗設計。我認為我們發現了很多——我們投入了大量的精力來思考能夠及時提供有意義的數據的臨床試驗。您在問題一中指出了一個問題，即缺乏安慰劑組，這對許多人來說是一種損害，因此消除安慰劑組並考慮可以在資源利用率（即樣本量）有限的情況下提供重要數據的給藥方案似乎對網站和患者都有吸引力。

Awesome, thank you.

太棒了，謝謝你。

Seema Sheoran, Evercore.

Seema Sheoran，Evercore。

Hi. Thank you for taking my questions. My first question is on the proof-of-concept data that is coming in first quarter. I know this study is small. But what do you think is a win in terms of reduction in HAE attack rates for this upcoming data readout?

你好。感謝您回答我的問題。我的第一個問題是關於第一季即將發布的概念驗證數據。我知道這項研究規模很小。但您認為在即將到來的資料讀取中降低 HAE 攻擊率的勝利是什麼？

Right, so the traditional way of looking at efficacy here is by looking at essentially the monthly attack rates overtime and what has been done in other Phase 1b and 2 trials, is looking at this endpoint. And there's been 75% to 100% reductions with small sample sizes at various dose levels.

是的，所以在這裡查看功效的傳統方法是透過查看每月的超時攻擊率以及其他 1b 期和 2 期試驗中所做的事情來查看這個終點。不同劑量水準下的小樣本量減少了 75% 到 100%。

Another way of looking at this is by looking at the proportion of people who were attack-free for defined periods of time. For us, that could be after a single dose, looking at proportion of people who were attack-free at three months, looking at people who were attack-free at six months.

另一種看待這一問題的方法是觀察在規定的時間內沒有受到攻擊的人的比例。對我們來說，這可能是在單次給藥後，觀察三個月內沒有發作的人的比例，觀察六個月後沒有發作的人的比例。

And that hasn't been previously reported in any significantly meaningful way. So that's something that I think would differentiate us in terms of and this drug's ability to impact meaningfully the lives of people with this disease. So we'll be looking for a high proportion of people that are attack-free for those pre-defined periods of time.

此前還沒有以任何有意義的方式報道過這一點。因此，我認為這將使我們與眾不同，並且這種藥物能夠對患有這種疾病的人的生活產生有意義的影響。因此，我們將尋找在預先定義的時間段內沒有受到攻擊的大部分人。

That's helpful. Thank you. And also just curious why there's less interest from docs and patients for six months dosing than three months.

這很有幫助。謝謝。我也很好奇為什麼醫生和病人對六個月給藥的興趣比三個月給藥的興趣還要小。

This is Andrew. A couple of comments there as we look through the data. First of all, there potentially could be some perception that happens with dosing intervals with other products that you might be able to -- you might be losing some levels of efficacy as you extend the dose.

這是安德魯。當我們查看數據時，有一些評論。首先，您可能會對其他您可能能夠使用的產品的給藥間隔產生一些看法——當您延長劑量時，您可能會失去一定程度的功效。

We don't intend that to happen. We understand that efficacy is an important element of treatment. So our intention is to develop highly effective treatment for both the three- and the six-month dose. So we believe that that might be an issue.

我們不希望這種情況發生。我們知道療效是治療的重要因素。因此，我們的目的是開發針對三個月和六個月劑量的高效治療方法。所以我們認為這可能是一個問題。

The second issue is that the patients that had the six-month dosing option had obviously two injections. And what quite a few patients, especially with Takhzyro experience, is injection site pain associated with the citrate buffer. We obviously, we're going to be developing a citrate-free buffer. And we expect to have that level of pain be significantly reduced.

第二個問題是，選擇六個月給藥方案的患者顯然接受了兩次注射。相當多的患者，尤其是 Takhzyro 患者，都經歷過與檸檬酸鹽緩衝液相關的注射部位疼痛。顯然，我們將開發一種不含檸檬酸鹽的緩衝液。我們預期疼痛程度會顯著降低。

So the numbers are relatively small in terms of the difference. I think the good news for us is that both physicians and patients are very excited about both dosing options. But again, I think if we can demonstrate high efficacy at both doses and have a formulation that reduces injection site pain, I think that those differences could be addressed.

