ACELYRIN Inc (SLRN) 2023 Q3 法說會逐字稿

Good day and thank you for standing by. Welcome to the ACELYRIN Q3 2023 Earnings Conference call. (Operator Instructions). Please be advised that today's conference is being recorded. I would now like to hand the conference over to Tyler Marciniak, Vice President of Investor Relations, Communications and Corporate Operations. Please go ahead.

美好的一天，感謝您的支持。歡迎參加 ACELYRIN 2023 年第三季財報電話會議。 （操作員說明）。請注意，今天的會議正在錄製中。現在我想將會議交給投資者關係、傳播和公司營運副總裁 Tyler Marciniak。請繼續。

Thank you, Operator. Good afternoon, everyone, and thank you for joining us. Before we begin, I'd like to remind the audience that this conference call will contain forward-looking statements, such as those related to progress of our clinical trials and anticipated data readouts, our future financial and operating results and investments, and our ability to commercialize our product candidates. These forward-looking statements involve risks and uncertainties that could cause our actual results and events to differ materially.

謝謝你，接線生。大家下午好，感謝您加入我們。在開始之前，我想提醒聽眾，本次電話會議將包含前瞻性陳述，例如與我們的臨床試驗進展和預期數據讀數、我們未來的財務和運營業績和投資以及我們的能力相關的陳述將我們的候選產品商業化。這些前瞻性陳述涉及風險和不確定性，可能導致我們的實際結果和事件出現重大差異。

We urge you to review the Risk Factors section of our Form 10-Q for the quarter ended June 30, 2023, filed with the SEC and also available on our website at acelyrin.com, along with statements in today's press release and our slide presentation, which identify certain factors that could cause our actual results, performance and events to differ materially.

我們敦促您查看我們向SEC 提交的截至2023 年6 月30 日季度的10-Q 表格中的風險因素部分，該部分也可在我們的網站acelyrin.com 上獲取，以及今天的新聞稿和幻燈片演示中的聲明，它確定了可能導致我們的實際結果、績效和事件出現重大差異的某些因素。

Additionally, these statements are based on information available to us today, November 7, 2023, and we undertake no obligation to update them as circumstances may change. Joining us on today's call are Dr. Shao-Lee Lin, our founder and CEO, and Gil Labrucherie, our Chief Financial Officer. I will now turn the call over to Dr. Lin. Shao-Lee?

此外，這些聲明是基於我們今天（2023 年 11 月 7 日）獲得的信息，我們不承擔因情況可能發生變化而更新這些信息的義務。加入我們今天電話會議的有我們的創始人兼首席執行官林少利博士和我們的首席財務官吉爾·拉布魯切裡。我現在將電話轉給林醫師。少李？

Thank you, Tyler. Good afternoon, everyone. Thank you for joining us for ACELYRIN's third quarter update call. As we approach the end of 2023, we feel fortunate for the progress we have made throughout the course of the year. We began in January with the transformative expansion of our portfolio through the acquisition of another private INI company.

謝謝你，泰勒。大家下午好。感謝您參加 ACELYRIN 第三季更新電話會議。隨著 2023 年的臨近，我們對這一年所取得的進展感到幸運。我們從一月份開始透過收購另一家私人 INI 公司來變革性地擴展我們的產品組合。

And in May, we were pleased to close a successful IPO in a challenging market environment. We are grateful to our investors for walking alongside with us in our journey as we remain focused on building a leading INI company and continuing to advance programs across multiple autoimmune and inflammatory diseases, with the goal to deliver transformative medicines for patients.

五月份，我們很高興在充滿挑戰的市場環境中成功完成了首次公開募股。我們感謝投資者在我們的旅程中與我們同行，我們仍然專注於打造一家領先的 INI 公司，並繼續推進針對多種自體免疫和發炎疾病的項目，目標是為患者提供變革性藥物。

Our strategy remains steadfast, to identify candidates we believe are diamonds in the rough, where, based on molecule characteristics, our collective experience and expertise, and the evolving scientific and medical understanding, we can establish a development plan that tests our hypotheses around clinical differentiation and the potential benefit for patients.

我們的策略仍然堅定不移，以確定我們認為是未加工的鑽石的候選人，根據分子特徵、我們的集體經驗和專業知識以及不斷發展的科學和醫學理解，我們可以製定一個開發計劃來測試我們圍繞臨床分化的假設以及對患者的潛在益處。

We are advancing our portfolio of programs across multiple indications, including izokibep, a next generation inhibitor of IL-17A being studied in multiple trials with registrational potential within the rheumatology, dermatology and ophthalmology settings. Lonigutamab, a subcutaneously delivered inhibitor of IGF-1 receptor being developed for thyroid eye disease, and ACELYRIN 517, an earlier stage program we are evaluating for allergy related mass cell driven diseases such as chronic urticaria.

我們正在跨多個適應症推進我們的計畫組合，包括 izokibep，一種下一代 IL-17A 抑制劑，正在多項試驗中進行研究，在風濕病學、皮膚病學和眼科領域具有註冊潛力。 Lonigutamab 是一種皮下注射的 IGF-1 受體抑制劑，正在開發用於治療甲狀腺眼疾；ACELYRIN 517 是我們正在評估過敏相關的大量細胞驅動疾病（如慢性蕁麻疹）的早期計畫。

In addition to our clinical progress, we continue to build our organizational capability and capacity to support our portfolio. Most recently, we announced the appointments of Patricia Turney as our Chief Technical Operations Officer responsible for overseeing technical operations, CMC regulatory, corporate quality, and facilities. Patricia brings to ACELYRIN more than 25 years of biopharmaceutical experience across R&D, clinical and commercial supply management and expands our capacity for multi asset, late-stage manufacturing at a pivotal time as we advance a robust portfolio with multiple large scale clinical trials underway and prepare for potential regulatory filings and commercial launches.

除了我們的臨床進展之外，我們還繼續建立我們的組織能力和能力來支持我們的產品組合。最近，我們宣布任命 Patricia Turney 為首席技術營運官，負責監督技術營運、CMC 監管、企業品質和設施。 Patricia 為ACELYRIN 帶來了超過25 年的生物製藥經驗，涉及研發、臨床和商業供應管理，並在關鍵時刻擴大了我們的多資產、後期製造能力，因為我們正在推進穩健的產品組合，正在進行多項大規模臨床試驗並準備好用於潛在的監管備案和商業發布。

We also welcomed in September Dr. Shep Mpofu, our Senior Vice President of Development responsible for clinical development and translational sciences. Shep brings more than 20 years of industry experience, including a long tenure at Novartis, where he most recently served as Senior Vice President and Chief Medical Officer for Novartis Gene Therapies. Prior to that, Shep was the global lead for [psychicidomab], where he advanced the product from early development through to multiple approvals across indications including psoriatic arthritis or PSA, hidradenitis suppurativa, or HS, uveitis and axial spondyloarthritis, or axSpA. His extensive experience will be key as we advance our pipeline across many of the same disease states.

9 月份，我們也迎來了負責臨床開發和轉化科學的開發資深副總裁 Shep Mpofu 博士。 Shep 擁有 20 多年的行業經驗，包括在諾華長期任職，最近擔任諾華基因治療公司的高級副總裁兼首席醫療官。在此之前，Shep 是[psychicidomab] 的全球負責人，他推動該產品從早期開發到多個適應症的批准，包括銀屑病關節炎(PSA)、化膿性汗腺炎(HS)、葡萄膜炎和中軸型脊椎關節炎(axSpA)。當我們在許多相同疾病狀態下推進我們的產品線時，他豐富的經驗將發揮關鍵作用。

While Gil will review our financials in greater detail later on the call, I do want to underscore our strong financial position. With nearly $800 million on our balance sheet, we can execute on our strategy over the coming months and years and achieve numerous key milestones across the entire portfolio of programs and indications. Let's turn now to a review of our progress across the portfolio.

