aTyr Pharma Inc (ATYR) 2024 Q4 法說會逐字稿

Good afternoon, ladies and gentlemen, and welcome to the aTyr Pharma fourth quarter and full year 2024 conference call. (Operator Instructions) As a reminder, this conference is being recorded for replay purposes.

女士們、先生們，下午好，歡迎參加 aTyr Pharma 2024 年第四季和全年電話會議。（操作員指示）提醒一下，本次會議將會被錄音以供重播。

It is now my pleasure to hand the conference call over to Ashlee Dunston, aTyr’s Senior Director of Investor Relations and Public Affairs. Ms. Dunston, you may begin.

現在我很高興將電話會議交給 aTyr 投資者關係和公共事務高級總監 Ashlee Dunston。鄧斯頓女士，你可以開始啦。

Thank you, and good afternoon, everyone. Thank you for joining us today to discuss aTyr’s fourth quarter and full year 2024 operating results and corporate update. We are joined today by Dr. Sanjay Shukla, our President and CEO; Ms. Jill Broadfoot, our CFO; and Dr. Leslie Nangle, Vice President of Research.

謝謝大家，下午好。感謝您今天加入我們，討論 aTyr 2024 年第四季和全年的經營業績和公司最新動態。今天與我們一起出席的是我們的總裁兼執行長 Sanjay Shukla 博士；我們的財務長 Jill Broadfoot 女士；以及研究副總裁 Leslie Nangle 博士。

On the call, Sanjay will provide an update on our corporate strategy, including our clinical program for efzofitimod. Leslie will discuss our research and discovery programs, while Jill will review the financial results and our current financial position before handing it back to Sanjay to open up the call for any questions.

在電話會議上，桑傑將介紹我們的公司策略的最新情況，包括我們的 efzofitimod 臨床計劃。萊斯利 (Leslie) 將討論我們的研究和發現計劃，而吉爾 (Jill) 將審查財務結果和我們當前的財務狀況，然後將其交還給桑傑 (Sanjay) 以開始回答任何問題。

Before we begin, I want to remind everyone that except for statements of historical facts, the statements made by management and responses to questions on this conference call are forward-looking statements under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. These statements involve risks and uncertainties that can cause actual results to differ materially from those in such forward-looking statements.

在我們開始之前，我想提醒大家，除了歷史事實陳述外，管理層在電話會議上所作的陳述和對問題的回答都是根據 1995 年《私人證券訴訟改革法》的安全港條款做出的前瞻性陳述。這些聲明涉及風險和不確定性，可能導致實際結果與此類前瞻性聲明的結果有重大差異。

Please see the forward-looking statement disclaimer in the company’s press release issued this afternoon, as well as the risk factors in the company’s SEC filings and included in our most recent annual report on Form 10-K, subsequently filed quarterly reports on Form 10-Q, and in our other SEC filings. Undue reliance should not be placed on our forward-looking statements, which speak only as of the date they are made as facts and circumstances underlying those forward-looking statements may change. Except as required by law, aTyr Pharma disclaims any obligation to update these forward-looking statements to reflect future information events or circumstances.

請參閱公司今天下午發布的新聞稿中的前瞻性聲明免責聲明，以及公司向美國證券交易委員會 (SEC) 提交的文件中以及我們最近的 10-K 表年度報告、隨後提交的 10-Q 表季度報告和我們的其他美國證券交易委員會 (SEC) 文件中包含的風險因素。不應過度依賴我們的前瞻性陳述，這些陳述僅代表其作出之日的觀點，因為這些前瞻性陳述背後的事實和情況可能會改變。除法律要求外，aTyr Pharma 不承擔更新這些前瞻性聲明以反映未來資訊事件或情況的義務。

I will now turn the call over to Sanjay.

現在我將電話轉給桑傑。

Thank you, Ashlee. Good afternoon, everyone, and thank you for joining us for our fourth quarter and full year 2024 results conference call.

謝謝你，阿什莉。大家下午好，感謝大家參加我們的 2024 年第四季和全年業績電話會議。

At aTyr, we’re on a mission to translate tRNA synthetase biology into new therapies for fibrosis and inflammation. Our lead therapeutic candidate, efzofitimod, is a first-in-class biologic immunomodulator that selectively modulates activated myeloid cells via neuropiln-2, or NRP2, to resolve inflammation without immune suppression and potentially prevent fibrosis progression. We’re developing efzofitimod as a treatment for patients with interstitial lung disease, or ILD, a group of rare immune-mediated disorders that can cause chronic inflammation and fibrosis of the lungs.

在 aTyr，我們的使命是將 tRNA 合成酶生物學轉化為治療纖維化和發炎的新療法。我們的主要治療候選藥物 efzofitimod 是一種一流的生物免疫調節劑，可透過神經纖維連接蛋白-2 (NRP2) 選擇性地調節活化的髓系細胞，從而無需免疫抑制即可消除炎症，並可能防止纖維化進展。我們正在開發 efzofitimod 作為間質性肺病（ILD）患者的治療方法，ILD 是一組罕見的免疫介導疾病，可導致肺部慢性發炎和纖維化。

2024 was an important year for aTyr as we completed enrolment in our global pivotal Phase 3 EFZO-FIT study of efzofitimod in patients with pulmonary sarcoidosis, a major form of ILD that is our lead indication. This is the largest interventional study ever conducted in pulmonary sarcoidosis, and we look forward to releasing top-line data from this study in the third quarter of this year. EFZO-FIT is a randomized, double-blind, placebo-controlled, 52-week study. It consists of three parallel cohorts randomized equally to either 3 milligrams per kilogram or 5 milligrams of kilogram of efzofitimod or placebo dosed intravenously monthly for a total of 12 doses.

2024 年對 aTyr 來說是重要的一年，因為我們完成了全球關鍵性 3 期 EFZO-FIT 研究的招募，該研究旨在研究 efzofitimod 對肺結節病患者的療效，肺結節病是 ILD 的主要形式，也是我們的主要適應症。這是迄今為止在肺結節病領域進行的最大規模的介入性研究，我們期待在今年第三季發布該研究的頂線數據。EFZO-FIT 是一項隨機、雙盲、安慰劑對照的 52 週研究。它由三個平行隊列組成，隨機分配接受每公斤 3 毫克或每公斤 5 毫克的依佐菲莫德或安慰劑，每月靜脈注射，共 12 劑。

The study enrolled 268 patients at 85 centers in nine countries. The trial design incorporates a forced steroid taper with steroid reduction as the primary endpoint of the study. Secondary endpoints include measures of sarcoidosis, quality of life, and lung function. Patients who complete the study and wish to receive treatment with efzofitimod outside of the clinical trial are eligible to participate in an Individual Patient Expanded Access Program, or EAP.

該研究招募了來自 9 個國家 85 個中心的 268 名患者。試驗設計採用強制減少類固醇，並將類固醇減少作為研究的主要終點。次要終點包括結節病、生活品質和肺功能的測量。完成研究並希望在臨床試驗之外接受 efzofitimod 治療的患者有資格參加個人患者擴展獲取計劃 (EAP)。

The EAP was implemented primarily based on feedback from multiple study principal investigators, or PIs, whose patients requested to continue treatment once they completed the study. These patients will receive 5 milligrams per kilogram of efzofitimod while in the EAP. However, PIs, patients, and the company remain blinded to the EFZO-FIT treatment assignments of these EAP patients.

EAP 的實施主要基於多位研究首席研究員（PI）的回饋，他們的患者要求在完成研究後繼續接受治療。這些患者在 EAP 期間將接受每公斤 5 毫克的 efzofitimod。然而，PI、患者和公司仍然不清楚這些 EAP 患者的 EFZO-FIT 治療分配。

Additionally, we have now held four positive Data and Safety Monitoring Board, or DSMB, reviews for this study, all of which have identified no safety concerns and recommended that the study continue unmodified. The most recent pre-planned independent review indicates that the study continues to track well from a safety standpoint. We remain confident in the favorable safety profile we have seen for efzofitimod to date, which we believe is a key value proposition of the drug.

此外，我們目前已對這項研究進行了四次積極的數據和安全監測委員會（DSMB）審查，所有審查均未發現任何安全問題，並建議繼續進行該研究而不進行修改。最新的預先計劃的獨立審查表明，從安全角度來看，該研究繼續進展良好。我們仍然對迄今為止看到的 efzofitimod 的良好安全性充滿信心，我們相信這是該藥物的關鍵價值主張。

And, finally, we’ll get our first look at the blinded baseline demographic and disease characteristics of the patients enrolled in the study at the upcoming American Thoracic Society Conference, or ATS, which is scheduled to take place mid-May in San Francisco. In a poster, we will be able to get a sense for the profile of the patients enrolled, including baseline steroid dose and background immunomodulator use, and how the profile matches the inclusion and exclusion criteria for the study.

最後，我們將在即將於 5 月中旬在舊金山舉行的美國胸腔科學會會議（ATS）上首次了解參與研究的患者的盲法基線人口統計學和疾病特徵。在海報中，我們將能夠了解入選患者的概況，包括基線類固醇劑量和背景免疫調節劑的使用情況，以及該概況如何與研究的納入和排除標準相符。

As part of our planning for the Phase 3 readout for EFZO-FIT, we recently held a Type C meeting with the US Food and Drug Administration, or FDA. The main objective of this meeting was to discuss the statistical analysis plan, or SAP, for the study, including how the primary and secondary endpoints are assessed statistically. For the primary endpoint, we determined how steroid reduction will be analysed in the SAP.

作為 EFZO-FIT 第三階段讀數規劃的一部分，我們最近與美國食品藥物管理局 (FDA) 舉行了 C 類會議。本次會議的主要目標是討論研究的統計分析計劃（SAP），包括如何統計評估主要和次要終點。對於主要終點，我們確定瞭如何在 SAP 中分析類固醇減少。

As we previously discussed, we initially proposed that we measure steroid reduction based on calculating the average daily steroid dose between week 12 and week 48, which is a protocol-specified post-steroid taper period. We viewed this as a conservative way of measuring steroid reduction in the study. Based on FDA feedback, we will now measure steroid reduction as the absolute change from baseline to week 48.