因此，就差異而言，數字相對較小。我認為對我們來說好消息是醫生和患者對這兩種劑量選擇都非常興奮。但我再次認為，如果我們能夠在兩種劑量下都表現出高效能，並且有一種可以減輕注射部位疼痛的配方，我認為這些差異可以得到解決。

That's very helpful. Thank you. My last question is on the ADARx data that was presented at ACAAI, if you can speak about the read-through from that data for your program? And thank you.

這非常有幫助。謝謝。我的最後一個問題是關於 ACAAI 上展示的 ADARx 數據，您能否談談您的程式對該數據的通讀？謝謝你。

Yeah, so with regards to -- yes, ADARx had presented this weekend at ACAAI as well as we have. I think based on the data that we saw presented by ADARx, we do believe that we have a better chance of technical and regulatory success with STAR-0215. And that we are more advanced.

是的，關於 - 是的，ADARx 已經在本週末的 ACAAI 上與我們一樣展示了。我認為，根據 ADARx 提供的數據，我們確實相信 STAR-0215 在技術和監管方面取得成功的機會更大。而且我們更先進。

I think what we learned over the weekend about their program is that, from what we understood, they are currently limited on which dose they can take forward based on safety concerns. And the two mg per kg dose that they are advancing first to patients does not appear that it will get them through every six months dosing, and so obviously, lots more information to come from them.

我認為我們週末了解到的有關他們的計劃的信息是，根據我們的了解，出於安全考慮，他們目前可以採取的劑量受到限制。他們首先向患者提供的每公斤 2 毫克的劑量似乎並不能讓他們每六個月服藥，因此顯然，他們還需要提供更多資訊。

That's helpful. Thank you for taking my questions.

這很有幫助。感謝您回答我的問題。

Hartaj Singh, Oppenheimer.

哈塔吉·辛格，奧本海默。

Great, thank you for a couple of questions. And then really, nice presentation. We had done a survey with 25 high-prescribing physicians and a lot of -- Andrew, what you've been saying was, we saw concordance in our survey. But I had just a couple of questions extending from that, from the survey that we did.

太好了，謝謝你提出幾個問題。然後是非常非常好的演示。我們對 25 名高處方醫生和許多人進行了一項調查——安德魯，你剛才說的是，我們在調查中看到了一致性。但我從我們所做的調查中衍生出了幾個問題。

One was, just what are you hearing from payers? This is a very competitive area. There's a lot of different options. The payer dynamic and the competitiveness is also, I imagine, a thing. So one, what are you hearing from payers or if you haven't gone there yet, what's the work you're thinking of doing there and preparing?

一是，您從付款人那裡聽到了什麼？這是一個競爭非常激烈的領域。有很多不同的選擇。我想，付款人的動態和競爭力也是一件事。那麼，您從付款人那裡聽到了什麼，或者如果您還沒有去過那裡，您打算在那裡做什麼並準備做什麼工作？

Secondly, there still seem to be somewhat of a lack of awareness. There was a core group of our 25 physicians that seem to really know 0215 very well and others that seem to be kind of aware of it. How are you going to tackle that?

其次，我們的認知似乎還有些欠缺。我們有一個由 25 名醫生組成的核心小組，他們似乎非常了解 0215，而其他人似乎也意識到了這一點。你打算如何解決這個問題？

And then lastly for Chris, just on biomarkers, Chris, the biomarkers you've been showing us from preclinical and Phase 1, could those in any way help in the Phase 3 trial incoming with the design that could be faster? Thank you for the questions.

