PureTech Health PLC (PRTC) 2021 Q4 法說會逐字稿

Greetings, and welcome to the PureTech Health 2021 Annual Report and Year-end Financial Results Conference Call. (Operator Instructions)

您好，歡迎來到 PureTech Health 2021 年年度報告和年終財務業績電話會議。 （操作員說明）

As a reminder, this conference is being recorded. It is now my pleasure to introduce your host, Kana DeLuca, Associate Director of Investor Relations. Thank you, Kana, you may begin.

提醒一下，這次會議正在錄製中。現在我很高興向您介紹主持人，投資者關係副總監 Kana DeLuca。謝謝你，假名，你可以開始了。

Thank you for joining us today for PureTech's 2021 Annual Results Webcast. Our annual report was made available this morning, portions of which will also be filed with our Form 20-F today. This information is available on the Investors portion of our website at puretechhealth.com.

感謝您今天參加我們的 PureTech 2021 年年度業績網絡廣播。我們的年度報告於今天上午發布，其中部分內容也將於今天與我們的 20-F 表格一起提交。此信息可在我們網站 puretechhealth.com 的投資者部分獲得。

PureTech is led by a proven and seasoned management team with significant experience in discovering and developing important new medicines, delivering them to market and maximizing shareholder value.

PureTech 由一支成熟且經驗豐富的管理團隊領導，他們在發現和開發重要新藥、將藥物推向市場和實現股東價值最大化方面擁有豐富的經驗。

Today, I'm pleased to be joined by the senior team, including Daphne Zohar, Founder and Chief Executive Officer; Bharatt Chowrira, President and Chief Business Legal and Operating Officer; George Farmer, Chief Financial Officer; Eric Elenko, Chief Innovation Officer and Strategy Officer; Joe Bolen, Chief Scientific Officer; and Julie Krop, Chief Medical Officer who will all be available for questions after the presentation.

今天，我很高興加入高級團隊，包括創始人兼首席執行官 Daphne Zohar； Bharatt Chowrira，總裁兼首席商業法務和運營官；首席財務官 George Farmer； Eric Elenko，首席創新官兼戰略官； Joe Bolen，首席科學官；和首席醫療官朱莉·克羅普 (Julie Krop)，他們將在演講結束後回答問題。

I would like to remind you that during today's call, we will be making certain forward-looking statements. These statements are subject to various important risks uncertainties and assumptions that could cause our actual results to differ materially, and we ask that you refer to our annual report in our SEC filings for a complete discussion of these risks, uncertainties and assumptions.

我想提醒您，在今天的電話會議中，我們將做出某些前瞻性陳述。這些陳述受各種重要風險、不確定性和假設的影響，可能導致我們的實際結果出現重大差異，我們要求您參考我們在 SEC 文件中的年度報告，以完整討論這些風險、不確定性和假設。

We undertake no obligation to revise or update any forward-looking statements or information, except as required by law. I also want to remind you that we will be referring to certain non-IFRS measures in this presentation. The presentation of this non-IFRS financial information is not intended to be considered in isolation or as a substitute for financial information presented in accordance with IFRS.

除非法律要求，否則我們不承擔修改或更新任何前瞻性陳述或信息的義務。我還想提醒您，我們將在本演示文稿中提及某些非 IFRS 措施。此非 IFRS 財務信息的列報不應被孤立地考慮或作為根據 IFRS 列報的財務信息的替代。

A reconciliation of the IFRS to non-IFRS measures, that we will be referring to today can be found in this presentation, is also available on our Investor Relations website at investors.puretechhealth.com and in our SEC filings. I will now turn the call over to Daphne Zohar, PureTech's Founder and Chief Executive Officer.

我們今天將提到的 IFRS 與非 IFRS 措施的協調可以在本演示文稿中找到，也可以在我們的投資者關係網站 investors.puretechhealth.com 和我們的 SEC 文件中找到。我現在將把電話轉給 PureTech 的創始人兼首席執行官 Daphne Zohar。

Thank you, Kana. Thank you for joining us this morning. We hope all of you and your families are keeping well. At PureTech, we are dedicated to improving lives and inspired by our mission to discover, develop and commercialize new therapies for devastating and often orphan diseases where limited or no treatment options currently exist for patients.