正如我們之前所討論的，我們最初建議透過計算第 12 週到第 48 週之間的平均每日類固醇劑量來衡量類固醇的減少量，這是協議指定的類固醇減量後期。我們認為這是研究中測量類固醇減少的保守方法。根據 FDA 的回饋，我們現在將類固醇的減少量測量為從基線到第 48 週的絕對變化。

We feel this change creates a more simplified assessment to capture potential steroid delta between groups. The statistical powering for this study remains intact, and we are pleased with the clarification around how we will measure steroid reduction. With limited clinical studies in sarcoidosis as a benchmark, we are pioneering a path forward to measure how we can potentially improve the lives of these patients.

我們認為，這項變化創造了一種更簡化的評估方法，可以捕捉各組之間潛在的類固醇差異。這項研究的統計動力保持不變，我們很高興能夠澄清如何測量類固醇的減少。以結節病有限的臨床研究為基準，我們正在開拓一條前進的道路，以衡量如何潛在地改善這些患者的生活。

While we brought you up to date on EFZO-FIT, I want to take a few minutes to provide you with critical insights into the pulmonary sarcoidosis landscape in the US that have emerged from some of our early pre-commercial activities. We believe these findings support a potentially larger market opportunity for efzofitimod in sarcoidosis. Pulmonary sarcoidosis is a disease characterized by the formation of granulomas or clumps of immune cells predominantly in the lungs.

在我們向您介紹 EFZO-FIT 的最新進展的同時，我想花幾分鐘時間向您提供一些來自我們早期商業化前活動中的有關美國肺結節病情勢的重要見解。我們相信這些發現為依佐菲莫德在治療結節病方面提供了更大的市場機會。肺結節病是一種以肺部主要形成肉芽腫或免疫細胞團塊為特徵的疾病。

The current standard of care is oral corticosteroids, which may help improve symptoms in the short-term, but come with serious side effects with long-term use. And despite the use of steroids and other off-label immunosuppressive agents, many patients have disease that progresses, with around 20% developing lung fibrosis, which can lead to organ failure and death. There remains a lack of safe and effective treatments available for these patients.

目前的標準治療方法是口服皮質類固醇，可能有助於短期改善症狀，但長期使用會帶來嚴重的副作用。儘管使用了類固醇和其他未列入藥品說明書的免疫抑制劑，但許多患者的病情仍在惡化，約有 20% 的患者出現肺纖維化，這可能導致器官衰竭和死亡。目前仍缺乏針對這些患者安全有效的治療方法。

It is typically reported that sarcoidosis affects close to 200,000 people in the US, with 90% of patients having lung involvement. A third-party claims analysis, which we conducted late last year, confirms that number and shows that the number of patients diagnosed with lung involvement similar to the population enrolled in our Phase 3 trial is 30% higher than previously estimated.

據報道，美國有近 20 萬人患有結節病，其中 90% 的患者肺部受損。我們去年年底進行的第三方索賠分析證實了這個數字，並顯示與我們 3 期試驗中招募的人群相似的肺部受累患者數量比之前估計的高出 30%。

Since the US Epidemiology numbers most frequently referenced were published nearly a decade ago, we were not surprised that the population has grown. Furthermore, when we looked at treatment practices such as the number of patients that require any treatment and those that are prescribed steroids, we saw that nearly 75% of diagnosed patients are prescribed steroids, which is well above previous estimates in the US and at the upper range as to what is reported globally. Furthermore, the claims also showed significant mortality and hospitalization rates, which speak to the high unmet medical need for this disease.

由於最常引用的美國流行病學數據是在近十年前發布的，因此我們對人口成長並不感到驚訝。此外，當我們查看治療實踐（例如需要治療的患者人數和被處方類固醇的患者人數）時，我們發現近 75％ 的確診患者被處方類固醇，這遠高於美國之前的估計數，並且處於全球報告的上限範圍。此外，索賠還顯示出較高的死亡率和住院率，這表明該疾病的醫療需求尚未得到滿足。

When it comes to pricing through additional payor research that we conducted, we continue to see positive feedback from payors regarding their willingness to reimburse for an on-label biologic and sarcoidosis. We are encouraged by the reimbursement landscape we’ve seen recently where some rare disease product launches have included steroid reduction as part of the label and are priced at a premium.

當我們透過進行的額外付款人研究進行定價時，我們繼續看到付款人關於他們願意報銷標籤生物製劑和結節病費用的積極反饋。我們對最近看到的報銷感到鼓舞，一些罕見疾病產品的發布將類固醇減少作為標籤的一部分，並且定價較高。

In some, we believe the findings from these recent activities support the patient’s and physician’s need and strong desire for a product like efzofitimod. We view efzofitimod as a potential frontline steroid-reducing agent in patients with moderate to severe disease, which could address 50% to 75% of all sarcoidosis patients.

在某些情況下，我們相信這些近期活動的發現支持了患者和醫生對 efzofitimod 等產品的需求和強烈渴望。我們認為依佐菲莫德是中度至重度疾病患者的潛在一線類固醇減量劑，可治療 50% 至 75% 的結節病患者。

We’ve previously stated that we estimate a total global market opportunity for efzofitimod in ILD at $2 billion to $5 billion, and our updated research supports a market where sarcoidosis represents a significant portion of that range. Some of these insights that we’ve discussed will be presented in two posters at ATS in May. And this work has enhanced our understanding of the sarcoidosis market in the US in a way that will be foundational for preparing for some of our upcoming commercial readiness activities.

我們先前曾表示，我們估計依佐菲莫德在治療間質性肝病 (ILD) 方面的全球市場總價值為 20 億至 50 億美元，而我們最新的研究支持了這一市場，其中結節病佔據了該範圍的很大一部分。我們討論過的一些見解將在 5 月的 ATS 上以兩張海報的形式展示。這項工作增強了我們對美國結節病市場的了解，為我們即將開展的一些商業準備活動奠定了基礎。

Finally, as we start to plan for commercial readiness, we recently appointed Eric Benevich, who is currently the Chief Commercial Officer for Neurocrine Biosciences to our Board of Directors. Eric brings a wealth of experience in launching high-value pharmaceuticals, including, most recently, a product for a rare disease that has a steroid reduction component as part of its Phase 3 clinical trial and FDA approval package. We anticipate his contributions will be highly valuable as we advance efzofitimod to a commercial product.

最後，當我們開始規劃商業準備時，我們最近任命了現任 Neurocrine Biosciences 首席商務官的 Eric Benevich 加入我們的董事會。Eric 在推出高價值藥品方面擁有豐富的經驗，包括最近推出的一款針對罕見疾病的產品，該產品含有類固醇減少成分，這是其 3 期臨床試驗和 FDA 批准方案的一部分。我們預計，在我們將 efzofitimod 推進為商業產品的過程中，他的貢獻將非常有價值。

Now, let’s turn to our second indication for efzofitimod, ILD-related systemic sclerosis, or SSc, which is also known as scleroderma. SSc is a form of connective tissue disease, where ILD commonly occurs, and is a leading cause of mortality. Current treatment options for SSc-ILD are limited, and like sarcoidosis, they do not treat the underlying disease or improve quality of life.

現在，讓我們來談談依佐菲莫德的第二個適應症，即 ILD 相關系統性硬化症，簡稱 SSc，也稱為硬皮症。系統性硬化症 (SSc) 是一種結締組織疾病，其中 ILD 很常見，並且是導致死亡的主要原因。目前，SSc-ILD 的治療選擇有限，而且與結節病一樣，它們不能治療潛在疾病或改善生活品質。

EFZO-CONNECT is a Phase 2 randomized, double-blind, placebo controlled, proof-of-concept, 28-week study to evaluate two fixed doses of efzofitimod, 270 milligrams or 450 milligrams compared to placebo. Patients are dosed intravenously monthly for a total of six doses. This study is currently enrolling patients with limited and diffuse SSc-ILD at multiple centers in the US The primary endpoint of the study is lung function as measured by forced vital capacity, and key secondary endpoints include symptom control and skin assessments.

EFZO-CONNECT 是一項為期 28 週的 2 期隨機、雙盲、安慰劑對照、概念驗證研究，旨在評估兩種固定劑量 efzofitimod（270 毫克或 450 毫克）與安慰劑相比的效果。患者每月接受靜脈注射，共六劑。這項研究目前正在美國多個中心招募局限性和瀰漫性 SSc-ILD 患者，研究的主要終點是透過用力肺活量測量的肺功能，關鍵次要終點包括症狀控制和皮膚評估。

We expect to release interim data from the study in the second quarter of this year. The interim data will focus on skin assessments, measured at baseline in week 12 for approximately eight patients, including patients on drug and placebo. We plan to present findings for skin histopathology, including immune biomarkers, and the modified Rodnan skin score, which will provide insight regarding potential changes in skin tissue. Skin manifestations in SSc highly impact the quality of life for these patients, and other therapies showing improvement in these measures have had limited to no success.

我們預計將在今年第二季發布該研究的中期數據。中期數據將集中於皮膚評估，在第 12 週對大約 8 名患者（包括服用藥物和安慰劑的患者）進行基線測量。我們計劃展示皮膚組織病理學的發現，包括免疫生物標記和改良的 Rodnan 皮膚評分，這將提供有關皮膚組織潛在變化的見解。系統性硬化症的皮膚表現嚴重影響這些患者的生活質量，而其他療法在這些方面有所改善，但效果有限甚至沒有效果。

This interim data may provide us with an early signal related to skin changes, and may help inform the clinical development strategy for this indication. Because we plan to evaluate skin assessments in the interim data, and do not plan to include any data related to lung function, we see limited read through from this data to the Phase 3 top-line data in pulmonary sarcoidosis, that we will present later this year.

這些中期數據可能為我們提供與皮膚變化相關的早期訊號，並可能有助於制定該適應症的臨床開發策略。因為我們計劃在中期數據中評估皮膚評估，並且不打算包含任何與肺功能相關的數據，所以我們認為從這些數據到我們將在今年稍後發布的肺結節病第 3 階段頂線數據的解讀有限。

I will now turn the call over to Leslie Nangle, our Vice President of Research, to discuss our research and discovery programs.