雖然吉爾將在稍後的電話會議上更詳細地審查我們的財務狀況，但我確實想強調我們強大的財務狀況。我們的資產負債表上有近 8 億美元，我們可以在未來幾個月和幾年內執行我們的策略，並在整個專案和適應症組合中實現眾多關鍵里程碑。現在讓我們回顧一下我們在整個產品組合中取得的進展。

As a recap, izokibep is a small protein therapeutic designed to inhibit IL-17A with a high potency through type binding affinity that has the potential for robust tissue penetration due to its small molecular size, which is about one 10th the size of a monoclonal antibody and has an albumin binding domain that extends half-life.

回顧一下，izokibep 是一種小蛋白治療劑，旨在透過類型結合親和力高效抑制 IL-17A，由於其分子尺寸小（約為單株抗體尺寸的十分之一），因此具有強大的組織滲透潛力並具有延長半衰期的白蛋白結合域。

We have hypothesized that the high potency and small size of izokibep can lead to clinically meaningfully differentiated responses for patients across multiple indications where this mechanism of action has been validated and that this can be achieved with a safety profile consistent with that of the IL-17A class, as has been demonstrated by the currently marketed monoclonal antibodies [psychicidomab and exicisimab].

我們假設，izokibep 的高效力和小尺寸可以為多種適應症的患者帶來臨床上有意義的差異化反應，其中這種作用機制已經得到驗證，並且這可以透過與IL-17A 一致的安全性來實現類，正如目前市售的單株抗體 [psychicidomab 和 exicisimab] 所證明的那樣。

IL-17A as a target has not demonstrated dose limiting toxicity over 10 years of postmarketing and millions of patient years of safety experience. This will be important as we discuss what appears to be an evolving understanding around targeting the IL-17 axis more broadly than selectively targeting IL-17A.

IL-17A 作為標靶，經過 10 年的上市後和數百萬患者年的安全經驗，尚未表現出劑量限制性毒性。當我們討論圍繞靶向 IL-17 軸（比選擇性靶向 IL-17A 更廣泛）似乎正在不斷發展的理解時，這一點非常重要。

Let me begin with psoriatic arthritis, which is our most advanced program and represents the largest potential indication for izokibep. Psoriatic arthritis is a chronic inflammatory disease with multiple clinical manifestations, including arthritis, psoriasis, spondylitis, dactylitis and importantly, enthesitis, which is an inflammation of the strong, dense, poorly vascular tissues that anchor our ligaments and tendons to bone.

讓我從乾癬性關節炎開始，這是我們最先進的計劃，也是 izokibep 最大的潛在適應症。乾癬性關節炎是一種慢性發炎性疾病，具有多種臨床表現，包括關節炎、乾癬、脊椎炎、指趾炎，重要的是附著點炎，這是一種將韌帶和肌腱固定在骨骼上的強而緻密、血管不良的組織的發炎。

Enthesitis impacts the majority of moderate to severe psoriatic arthritis patients and has been historically very difficult to treat. It is a marker of disease severity and a source of residual pain and physical dysfunction which impacts quality of life for patients.

附著點炎影響大多數中度至重度乾癬關節炎患者，且歷來很難治療。它是疾病嚴重程度的標誌，也是影響患者生活品質的殘餘疼痛和身體功能障礙的根源。

There are approximately 1.6 million PSA patients in the U.S. And the 2022 PSA treatment market was valued at $8.8 billion globally and is estimated to grow to nearly $18 billion by 2030. Historically, PSA treatments have been more effective in the joints and skin, but not the harder to treat manifestations of the disease, such as enthesitis.

美國約有 160 萬名 PSA 患者，2022 年全球 PSA 治療市場價值為 88 億美元，預計到 2030 年將增長到近 180 億美元。從歷史上看，PSA 治療對關節和皮膚更有效，但並非如此疾病的表現越難治療，例如附著點炎。

Rapid, deeper and more durable resolution of disease across clinical measures is the key to improving overall quality of life, which is ultimately our goal for our patients. We have already shared results from a phase two placebo-controlled trial of izokibep in PSA, which demonstrated differentiated dose ordered responses as early as one month into treatment and increasing over time. This included an ACR 50 response of 50% at week twelve or 44%. placebo adjusted. Resolution of enthesitis, as measured by the Leeds Enthesitis Index, was 82% at week eight at our 80 milligram every other week dose.

透過臨床措施快速、更深入、更持久地解決疾病是改善整體生活品質的關鍵，這也是我們為患者提供的最終目標。我們已經分享了 izokibep 在 PSA 中的第二階段安慰劑對照試驗的結果，該試驗表明早在治療一個月後就有不同的劑量順序反應，並且隨著時間的推移而增加。其中包括第 2 週時 ACR 50 反應為 50% 或 44%。安慰劑調整。根據利茲附著點炎指數測量，在每隔一週服用 80 毫克的劑量下，第八週時附著點炎的緩解率為 82%。

Week twelve was not a protocol specified time point for this measure. (Inaudible) resolution is the standard approach to reporting improvements for enthesitis. To enable comparison with recently reported enthesitis data for one of the IL-17AF AF inhibitors, we also analyzed subjects with LEI of two plus at baseline, with an improvement of two plus points at our week eight versus the other agents data at week twelve. This analysis showed 100% response at week eight in patients receiving 80 milligrams of izokibep versus zero percent in placebo.

第十二週不是該措施的方案指定時間點。 （聽不清楚）解析度是報告附著點炎改善的標準方法。為了與最近報告的一種IL-17AF AF 抑制劑的附著點炎數據進行比較，我們也分析了基線時LEI 為2+ 的受試者，與第12 週其他藥物的數據相比，我們在第八週時改善了2+ 點。分析顯示，接受 80 毫克 izokibep 治療的患者在第八週有 100% 的緩解，而安慰劑組的緩解率為 0%。

These results are relative to 71% reported at 120 milligrams for the IL-17AF agent at twelve weeks without disclosure of a placebo as a reference for that agent. At [ULR] in June of 2022, we presented primary endpoint 16-week data showing that izokibep demonstrated clinically meaningful benefits across disease manifestations, including 52% ACR 50 response, 85% [POSI] 75 response, and 88% resolution of enthesitis, which, to our knowledge, is a level of resolution not previously reported for any other agent.

這些結果與 12 週時 120 毫克 IL-17AF 藥物報告的 71% 相關，而沒有透露安慰劑作為該藥物的參考。在2022 年6 月的[ULR] 上，我們提供了主要終點16 週數據，顯示izokibep 在各種疾病表現中表現出具有臨床意義的益處，包括52% ACR 50 緩解率、85% [POSI] 75緩解率和88% 的附著點炎消退率，據我們所知，這是之前任何其他代理都沒有報導過的分辨率水平。

These clinical benefits subsequently drove significant improvements in quality of life across all domains, and importantly, this included statistically significant improvements in pain, functional capacity and sleep disturbance, as measured by the Psoriatic Arthritis Impact of Disease Questionnaire, or PSAID. The PSAID is a validated psoriatic arthritis specific patient reported outcome measurement.