謝謝你，假名。感謝您今天早上加入我們。我們希望你們所有人和你們的家人都保持健康。在 PureTech，我們致力於改善生活，並受到我們的使命的啟發，即發現、開發和商業化新療法，以治療目前患者治療選擇有限或沒有治療選擇的破壞性且通常是孤兒疾病。

I am immensely proud of our team's accomplishments in 2021, and we are so pleased to have a strong cash position and the ability to support our activities. We are also excited to share more with you today about our capital allocation strategy to drive additional value to our shareholders. It was a productive year for PureTech with significant advances, important achievements and further validation of our unique R&D model for developing new medicines.

我為我們團隊在 2021 年取得的成就感到無比自豪，我們很高興擁有強大的現金狀況和支持我們活動的能力。今天，我們也很高興能與您分享更多關於我們為股東創造更多價值的資本配置戰略。對於 PureTech 來說，這是富有成效的一年，取得了重大進展、取得了重要成就，並進一步驗證了我們用於開發新藥的獨特研發模式。

Today, we would like to go over a few clinical and business updates, including the progress we have been making across our pipeline, a review of our strong financial position and how we are building value for our investors, including a discussion of our capital allocation strategy and our environmental, social and governance achievements and progress of which we are very proud.

今天，我們想回顧一些臨床和業務更新，包括我們在整個管道中取得的進展、對我們強大財務狀況的回顧以及我們如何為投資者創造價值，包括對我們資本配置的討論戰略以及我們引以為豪的環境、社會和治理成就和進步。

Let's start by looking at our strong track record of clinical success. We have a unique R&D model that has been successful in identifying, inventing and advancing novel candidates through our network of scientists, clinicians and industry leaders before the rest of the world knows about key discoveries.

讓我們首先看看我們在臨床成功方面的良好記錄。我們擁有獨特的研發模式，通過我們的科學家、臨床醫生和行業領導者網絡，成功地在世界其他地方知道關鍵發現之前識別、發明和推進新候選藥物。

We're proud of our track record, having now generated 27 therapeutics and therapeutic candidates, of which 16 are clinical stage, and 2 have gone from inception at PureTech through successful FDA and EU regulatory clearances for marketing.

我們為自己的業績感到自豪，現在已經產生了 27 種治療藥物和治療候選藥物，其中 16 種處於臨床階段，2 種從 PureTech 成立之初就成功通過了 FDA 和歐盟監管機構的營銷許可。

Notably, our track record of clinical success outperforms industry averages by 5.5x. We think part of that is due to our approach of building on validated biology and bringing an important inventive step that enables key benefits for patients such as significantly improved tolerability or localized targeting, for example, to immune cells or sites of inflammation.

值得注意的是，我們的臨床成功記錄比行業平均水平高出 5.5 倍。我們認為，部分原因是我們的方法建立在經過驗證的生物學基礎上，並帶來了重要的創造性步驟，為患者帶來了關鍵益處，例如顯著提高耐受性或局部靶向，例如免疫細胞或炎症部位。

So across our pipeline, there are examples where we take an approach that has proof of human efficacy, but the class has been held back from its full potential by some key limitation and then we apply our technology to overcome that key deficit to enable a new class of therapeutics to be unlocked. One of our founded entities, Karuna, is a good example of this.

因此，在我們的管道中，有一些例子表明我們採用了一種證明人類有效性的方法，但該類由於一些關鍵限製而無法充分發揮其潛力，然後我們應用我們的技術來克服這一關鍵缺陷以實現新的要解鎖的治療類別。我們創立的實體之一 Karuna 就是一個很好的例子。

We were struck by the fact that there hadn't been a new mechanism for treating schizophrenia in over 50 years. So we engaged with a group of leading schizophrenia experts, who are most excited about muscarinic agonists, pointing to the powerful data generated by Eli Lilly with xanomeline, which was held back at the time due to tolerability issues.

50 多年來一直沒有治療精神分裂症的新機制，這讓我們感到震驚。因此，我們與一群對毒蕈鹼激動劑最感興趣的主要精神分裂症專家進行了接觸，指出禮來公司使用 xanomeline 生成的強大數據，當時由於耐受性問題而被擱置。

We invented the concept of combining a muscarinic receptor agonist with a peripherally acting antagonist, which improved the AE profile and unlocked a new class of antipsychotics, which may potentially improve the lives of millions of people living with psychosis.