現在，我將把電話轉給我們的研究副總裁 Leslie Nangle，討論我們的研究和發現計劃。

Thank you, Sanjay. While we have focused quite a bit on efzofitimod in the clinic, it will be useful to comment on efzofitimod’s unique mechanisms of action, or MOA, as this is truly a first-in-class drug candidate. Since we started this program, we have greatly enhanced our mechanistic understanding of efzofitimod’s immunomodulatory activity. And we are pleased to report that just yesterday, we published an extensive manuscript in the journal Science Translational Medicine, which outlines the MOA and all of the preclinical data generated for efzofitimod from concept to clinic.

謝謝你，桑傑。雖然我們在臨床上對 efzofitimod 進行了大量的研究，但評論一下 efzofitimod 獨特的作用機制（MOA）將會很有用，因為它確實是一流的候選藥物。自從我們啟動這個計畫以來，我們大大增強了對 efzofitimod 免疫調節活性的機制理解。我們很高興地報告，就在昨天，我們在《科學轉化醫學》雜誌上發表了一篇詳盡的手稿，概述了 efzofitimod 從概念到臨床的 MOA 和產生的所有臨床前數據。

The article describes the foundational science, detailed preclinical studies, and discovery work behind efzofitimod. This includes how it is engineered from a splice variant of the tRNA synthetase HARS, which is enriched in human lung tissue and upregulated by inflammatory cytokines in lung and immune cells. It also describes its specific and selective binding to NRP2, which is a cellular receptor highly expressed by myeloid cells in active sites of inflammation.

本文介紹了 efzofitimod 背後的基礎科學、詳細的臨床前研究和發現工作。這包括它是如何從 tRNA 合成酶 HARS 的剪接變體設計而來的，這種酶在人體肺組織中含量豐富，並被肺和免疫細胞中的發炎細胞因子上調。它還描述了其與 NRP2 的特異性和選擇性結合，NRP2 是一種在發炎活性部位的髓細胞中高度表達的細胞受體。

Through this binding, it inhibits the expression of pro-inflammatory receptors and cytokines, thereby downregulating inflammatory pathways in macrophages. This mechanism can subsequently disrupt the cycle of chronic inflammation and fibrosis. This type of top-tier peer-reviewed journal requires extensive vetting by the broader scientific community, with multiple independent reviewers performing a comprehensive audit of all of the work that we have generated. This process itself demands the utmost transparency in our work.

透過這種結合，它抑制促炎受體和細胞因子的表達，從而下調巨噬細胞中的發炎途徑。這種機制隨後可以破壞慢性發炎和纖維化的循環。這本頂級同行評審期刊需要更廣泛的科學界的廣泛審查，多名獨立評審員對我們所做的所有工作進行全面審核。這個過程本身要求我們的工作具有最大的透明度。

Therefore, we believe this publication validates the immune regulatory properties and extracellularly mediated mechanisms we have demonstrated for efzofitimod as it relates to reducing inflammation and fibrosis. Furthermore, it considerably reinforces the basis for the application of efzofitimod in chronic inflammatory conditions. It strengthens the scientific rationale for our clinical program in ILD, as well as encourages the potential development of other tRNA synthetase-based therapeutics for disease prevention.

因此，我們相信該出版物驗證了我們所證明的依佐菲莫德與減少發炎和纖維化有關的免疫調節特性和細胞外介導機制。此外，它大大加強了依佐菲莫德在慢性發炎應用中的基礎。它加強了我們在 ILD 臨床計劃中的科學原理，並鼓勵了其他基於 tRNA 合成酶的疾病預防療法的潛在開發。

We are very proud that the novel science that drives efzofitimod is being recognized on the world stage. To publish this extensive body of work in such an esteemed journal is a momentous accomplishment for our research team and speaks to the nature of the high quality work that aTyr produces.

我們非常自豪，推動 efzofitimod 發展的新科學正在世界舞台上得到認可。在如此受人尊敬的期刊上發表如此大量的研究成果對於我們的研究團隊來說是一項重大成就，也體現了 aTyr 所產成果的高品質性質。

While we have focused much of today’s conversation around efzofitimod, I want to remind you that the splice variant that forms the backbone of efzofitimod comes from our robust intellectual property estate, covering domains from all 20 human tRNA synthetases. And we utilize our platform and unique drug discovery process as an engine to generate new pipeline candidates.

雖然我們今天的討論主要集中在 efzofitimod 上，但我想提醒您，構成 efzofitimod 主幹的剪接變體來自我們強大的知識產權資產，涵蓋所有 20 種人類 tRNA 合成酶的領域。我們利用我們的平台和獨特的藥物發現流程作為引擎來產生新的候選藥物。

With efzofitimod and HARS, we have demonstrated that this tRNA synthetase fragment has a previously undiscovered extracellular function. And we continue to interrogate other tRNA synthetase fragments to identify roles they may play in cellular response and altered disease states. We currently have two preclinical candidates from other tRNA synthetases, where we have identified their interactions with targets and therapeutic areas where they may play a role.

利用 efzofitimod 和 HARS，我們證明了此 tRNA 合成酶片段具有先前未被發現的細胞外功能。我們將繼續研究其他 tRNA 合成酶片段，以確定它們在細胞反應和改變疾病狀態中可能發揮的作用。我們目前有兩種來自其他 tRNA 合成酶的臨床前候選藥物，我們已經確定了它們與標靶的相互作用以及它們可能發揮作用的治療領域。

Both of these candidates, ATYR0101 and ATYR0750, interact with receptors that affect fibrosis. We are exploring ATYR0101 in both lung and kidney fibrosis where we recently presented data at a Keystone Symposia that shows its ability to induce myofibroblast apoptosis through a novel anti-fibrotic mechanism. We are exploring ATYR0750 in liver disorders based on the strong connection to its target, which is FGFR4.

這兩種候選藥物 ATYR0101 和 ATYR0750 都與影響纖維化的受體相互作用。我們正在研究 ATYR0101 在肺部和腎臟纖維化中的作用，最近我們在 Keystone 研討會上展示了數據，表明它能夠透過一種新的抗纖維化機制誘導肌成纖維細胞凋亡。我們正在探索 ATYR0750 在肝臟疾病中的作用，因為它與 FGFR4 標靶有密切的關聯。

We are really proud of the innovative work that we have done with efzofitimod and the advancement of the program to date. We look forward to replicating that process with some of our current and yet to be discovered candidates.

我們對利用 efzofitimod 所做的創新工作以及該計劃迄今為止的進展感到非常自豪。我們期待與一些現有和尚未發現的候選人一起複製這一過程。

I will now turn it over to our Chief Financial Officer, Jill Broadfoot, to review our financial results.

現在我將把責任轉交給我們的財務長吉爾‧布羅德富特 (Jill Broadfoot)，來審查我們的財務結果。

Thank you, Leslie. We ended 2024 with $75.1 million in cash, restricted cash, cash equivalents, and investments. Subsequent to the end of the fourth quarter 2024, we raised approximately $18.8 million in gross proceeds from our at-the-market, or ATM, offering program. Collaboration and license revenue related to the Kyorin agreement was $0.2 million for the year ended 2024, which consisted of drug product material sold to Kyorin for the Japan portion of EFZO-FIT.

謝謝你，萊斯利。截至 2024 年，我們擁有現金、限定現金、現金等價物及投資 7,510 萬美元。截至 2024 年第四季末，我們透過市場發行（或 ATM）計畫籌集了約 1,880 萬美元的總收益。截至 2024 年的年度，與 Kyorin 協議相關的合作和授權收入為 20 萬美元，其中包括出售給 Kyorin 用於 EFZO-FIT 日本部分的藥品材料。

Kyorin is our partner for the development and commercialization of efzofitimod for ILD in Japan, and we now have received over $20 million under this agreement to date, including milestones, where we are eligible to receive up to $155 million in additional milestone payments, which are primarily geared towards regulatory and commercial milestones for sarcoidosis.

Kyorin 是我們在日本開發和商業化用於治療間質性肝病的 efzofitimod 的合作夥伴，迄今為止，我們已根據該協議收到超過 2000 萬美元，其中包括里程碑付款，其中我們有資格獲得高達 1.55 億美元的額外里程碑付款，主要用於結節病的監管和商業里程碑。

Research and development expenses were $54.4 million for the year ended 2024, which consisted primarily of clinical trial costs for the EFZO-FIT and EFZO-CONNECT studies, manufacturing costs for the efzofitimod program, and research and development costs for the efzofitimod and discovery programs.

截至 2024 年的年度研發費用為 5,440 萬美元，主要包括 EFZO-FIT 和 EFZO-CONNECT 研究的臨床試驗費用、efzofitimod 計劃的製造費用以及 efzofitimod 和發現計劃的研發費用。

General and administrative expenses were $13.8 million for the year ended 2024. Based on our current cash position, we have updated our financial guidance and believe our cash runway is expected to be sufficient to fund the company’s operations through one year following the Phase 3 EFZO-FIT readout. We view this runway as important as it covers key upcoming inflection points for the company, including the Phase 3 EFZO-FIT readout and a potential filing of a Biologics License Application for efzofitimod in pulmonary sarcoidosis. In addition to extending our cash runway, we plan to use some of the ATM proceeds to help fund our commercial readiness plan.

截至 2024 年的年度一般及行政開支為 1,380 萬美元。根據我們目前的現金狀況，我們更新了財務指導，並相信我們的現金儲備足以資助公司在第三階段 EFZO-FIT 讀數之後一年的營運。我們認為這條跑道非常重要，因為它涵蓋了公司即將到來的關鍵轉折點，包括第 3 階段 EFZO-FIT 讀數和可能提交用於治療肺結節病的 efzofitimod 的生物製品許可申請。除了延長我們的現金流量之外，我們還計劃使用部分 ATM 收益來資助我們的商業準備計劃。

Now, I’d like to turn the call back over to Sanjay before we open it up to Q&A.

現在，在我們開始問答環節之前，我想把電話轉回給桑傑。

Thanks Jill. When we assess our current position, we feel incredibly pleased with our efzofitimod program and are enthusiastic about the future. We’re poised to seize an extraordinary opportunity and our excitement for the rest of 2025 is unmatched. Our latest validating publication in Science Translational Medicine confirms our understanding of efzofitimod’s mechanism of action.