最後，克里斯，就生物標記而言，克里斯，您在臨床前和第一階段向我們展示的生物標誌物，這些生物標誌物是否可以以任何方式幫助進入第三階段試驗，設計可能會更快？謝謝你的提問。

Sure. So we did a payer landscape assessment earlier this year. And what we learned is that at least right now, ultimately patients can get the product that physicians will prescribe in HAE. But the class is going to continue to be managed.

當然。因此，我們在今年稍早進行了付款人格局評估。我們了解到，至少現在，患者最終可以獲得醫生在 HAE 中開出的產品。但班級仍將繼續管理。

So I think like in other rare diseases, there might be some work associated with getting patients onto the treatment that they want. But generally, you can get there. But again, the class will continue to be managed more actively as more treatments become available.

因此，我認為就像其他罕見疾病一樣，可能需要做一些與讓患者接受他們想要的治療相關的工作。但一般來說，你可以到達那裡。但同樣，隨著更多治療方法的出現，班級將繼續更積極地管理。

The other thing that we heard is that efficacy continues to be a very important element of what the payers are looking for. So again, given the profile that we're looking to develop, we're looking to develop a treatment that hopefully can provide comparable efficacy in terms of attack rate reduction. There's an opportunity for us to keep even more patients attack-free, but then also combine that with a product that patients obviously would be more compliant with.

我們聽到的另一件事是，功效仍然是付款人尋求的一個非常重要的因素。因此，考慮到我們希望開發的概況，我們希望開發一種治療方法，希望能夠在降低發病率方面提供類似的功效。我們有機會讓更多的患者免受攻擊，但也可以將其與患者顯然更願意使用的產品結合。

So that's what we're learning from the payers in the US. I would say that from an awareness perspective, obviously, we're generating additional data that we're going to continue to share at conferences. We are creating a medical affairs function. And we started that process earlier this year. We're looking to grow that.

這就是我們從美國付款人那裡學到的東西。我想說，從意識的角度來看，顯然我們正在產生額外的數據，我們將繼續在會議上分享這些數據。我們正在創建醫療事務職能。我們在今年早些時候開始了這個過程。我們正在尋求發展這一點。

So I think that our awareness amongst the top one KOLs is very high. I think our awareness within the HAE community and continues to grow. But I do believe that we'll continue to publish hopefully very impressive encouraging data that both physicians and patients will be interested in. And as we continue to grow our organization, hopefully, we can increase that share of voice within the community.

所以我認為我們在頂級 KOL 的知名度非常高。我認為我們在 HAE 社區中的意識正在不斷增強。但我確實相信，我們將繼續發布令人印象深刻的令人鼓舞的數據，醫生和患者都會感興趣。隨著我們不斷發展我們的組織，希望我們能夠增加社區內的發言權。

And, Hartaj, regarding biomarkers, the biomarkers that we and others use in this space are useful for target engagement. But I don't want to, I think, get up to the level of surrogacy. So I think we'll deal with the use of PD to inform the potential dataset that will bring to regulators but not rely on it.

Hartaj，關於生物標誌物，我們和其他人在這個領域使用的生物標記對於目標參與非常有用。但我認為，我不想達到代孕的程度。因此，我認為我們將使用 PD 來告知潛在的資料集，這些資料集將為監管機構帶來但不依賴它。

As I mentioned before, in other meetings that we've had here in investor settings, the PK in itself, I think, is a stronger supporter of potential effectiveness. We target 12 micrograms per mL as the threshold, we believe, confirms the potential for effectiveness. So we've been looking very closely at that.

正如我之前提到的，在我們在投資者環境中舉行的其他會議中，我認為 PK 本身是潛在有效性的更強有力的支持者。我們的目標是每毫升 12 微克作為閾值，我們相信，這證實了有效性的潛力。所以我們一直在非常密切地關注這一點。

We will be looking obviously at PK in patients in our Phase 3 trial. So PK and PD will support but I don't think replace the dataset we'll be able to use for Phase three.

在我們的 3 期試驗中，我們將明顯地關注患者的 PK。因此 PK 和 PD 將支持，但我認為不會替換我們能夠在第三階段使用的資料集。

Great. Thank you for all the questions.