這些臨床益處隨後推動了各個領域生活品質的顯著改善，重要的是，這包括透過銀屑病關節炎疾病影響問卷 (PSAID) 測量的疼痛、功能能力和睡眠障礙的統計顯著改善。 PSAID 是經過驗證的乾癬性關節炎特定患者報告的結果測量。

Furthermore, earlier this year, we were delighted to report initial long-term efficacy from the same phase two trial that showed that with longer duration of treatment, patients experienced durable and deepening resolution of disease across clinical manifestations of PSA, leading to further improvements in quality of life as measured by the PSAID.

此外，今年早些時候，我們很高興地報告了同一二期試驗的初步長期療效，該試驗表明，隨著治療時間的延長，患者的 PSA 臨床表現得到持久且深入的疾病緩解，從而進一步改善由PSAID 衡量的生活品質。

Additional data demonstrating that increased duration of therapy continues to enhance resolution of disease will be presented in both poster and oral podium sessions taking place next Monday during the upcoming American College of Rheumatology's Convergence in San Diego.

更多數據表明，增加治療持續時間可以繼續提高疾病的解決率，這些數據將在下週一即將在聖地牙哥舉行的美國風濕病學會會議期間舉行的海報和口頭講台會議上公佈。

At 46 weeks of participants receiving izokibep 80 milligrams every other week, 79% achieved ACR 50 response, up from 52% at week 16, and even higher orders of clinicals of response in measures approximating resolution of disease were observed, with 52% achieving ACR 70, 71% achieving POSI 100, and 89% achieving enthesitis resolution. Notably, patients who switched from placebo to 80 milligrams every other week at week 16 responded quickly, with more than 60% of patients in both the switch group, as well as the original 80 milligram every other week group achieving minimal disease activity by week 46.

在第46 週，每隔一周接受izokibep 80 毫克的參與者中，79% 的人實現了ACR 50 緩解，高於第16 週時的52%，並且在接近疾病消退的措施中觀察到了更高級別的臨床緩解，其中52% 的人實現了ACR 70%，71% 達到 POSI 100，89% 達到附著點炎解決。值得注意的是，在第16 週從安慰劑改為每隔一周80 毫克的患者反應迅速，轉換組和最初每隔一周80 毫克的組中超過60% 的患者在第46 週時達到了最低的疾病活動度。

Importantly, this efficacy was delivered with a safety profile consistent with previous izokibep experience and that of the IL-17A class as a whole with no evidence of dose limiting toxicity. Modeling from the phase two PSA data predicted the potential to increase response over time as has been demonstrated with the 46 week data. The modeling further predicts the potential for increased efficacy with higher doses over the 80 milligrams every other week utilized in the phase two trial.

重要的是，這種功效的安全性與先前 izokibep 的經驗以及整個 IL-17A 類的安全性一致，沒有劑量限制毒性的證據。根據第二階段 PSA 數據進行的建模預測了隨著時間的推移，反應增加的潛力，正如 46 週數據所證明的那樣。該模型進一步預測，與第二階段試驗中每隔一週使用 80 毫克的劑量相比，更高的劑量可能會提高療效。

To that end, the ongoing phase 2b/3 trial in PSA is evaluating both 160 milligrams weekly and every other week to continue to maximize potential responses for patients. Aside from the higher dosing, the design of this trial is consistent with that of the phase two, with a few notable exceptions. Firstly, this is a truly global study with 352 patients across 71 sites, including 40 in the U.S. and 30 internationally to enable the potential for registration across geographies.

為此，正在進行的 PSA 2b/3 期試驗正在評估每周和每隔一周 160 毫克的劑量，以繼續最大限度地提高患者的潛在反應。除了劑量較高外，該試驗的設計與第二階段的設計一致，但有一些值得注意的例外。首先，這是一項真正的全球性研究，涉及 71 個地點的 352 名患者，其中 40 名患者在美國，30 名患者在國際上，從而實現跨地域註冊的潛力。

In addition, there is an increased percentage of enthesitis at baseline and an increased percentage of TNF failures, meaning individuals who have had an inadequate response intolerance or contraindication. These aspects all have the potential to impact the specific point estimates relative to phase two, but are important in understanding the potential benefits of izokibep for PSA patients. Both are important given the contribution of enthesitis to severity of disease, including continued pain and disability, and also the increasing number of patients who have not simply been exposed to TNF inhibitors but have demonstrated an inadequate clinical response.

此外，基線時附著點炎的百分比增加，TNF 失敗的百分比也有所增加，這意味著個體有反應不足、不耐受或禁忌症。這些方面都有可能影響相對於第二階段的具體點估計，但對於了解 izokibep 對 PSA 患者的潛在益處很重要。考慮到附著點炎對疾病嚴重程度（包括持續的疼痛和殘疾）的影響，以及越來越多的患者不僅暴露於 TNF 抑制劑，而且表現出臨床反應不足，兩者都很重要。

This phase 2b/3 trial in PSA completed enrollment in the second quarter of 2023. Over 75% of patients have completed through the primary endpoint at week 16, and the discontinuation rate is 5.9%. Top line data continues to be expected in the first quarter of 2024. Now, we'll turn our attention to hidradenitis ?suppurativa, which continues to be an area of rapid evolution. Just last week, only the second treatment for HS and the first new option for patient in almost a decade was approved by the FDA.

這項 PSA 2b/3 期試驗於 2023 年第二季完成入組。超過 75% 的患者在第 16 週完成了主要終點，中止率為 5.9%。預計 2024 年第一季將繼續發布頂線數據。現在，我們將注意力轉向化膿性汗腺炎，它仍然是一個快速發展的領域。就在上週，FDA 僅批准了第二種針對 HS 的治療方法，也是近十年來患者的第一個新選擇。

We have the great fortune at ACELYRIN of having members of our team who held important roles in the context of each of these approved therapies, and for all of us it's always gratifying to see new treatment options for patients. At the same time, while the IL-17A safety profile is well established, we have also seen, especially recently, our understanding of the safety profile of targeting subunits beyond IL-17A continues to evolve and may become a more important consideration. Targeting both A and F leads to dose responsive increase in fungal infections. This was seen in data from both agents targeting inhibition of IL-17A and F.

我們 ACELYRIN 非常幸運，我們的團隊成員在每種已批准的療法中都發揮了重要作用，對於我們所有人來說，看到患者的新治療選擇總是令人欣慰的。同時，雖然IL-17A 的安全性已得到充分確立，但我們也看到，尤其是最近，我們對IL-17A 以外的靶向亞基的安全性的理解不斷發展，並可能變得更重要的考慮因素。同時靶向 A 和 F 會導致真菌感染的劑量反應性增加。這可以從兩種標靶抑制 IL-17A 和 F 的藥物的數據中看出。

After 24 weeks of treatment, one demonstrated an approximate doubling of fungal infection risk from twelve weeks, which increased to about 20% in the planned dose and almost 30% in their higher dose with the beginnings of reports of recurrence of these fungal infections in areas beyond just skin. Additionally, the risk of suicidal ideation and behavior was noted in a recent label of an IL-17AF inhibitor.