謝謝吉爾。當我們評估我們目前的狀況時，我們對我們的 efzofitimod 計劃感到非常滿意，並對未來充滿熱情。我們已準備好抓住非凡的機遇，我們對 2025 年剩餘時間的期望無與倫比。我們在《科學轉化醫學》上發表的最新驗證出版物證實了我們對 efzofitimod 作用機制的理解。

Our Phase 3 sarcoidosis trial has progressed through four successful DSMB reviews, bolstering our confidence in the therapy safety profile. And new claims data from sarcoidosis patients suggest a growing multi-billion-dollar market with little competition. Our journey began with our innovative biology platform which advanced from research to clinical stage through transparent seamless execution, while upholding a high level of scientific and medical rigor.

我們的 3 期結節性多發性硬化症試驗已成功通過四次 DSMB 審查，增強了我們對治療安全性的信心。來自結節病患者的新索賠數據表明，這是一個規模達數十億美元的市場，且競爭很少。我們的旅程始於創新的生物學平台，該平台透過透明的無縫執行從研究發展到臨床階段，同時保持高水準的科學和醫學嚴謹性。

A groundbreaking advancement for sarcoidosis may be within our reach. One that could greatly enhance the company’s trajectory and elevate aTyr to new heights in the biotechnology sector. We greatly appreciate your interest.

我們或許能夠取得治療結節性多發性肌炎的突破性進展。這可以極大地促進公司的發展，並將 aTyr 提升到生物技術領域的新高度。我們非常感謝您的關注。

At this time, we’ll be happy to take your questions.

現在，我們很樂意回答您的問題。

(Operator Instructions) Derek Archila, Wells Fargo.

（操作員指示）德里克·阿奇拉，富國銀行。

Congrats on the progress. So just first question, just maybe, Sanjay, can you shed some light on how measuring the absolute change in steroid reduction at baseline now to week 48 versus the current way that you had set it up in terms of the average cumulative steroid dose, how does that impact the trial?

恭喜你取得進展。所以第一個問題，桑傑，你能否解釋一下，如何測量現在到第 48 週基線類固醇減少的絕對變化，以及你目前根據平均累積類固醇劑量設置的方式，這對試驗有何影響？

I know you noted the powering remains intact, but I guess maybe just to remind us of the powering of the trial. And I have a follow-up.

我知道您注意到了供電仍然完好，但我想也許只是為了提醒我們試驗的供電。我還有一個後續問題。

Sure, Derek. So previously, as I mentioned, we were looking at the average steroid dose in that week 12 through week 48 period, basically taking the patient diary information from every single day, they report their prednisone and dividing by the number of dose. It’s a fairly conservative way of looking at all the peaks and valleys combined with our steroid taper and that protocol that’s occurring simultaneous to that treatment period. But after some feedback and discussions with the FDA, the view was to look at just the change from week 0 to week 48. This is something that we’re very happy with.

當然，德里克。因此，正如我之前提到的，我們正在觀察第 12 週到第 48 週期間的平均類固醇劑量，基本上是從患者每天的日記中獲取信息，報告他們的潑尼松劑量，然後除以劑量數。這是一種相當保守的方式來觀察所有的高峰和低谷，結合我們的類固醇逐漸減少和治療期間同時發生的治療方案。但在與 FDA 進行一些回饋和討論之後，我們的觀點是只關注從第 0 週到第 48 週的變化。這是我們非常高興的事情。

I think in many ways this allows us to simplify the manner in which we analyze our data. It allows us to look simply at the starting dose essentially and the ending dose. Remember, during this period, we’re trying our best to taper patients and continue to re-taper to zero. The assumption now is many of those peaks and valleys by the time the study ends should allow us to potentially maximize the steroid delta that we see in these patients.

我認為，從很多方面來說，這使我們能夠簡化分析資料的方式。它使我們能夠簡單地查看起始劑量和結束劑量。請記住，在此期間，我們正在盡最大努力減少患者人數，並繼續減少至零。現在的假設是，研究結束時的許多峰值和谷值應該可以讓我們潛在地最大化我們在這些患者身上看到的類固醇增量。

With regard to powering, it remains over 90%, 90% powered that either 3 or the 5 milligram dose shows a STAT-SIG steroid reduction compared to placebo. That has not changed. And with focusing now on the absolute change as opposed to percent change, we think that’s also a better framework that’s more relevant to patients and providers.

就功效而言，與安慰劑相比，3 毫克或 5 毫克劑量顯示 STAT-SIG 類固醇減少的功效仍超過 90%，90%。這一點沒有改變。現在我們關注的是絕對變化而不是百分比變化，我們認為這也是一個更好的框架，與患者和提供者更相關。

Super helpful. And then just a follow-up here. I know you highlighted in the prepared comments, there was investigator and patient enthusiasm for the EAP. So just wanted to ask, if you have any idea in terms of the percent of the patients who are in the trial rolling over into the expanded access or a new program there? Thanks.

超有幫助。然後這裡只是後續內容。我知道您在準備好的評論中強調了研究人員和患者對 EAP 的熱情。所以只是想問一下，您是否知道參與試驗的患者中有多少人轉入擴大准入或新項目？謝謝。

Yeah, it's a common question I get: how many patients? What's the percent? And I want to start by saying we have seen continued interest, growing interest. But the issue really here is that not all countries and not all centers can participate based on their local regulatory requirements. I've said this before: countries like Japan, for example, do not have a pathway to participate in an EAP-type program.

是的，這是我常被問到的問題：有多少病人？百分比是多少？首先我想說的是，我們看到了持續的興趣，而且興趣日益增長。但真正的問題是，並非所有國家和所有中心都能根據當地的監管要求參與。我以前說過：例如，像日本這樣的國家沒有參與 EAP 類型計畫的途徑。

So you'd have to subtract out all of those regions that aren't involved and then try to come up with a "crude measure of response, which is what I think a lot of investors want to do here.

因此，你必須減去所有未涉及的區域，然後嘗試得出“粗略的反應衡量標準”，我認為很多投資者都想這樣做。

What I can say is that the interest is still very robust. I was just with about 30 experts recently this past weekend. There continues to be more and more interest in participating in the EAP.

我可以說的是，人們的興趣仍然非常濃厚。上週末我剛剛和大約 30 位專家在一起。人們對參與 EAP 的興趣越來越濃厚。

We have committed to helping patients who are performing well in the trial to roll into the EAP, but it's an individual site-by-state site decision because, of course, we are not in a formal open-label type extension. So very pleased with the progress. I think it's a great signal, a great interim biomarker, if you will. And we're going to continue to support those patients to move into that EAP. But again, to get into specific numbers and try to get into the math, it's probably not helpful.

我們致力於幫助在試驗中表現良好的患者加入 EAP，但這是每個州自行決定的，因為我們當然不屬於正式的開放標籤類型擴展。我對這項進展非常滿意。我認為這是一個很好的信號，一個很好的中期生物標誌物，如果你願意的話。我們將繼續支持這些患者進入 EAP。但再次強調，要得到具體的數字並嘗試數學運算，可能沒有幫助。

And just as a reminder, we are blinded. We're blinded to what these patients are on during the trial. So there's always a chance that all of these patients are on placebo and that they have been able to taper more or less off their steroids and it doesn't have anything to do with the drug.

提醒一下，我們被蒙蔽了。我們不知道這些患者在試驗期間經歷了什麼。因此，所有這些患者都有可能服用安慰劑，並且他們能夠或多或少地減少類固醇用量，而這與藥物無關。

So people know me to be rather conservative in my messaging. I just think it's a great signal to see that patients who are finishing a trial want to remain in the trial. That, to me, as a former clinician, speaks very powerful to what something is happening during the trial.

所以人們知道我在傳遞訊息方面相當保守。我只是認為這是一個很好的信號，表明完成試驗的患者希望繼續參加試驗。對我來說，作為一名前臨床醫生，這有力地說明了試驗期間發生的事情。

Yasmeen Rahimi, Piper Sandler.

亞斯明·拉希米、派珀·桑德勒。

Great. Thank you so much for taking the questions and congrats on all the exciting progress and exciting year ahead of us. I got two quick questions. One is maybe, was it the market research around managing patients with steroid reduction that led to engage with the agency to make this change from a sort of clinical perspective? Just maybe if you could kind of shed light how that meeting came about and why that change – the change makes absolute sense, but maybe the question would be why implement it now and the rationale behind it. That’s sort of question one.

偉大的。非常感謝您回答這些問題，並祝賀我們取得的所有令人興奮的進展以及即將到來的激動人心的一年。我有兩個簡單的問題。一個可能是，是否是圍繞管理減少類固醇患者的市場研究促使我們與該機構合作，從臨床角度做出這項改變？也許你可以解釋一下那次會議是如何召開的，以及為什麼會發生這樣的變化——這種變化絕對有意義，但問題可能是為什麼現在要實施它，以及背後的理由。這是第一個問題。

And question two is really exciting to see the baseline demographics from the study here upcoming at ATS. Could you maybe help us understand what we should be looking for? Obviously, it’s a tremendous study with globally lots of work went into it. So just kind of help us framework on what are some of the measures that we should be looking closely to in terms of this patient population? And I’ll jump back in the queue.

第二個問題是，我們很高興看到 ATS 即將進行的研究的基線人口統計。您能幫助我們了解我們應該尋找什麼嗎？顯然，這是一項巨大的研究，全球為此投入了大量心血。那麼，能否幫助我們了解針對這群患者應該密切關注哪些措施？我將重新回到隊列中。

Sure. Yes. Three questions. I will take the first one and say that the market research is not necessarily really connected to this type of meeting. This is a little inside baseball biostatistics that typically before you lock your database, you would have all the rules set up with the biostats division. And as a former biostatistician, it’s important that we really agree to all the pre-hoc analysis.