我們發明了將毒蕈鹼受體激動劑與外周作用拮抗劑相結合的概念，這改善了 AE 概況並解鎖了一類新的抗精神病藥，這可能會改善數百万精神病患者的生活。

As many of you may know, KarXT now represents a potential first-in-class and best-in-class therapy for schizophrenia. Financially, this was also a big success for us, as we had allocated a total of $18.5 million to that program and generated over 40x returns on that capital without even accounting for the fact that we are do royalties and sublicense revenues as a co-inventor of certain underlying intellectual property.

正如你們中的許多人所知，KarXT 現在代表了一種潛在的一流和一流的精神分裂症療法。在財務上，這對我們來說也是一個巨大的成功，因為我們已經為該項目分配了總計 1850 萬美元，並產生了超過 40 倍的資本回報，甚至沒有考慮到我們作為共同發明人獲得版稅和再許可收入這一事實某些基礎知識產權。

We think that our approach has enabled us to have better success rates because one clinical component has been substantially derisked. A second important point is that we set up key experiments to derisk the programs early, and are willing to move resources and shut down programs that have mixed or negative results so that we focus our resources on the programs that have higher chances of success.

我們認為我們的方法使我們能夠獲得更高的成功率，因為一個臨床組成部分已被大大降低風險。第二個重要的一點是，我們設置了關鍵實驗來儘早消除項目的風險，並願意轉移資源並關閉結果喜憂參半或負面的項目，以便我們將資源集中在成功機會更高的項目上。

This is supported by the fact that we are not reliant on any one binary program. That means we have choices about how to spend our time and money, and we are entirely aligned with our shareholders to advance the winners. That is something that is more difficult to do if the company has only one platform or program.

我們不依賴任何一個二進製程序這一事實支持了這一點。這意味著我們可以選擇如何花費我們的時間和金錢，並且我們完全與我們的股東保持一致以推動贏家。如果公司只有一個平台或程序，那就更難做到這一點。

I'll note that our network of scientific collaborators, you see pictured here, enables us to identify and co-invent (inaudible) before it's published in major journals. In fact, there have been around 30 papers published in major journals like science, cell in nature, most of which were published after we in-licensed the key technology.

我會注意到，我們的科學合作者網絡，如圖所示，使我們能夠在主要期刊上發表之前識別和共同發明（聽不清）。事實上，在 science、cell in nature 等主要期刊上發表了大約 30 篇論文，其中大部分是在我們獲得關鍵技術授權後發表的。

Through this unique approach, we have built a pipeline of novel therapeutic candidates that are being advanced both internally, which you see at the top of this slide and through our founded entities, which you can see across the bottom of the slide. You can think of our founded entities like partnered programs, where we co-invented and advanced them through initial milestones.

通過這種獨特的方法，我們已經建立了一系列新的候選治療藥物，這些候選藥物在內部得到推進，您可以在這張幻燈片的頂部看到，也可以通過我們創建的實體，您可以在幻燈片的底部看到。您可以將我們創建的實體想像成合作夥伴計劃，我們共同發明並通過最初的里程碑推進它們。

We hold sizable equity ownership in these 8 founded entities and continue to benefit from their growth, as they have many upcoming catalysts and can serve as a potential source of non-dilutive funding to us over time from events such as M&A transactions, IPOs and royalties. Just last year, for example, we received $218 million from the sales of some of our equity and founded entities.

我們在這 8 家成立的實體中持有大量股權，並繼續受益於它們的增長，因為它們有許多即將到來的催化劑，並且隨著時間的推移，它們可以成為我們從併購交易、首次公開募股和特許權使用費等事件中獲得非稀釋性資金的潛在來源.例如，就在去年，我們通過出售部分股權和成立的實體獲得了 2.18 億美元的收入。

We have been able to use these resources to advance our wholly owned pipeline, which we see as a major value driver going forward. We have a strong balance sheet and ended the year with $418.9 million in cash and cash equivalents at the PureTech level.

我們已經能夠利用這些資源來推進我們的全資管道，我們認為這是未來的主要價值驅動力。我們擁有強大的資產負債表，到年底，PureTech 層面的現金和現金等價物為 4.189 億美元。

Our founded entities are also well capitalized having raised $1.9 billion over the last few years, of which 94% came from third parties. 2021 was rich in accomplishments. As we look at the progress across our wholly owned pipeline on the upper half of this slide, it's important to highlight that we initiated 5 clinical studies in 2021, 4 of which read out so far and 1 that is ongoing.