治療24 週後，真菌感染風險比12 週增加了約一倍，在計劃劑量中增加到約20%，在較高劑量中增加了近30%，並且開始有報導稱這些真菌感染在某些地區復發不僅僅是皮膚。此外，最近的 IL-17AF 抑制劑標籤中還指出了自殺意念和自殺行為的風險。

This has been noted previously in the label of an anti-IL-17 receptor inhibitor which blocks all the subunits of IL-17, including IL-17F. Cumulative data from these two agents over the registrational programs raises the question of relationship between inhibiting IL-17 more broadly than IL-17A, specifically the potential association with the inhibition of IL-17F.

先前在抗 IL-17 受體抑制劑的標籤中已註意到這一點，該抑制劑可阻斷 IL-17 的所有亞基，包括 IL-17F。這兩種藥物在註冊計劃中的累積數據提出了比 IL-17A 更廣泛地抑制 IL-17 之間的關係問題，特別是與抑制 IL-17F 的潛在關聯。

This recent label also noted the requirement for routine laboratory monitoring for liver toxicity, which has not previously been noted for the IL-17A inhibitors. So, the landscape is actively evolving in terms of balancing efficacy and safety hurdles for new treatments for HS patients.

最近的標籤還指出了對肝毒性進行常規實驗室監測的要求，此前 IL-17A 抑制劑並未註意到這一點。因此，在平衡熱射病患者新療法的療效和安全性障礙方面，情況正在積極發展。

We believe in izokibep's potential in HS, with roughly 25% of patients achieving high score 100 responses within twelve weeks, which means they rapidly achieve resolution of all abscesses and nodules without new training tubs. This is a level of responders achieved in half the time reported by others and without the safety or tolerability considerations of targeting IL-17F in addition to IL-17A.

我們相信 izokibep 在治療 HS 方面的潛力，大約 25% 的患者在 12 週內達到高分 100 分，這意味著他們無需新的訓練池即可快速解決所有膿腫和結節。這是在其他人報告的一半時間內達到的應答水平，並且沒有考慮除了 IL-17A 之外還靶向 IL-17F 的安全性或耐受性。

As we've previously shared, both our Phase 2b/3 and our ongoing Phase 3 trial are moving forward and discussions with the FDA will help inform next steps to advance our registrational program. We expect to have an update by end of this year or early next year.

正如我們之前所分享的，我們的 2b/3 期和正在進行的 3 期試驗都在向前推進，與 FDA 的討論將有助於為下一步推進我們的註冊計劃提供資訊。我們預計將在今年年底或明年初進行更新。

And in addition to PSA and HS, we continue to explore the potential for izokibep to make a meaningful difference for patients with both axSpA and uveitis. Enthesitis is a central feature of axSpA, and we believe the rates of enthesitis resolution demonstrated in the Phase Two PSA trial suggest the potential for clinically meaningful differentiated benefits for patients with this disease.

除了 PSA 和 HS 之外，我們還繼續探索 izokibep 對 axSpA 和葡萄膜炎患者產生有意義的影響的潛力。附著點炎是 axSpA 的一個核心特徵，我們相信第二階段 PSA 試驗中證明的附著點炎消退率表明該疾病患者有可能獲得具有臨床意義的差異化益處。

We will use the optimal dose from the PSA program to inform a planned future Phase 3 program in axSpA. We also continue to enroll our Phase 2b/3 clinical trial of izokibep as a treatment for uveitis. Previously reported data for another IL-17A inhibitor delivered intravenously has validated the inhibition of IL-17A as a potential therapeutic for uveitis. While izokibep is the lead program in our portfolio, we have two other programs, lonigutamab and ACELYRIN 517, which we are developing in thyroid eye disease and [mass filtered] of diseases.

我們將使用 PSA 計劃的最佳劑量來為 axSpA 計劃的未來 3 期計劃提供資訊。我們也繼續進行 izokibep 治療葡萄膜炎的 2b/3 期臨床試驗。先前報告的另一種靜脈注射 IL-17A 抑制劑的數據證實了 IL-17A 的抑製作用是葡萄膜炎的潛在治療方法。雖然 izokibep 是我們產品組合中的主導項目，但我們還有另外兩個項目，lonigutamab 和 ACELYRIN 517，我們正在開發用於甲狀腺眼疾和疾病的[品質過濾]。

Thyroid eye disease is a vision threatening progressive chronic autoimmune disease, and similar to HS, the TED landscape is evolving rapidly. Our team has deep experience in this indication, with many involved in developing the only currently approved treatment. Recent clinical data demonstrating the effectiveness of inhibiting IGF-1 receptor in chronic TED supports our approach to developing lonigutamab, not just for acute disease, but also more like treatments for chronic inflammatory autoimmune diseases.

甲狀腺眼疾是一種威脅視力的進行性慢性自體免疫疾病，與 HS 類似，TED 領域正在迅速發展。我們的團隊在這一適應症方面擁有豐富的經驗，其中許多人參與了目前唯一批准的治療方法的開發。最近的臨床數據證明抑制 IGF-1 受體在慢性 TED 中的有效性支持了我們開發 lonigutamab 的方法，不僅用於急性疾病，而且更像是慢性發炎性自體免疫疾病的治療。

This includes targeting greater depth and durability of response with longer term dosing and the goal of achieving resolution of disease. Recent updates from the FDA to the warnings and precautions of the currently approved therapy also highlight hearing impairment as a serious, potentially permanent side effect of treatment. We have hypothesized this hearing impairment may be directly related to the inhibition of the normal function of IGF-1, given its role in regenerating cells of the inner ear subsequent to routine auditory insults.

這包括透過長期給藥來實現更大深度和持久的反應以及實現疾病解決的目標。 FDA 最近對目前批准的治療的警告和預防措施的更新也強調聽力障礙是一種嚴重的、可能永久性的治療副作用。鑑於 IGF-1 在常規聽覺損傷後內耳細胞再生中的作用，我們假設這種聽力損傷可能與 IGF-1 正常功能的抑制直接相關。

The unique characteristics of lonigutamab may allow us to optimize efficacy by maintaining minimum drug levels needed to achieve improved depth and durability of response, limit safety liability, including hearing impairment potentially associated with high maximum drug concentrations, and maximize patient convenience through subcutaneous delivery. The phase 1/2 trial of lonigutamab delivered subcutaneously in TED patients is ongoing.

羅尼古他單抗的獨特特性可能使我們能夠透過維持實現改善的反應深度和持久性所需的最低藥物水平來優化療效，限制安全責任，包括可能與高最大藥物濃度相關的聽力損傷，並透過皮下給藥最大限度地提高患者的便利性。在 TED 患者中皮下注射 lonigutamab 的 1/2 期試驗正在進行中。

We anticipate initial proof of concept data, including [proptosis] response and clinical activity score by end of first quarter 2024. ACELYRIN 517 is a fully human, highly potent IgG monoclonal antibody directed against c-Kit with the potential to address mass cell driven diseases. We are conducting a phase 1/2 proof of concept trial of ACELYRIN 517 and expect top line results in the second half of 2024. With that overview of the portfolio, let me now turn the call over to Gil for a review of our financials. Gil?

我們預計到2024 年第一季末可獲得初步概念驗證數據，包括[眼球突出]反應和臨床活動評分。ACELYRIN 517 是一種全人源高效IgG 單株抗體，針對c-Kit，具有解決大量細胞驅動疾病的潛力。我們正在進行 ACELYRIN 517 的 1/2 階段概念驗證試驗，預計在 2024 年下半年獲得頂線結果。在概述了產品組合之後，現在讓我將電話轉給 Gil，以審查我們的財務狀況。吉爾？

Thank you, Shao-Lee, for that overview of our portfolio. And good afternoon, everyone. As Shao-Lee mentioned, we are fortunate to be operating from a strong financial position, as we not only advance our portfolio of clinical stage programs, but also build our organizational capability and identify potential additional diamonds in the rough to add to our pipeline.