當然。是的。三個問題。我選擇第一個觀點，即市場調查並不一定與此類會議真正相關。這是棒球生物統計學的一些內部知識，通常在鎖定資料庫之前，您需要與生物統計部門一起設定所有規則。作為前生物統計學家，我們真正同意所有的預先分析非常重要。

I think far too many times in biotech, we implement rules and then after data comes out, we start to do post-hoc analysis and cherry pick and cut and slice the data. And I wish more biopharmas wouldn’t do that. So we’re very rigorous and I like to be very rigorous around, hey, let’s get everything pre-hoc, organized down to the details exactly how do you want us to program and even look at some of this steroid reduction. Now, we have proposed something that I viewed as a fairly conservative way of looking at steroids and the average daily steroid dose.

我認為在生物技術領域，很多時候我們實施規則，然後在資料出來後，我們開始進行事後分析並挑選、剪切和切片資料。我希望更多的生物製藥公司不要這麼做。所以我們非常嚴謹，我喜歡非常嚴謹，嘿，讓我們把所有事情都預先安排好，組織到細節，確切地說，你希望我們如何編程，甚至看看一些類固醇的減少。現在，我們提出了一種我認為是相當保守的看待類固醇和平均每日類固醇劑量的方法。

Upon interacting with the FDA here, their view was this approach would be fine. The suggested approach where we’re looking at just a simplified change from baseline. I’m not going to disagree with that. I’m going to go ahead and implement that approach. Because as I said, I think this actually allows us to potentially maximize a signal at the end of the trial.

在與這裡的 FDA 互動後，他們認為這種方法很好。建議的方法是，我們只關注基線的簡化變化。我不會反對這一點。我將繼續實施這項方法。因為正如我所說，我認為這實際上使我們能夠在試驗結束時最大化訊號。

Remember, there’s a forced steroid taper component. Placebo patients will get the benefit of that reduction of the forced steroid taper. But, now, looking at the end of the trial, the clinical team and I view this as potentially a way to maximize a signal here, because as I pointed out, all those peaks and valleys that occur over the course of the trial now should be adequately handled, observed and, now, we’ll have a true measure at the end of the trial.

請記住，有一個強制減少類固醇的成分。安慰劑患者將因強制減少類固醇劑量而受益。但是，現在，看看試驗的結束，臨床團隊和我認為這是最大化訊號的一種方法，因為正如我指出的那樣，現在應該充分處理和觀察試驗過程中出現的所有高峰和低谷，現在，我們將在試驗結束時得到真正的衡量標準。

Your second question was really around the baseline demographics. It’s important to put this out. The community is really interested. They want to see data as quickly as possible. Many of our PIs have said, can we take a look at background immunomodulator use? We just want to see the data. We like to see what the average daily steroid dose is, duration of disease, things of that nature. So these are all important things for us to show to the community, and we already have that data. It’s just baseline data. So why not put it out at a major medical conference?

您的第二個問題實際上是關於基線人口統計的。把這個說出來很重要。社區確實很有興趣。他們希望盡快看到數據。我們的許多 PI 都說過，我們可以看看免疫調節劑的背景使用嗎？我們只是想查看數據。我們想了解每日類固醇的平均劑量、疾病持續時間以及諸如此類的事情。所以這些都是我們要向社群展示的重要內容，而且我們已經擁有了這些數據。這只是基線數據。那麼為什麼不在大型醫學會議上公佈這項消息呢？

The important thing for investors to pay attention to is that average prednisone dose. I’ll remind everyone in the last trial, the Phase 2 trial, we had an average dose somewhere in that 11 to 13 range. This trial where we’re enrolling patients with a slightly lower basement dose of 7.5 milligrams, expect that prednisone dose maybe a little bit lower, but we want to take a look at that. And then that helps with all the investors that want to do the modelling with regards to how much steroid delta you want to see there. So, it’s important to get this baseline data out there, make sure we more or less enrol per the IE criteria in our trial.

投資人需要關注的重要一點是潑尼鬆的平均劑量。我要提醒大家，在上次試驗，第 2 階段試驗中，我們的平均劑量在 11 到 13 的範圍內。在本次試驗中，我們招募的患者的基礎劑量略低，為 7.5 毫克，預計潑尼松劑量可能會稍微低一些，但我們想對此進行觀察。然後，這有助於所有想要建模的投資者了解想要看到的類固醇增量數量。因此，取得這些基線數據非常重要，確保我們在試驗中或多或少符合 IE 標準。

Faisal Khurshid, Leerink Partners.

Faisal Khurshid，Leerink Partners。

Hey, Sanjay, thanks for taking the question. Nice to be on the call with you guys. I just wanted to ask, so in terms of the placebo arm, I guess for the steroid tapering in general, I think in the past you said that patients would have to try to taper to 03 times over the course of this 48 weeks. So with this change now, like what happens if a patient is mid taper at week 48? Like does that mean that they’ll have a steroid level that’s being impacted by this forced taper for what you’re measuring for the primary endpoint?

嘿，桑傑，謝謝你回答這個問題。很高興和你們通話。我只是想問一下，就安慰劑組而言，我想對於類固醇的總體減少，我認為過去您說過患者必須在這 48 週內嘗試減少到 03 次。那麼現在有了這個變化，如果患者在第 48 週逐漸減量，會發生什麼事？這是否意味著他們的類固醇水平會受到強制減量的影響，而這正是您所測量的主要終點？

Yeah, great question. So the first thing I’ll say is with the relative length of the trial, our expectation is in particular in those placebo patients, we have adequate time here to unmask their disease and not only unmask the disease, but have as you point out several rounds of trying to basically re-taper them. So, we still are going to continue with that protocol in that manner. Now, you point out an example, I would say maybe an extreme example, what if a patient in that last dosing period is actually trying to be re-tapered. So, again, this is a very, very specific question for a specific circumstance.

是的，很好的問題。因此，我要說的第一件事是，鑑於試驗的相對長度，我們的期望是，特別是對於那些安慰劑患者，我們有足夠的時間來揭示他們的疾病，不僅揭示疾病本身，而且正如您所指出的，我們已經進行了幾輪嘗試，基本上重新減少他們的用藥量。因此，我們仍將以這種方式繼續執行該協議。現在，您指出一個例子，我想說這可能是一個極端的例子，如果最後一個給藥期間的患者實際上正在嘗試重新減少劑量，該怎麼辦。所以，再次強調，這是一個針對特定情況的非常非常具體的問題。

But, typically, when you look at a change from baseline, it’s not that you’re looking at the point estimate on that day of that visit. Typically, what you’re looking at is a trailing average of, say, 28 days. So that’s, again, a very wonky biostats and programming question that you’ve asked there. So in that case, if somebody is in an active taper, we have a look back there of those 28 days. That’s occurring for all of the patients there.

但是，通常情況下，當您查看基準的變更時，您並不是在查看訪問當天的點估計。通常，您查看的是過去 28 天的平均值。所以，您又問了一個非常奇怪的生物統計和程式設計問題。因此，在這種情況下，如果有人正在積極縮減，我們會回顧這 28 天。那裡的所有病人都是這樣的。

My view is most patients will have reached their, what I would call, resting dose as a placebo patient and their resting dose of a potential EFZO treated patient. And we’ll know that over the course of those last 28 days. That’s why we believe that this allows us to potentially maximize the differences you may see from change from baseline within each cohort. Does that help?

我的觀點是，大多數患者都會達到我所說的安慰劑患者的靜止劑量和潛在 EFZO 治療患者的靜止劑量。我們將在過去 28 天內了解這一點。這就是為什麼我們相信這可以讓我們最大程度地擴大您可能看到的與每個群組的基線變化之間的差異。這樣有幫助嗎？

Thank you for clarifying. And then if I could ask, just in terms of the how should we think about the durability of the drug impact now that you’re doing the analysis in a way that really emphasizes the end of the study?

感謝您的澄清。然後我可以問一下，既然您現在以一種真正強調研究結束的方式進行分析，那麼我們應該如何看待藥物影響的持久性？

Oh, I love that you asked that question, because we were talking about this week. Durability is going to be really important with this trial. And this is one way that it signals a potential durable response. I wouldn’t say things like time to relapse and time to clinical worsening are other ways that you can look at it. I’ll remind everyone that from our last data, the pooled analysis showed that these two treatment doses kept people 93% of the patients in that small dataset from relapsing in 6 months, whereas you saw 55% of the sub-therapeutic and placebo patients relapse.

哦，我很高興你問了這個問題，因為我們正在談論這週的事情。對於這次試驗來說，耐用性非常重要。這表明，這一反應具有潛在的持久性。我不會說復發時間和臨床惡化時間等是可以觀察它的其他方式。我要提醒大家，從我們上次的數據來看，總結分析顯示，這兩種治療劑量使該小數據集中 93% 的患者在 6 個月內沒有復發，而接受亞治療和使用安慰劑的患者中，有 55% 出現復發。

So as a comparison, that’s an indication of durability. This is the way we’re measuring this endpoint is certainly going to allow us a clue to see if the drug is actually has durable response, but we’re also going to be looking at time to relapse as a tertiary analysis. Many of the experts, they really care about that. So that’s something that also, I think, we can potentially see a statistical win on, albeit it’s not a primary or secondary endpoint. But definitely durability is something that we’re bullish on right now with our therapy.

因此，作為比較，這表明了耐用性。這是我們測量該終點的方式，肯定會給我們線索，看看該藥物是否真的有持久的反應，但我們也將把復發時間作為三級分析。許多專家確實關心這一點。因此，我認為，儘管這不是主要或次要終點，但我們也有可能看到統計上的勝利。但毫無疑問，我們目前對這種療法的持久性非常看好。

Prakhar Agrawal, Cantor Fitzgerald.

普拉哈·阿格拉沃爾，坎托·菲茨杰拉德。

Hi. Thank you for taking my questions and congrats on the progress. So, firstly, I think in the Phase 1/2 for the 5 milligram per kg dose, the 1.6 milligram per day steroid reduction that was seen was during the post-taper period. So if you can remind us what would you see in the overall time period based on the new definition here? That’s my first question.