我們成立的實體也資本充足，在過去幾年籌集了 19 億美元，其中 94% 來自第三方。 2021 年收穫頗豐。當我們在這張幻燈片的上半部分查看我們全資擁有的管道的進展時，重要的是要強調我們在 2021 年啟動了 5 項臨床研究，其中 4 項目前已宣讀，1 項正在進行中。

Our founded entities have also achieved many value-building milestones in 2021, including Vedanta's positive top line results from the Phase II data of VE303 in C. difficile infections, which led BARDA to exercise its option for the additional funding of $23.8 million. We saw the beginnings of the broad commercial launch of Gelesis' Plenity and the commercial launch preparations of Akili’s EndeavorRx.

我們成立的實體也在 2021 年實現了許多價值建設里程碑，包括 Vedanta 從艱難梭菌感染中 VE303 的 II 期數據中獲得的積極頂線結果，這導致 BARDA 行使其選擇權，獲得 2380 萬美元的額外資金。我們看到了 Gelesis 的 Plenity 廣泛商業發布的開始以及 Akili 的 EndeavorRx 的商業發布準備。

So far in the 2022 post period, Gelesis has completed a public listing on the New York Stock Exchange, becoming the third PureTech-founded entity to be listed publicly and Akili has announced an upcoming merger with Social Capital Suvretta Holdings valued at $1 billion, expected to close in mid-2022, which would then become our fourth publicly listed founded entity.

到目前為止，在 2022 年後，Gelesis 已完成在紐約證券交易所的公開上市，成為 PureTech 創立的第三家上市實體，Akili 宣布即將與 Social Capital Suvretta Holdings 合併，預計價值 10 億美元將於 2022 年年中關閉，屆時它將成為我們第四家公開上市的創立實體。

Our 3 currently public founded entities, Gelesis, Vor and Karuna are valued at a total of around $4.5 billion, with important catalysts that could potentially further impact those values. And we have several other private founded entities who we believe also have substantial value potential.

我們目前的 3 個公共實體 Gelesis、Vor 和 Karuna 的總價值約為 45 億美元，重要的催化劑可能會進一步影響這些價值。我們還有其他幾個私人創立的實體，我們認為它們也具有巨大的價值潛力。

In our wholly owned pipeline, we created significant fundamental value and achieved a number of additional clinical and business milestones towards our mission of developing transformational medicines for millions of people, who have long struggled to find effective treatments.

在我們全資擁有的管道中，我們創造了重要的基本價值，並實現了我們為數百萬人開發轉化藥物的使命的額外臨床和業務里程碑，這些人長期以來一直在努力尋找有效的治療方法。

These milestones are highlighted in our annual report, and I'll touch on just a few of them here. We currently have 7 therapeutic candidates in our wholly owned pipeline, including 1 therapeutic candidate that has been licensed out to and is being developed by a partner.

這些里程碑在我們的年度報告中得到了強調，我將在這裡僅介紹其中的幾個。我們目前在我們的全資管線中擁有 7 種治療候選藥物，其中包括 1 種已獲得合作夥伴許可並由合作夥伴開發的治療候選藥物。

LYT-100 is our lead therapeutic candidate, which we believe may have therapeutic potential across a range of conditions involving inflammation and fibrosis. These include lung diseases, such as idiopathic pulmonary fibrosis or IPF, and orphan disease, and Long COVID respiratory complications, as well as disorders of lymphatic flow such as lymphedema.

LYT-100是我們的主要治療候選藥物，我們認為它可能在涉及炎症和纖維化的一系列疾病中具有治療潛力。這些包括肺部疾病，如特發性肺纖維化或 IPF、孤兒病、Long COVID 呼吸道並發症，以及淋巴流動障礙，如淋巴水腫。

Earlier this year, we announced positive top line results from a crossover study comparing LYT-100, deupirfenidone that showed a 50% reduction in the incidence of GI-related adverse events compared to perfinidone in healthy older adults.

今年早些時候，我們公佈了一項比較 LYT-100 和去吡非尼酮的交叉研究的積極頂線結果，該研究表明與健康老年人相比，胃腸道相關不良事件的發生率比培非尼酮降低了 50%。

And we also outlined our plans to advance LYT-100 into late-stage clinical development for the treatment of IPF. Julie will dig deeper into the data shortly. We have an ongoing Phase II study of LYT-100 in Long COVID-related pulmonary complications, which we expect to read out in the first half of 2022. We're also advancing LYT-100 in lymphedema, for which there are over 1 million patients in the U.S. with no pharmaceutical treatment options.