謝謝 Shao-Lee 對我們產品組合的概述。大家下午好。正如Shao-Lee 所提到的，我們很幸運能夠在強大的財務狀況下運營，因為我們不僅推進我們的臨床階段項目組合，而且還建立我們的組織能力並確定潛在的額外毛坯鑽石以添加到我們的管道中。

At September 30, 2023, cash and cash equivalents and short-term marketable securities totaled 788.4 million, which we expect to fund operations through key value driving milestones across all three programs. Research and development expenses were 74.6 million for the third quarter as compared to 12.5 million for the same period in 2022. Comparing 2023 to 2022, the company has undergone significant growth, including expansion of the izokibep program across multiple indications and the addition of two programs in 2023, both of which are now in clinical stage development.

截至 2023 年 9 月 30 日，現金和現金等價物以及短期有價證券總計 7.884 億美元，我們預計將透過所有三個計劃的關鍵價值驅動里程碑為營運提供資金。第三季研發費用為7,460萬美元，而2022年同期為1,250萬美元。與2023年和2022年相比，該公司經歷了顯著成長，包括將izokibep專案擴展到多個適應症以及增加兩個計畫2023 年，兩者目前均處於臨床階段開發。

General and administrative expenses were 19.9 million for the third quarter as compared to 2.9 million for the same period in 2022. The quarter ended September 30, 2023, includes stock-based compensation expense of 11.7 million. These increases in expenses were primarily a result of expanding our organizational capability to support the development of our broad portfolio of immunology product candidates.

第三季的一般及管理費用為 1,990 萬美元，而 2022 年同期為 290 萬美元。截至 2023 年 9 月 30 日的季度包括 1,170 萬美元的股票補償費用。費用的增加主要是由於我們擴大了組織能力，以支持我們廣泛的免疫學候選產品組合的開發。

Finally, our net loss for the third quarter of 2023 totaled 83.9 million, or $0.87 per share, compared to 14.4 million, or $8.17 per share, for the third quarter of 2022. The total net loss for the current quarter includes stock-based compensation expense of 15.3 million. As you can see, we continue to carefully allocate capital across our robust clinical portfolio, and we're delighted to have a strong financial position from which to continue our important work for patients. And now, I will turn the call back to Shao-Lee. Shao-Lee?

最後，我們2023 年第三季的淨虧損總計8,390 萬美元，即每股0.87 美元，而2022 年第三季的淨虧損為1,440 萬美元，即每股8.17 美元。本季的淨虧損總額包括股票薪資費用1530萬。正如您所看到的，我們繼續在強大的臨床投資組合中謹慎分配資本，我們很高興擁有強大的財務狀況，可以繼續為患者開展重要的工作。現在，我將把電話轉回給少李。少李？

Thanks, Gil. As you've heard, we continue to make steady progress in our efforts to build a leading immunology company. We feel fortunate to have an experienced team, a robust pipeline, and a strong financial position providing runway through multiple key milestones across all three clinical programs.

謝謝，吉爾。正如您所聽說的，我們在打造領先的免疫學公司的努力中不斷取得穩步進展。我們很幸運擁有一支經驗豐富的團隊、強大的管道和強大的財務狀況，為所有三個臨床項目的多個關鍵里程碑提供了跑道。

We remain committed to our long-term vision to accelerate the development and commercialization of transformative medicines, to address unmet medical needs, and to deliver sustainable value to our shareholders, partners, and most importantly, to the patients we serve.

我們仍然致力於實現我們的長期願景，即加速變革性藥物的開發和商業化，解決未滿足的醫療需求，並為我們的股東、合作夥伴，最重要的是，為我們服務的患者提供可持續的價值。

In the ever evolving landscape of our industry, we understand the importance of adaptability and resilience. We are committed to making data driven, disciplined decisions, as well as being responsible stewards of our human and financial resources in navigating challenges and embracing opportunities. Once again, I thank you for your trust and support. We look forward to your continued partnership as we journey ahead together. Operator, we are now ready to open the call to questions.

在我們行業不斷發展的格局中，我們了解適應性和彈性的重要性。我們致力於做出數據驅動、嚴格的決策，並在應對挑戰和擁抱機會時負責任地管理我們的人力和財務資源。再次感謝您的信任與支持。我們期待與您繼續合作，共同前進。接線員，我們現在準備開始提問。

(Operator Instructions). Our first question comes from Yasmeen Rahimi from Piper Sandler. Please go ahead.

（操作員說明）。我們的第一個問題來自 Piper Sandler 的 Yasmeen Rahimi。請繼續。

Good afternoon, team, and thank you so much for all your really thoughtful remarks for us. Team, as we're awaiting that PSA data and early next year, could you maybe comment on sort of how soon post the second phase 2b, phase 3 would you be in a position to get ready and file for approval in PSA and whether the data would be sufficient on the heels of both of the results? If you could just provide color in that regard.

下午好，團隊，非常感謝您為我們提供的所有深思熟慮的評論。團隊，當我們等待 PSA 數據和明年初時，您能否評論一下第二階段 2b、第三階段之後您是否能夠做好準備並在 PSA 中申請批准，以及是否根據這兩個結果，數據就足夠了嗎？如果你能在這方面提供顏色的話。

And then two, if you could just maybe comment on how you're tracking, or have been tracking or tracking currently, like suicide ideation, liver enzyme abnormalities to the extent you can across all studies, and I'll jump back into the queue. And thank you again.

然後是兩個，如果您可以評論一下您正在如何跟踪，或者目前正在跟踪或正在跟踪，例如自殺意念，肝酶異常，您可以在所有研究中做到這一點，我會跳回隊列。再次感謝您。

Thank you, Yas. This is Shao-Lee. So, with regards to PSA, we anticipate that registration will require both the ongoing Phase 2b/3 that we hope to be part of that package, as well as a confirmatory study, which is standard for these indications. We haven't yet provided guidance specifically at the time post this study readout relative to when we think that will be.

謝謝你，亞斯。這是少李。因此，就 PSA 而言，我們預計註冊將需要正在進行的 2b/3 期（我們希望成為該計劃的一部分）以及驗證性研究（這是這些適應症的標準）。在發布本研究報告時，我們尚未提供與我們認為的時間相關的具體指導。

But obviously, we'll sort of move forward expeditiously as expeditiously as possible with regards to the signals, that you've noted, really, since the brodalumab experience with this group, these have been endpoints that have been followed across the IL-17 class, and we're following the standard approaches there as well.

但顯然，我們將盡可能迅速地推進關於信號的進展，您實際上已經註意到，自從該組的 brodalumab 經驗以來，這些都是 IL-17 中遵循的終點類，我們也遵循那裡的標準方法。

Okay, thank you. I'll jump back into the queue. Thank you.

好的謝謝。我會跳回隊列。謝謝。

Thank you. One moment for our next question. Our next question comes from Tyler Van Buren from TD Cowen, please go ahead.

謝謝。請稍等一下我們的下一個問題。我們的下一個問題來自 TD Cowen 的 Tyler Van Buren，請繼續。

Hi. This is Beth on for Tyler. Thank you guys for taking our questions. We have two for you, so first, looking forward to the top line PSA Phase 2/3 readout in Q1. How are you thinking about the bar for success given the bimekizumab Phase Three data and other recent competitor readouts.