你好。感謝您回答我的問題並祝賀您的進展。因此，首先，我認為在 1/2 階段，對於每公斤 5 毫克的劑量，每天減少 1.6 毫克的類固醇是在減量後時期。那麼，如果您能提醒我們，根據這裡的新定義，您會看到整個時間段發生什麼？這是我的第一個問題。

And the second question, maybe if you mentioned that the powering remains intact, but did the powering decrease versus the initial assumption that may have been very conservative to begin with? And lastly, if you can comment on what did the FDA say on FEV1 at the Type C meeting or was there any discussion around that? Thank you so much.

第二個問題是，如果您提到動力保持不變，那麼與最初的假設相比，動力是否有所下降？最初的假設可能非常保守。最後，您能否評論一下 FDA 在 C 型會議上對 FEV1 的看法，或者是否對此進行過討論？太感謝了。

Yeah, I’ll take the last part first. Little to no discussions on PFTs. I think this speaks to a much greater interest in steroid reduction and frankly the king sarcoidosis. So with regard to FEV1 specifically, that is an important PFT for obstructive disease and many of these patients of course have obstructive disease. We’ll look at that again as a tertiary endpoint. But my general sense is, there’s much more of a focus and we had much more of a discussion around steroid reduction.

是的，我先講最後一部分。關於 PFT 的討論很少或根本沒有。我認為這說明人們對減少類固醇和坦率地說對結節病有更大的興趣。因此，具體到 FEV1，它是阻塞性疾病的重要 PFT，當然，這些患者中有很多都患有阻塞性疾病。我們將再次將其視為第三終點。但我的整體感覺是，我們更加關注類固醇的減少，並且進行了更多的討論。

You asked around powering, again, the powering assumptions still remain the same. If anything, and I’m going to probably have to set some time aside with you and our biostatistician, the powering remains the same over 90% powered. We may in fact be able to, as I’ve said before, looked for a 3 and 3.5 milligram percent, absolute difference – excuse me, not percent. Now, I think it’s probably skewing closer to 3 milligrams.

您詢問了有關供電的問題，同樣，供電假設仍然保持不變。如果有的話，我可能必須留出一些時間與您和我們的生物統計學家討論，供電量仍保持在 90% 以上。事實上，正如我之前所說，我們可能能夠找到 3 毫克和 3.5 毫克的絕對差異——對不起，不是百分比。現在，我認為它可能更接近 3 毫克。

So even with the same powering assumptions, this new way of analyzing the data may allow us to, as I said, potentially maximize the difference here, maybe not even as high a bar, slightly lower, but that’s something that we’ll confirm. And, again, I want to keep the powering here at 90%.

因此，即使採用相同的動力假設，這種分析數據的新方法也可能使我們盡可能地擴大差異，正如我所說，甚至可能不會設定太高的標準，而是稍微低一些，但這是我們將要確認的事情。而且，我再次希望將這裡的供電保持在 90%。

Your first part of the question, Prakhar, was – can you just repeat that again?

普拉卡爾，你問題的第一部分是──你能再重複一次嗎？

Yeah. So, I think, in the Phase 1/2 for the high dose, the 1.6 milligram per day steroid reduction was for the post-taper period. So if you apply the same definition as the new endpoint, if you can remind us what would you see there?

是的。因此，我認為，在高劑量的第 1/2 階段，每天減少 1.6 毫克的類固醇是為了減量後期。因此，如果您應用與新端點相同的定義，如果您可以提醒我們您會在那裡看到什麼？

Right. So we haven’t analysKyorin ed it in that manner. What I can tell you is the placebo population had the benefit of the forced steroid reduction in that trial. So if you just sort of qualitatively think about this, if you remove that and you just focus at the end of the trial, we knew that over 50% of the patients in those sub-therapeutic doses were not doing well at the end of the trial. They were, have been rescued and managed at a much higher dose.

正確的。因此我們還沒有以那種方式對它進行分析。我可以告訴你的是，在那次試驗中，安慰劑組因強制減少類固醇而受益。因此，如果你只是從定性角度考慮這個問題，如果你去掉這一點，只關注試驗結束時的情況，我們就會知道，超過 50% 的接受亞治療劑量的患者在試驗結束時情況並不好。他們已經獲救，並且接受了更高劑量的治療。

So, just from a qualitative standpoint, given the fact that we held the line and did pretty well with our 3 and 5 milligram doses and placebo got worse over time, I think, you can see that that number would grow, but we haven’t gone back and back calculated that. It’s a good question. But, I think qualitatively you could probably understand that delta would be certainly larger than 1.6.

因此，僅從定性角度來看，考慮到我們堅持這一原則，並且 3 毫克和 5 毫克劑量的效果相當好，而安慰劑的效果隨著時間的推移而惡化，我認為，你可以看到這個數字會增加，但我們還沒有回過頭來計算這一點。這是個好問題。但是，我認為從質量上來說您可能可以理解 delta 肯定會大於 1.6。

Gregory Renza, RBC Capital Markets.

加拿大皇家銀行資本市場 (RBC Capital Markets) 的 Gregory Renza。

Congrats on the progress and thanks for taking my question. Sanjay, maybe just spinning to EFZO-CONNECT and scleroderma ILD, it’s nice to see the detail on the eight patients on the dataset you’ll be showing on drug and placebo coming up soon. Just curious as you’ve certainly cautioned on not reading through to EFZO-FIT, of course, just wanted to have you comment a bit on what you are looking for, what do you want to learn from the dataset and especially as you talk about the white space with EFZO and other fibrotic diseases, to what extent could this data help guide the directionality there? Thanks so much.

恭喜您取得進展並感謝您回答我的問題。Sanjay，也許只是旋轉到 EFZO-CONNECT 和硬皮症 ILD，很高興看到您即將在藥物和安慰劑上展示的資料集中 8 名患者的詳細資訊。只是好奇，正如您肯定告誡過不要通讀 EFZO-FIT 一樣，當然，只是想讓您稍微評論一下您正在尋找什麼，您想從數據集中了解到什麼，特別是當您談到 EFZO 和其他纖維化疾病的空白時，這些數據在多大程度上可以幫助指導那裡的方向性？非常感謝。

So, absolutely, I think the focus on skin, as you can imagine, we’re not really looking so much really at all for skin for sarcoidosis. The skin readouts represent an extremely high bar. Let me first start by saying scleroderma ILD patients, the primary morbidity that they really complain about and care about and, unfortunately, have not been able to address with any of the therapies is improving skin. None of the approved therapies made a dent in helping with clinical symptom or quality of life. So, we take this seriously.

所以，絕對地，我認為重點放在皮膚上，正如你可以想像的，我們實際上並沒有那麼關注結節病的皮膚。皮膚讀數代表了極高的標準。首先我要說的是，硬皮症 ILD 患者真正抱怨和關心的主要問題是改善皮膚，但不幸的是，任何療法都無法解決這個問題。所有核准的療法均無法有效改善臨床症狀或改善生活品質。因此，我們非常重視這一點。

We also know it’s a very high bar. Why do we think it’s worth looking at skin pathology? Well, we saw a lot of neuropilin expression and even our paper from Science TM that just came out has experts in other areas of inflammatory disease with refractory therapies very much interested. Scleroderma is an area where we see neuropilin expression in those skin plaques. So it makes sense for us from an experimental point of view to really interrogate what’s happening there. Do we see any pathology benefit? Do we see any kind of impact? Again, no therapy has been able to move the needle at all. Can we see something there with immune biomarkers?

我們也知道這是一個非常高的標準。為什麼我們認為皮膚病理學值得研究？嗯，我們看到了很多神經纖毛蛋白的表達，甚至我們剛剛在 Science TM 上發表的論文也引起了其他發炎疾病領域和難治性療法的專家的極大興趣。硬皮症是我們在皮膚斑塊中看到神經纖毛蛋白表現的區域。因此，從實驗的角度來看，我們真正探討那裡發生的事情是有意義的。我們看到任何病理學益處了嗎？我們看到任何影響了嗎？再次，沒有任何療法能夠起到任何作用。我們可以透過免疫生物標記看到一些東西嗎？

Now, with that as a context, it’s okay then in my mind to look at a small dataset, because if we do see something, I think it would be pretty amazing. And, I think, it could open up EFZO’s potential in a number of other systemic diseases, which is where experts continually ask me, can this be used outside of the lung? With our recent paper that just came out, it has attracted more interest from other areas in rheumatology, dermatology. This is something that could be quite exciting for the therapy.

現在，以此為背景，我認為查看一個小資料集是可以的，因為如果我們確實看到了一些東西，我認為那將是非常令人驚奇的。而且我認為，它可以在許多其他全身性疾病中發揮 EFZO 的潛力，專家們不斷問我，它可以在肺部之外使用嗎？我們的論文剛剛發表，引起了風濕病學、皮膚病學等其他領域的更多興趣。這對於治療來說是一件相當令人興奮的事情。

So as of now, we’re really focused on the lung as a franchise with efzofitimod. But you can start to see with the mechanistic validation that we, Leslie outlined in the Science TM paper, this really looks like an opportunity that how do you best position efzofitimod and this is a first step looking at skin perhaps in scleroderma patients. So, I think, it’s a fair fight right now to take a look here, see if we can actually move the needle. It may actually impact where we want to go with efzofitimod with regard to scleroderma patients. Could it open up a more systemic opportunity? We know that’s a much, much larger market. And, we’re also competing with some rather large players right now in that space. But we feel as though we can go toe to toe with them regardless of how big they are from a pharmaceutical perspective.

因此，截至目前，我們真正專注於將 efzofitimod 作為肺部治療的特許經營權。但是，您可以開始透過我們 Leslie 在 Science TM 論文中概述的機制驗證來看到，這確實看起來像是一個機會，即如何最好地定位 efzofitimod，這是觀察硬皮症患者皮膚的第一步。所以，我認為，現在是一場公平的鬥爭，看看我們是否真的能夠取得進展。它實際上可能會影響我們對硬皮症患者使用依佐菲莫德的期望。它能否帶來更有系統性的機會？我們知道這是一個更大的市場。而且，我們目前也正在與該領域的一些相當大的公司競爭。但我們覺得，無論從製藥角度看他們的規模有多大，我們都可以與他們並駕齊驅。

Joe Pantginis, HC Wainwright.