我們還概述了將 LYT-100 推進 IPF 治療後期臨床開發的計劃。 Julie 將很快深入挖掘數據。我們正在進行一項關於 LYT-100 治療長期 COVID 相關肺部並發症的 II 期研究，我們預計將在 2022 年上半年宣讀。我們還在推進 LYT-100 治療淋巴水腫，其中有超過 100 萬美國的患者沒有藥物治療選擇。

We are in a Phase IIa study, which we'll read out later this year. Importantly, we are one of the only companies advancing novel therapeutic options for lymphedema and for Long COVID. Beyond pulmonary conditions in lymphedema, we are also exploring the potential of LYT-100, in other inflammatory and fibrotic conditions, such as radiation-induced fibrosis, myocardial fibrosis and other organ system fibrosis based on clinical data around the use of pirfenidone in those indications.

我們正在進行 IIa 期研究，我們將在今年晚些時候宣讀。重要的是，我們是為淋巴水腫和 Long COVID 提供新型治療方案的僅有的幾家公司之一。除了淋巴水腫中的肺部疾病外，我們還在探索 LYT-100 在其他炎症和纖維化疾病中的潛力，例如輻射誘導的纖維化、心肌纖維化和其他器官系統纖維化，基於這些適應症中使用吡非尼酮的臨床數據.

Outside of LYT-100, we have 2 oncology programs, one of which is LYT-200 for the potential treatment of a range of cancer indications and which has orphan drug designation from the FDA. The Phase I portion of the study is ongoing and a maximum tolerated dose has not yet been reached.

在 LYT-100 之外，我們還有 2 個腫瘤學項目，其中一個是 LYT-200，用於潛在治療一系列癌症適應症，並獲得 FDA 的孤兒藥稱號。該研究的 I 期部分正在進行中，尚未達到最大耐受劑量。

We also have a preclinical oncology therapeutic candidate, LYT-210, designed to inactivate a subset of tumor-promoting gamma delta-1 T cell receptors, which we are developing for a range of cancer indications.

我們還有一個臨床前腫瘤學治療候選藥物 LYT-210，旨在滅活促進腫瘤的 gamma delta-1 T 細胞受體的一個子集，我們正在為一系列癌症適應症開發這種受體。

In December, we initiated a clinical trial for LYT-300, which is an oral version of a clinically validated drug that is currently only administered via a 60-hour IV infusion. We are advancing LYT-300 for a range of neurological and neuropsychological conditions. This program came from our Glyph lymphatic targeting program.

12 月，我們啟動了 LYT-300 的臨床試驗，這是一種經臨床驗證的藥物的口服版本，目前僅通過 60 小時靜脈輸注給藥。我們正在推進 LYT-300 用於一系列神經和神經心理疾病。該程序來自我們的 Glyph 淋巴靶向程序。

We have powerful lymphatic and inflammation technology platforms, which serve as a source for generating potential future candidates for the internal pipeline. Including LYT-300, we have now generated 4 therapeutic units from these platforms. I'm now going to hand over the call to Julie Krop, MD, our Chief Medical Officer, to walk us through our therapeutic development pipeline in depth, starting with LYT-100, which is a perfect case study for our R&D model.

我們擁有強大的淋巴和炎症技術平台，可作為內部管道未來潛在候選人的來源。包括 LYT-300，我們現在已經從這些平台生成了 4 個治療單元。我現在要將電話轉給我們的首席醫療官 Julie Krop 醫學博士，讓我們深入了解我們的治療開發管道，從 LYT-100 開始，這是我們研發模型的完美案例研究。

Thank you, Daphne. I'm thrilled to be part of the PureTech team. Having worked at a number of outstanding companies over the course of my career in drug development, PureTech really stands out as the best placement worked. In my opinion, PureTech uniquely possesses all 3 critical ingredients for a successful biotech, an uncommon trifecta that includes an experienced CEO and leadership team with a proven track record of success, a broad and innovative pipeline, and last but not least, the internal capital to efficiently execute on it.

謝謝你，達芙妮。我很高興成為 PureTech 團隊的一員。在我的藥物開發職業生涯中，我曾在許多傑出的公司工作過，PureTech 確實脫穎而出，成為最佳安置工作。在我看來，PureTech 獨特地擁有成功生物技術的所有 3 個關鍵要素，一個不常見的三重奏，包括經驗豐富的首席執行官和具有成功記錄的領導團隊、廣泛和創新的管道，以及最後但並非最不重要的內部資本有效地執行它。

LYT-100 is our lead candidate, which we believe may have therapeutic benefit across a range of conditions involving inflammation and fibrosis. We initially discovered this program through our focus on evaluating therapies for treating lymphedema, a serious disorder associated with (inaudible) lymphatic flow and no approved therapeutics.