你好。這是泰勒的貝絲。謝謝你們回答我們的問題。我們為您準備了兩個，所以首先，請期待第一季 PSA 第 2/3 階段的頂線讀數。鑑於 bimekizumab 三期數據和其他最近競爭對手的數據，您如何看待成功的標準。

And then two, for the [lonigutamab mad] TED patient readout in Q1. How many patients worth of data might we see across the three to four dose cohorts? And how derisking do you expect the early proptosis data to be as we think about efficacy in later stage trials? Thank you.

然後是兩個，用於第一季的 [lonigutamab mad] TED 患者讀數。在三到四個劑量組中，我們可以看到多少患者的數據？當我們考慮後期試驗的有效性時，您預期早期眼球突出數據的風險如何？謝謝。

Super. Thanks for that, Beth. So, your first question was about the upcoming PSA 2b/3 readout in first quarter of '24 and the bar for success. The way we think about this is that the phase Two study that we've already completed that went up to 80 milligrams, and we're going to share the long-term data, even additional measures of resolution of disease at the upcoming ACR meeting. We feel like that study already demonstrated the potential for differentiation with izokibep, especially the top dose, 80 milligrams every other week.

極好的。謝謝你，貝絲。因此，您的第一個問題是關於 24 年第一季即將發布的 PSA 2b/3 讀數以及成功的標準。我們的想法是，我們已經完成的第二階段研究的劑量達到了 80 毫克，我們將在即將舉行的 ACR 會議上分享長期數據，甚至是解決疾病的其他措施。我們認為研究已經證明了 izokibep 的差異化潛力，尤其是最高劑量，每隔一周 80 毫克。

We've seen top range results with regards to joints and skin at the week 16 primary endpoint, and really outsized enthesitis results as we've recapped today within that time frame, and that just haven't been seen before with other agents. And we've shared that at the 46-week time frame, we see sort of even continued deepening of those responses, again, as we've shared today with ACR 50s, or sorry, ACR 70s, up at above 50% POSI 100 scores up over 70%, and enthesitis is still in the kind of 80 to 90% range. So, we're very, very pleased with those results.

我們在第16 週的主要終點時看到了關於關節和皮膚的頂級結果，並且正如我們今天在該時間範圍內回顧的那樣，確實出現了巨大的附著點炎結果，這是其他藥物之前從未見過的。我們已經分享過，在 46 週的時間範圍內，我們再次看到這些反應甚至持續深化，正如我們今天分享的 ACR 50，或者抱歉，ACR 70，上升至 50% POSI 100 以上評分上升超過70%，附著點炎仍處於80% 至90% 的範圍內。所以，我們對這些結果非常非常滿意。

We think that they fundamentally derisk the 2b/3 that's coming up. We conducted that 2b/3, really because our modeling from that phase two suggested to us that we could get some additional efficacy out of pushing the exposure a bit more, within the context of this disease state. And so, that's the reason for the additional dose ranging, the 2b portion, if you will, of the 2b/3 that's upcoming. As a for instance, we know from our earlier psoriasis experience that moving from 80 every other week to 160 every other week in psoriasis did give us a bit of a bump with regards to efficacy.

我們認為他們從根本上消除了即將出現的 2b/3 的風險。我們進行了 2b/3，實際上是因為我們第二階段的模型表明，在這種疾病狀態的背景下，我們可以透過增加暴露量來獲得一些額外的功效。因此，這就是額外劑量範圍的原因，即即將推出的 2b/3 的 2b 部分（如果您願意的話）。舉例來說，我們從早期的牛皮癬治療經驗中得知，牛皮癬治療從每隔一周 80 次改為每隔一周 160 次，確實為我們的療效帶來了一些提升。

So, at a minimum, we hope to recapitulate that. But already we feel like we have a differentiated offering. And then your second question was about lonigutamab and how much data we would have moving forward and how derisking that is sort of overall.

因此，至少，我們希望重述這一點。但我們已經覺得我們提供了差異化的產品。然後你的第二個問題是關於 lonigutamab 以及我們將有多少數據向前推進以及總體上如何降低風險。

I think what you can anticipate is that from a initial proof of concept perspective, we'll have a number of patients that are very similar to what's been demonstrated previously for the [Viridian] and [immuninab] sort of compounds on the order of six or so patients in those experiences have been sufficient to really demonstrate the potential for a signal across both proptosis as well as clinical activity score.

我認為您可以預見的是，從最初的概念驗證角度來看，我們將擁有許多與先前針對 [Viridian] 和 [immuninab] 類化合物所展示的患者非常相似的患者，數量約為六種或者說，這些經歷中的患者已經足以真正證明跨突眼和臨床活動評分的訊號的潛力。

So, we'll have those measures within the context of TED patients to evaluate. We may have more patients than that, but as we move forward, we'll have a better beat on that. Because of the strong signal, in terms of efficacy that we see with this axis, we anticipate it's not going to take much more than that to see a signal for these agents. Again, as has been demonstrated already.

因此，我們將在 TED 患者的背景下對這些措施進行評估。我們的病人可能比這個多，但隨著我們的前進，我們將會有更好的進展。由於訊號很強，就我們在該軸上看到的功效而言，我們預計不需要太多時間就能看到這些藥物的訊號。再次，正如已經證明的那樣。

Thank you. One moment for our next question. Our next question comes from Vikram Purohit from Morgan Stanley. Please go ahead.

謝謝。請稍等一下我們的下一個問題。我們的下一個問題來自摩根士丹利的 Vikram Purohit。請繼續。

Hi, everyone. This is [Garth] on for Vikram. We have two questions regarding PSA and HS. So, for PSA, I was wondering, I was wondering what the competitor data readout data tells you, if anything, about the importance of molecule size for the treatment of PSA. And then in regards to HS, I was wondering, have you been able to further analyze the result to better understand the placebo response and discontinuation rate observed? If so, did you currently see any read across to the ongoing PSA readout? And are there measures that have been put in place for that study to prevent similar issues from arising? Thank you.

大家好。這是維克拉姆的[Garth]。我們有兩個關於 PSA 和 HS 的問題。所以，對於 PSA，我想知道，我想知道競爭對手的數據讀出數據告訴你什麼，如果有的話，關於分子大小對於 PSA 治療的重要性。然後，關於 HS，我想知道，您是否能夠進一步分析結果，以便更好地了解觀察到的安慰劑反應和停藥率？如果是這樣，您目前是否看到任何關於正在進行的 PSA 數據的解釋？研究是否採取了措施來防止類似問題的發生？謝謝。

Thank you for that, Garth. You know, maybe I'll start backwards a little bit to tie it back in, which is, and I appreciate the question. Obviously, given our HS readout that we shared in September, we've been extraordinarily hyper vigilant, with regards to putting in any measures such that we understand in real time are- continue to understand and ensure that we are understanding in real time any discontinuations, as well as putting into place anything that could help from a placebo response perspective.

謝謝你，加斯。你知道，也許我會稍微倒退一下，把它重新綁起來，我很欣賞這個問題。顯然，考慮到我們在 9 月分享的 HS 數據，我們一直非常高度警惕，採取任何措施，以便我們實時了解 - 繼續了解並確保我們實時了解任何停產情況，以及從安慰劑反應的角度採取任何可能有幫助的措施。

We don't anticipate any read through to our PSA, and we think that our sort of blinded, continued analysis hasn't suggested to us any issues in that regard. We have continued further deep dives with regards to the HS data set. And as I shared in our prepared remarks, we anticipate having more information with regards to that program by end of year, early next year to share when we have relevantly compiled both our conversations with the health authorities, as well as the deep dives that continue to be ongoing.