喬潘特吉尼斯、HC溫賴特。

A couple of questions, if you don’t mind. So first, Sanjay, the later part of your comments, you’re talking about patients that may not go on to an EAP, maybe not knowing what the drug is on, etcetera. You listed several reasons. So just curious, maybe you can share some nuances of the disease itself in that, what is the potential to see steroid reductions or even going to zero without therapeutic interventions?

如果您不介意的話，我有幾個問題。首先，桑傑，您評論的後半部分，您談到了可能不會繼續進行 EAP 的患者，他們可能不知道該藥物的作用是什麼，等等。您列舉了幾個原因。所以只是好奇，也許您可以分享一些有關這種疾病本身的細微差別，即如果不進行治療幹預，類固醇減少甚至降至零的可能性有多大？

And I think what we are now really uncovering and want to really think about with this EAP is as patients start to get into longer-term therapy with efzofitimod. Again, I don’t know what they were on during the trial, but now I know they’re receiving 5 milligrams per kilogram. And as they continue to remain in the EAP, the question becomes, are we inducing things more than just management of active inflammation? Is there are we inducing any signs of remission? So this is a different study. It’s quite exciting to those patients, but for them to be off steroids many times for the first time in maybe a decade, this is just a welcome relief to them.

我認為我們現在真正發現並真正想要透過 EAP 思考的是患者開始接受 efzofitimod 的長期治療。再說一次，我不知道他們在試驗期間服用了什麼，但現在我知道他們每公斤攝取 5 毫克。當它們繼續留在 EAP 時，問題就變成了，我們誘導的不僅僅是活動性發炎的管理嗎？我們是否有任何緩解的跡象？所以這是一項不同的研究。這對這些患者來說是相當令人興奮的，但對他們來說，這可能是十年來第一次多次停止使用類固醇，這對他們來說是一種可喜的解脫。

So the EAP is something that I’m really proud of as we look to get more patients in this EAP, how do we then potentially, if our drug is successful with the readouts, how do we then morph that into a more formal EAP or a registry? This is going to answer some of those questions where you start to say, okay, what is the drug doing long-term? It’s that durability question. I think it’s both exciting, but it also opens up some questions around once we get into 18 or 24 months of good management of these patients, what are the implications for a drug like ours? How does it impact pricing? And how do we as a company prepare ourselves for what seems to be a larger market than anyone ever anticipated. So both exciting, challenging, but I think it’s something that we look forward to knowing once we unlock and unblind from this current trial.

因此，EAP 是我真正引以為傲的事情，因為我們希望讓更多的患者參與這個 EAP 中，那麼如果我們的藥物在讀數方面取得成功，我們如何將其轉變為更正式的 EAP 或註冊？這將回答您開始問的一些問題，好吧，這種藥物的長期作用是什麼？這是耐用性的問題。我認為這既令人興奮，但也引發了一些問題：一旦我們對這些患者進行 18 或 24 個月的良好管理，對我們這樣的藥物會有何影響？它如何影響定價？作為一家公司，我們該如何為這個似乎比任何人預期的都要大的市場做好準備呢？所以這既令人興奮，又充滿挑戰，但我認為這是我們在當前試驗結束後期待知道的事情。

And then maybe from a reminder standpoint, can you let us know about your current manufacturing readiness, not only for development indications, but also for potential early commercialization, any early on needs?

然後也許從提醒的角度來看，您能否讓我們了解您目前的製造準備情況，不僅針對開發適應症，還針對潛在的早期商業化，以及任何早期需求？

Yeah. We invested significant capital a few years ago ahead of time to prepare for a commercial readiness strategy with our drug supply, a launch readiness plan, and we made those changes from a clinical group grade partner to a commercial grade partner. Now, we remain on track. That’s going to be an important component to our submission. It’s something the FDA CMC division, CMC group certainly keeps tabs on where we are. Because if we have good data, we want to have drug ready for these patients. As I told you, 20% of these patients, upwards to 20% have significant morbidity and a potential mortality rate in certain age groups that are even higher than that. So these patients can’t wait. So for us to be ready as a biopharma, we made those investments.

是的。幾年前，我們提前投入了大量資金，制定了藥品供應商業準備策略和上市準備計劃，並從臨床組級合作夥伴轉變為商業級合作夥伴。現在，我們仍在繼續前進。這將是我們提交的一個重要組成部分。FDA CMC 部門、CMC 小組肯定會密切關注我們的進展。因為如果我們有良好的數據，我們希望為這些患者準備好藥物。正如我所說的，這些患者中有 20% 甚至高達 20% 的人發病率很高，而且某些年齡層的潛在死亡率甚至更高。所以這些病人不能等待。因此，為了做好成為生物製藥公司的準備，我們進行了這些投資。

If anything right now, we have to look at this new epi data and, say, do we have to be ready to have this as a bigger opportunity? We know I can tell you that and I’ve said this to many of you, the interest from strategics, for example, is the highest it’s ever been because I think the market even with some of those potential strategics we talked to, they are realizing it’s a much larger market. We’ve had a hand in that by leading the way in sarcoidosis, we’ve opened up people’s eyes, more data equals more publications, more understanding. We continue to lead that way with this claims database that we’ll have some data around and the treatment landscape posted at ATS. This is going to fundamentally start to establish a burgeoning market of which we’re really the worldwide leader right now with EFZO.

如果現在有什麼事情的話，我們必須看看這個新的 epi 數據，並且說，我們是否必須做好準備來將其視為一個更大的機會？我們知道我可以告訴你們這一點，而且我已經對你們中的許多人說過這一點，例如，來自戰略方面的興趣達到了有史以來的最高水平，因為我認為，即使對於我們談到的一些潛在戰略，市場也意識到這是一個更大的市場。我們在這方面發揮了主導作用，在結節病研究方面處於領先地位，開闊了人們的視野，更多的數據意味著更多的出版物，更多的理解。我們將繼續透過這個索賠資料庫引領這一方向，我們將擁有一些數據，並在 ATS 上發布治療概況。這將從根本上開始建立一個新興市場，目前我們憑藉 EFZO 已成為該市場的全球領導者。

Liang Cheng, Jefferies.

梁程，傑富瑞。

Hey, good afternoon. Thank you for taking our questions. This is Liang on for Roger. So, just want to circle back to the statistical plan change. So wondering if you can give us any color on what are the drivers from FDA side to change that statistical analysis plan to the current one? Anything more you see from your Phase 1/2 that’s more supporting this plan, current plan?

嘿，下午好。感謝您回答我們的問題。梁先生代替羅傑上場。因此，我只想回到統計計劃的變更。所以想知道您是否可以告訴我們 FDA 方面將統計分析計劃更改為當前計劃的驅動因素是什麼？您從第 1/2 階段中看到什麼內容更能支持該計劃或當前計劃嗎？

Well, I’m probably not going to comment what exactly is in the FDA’s head, because if I knew that, I’d have another career. But, I think, it’s really about simplification. And if anything, what we proposed, we thought was rather conservative, as I said, lacking in bias approach, a simplified assessment was certainly always on the table. But when you sit down with the FDA and specifically the biostats reviewers, you listen to what they guide you towards and sometimes you take it quickly, I will say that. So this is an approach, I think, again, as we are trailblazing here, creating a new path, some of this is working closely with the regulators there.

好吧，我可能不會評論 FDA 到底在想什麼，因為如果我知道的話，我會選擇其他職業。但我認為，這其實是一種簡化。而且如果有什麼不同的話，那就是我們認為我們所提出的建議是相當保守的，正如我所說的，缺乏偏見的方法，簡化的評估肯定始終是可以考慮的。但是當你與 FDA 特別是生物統計審查人員坐下來討論時，你會聽取他們的指導，有時你會很快接受，我會這麼說。所以我認為這是一種方法，因為我們在這裡開拓創新，開闢一條新道路，其中一些是與那裡的監管機構密切合作。

So we may have ways in which we are thinking about analyzing things that from an academic or clinical point of view makes sense to us, but they’re going to provide a little bit of that regulatory color. And, again, if something is a little bit more simplified for them, like I said, we’re going to go ahead and take that win. And we do see this as a more streamlined approach that as I said, we think can help us.

因此，我們可能會考慮從學術或臨床的角度分析對我們來說有意義的事物，但它們會提供一點監管色彩。而且，如果事情對他們來說稍微簡化一點，就像我說的，我們將繼續前進並取得勝利。我們確實認為這是一種更簡化的方法，正如我所說，我們認為它可以幫助我們。

Maybe one more question on upcoming interim analysis for scleroderma program. So I understand there will be like eight patients. So, what’s the distribution between different doses and placebo? And how I understand that that will be focusing on high bar of the skin analysis. So just wonder how would that result affect your ongoing plan?

關於硬皮症計畫即將進行的中期分析，可能還有一個問題。所以我知道會有八名患者。那麼，不同劑量和安慰劑之間的分佈是怎麼樣的呢？我的理解是，這將重點放在皮膚分析的高標準。所以我想知道這個結果會如何影響您正在進行的計劃？

Yes, I’d imagine, I don’t have obviously the treatment assignments for these patients as of yet. We’ll do that when we take, when we pull down on these 8 patients. But I anticipate they will include treated and placebo patients, just based on the block randomization and how we enrol these patients. That’s what I anticipate at this time.

是的，我想，目前我還沒有為這些病人安排治療任務。當我們接收這 8 位患者時，我們會這樣做。但我預計他們將包括接受治療的患者和接受安慰劑的患者，僅基於區組隨機化以及我們如何招募這些患者。這正是我目前的預期。

And how should we think about the results regarding any changes on your ongoing clinic trial?

我們應該如何看待您正在進行的臨床試驗的任何變化的結果？

Any change – you’re saying what are the assessments we’ll look at with those eight patients?

有什麼變化嗎—您說我們將對這八名患者進行哪些評估？

Yeah.

是的。

Yeah, it’s going to largely --

是的，這在很大程度上--

What’s your impact?