偉大的。謝謝你提出的所有問題。

Joe Pantginis, H.C. Wainwright. Joe, are you there? Okay, we'll go to the next analyst until Joe is able to connect.

喬潘吉尼斯，H.C.溫賴特。喬，你在嗎？好的，我們會去找下一位分析師，直到 Joe 能夠接通為止。

Ingrid Reichermeier, Wedbush. Ingrid, you might be on mute. Ingrid, are you on mute? To the audience, please give us a second.

英格麗德‧賴歇梅爾，韋德‧布希。英格麗德，你可能處於靜音狀態。英格麗德，你靜音了嗎？各位觀眾，請給我們一點時間。

Farhana Sakloth, Ladenburg.

Farhana Sakloth，拉登堡。

Hi, good morning. This is Farhana on behalf of Michael. Firstly, congrats on the quarter. As most of our questions have been asked, we will just follow up on one. You guys said that the Phase 1b was enrolling faster because there was no placebo arm. For the Phase 3, if I heard correctly, for the design, there is going to be a placebo arm. So do you see that there will be an impact on enrollment?

早安.我是法爾哈納，代表麥可。首先，恭喜本季。由於我們的大部分問題都已被問到，我們將只跟進其中一個。你們說 1b 期的入組速度較快，因為沒有安慰劑組。對於第三階段，如果我沒聽錯的話，對於設計，將會有一個安慰劑組。那麼您認為這會對入學產生影響嗎？

I do think that there will be an impact on enrollment. But I think that we'll be able to mitigate it with a variety of factors, including ideally strong proof-of-concept data that will continue to support the profile and raise awareness among sites. We have intentions of making this a global trial as well, which will increase the opportunity for patients around the world to experience 0215 and also to contribute to our dataset.

我認為這會對入學產生影響。但我認為我們將能夠透過多種因素來緩解這個問題，包括理想情況下強大的概念驗證數據，這些數據將繼續支持個人資料並提高網站之間的認識。我們也打算將此作為一項全球試驗，這將增加世界各地患者體驗 0215 並為我們的數據集做出貢獻的機會。

We've been working very closely with the community and not just talking about the profile, but also in the development of this medicine. And I think we all already have strong support from the community demonstrated by the enrollment that we've talked about with 0215. And ideally that support will translate into support for Phase 3 and then enrollment into the trial in Phase 3. Thank you.

我們一直與社區密切合作，不僅討論概況，還討論這種藥物的開發。我認為我們都已經得到了社區的大力支持，這從我們與0215 討論的註冊中可以看出。理想情況下，這種支持將轉化為對第3 階段的支持，然後註冊進入第3 階段的試驗。謝謝。

Thanks for the questions, Farhana.

謝謝你的提問，法爾哈納。

Joe Pantginis, H.C. Wainwright.

喬潘吉尼斯，H.C.溫賴特。

Hey, everybody, sorry about that. That was Murphy's Law of connectivity issue timing. But I appreciate the getting back in. So my question is also on the Phase 3. I guess I'll ask it this way. Your goal is to accelerate the timing that you talked about. What do you consider the rate-limiting steps?

嘿，大家，對此感到抱歉。這就是連結問題時機的墨菲定律。但我很高興回到這裡。所以我的問題也是關於第三階段的。我想我會這樣問。你的目標是加快你所說的時間安排。您認為速率限制步驟是什麼？

I mean, there's a lot going on over the next several months. Do you need to be able to get to more solar oil lead data, additional follow-up across the board? What kind of logistics, design, regulatory discussions in CMC. I basically listed a lot there. But what do you think of the rate-limiting steps?