LYT-100 是我們的主要候選藥物，我們認為它可能對涉及炎症和纖維化的一系列疾病具有治療益處。我們最初是通過專注於評估治療淋巴水腫的療法發現該計劃的，淋巴水腫是一種與（聽不清）淋巴流動相關的嚴重疾病，並且沒有批准的療法。

Lymphedema is a chronic and painful condition that affects 1 million people in the United States alone, and is characterized by severe swelling in effective parts of the body due to the buildup of lymph, which over time leads to chronic inflammation and eventually fibrosis.

淋巴水腫是一種慢性疼痛性疾病，僅在美國就影響了 100 萬人，其特徵是由於淋巴積聚導致身體有效部位嚴重腫脹，隨著時間的推移會導致慢性炎症並最終導致纖維化。

As is typical for us, unique insights and unpublished data from our collaborators and business network enabled us to identify LYT-100 and acquire the related IP. LYT-100 is a derated form of pirfenidone that is designed to retain the potent and clinically validated anti-inflammatory and antifibrotic activity of pirfenidone with a differentiated pharmacokinetic profile.

正如我們的典型做法，來自我們的合作者和業務網絡的獨特見解和未發表的數據使我們能夠識別 LYT-100 並獲得相關 IP。 LYT-100是吡非尼酮的一種降級形式，旨在保留吡非尼酮有效且經臨床驗證的抗炎和抗纖維化活性，具有差異化的藥代動力學特徵。

Pirfenidone has been approved for the treatment of idiopathic pulmonary fibrosis, condition characterized by progressive irreversible scarring of the lungs that is associated with a significantly reduced life span with a median survival between 3 to 5 years.

吡非尼酮已被批准用於治療特發性肺纖維化，這種疾病的特徵是肺部出現進行性不可逆的瘢痕形成，與壽命顯著縮短相關，中位生存期為 3 至 5 年。

The current standard of care includes pirfenidone and nintedanib, both of which are efficacious therapies for patients who have IPF. Despite their proven efficacy, their clinical benefit has been significantly limited by gastrointestinal-related adverse events, which include nausea, abdominal discomfort and diarrhea.

目前的標準治療包括吡非尼酮和尼達尼布，這兩種藥物對 IPF 患者都是有效的治療方法。儘管它們已被證明有效，但它們的臨床益處受到胃腸道相關不良事件的顯著限制，這些不良事件包括噁心、腹部不適和腹瀉。

Approximately half of the patients on pirfenidone discontinue treatment, dose adjust or switch to an alternative treatment due to tolerability issues with pirfenidone. And according to one study, only about 26% of IPF patients are treated with the current standard of care treatment despite their proven efficacy.

由於吡非尼酮的耐受性問題，大約一半的吡非尼酮患者停止治療、調整劑量或轉為替代治療。根據一項研究，只有約 26% 的 IPF 患者接受了當前標準的護理治療，儘管這些治療已被證明有效。

This suggests that the vast majority of IPF patients are not currently being treated and supports the significant unmet need for new, more tolerable treatment options that would enable patients to stay on treatment for this deadly condition. We believe that this represents a substantial opportunity for LYT-100 that we believe could really make a meaningful difference for patients with IPF by improving the tolerability profile of pirfenidone.

這表明絕大多數 IPF 患者目前沒有接受治療，並支持對新的、更耐受的治療方案的重大未滿足需求，這些方案將使患者能夠繼續接受這種致命疾病的治療。我們認為，這對 LYT-100 來說是一個重要的機會，我們相信它可以通過改善吡非尼酮的耐受性，真正為 IPF 患者帶來有意義的改變。

For these reasons, we believe the LYT-100 profile has the potential to replace the current standard of care. LYT-100 maintains the pharmacology of pirfenidone with a differentiated PK profile, enabling an improved tolerability profile. LYT-100 demonstrated comparable total exposure to pirfenidone based on PK modeling from prior studies while improving on the gastrointestinal-related adverse events.