你的影響是什麼？

Right, right. Well, again, these are patients, these skin samples will look at histopathology to see if there’s any kind of fibrotic improvement. We’ll be looking at immune biomarkers. We’ve seen of course in animals that the drug performs quite well, but now we have access at the cellular level to potentially see things. The one thing with sarcoidosis not having the ability to biopsy the granulomas that wouldn’t be ethical in the trial. This allows us in this trial to really look at what’s happening right there at the site of inflammation with these patients. So having the access to the skin samples allows us to see if things are really moving right there in these patients.

對，對。嗯，再說一次，這些都是病人，這些皮膚樣本將進行組織病理學檢查，看看是否有任何類型的纖維化改善。我們將研究免疫生物標記。當然，我們已經在動物身上看到了這種藥物的效果，但現在我們可以在細胞層面上觀察這種藥物的作用。結節性多發性硬化症的一個問題是無法對肉芽腫進行活檢，這在試驗中是不道德的。這使得我們在這次試驗中能夠真正觀察這些患者發炎部位發生的情況。因此，透過取得皮膚樣本，我們可以了解這些患者的情況是否真的會改變。

And, of course, there’s also some clinical sub-scoring with something called the Rodnan skin score. Again, that’s something that no approved therapies have improved. So this is why those rheumatologists in particular are really interested to see if efzofitimod moves a needle at all in these samples. If it does, I think as I said, it unlocks a number of other potential systemic opportunities in the rheumatology space.

當然，還有一些臨床評分標準，稱為 Rodnan 皮膚評分。再說一次，這是目前任何核准的療法都無法改善的。這就是為什麼那些風濕病學家特別感興趣看看 efzofitimod 是否會對這些樣本產生任何影響。如果確實如此，我認為正如我所說的，它將釋放風濕病學領域的許多其他潛在的系統性機會。

Dev Prasad, Lucid Capital Markets.

德夫·普拉薩德（Dev Prasad），Lucid Capital Markets。

Congrats on the progress and thank you for taking my question. I have a couple of questions. One on Expanded Access Program. I’m wondering whether you plan to use the data in BLA in any ways. And, secondly, like, do you have significant data from EAP prior to BLA submission?

恭喜您取得進展，並感謝您回答我的問題。我有幾個問題。一個是關於擴大准入計劃的。我想知道您是否計劃以任何方式使用 BLA 中的資料。其次，在提交 BLA 之前，您是否擁有來自 EAP 的重要資料？

Okay. So the first question – answer the second. The first thing is, we’re not slowing down our BLA timelines by wanting to really take a look at this data. Now, this is outside of our trial. So it’s not housed in a database that we own. There are a number of investigators that they have the ability to, if they wanted to pull together investigator-initiated trial, that could be a possibility. I’m in discussions with some of them about potentially what would that look like. Again, that would sit outside of our trial. So I don’t want I want everyone to understand about slowing down the BLA timelines.

好的。因此，第一個問題──回答第二個問題。首先，我們並不會因為真正查看這些數據而減慢我們的 BLA 時間表。現在，這已經超出了我們的審判範圍。所以它不會儲存在我們擁有的資料庫中。他們有能力組織多位研究人員進行研究，如果他們想組織由研究人員發起的試驗，那麼這是有可能的。我正在和他們中的一些人討論那可能會是什麼樣子。再說一遍，這不在我們的審判範圍內。所以我不想讓每個人都了解放慢 BLA 時間表的事情。

And, again, we updated our guidance today that we preserved not only the readout, our BLA timelines, but now effectively have more than a year of cash from our readout, our Phase 3 readout. So we don’t want to slow anything down. Will there be any meaningful analysis from those EAP patients? Again, that depends on whether or not investigators want to have some data out, whether anecdotally or bundled together with some of the sites there. So stay tuned for that. I would love to actually have some data come out in parallel. I think it could potentially really help our BLA discussions if we show in fact long-term durable effects of EFZO. And then, of course, from a safety perspective, it doesn’t hurt to even have some more data. So stay tuned. I do think that’s something that could potentially really benefit us in 2026.

而且，我們今天再次更新了我們的指導方針，我們不僅保留了讀數、我們的 BLA 時間表，而且現在實際上從我們的讀數、我們的第三階段讀數中獲得了一年多的現金。所以我們不想減慢任何事情的速度。那些 EAP 患者會得到任何有意義的分析嗎？同樣，這取決於調查人員是否願意獲取一些數據，無論是軼事數據還是與那裡的一些地點捆綁在一起的數據。因此請繼續關注。我非常希望能夠同時獲得一些數據。我認為，如果我們確實展示 EFZO 的長期持久效果，那麼這可能會真正有助於我們的 BLA 討論。當然，從安全角度來看，擁有更多的資料並沒有什麼壞處。敬請關注。我確實認為這可能會在 2026 年為我們帶來真正的好處。

Just one more. If you can talk about the next pipeline product and potential IND, do you plan to evaluate EFZO in other ILD diseases or the path will be to bring next program like 101 or 750 into clinic? Thank you.

再來一個。如果您可以談論下一個管道產品和潛在的 IND，您是否計劃評估 EFZO 在其他 ILD 疾病中的作用，或者途徑是將下一個項目（如 101 或 750）引入臨床？謝謝。

I think right now we’re enthusiastic to do both. I think efzofitimod clearly mechanistically now could have relevance in a number of other ILDs. And as I pointed out here, we’re talking about upwards to a $5 billion market. When you get outside of sarcoidosis, scleroderma, ILD, RA, myositis ILD, these are all markets that incrementally, there’s no therapy out there that would be considered above ours if we are successful here with sarcoidosis. There’s a lot of legacy products, biologics, other immunosuppressive agents. So I’m continually, for example, in discussions with those autoimmune ILD experts that how can we move into these areas. Pneumonitis, hypersensitivity pneumonitis is another big area that EFZO could potentially work from a mechanistic standpoint.

我認為現在我們熱衷於做這兩件事。我認為 efzofitimod 從機制上顯然與許多其他 ILD 具有相關性。正如我在這裡指出的，我們正在談論一個高達 50 億美元的市場。除了結節性多發性硬化症、硬皮症、間質性肺病 (ILD)、類風濕性關節炎 (RA)、肌炎 (ILD) 之外，這些都是逐步發展的市場，如果我們在結節病治療方面取得成功，那麼沒有任何療法能夠被認為超越我們的療法。有許多遺留產品、生物製劑和其他免疫抑制劑。因此，我不斷地與那些自體免疫 ILD 專家討論我們如何進入這些領域。從機轉角度來看，肺炎、過敏性肺炎是 EFZO 可能發揮作用的另一個重要領域。

With regard to pipeline, 101 has produced some rather outstanding effects as an anti-fibrotic and what I would consider a true anti-fibrotic in that it is initially looking like it modulates myofibroblasts. So our goal would be to expand efzofitimod look at other indications. I think there would be a significant demand in other ILDs certainly. And then with regard to our pipeline, we clearly have a first class research team here that can generate outstanding discoveries. So moving 0101 and 0750 into areas like lung fibrosis, kidney fibrosis, liver disorders, that would certainly be in the cards here. And it’s why I think this is a real big inflection moment for us as a company with this Phase 3 readout.

就管道而言，101 作為抗纖維化藥物產生了一些相當出色的效果，我認為它是一種真正的抗纖維化藥物，因為它最初看起來像是調節肌成纖維細胞。因此，我們的目標是擴大 efzofitimod 的應用範圍，以研究其他適應症。我認為其他 ILD 肯定會有很大的需求。就我們的管道而言，我們顯然擁有一流的研究團隊，可以取得傑出的發現。因此，將 0101 和 0750 轉移到肺纖維化、腎臟纖維化、肝臟疾病等領域肯定是可行的。這就是為什麼我認為對於我們公司來說，第三階段的讀數是一個真正的重大轉折時刻。

I show no further questions at this time. I would now like to turn the call back over to Sanjay for closing remarks.

我目前沒有其他問題。現在我想將電話轉回給桑傑，請他做最後發言。

Sanjay Shukla

桑傑·舒克拉

Well, I want to thank everyone for a number of great questions today. A lot of enthusiasm and interest that I can hear on the other side of the line. We certainly appreciate everyone’s interest. It has been a journey for us. We’re really proud of the work we’ve done.

好吧，我想感謝大家今天提出的許多很棒的問題。我可以聽到電話那頭傳來很多熱情和興趣。我們非常感謝大家的關注。對我們來說這是一趟旅程。我們對於我們所做的工作感到非常自豪。

I’ll just highlight one last thing here. Again, I go back to that publication. As a company here with 20 to 25 researchers, we’re competing with companies, for example, like Roche and Novartis, places I’ve worked with thousands in research departments. And to have a publication in Science TM, I think this is our second one in the last 5 years, thousands of publications over the last five years in that journal. I can only count five companies who have had two major publications and we made the cover this time with these discoveries. And of those five, we’re talking about major big pharma players with thousands of people. So a big shout out to our research team here in San Diego, 20 to 25 folks here strong under the leadership of Leslie. And we’re producing discoveries and insights and really fulfilling the mission of translating this rather unique biology into meaningful medicine. So really, really proud of the work we’ve done here.

我在這裡只想強調最後一件事。我再次回顧該出版物。作為一家擁有 20 至 25 名研究人員的公司，我們正在與羅氏和諾華等公司競爭，我曾與這些公司的研究部門的數千名研究人員合作。在《Science™》上發表文章，我想這是我們在過去五年發表的第二篇文章，過去五年我們在該期刊上發表了數千篇文章。我數一數，只有五家公司發表過兩篇重要出版物，而我們這次憑藉這些發現登上了封面。在這五家公司中，我們談論的是擁有數千名員工的大型製藥公司。因此，我們要向我們位於聖地牙哥的研究團隊致以最誠摯的謝意，這裡有 20 到 25 名成員，在 Leslie 的領導下，實力雄厚。我們不斷取得發現和見解，真正履行將這獨特的生物學轉化為有意義的醫學的使命。我真的非常為我們在這裡所做的工作感到自豪。

I’ll end with that. Look forward to seeing all of you, many of you on the road as we get closer here to Phase 3 readouts later this year. So thank you all for your interest.

我的發言就到此結束。期待與大家見面，隨著今年晚些時候我們越來越接近第三階段的讀數，你們中的許多人都將在路上。謝謝大家的關注。

This does conclude 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。