我們預計不會有人通讀我們的 PSA，我們認為我們這種盲目的、持續的分析並沒有向我們表明這方面的任何問題。我們繼續深入研究 HS 資料集。正如我在準備好的發言中所分享的那樣，我們預計到今年年底、明年初我們將獲得有關該計劃的更多信息，屆時我們將與衛生當局進行相關對話，以及繼續進行的深入研究持續進行。

So, bottom line is, HS continues to move forward with regards to the 2b/3 study that ran out as primary as well as the ongoing phase three as planned, as we had previously discussed. We don't anticipate a read through to PSA. And from the PSA perspective, we do think that there is importance still with regards to the molecule size and the potential for differentiation. We think our phase two results, especially in enthesitis, point to that, exactly where the threshold was for the size cut off that could enable us to get into that dense, strong, sort of poorly vascular tissue relative to other molecules wasn't entirely clear.

因此，底線是，正如我們之前討論的那樣，HS 繼續推進主要的 2b/3 研究以及按計劃進行的第三階段研究。我們預計不會通讀 PSA。從 PSA 的角度來看，我們確實認為分子大小和分化潛力仍然很重要。我們認為我們的第二階段結果，特別是在附著點炎方面，表明，確切地說，尺寸截斷的閾值可以使我們進入相對於其他分子而言密集、堅固、血管較差的組織並不完全是這樣。清除。

I will say that the data more recently suggests that not only is the threshold between our 18 kilo Daltons and the 150 or so for the marketed monoclonals but perhaps is even between the 18 and the 40. That was kilo Daltons of the recently sort of released AF data. Given the difference in enthesitis. I've shared with you today, in our prepared remarks, our best attempt at an apples-to-apples comparison, given the data that was presented, not with regards to LEI resolution, which we've shared previously.

我要說的是，最近的數據表明，對於市售單株抗體，閾值不僅在18 公斤道爾頓與150 左右之間，甚至可能在18 與40 之間。這是最近發布的公斤道爾頓。自動對焦資料。鑑於附著點炎的差異。今天，我在準備好的發言中與您分享了我們在同類比較方面的最佳嘗試，考慮到所提供的數據，而不是我們之前分享過的 LEI 解析。

But with regards to LEI two plus at baseline, improving more than two plus points over the course of the study. And recall that that was for us at week eight, an earlier time point, because we didn't collect it at week twelve. 100% response for that degree of change or improvement, versus a placebo of 0%, relative to 71% without the placebo reported.

但就 LEI 基線而言，在研究過程中提高了兩個以上，提高了兩個以上。請記住，這是我們在第八週（較早的時間點）進行的，因為我們在第十二週沒有收集它。對於這種程度的變化或改善，有 100% 的反應，而安慰劑為 0%，而沒有報告安慰劑的反應為 71%。

Thank you. One moment for our next question. Our next question comes from Emily Bodnar from H.C. Wainwright. Please go ahead.

謝謝。請稍等一下我們的下一個問題。我們的下一個問題來自 H.C. 的 Emily Bodnar。溫賴特。請繼續。

Hi, thanks for taking the questions. Kind of along the lines of some of the other questions on PSA. I was wondering if you can maybe discuss what endpoints or metrics that physicians are most looking to see improved upon or where they kind of see the largest unmet need. Where you think you can differentiate. I know you've talked about enthesitis already but are there any other places where you kind of see izokibep differentiating.

您好，感謝您提出問題。有點類似 PSA 的其他一些問題。我想知道您是否可以討論醫生最希望看到哪些終點或指標得到改進，或者他們認為最大的未滿足需求在哪裡。您認為自己可以脫穎而出的地方。我知道您已經談論過附著點炎，但是您是否在其他地方看到 izokibep 的差異化。

Then maybe just on expenses, if you can touch on, it looks like in 3Q the expenses kind of doubled from the second quarter. So, is that kind of a base level for you going forward, or any guidance you can give on [sensitive] for the remainder of either year or next year? Thank you.

然後也許只是在支出方面，如果你能提到的話，看起來第三季的支出比第二季增加了一倍。那麼，這是您今後前進的基本水平，還是您可以在今年剩餘時間或明年的[敏感]方面提供的任何指導？謝謝。

Yeah, thanks for that, Emily. Maybe I'll start with PSA, sort of disease state manifestations, et cetera. And I'll let Gil handle the second question. So, with regards to where we think the field is going and what's important for patients, and therefore for our investigators and DOLs as well, is that we really need to do better with regards to our treatment offerings for these patients.

是的，謝謝你，艾米麗。也許我會從 PSA、某種疾病狀態表現等開始。我會讓吉爾來處理第二個問題。因此，關於我們認為該領域的發展方向以及對患者、因此對我們的研究人員和 DOL 來說最重要的是，我們確實需要在為這些患者提供的治療方案方面做得更好。

We've traditionally been talking about an ACR 50 response in the 50% sort of range and what that means is that half the people will get 50% better with regards to their joint disease, which is a pretty low bar still, if you think about how much unmet need, how much better we should be able to do.

我們傳統上一直在談論 50% 範圍內的 ACR 50 反應，這意味著一半的人的關節疾病會好轉 50%，如果您認為這仍然是一個相當低的標準關於有多少未滿足的需求，我們應該能夠做得更好多少。

So, things like ACR 70s are as close to remission as we've been able to have within the ACR scoring system. POSI 100s are sort of all clear skin, enthesitis resolution means that I don't have any more enthesitis that I can measure, which is terrific. And so, it's really the totality of all of the manifestations of this disease, that therefore, as you can imagine, impact most the overall quality of life of a given patient.

因此，像 ACR 70 這樣的情況是我們在 ACR 評分系統中所能達到的最接近緩解的水平。 POSI 100 幾乎都是透明皮膚，附著點炎分辨率意味著我不再有任何可以測量的附著點炎，這太棒了。因此，它實際上是這種疾病所有表現的總和，因此，正如您可以想像的那樣，它對特定患者的整體生活品質影響最大。

So, it's important not just to hit the joints in the skin, although, of course, one wants to hit them as hard as one can to really be able to talk about remission or resolution. ACR 70s and the majority of people achieving ACR 70s, the vast majority of people achieving POSI 100. And now, we feel like within the [Tibet], the vast majority of people achieving resolution of their enthesitis, which is again, a marker of severity of disease, of residual pain and dysfunction for these patients, that obviously adds up to the quality of life.

因此，重要的不僅僅是打擊皮膚的關節，當然，人們希望盡可能地打擊它們，以便真正能夠談論緩解或解決。 ACR 70 和大多數人達到 ACR 70，絕大多數人達到 POSI 100。現在，我們感覺在[西藏]，絕大多數人實現了附著點炎的解決，這又是一個標誌這些患者的疾病嚴重程度、殘餘疼痛和功能障礙，這顯然會提高生活品質。

And one of the measures of sort of this overarching resolution of disease is also minimal disease activity. And as we've shared both our switch from placebo to active in the Phase two study, as well as the 80 milligram from the get go, those subjects are achieving about 60% minimal disease activity in the upcoming data set that will be presented.