由於這些原因，我們相信 LYT-100 概況有可能取代目前的護理標準。 LYT-100 保持了吡非尼酮的藥理學特性，具有差異化的 PK 特性，從而提高了耐受性。 LYT-100 在改善胃腸道相關不良事件的同時，基於先前研究的 PK 模型證明了吡非尼酮的總暴露量相當。

Because of LYT-100's potential tolerability advantage, there is also the opportunity to test the dose with higher drug exposure than the currently approved dose of pirfenidone, which would have the potential for even better efficacy. I'll touch more on this on the next slide.

由於 LYT-100 的潛在耐受性優勢，還有機會測試比目前批准的吡非尼酮劑量更高的藥物暴露劑量，這將有可能獲得更好的療效。我將在下一張幻燈片中詳細介紹這一點。

Importantly, we have a composition of matter patents with exclusivity up to 2033 and additional IP that covers dosing, formulation and method of treatment that would further extend the period of exclusivity to 2040.

重要的是，我們擁有一系列物質專利，其獨占期可達 2033 年，另外還有涵蓋劑量、配方和治療方法的知識產權，可進一步將獨占期延長至 2040 年。

LYT-100 also has the potential for NCE designation and orphan drug exclusivity for IPF and other indications. This is important because there is demonstrated clinical efficacy data with pirfenidone in a range of indications in addition to IPF, but those have not been pursued commercially with pirfenidone. What we really like about the LYT-100 is its derisked clinical profile due to its close chemical similarity to pirfenidone.

LYT-100還有可能獲得 NCE 指定和 IPF 及其他適應症的孤兒藥獨占權。這很重要，因為除 IPF 外，吡非尼酮在一系列適應症中的臨床療效數據已得到證實，但尚未將這些數據用於吡非尼酮的商業化研究。我們真正喜歡 LYT-100 的是它的臨床特徵，因為它與吡非尼酮的化學成分非常相似。

This is reminiscent of Karuna's KarXT, which Daphne noted earlier, was a program PureTech coinvented. Our team knew a lot about the parent compound efficacy and created an improvement to address the tolerability issues that has the potential to significantly improve the lives of patients with schizophrenia.

這讓人想起 Karuna 的 KarXT，Daphne 之前指出，它是 PureTech 共同發明的一個程序。我們的團隊對母體化合物的功效了解很多，並進行了改進以解決耐受性問題，這有可能顯著改善精神分裂症患者的生活。

LYT-100's value proposition is very similar. As Daphne mentioned, we were excited to announce the results from our randomized double-blind crossover study in healthy older adults earlier this year. The study evaluated the tolerability of LYT-100 at 550 milligrams TID dosing, which based on prior studies, achieved similar exposure levels as FDA-approved dosing of pirfenidone for the treatment of IPF, but with a lower Cmax.

LYT-100 的價值主張非常相似。正如 Daphne 提到的，我們很高興在今年早些時候宣布我們在健康老年人中進行的隨機雙盲交叉研究的結果。該研究評估了 LYT-100 在 550 毫克 TID 劑量下的耐受性，該劑量基於先前的研究，達到了與 FDA 批准的用於治療 IPF 的吡非尼酮劑量相似的暴露水平，但 Cmax 較低。

This is important because we believe that higher Cmax levels correlate with an increased incidence of adverse events. The data demonstrated approximately 50% fewer subjects treated with LYT-100 experienced gastrointestinal-related adverse events compared to subjects treated with pirfenidone while maintaining similar exposure levels.

這很重要，因為我們認為較高的 Cmax 水平與不良事件發生率的增加相關。數據表明，與接受吡非尼酮治療的受試者相比，接受 LYT-100 治療的受試者發生胃腸道相關不良事件的人數減少了約 50%，同時保持了相似的暴露水平。

We also saw a clinically meaningful reduction in the incidence of neurologic adverse events. Based on these data and data from our multiple extending dose studies, we believe LYT-100's differentiated profile will have reduced gastrointestinal and other adverse events and as a result, potentially improve patient compliance.

我們還看到神經系統不良事件發生率的臨床意義降低。基於這些數據和我們多次擴展劑量研究的數據，我們相信 LYT-100 的差異化特徵將減少胃腸道和其他不良事件，並因此有可能提高患者的依從性。

The longer patients can stay on the drug at the approved dose exposure, the more efficacious we believe the drug will be. We also completed additional Phase I studies, which have demonstrated that LYT-100 was well tolerated at higher doses with low rates of gastrointestinal adverse events that were comparable to placebo.