我的意思是，接下來的幾個月將會發生很多事情。您是否需要獲得更多太陽能油鉛數據以及全面的額外跟進？ CMC 進行什麼樣的物流、設計、監管討論。我基本上在那裡列出了很多。但您如何看待速限步驟？

You've answered the question yourself. I think you've outlined all of the things that we have to think about as we think about the plan for the start of the Phase 3. And without knowing the data, it's difficult for me to identify what factor could be contributing as a critical path or rate-limiting.

你自己已經回答了這個問題。我認為您已經概述了我們在考慮第三階段開始計劃時必須考慮的所有事情。在不了解數據的情況下，我很難確定哪些因素可能起到關鍵作用路徑或速率限制。

Just to repeat what you said, after we get the data, we need to analyze them, understand them, and finalize the approach for Phase 3. We need to get regulatory input from not just the US but around the world, as I mentioned, as we plan to make this a global trial.

重複你所說的，在我們獲得數據後，我們需要分析它們、理解它們，並最終確定第三階段的方法。正如我所提到的，我們不僅需要從美國而且需要從世界各地獲得監管意見，因為我們計劃將其作為全球試驗。

Obviously, we're making drug thinking that we're going to continue dosing people with this disease as hopefully CMC. Does it impact timelines too much? But we'll have to do some work on dose selection, which can impact the timing for the start of the Phase 3.

顯然，我們在開發藥物時認為我們將繼續為患有這種疾病的患者提供 CMC 劑量。對時間軸影響太大嗎？但我們必須在劑量選擇上做一些工作，這可能會影響第三階段的開始時間。

So we're going to be looking very deeply at all of those steps, and as mentioned before, look for opportunities to accelerate. And when we share the updates with the Q1 data, we anticipate being able to share a more robust timeline to Phase 3 as well as the Phase 3 trial itself.

因此，我們將非常深入地研究所有這些步驟，並且如前所述，尋找加速的機會。當我們分享第一季數據的更新時，我們預計能夠分享更可靠的第三階段時間表以及第三階段試驗本身。

I appreciate the color. Thanks.

我很欣賞它的顏色。謝謝。

Ingrid Reichermeier, Wedbush.

英格麗德‧賴歇梅爾，韋德‧布希。

Hi, this is Ingrid on for Laura Chico. Just any color on the baseline characteristics you can share at this time of the patients who have enrolled in the ALPHA-STAR trial. Just trying to get a sense of demographics if you can share that. Thank you.

大家好，我是勞拉·奇科的英格麗。您此時可以分享已參加 ALPHA-STAR 試驗的患者的基線特徵上的任何顏色。如果你能分享的話，只是想了解人口統計。謝謝。

Yeah, I can't share the specifics about the demographics at this point. But I can tell you that the inclusion and exclusion criteria of our trial are very similar to what's been done in other diseases in the space. And in fact, we decided ours based on other trials. So we would anticipate a similar set of baseline demographics in terms of the severity of the disease and background or history of medication use has been demonstrated with other trials.

是的，目前我無法分享有關人口統計數據的具體資訊。但我可以告訴你，我們試驗的納入和排除標準與該領域其他疾病的納入和排除標準非常相似。事實上，我們是根據其他試驗所做的決定。因此，我們預計其他試驗已經證明了在疾病嚴重程度和藥物使用背景或歷史方面有一組類似的基線人口統計。

I can tell you that we've been up, as you well know, from ClinicalTrials.gov. We've been up in the US and Canada. So the data will be limited to patients from US and Canada.

我可以告訴您，正如您所知，我們已經從 ClinicalTrials.gov 上獲取資訊。我們已經去過美國和加拿大了。因此，這些數據將僅限於來自美國和加拿大的患者。

Thank you.

謝謝。

This concludes today's Q&A session. I'll now turn the call back over to Jill.

今天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 at the company, including our STAR-0310 program. We look forward to speaking with you again soon. Liz.

謝謝你，接線生。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，包括我們的 STAR-0310 計劃。我們期待很快再次與您交談。莉茲。

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。您可以透過我們網站 www.astriatx.com 上的投資者關係頁面進行為期 90 天的網路廣播重播。謝謝。