這種疾病整體解決方案的措施之一也是最小化疾病活動。正如我們在第二階段研究中分享的從安慰劑到活性藥物的轉變，以及從一開始就服用 80 毫克的情況，這些受試者在即將發布的數據集中實現了約 60% 的最小疾病活動。

So, we're excited about this. We think that the 2b/3 gives us the potential to impact this even further. And we already know that the opportunity exists based on our existing data to do that from a skin improvement perspective. Gil?

所以，我們對此感到興奮。我們認為 2b/3 使我們有可能進一步影響這一點。我們已經知道，根據我們現有的數據，從皮膚改善的角度來看，有這樣做的機會。吉爾？

Great. And to the financial question, Emily, as I said in my prepared remarks, we ended the quarter with over $788 million in cash on the balance sheet. So, obviously we're in a very strong financial position. We have sufficient funding to go through catalysts across our pipeline.

偉大的。至於財務問題，艾米麗，正如我在準備好的發言中所說，本季結束時，我們的資產負債表上有超過 7.88 億美元的現金。因此，顯然我們的財務狀況非常強勁。我們有足夠的資金來推動整個管道的催化劑。

At this stage, we're not giving specific line-item guidance, but I can tell you that we're thinking very carefully about how we allocate capital stage appropriate. We're scaling the investments as we scale the trials and go through. So, we are obviously in 2024 planning, and we're looking very closely at that and being prudent with our capital, but we're really pleased with where we are at this point.

在現階段，我們不會提供具體的專案指導，但我可以告訴你，我們正在非常仔細地考慮如何適當地分配資本階段。隨著試驗規模的擴大和實施，我們正在擴大投資規模。因此，我們顯然正在規劃 2024 年，我們正在密切關注這一點，並對我們的資本持謹慎態度，但我們對目前的狀況感到非常滿意。

Got it. Okay, thank you.

知道了。好的謝謝。

(Operator Instructions). Our next question comes from Akash Tewari from Jefferies. Please go ahead.

（操作員說明）。我們的下一個問題來自 Jefferies 的 Akash Tewari。請繼續。

Hey, thanks so much for taking my questions. So, I remember, as of September, you had mentioned the blinded dropout rate for your upcoming psoriatic arthritis trial was around 5%. Any color on what that's tracking through as we get into November? And what level of dropouts do you plan with for this trial with your current [powering] assumptions?

嘿，非常感謝您回答我的問題。所以，我記得，截至 9 月份，您曾提到即將進行的乾癬性關節炎試驗的盲態退出率約為 5%。進入 11 月後，有什麼進展嗎？根據您目前的[有力]假設，您計劃在本次試驗中退出多少等級？

And then I guess maybe on HS, can you go over precisely what your HS protocol deemed to be drug related or not? For example, in the circumstance by which a participant had an injection site reaction and also stopped treatment, how would you determine whether that was a drug related discontinuation or otherwise? Thanks so much.

然後我想也許在 HS 方面，您能否準確地回顧一下您的 HS 協議中認為與藥物相關或無關的內容？例如，在參與者出現注射部位反應並停止治療的情況下，您如何確定這是與藥物相關的停藥還是其他原因？非常感謝。

Thanks, Akash. So, with regards to your first question about the PSA study that's about to read out and discontinuation rates. So, as I shared in our prepared remarks, we are at over 75% of patients within the context of that trial having completed through the primary endpoint, and our discontinuation rate currently is 6.9%.

謝謝，阿卡什。那麼，關於你關於 PSA 研究的第一個問題，即將讀出和停藥率。因此，正如我在準備好的發言中所分享的那樣，該試驗中超過 75% 的患者已完成主要終點，目前我們的停藥率為 6.9%。

So, we feel, oh, apologies, 5.9%. You know, and it just speaks to my mindset with regards to my next comment, which is really that anything below 10% is the usual threshold that we think about for clinical trials in general, and if it bounces around within the context of that number but is below 10%, we really aren't concerned.

所以，我們覺得，哦，抱歉，5.9%。你知道，這只是表達了我對下一則評論的看法，實際上，低於 10% 的任何值都是我們通常考慮的臨床試驗的閾值，如果它在該數字的背景下反彈但低於10% ，我們真的不擔心。

So, we're feeling very good about where we are with that study at this juncture. And as I said earlier to Emily's comments, really don't feel like there's any read through. And we wouldn't have expected that, but we don't think we're seeing that. Separately, with regards to HS and scoring of ISRs and whether or not those are adverse events, we take that, as reported to us, ISRs and whether or not they were dropouts due to ISRs.

因此，我們對目前這項研究的進展感到非常滿意。正如我之前對艾米麗的評論所說的那樣，我真的不覺得有任何通讀。我們沒有預料到會出現這種情況，但我們認為我們沒有看到這一點。另外，關於 HS 和 ISR 評分以及這些是否是不良事件，我們認為，正如向我們報告的那樣，ISR 以及它們是否因 ISR 而退出。

When we talk about our dropouts as discontinuations who were responders without adverse events, we actually went back through and didn't just take at face value whether or not it was reported to us as whether it was a loss to follow up or withdrew consent, et cetera. We went back through the entire electronic data set and evaluated for whether or not there was a pattern, including looking for ISRs that weren't necessarily reported as an AE. And that pattern also does not exist, which I think is probably your underlying question.

當我們談論我們的退出者作為沒有不良事件的反應者的中止者時，我們實際上回顧了一遍，並不僅僅從表面上看是否向我們報告了這是否是失訪或撤回同意，等等。我們回顧了整個電子資料集並評估是否存在模式，包括尋找不一定報告為 AE 的 ISR。而且這種模式也不存在，我認為這可能是您的根本問題。

Awesome. Thanks so much.

驚人的。非常感謝。

Thank you. I am showing no further questions. I will now turn the conference over to Tyler Marciniak for closing remarks.

謝謝。我沒有提出任何進一步的問題。我現在將會議交給泰勒·馬爾齊尼亞克（Tyler Marciniak）作閉幕詞。

Thank you all for joining today's opportunity for us to share with you our third quarter financial results and corporate updates. As Shao-Lee and Gil mentioned, thank you for your trust and support as we continue to build ACELYRIN into a leading INI company. We look forward to engaging with you regularly and transparently. And in that vein, I would like to highlight once again our upcoming PSA data presentations at ACR and the several investment conferences we are attending in the coming weeks.

感謝大家參加今天的機會，讓我們與您分享我們第三季的財務表現和公司最新動態。正如 Shao-Lee 和 Gil 所提到的，感謝您在我們繼續將 ACELYRIN 打造成領先的 INI 公司的過程中的信任和支持。我們期待與您定期、透明地互動。本著這項精神，我想再次強調我們即將在 ACR 上進行的 PSA 數據演示以及我們在未來幾週內將參加的幾場投資會議。

We hope to see you in person soon and would encourage you to view the fireside chat and other resources we regularly post to our website. And of course, please feel free to contact our investor relations team at any time if we can be of service to you. With that, we'll conclude our call for today. Thank you very much.

我們希望很快能見到您，並鼓勵您查看爐邊談話和我們定期在網站上發布的其他資源。當然，如果我們能為您服務，請隨時聯繫我們的投資者關係團隊。至此，我們就結束今天的通話。非常感謝。

This concludes today's conference call. Thank you for participating. You may now disconnect.

今天的電話會議到此結束。感謝您的參與。您現在可以斷開連線。