患者在批准的劑量暴露下服用藥物的時間越長，我們相信該藥物的療效就越好。我們還完成了額外的 I 期研究，這些研究表明 LYT-100 在較高劑量下具有良好的耐受性，胃腸道不良事件發生率較低，與安慰劑相當。

Based on these results, we will proceed with the dose ranging study in treatment-naive IPF patients with 4 treatment arms as seen in this slide.

基於這些結果，我們將繼續在具有 4 個治療組的初治 IPF 患者中進行劑量範圍研究，如本幻燈片所示。

There will be 2 arms of LYT-100, a dose that matches pirfenidone exposure and a dose that has higher exposure as well as the placebo arm in a pirfenidone arm is a benchmark. A previous clinical study comparing a lower dose of pirfenidone than the FDA-approved dose noted a dose efficacy response, but whether a dose higher than the marketed dose can achieve increased efficacy has not yet been explored in patients with IPF.

將有 2 個 LYT-100 臂，一個劑量與吡非尼酮暴露量相匹配，一個劑量與吡非尼酮臂中的安慰劑臂具有更高的暴露量和安慰劑臂是基準。之前的一項臨床研究比較了比 FDA 批准的劑量更低的吡非尼酮劑量，注意到劑量療效反應，但尚未在 IPF 患者中探索高於上市劑量的劑量是否可以實現更高的療效。

In the upcoming dose ranging study, we plan to investigate LYT-100 in IPF patients at a dose with a higher total drug exposure than the currently approved dose of pirfenidone to see if higher exposure results in improved efficacy.

在即將進行的劑量範圍研究中，我們計劃在 IPF 患者中調查 LYT-100 的總藥物暴露劑量高於目前批准的吡非尼酮劑量，以查看更高的暴露是否會導致療效提高。

Guided by our clinical advisory board that includes many of the world's experts in IPF clinical development and our data generated to date as well as recent regulatory feedback, we will advance LYT-100 into late-stage clinical development for the treatment of IPF, beginning with a dose-ranging study initiating in the first half of 2022, with top line results expected by the end of 2023.

在我們的臨床顧問委員會的指導下，該委員會包括世界上許多 IPF 臨床開發專家和我們迄今為止生成的數據以及最近的監管反饋，我們將把 LYT-100 推進到治療 IPF 的後期臨床開發，從一項於 2022 年上半年啟動的劑量範圍研究，預計將在 2023 年底獲得最高結果。

The dose-ranging study will enroll approximately 250 treatment-naive IPF patients to evaluate LYT-100 efficacy relative to placebo. The study will also compare LYT-100 tolerability and efficacy with pirfenidone.

劑量範圍研究將招募大約 250 名初治 IPF 患者，以評估 LYT-100 相對於安慰劑的療效。該研究還將比較 LYT-100 與吡非尼酮的耐受性和療效。

The primary endpoint will measure the rate of decline in FVC for LYT-100 compared to placebo over 6 months. We intend to capitalize on efficiencies of the 505(b)(2) pathway for our IPF development plan, and we believe that compelling efficacy data from the upcoming dose-ranging study, together with a Phase III study could serve as the basis for us to file for FDA approval for the treatment of IPF in the United States.

主要終點將衡量 LYT-100 與安慰劑相比在 6 個月內的 FVC 下降率。我們打算利用 505(b)(2) 途徑的效率來實現我們的 IPF 開發計劃，我們相信來自即將進行的劑量範圍研究的令人信服的療效數據以及 III 期研究可以作為我們的基礎申請 FDA 批准在美國治療 IPF。

We also have 2 ongoing Phase II studies with LYT-100, one in Long COVID related pulmonary complications, which we expect to read out in the first half of 2022 and a Phase IIa study in lymphedema, which we'll read out in 2022.

我們還有 2 項正在進行的 LYT-100 的 II 期研究，一項是與 Long COVID 相關的肺部並發症，我們預計將在 2022 年上半年公佈，以及一項關於淋巴水腫的 IIa 期研究，我們將在 2022 年公佈。

As previously mentioned, we will be initiating our dose-ranging study in IPF in the first half of 2022 and expect top line results by the end of 2023. Beyond the pulmonary conditions in lymphedema, we are also exploring the potential LYT-100 in other inflammatory and fibrotic conditions, such as radiation-induced fibrosis, myocardiofibrosis and other organ system fibrosis based on validated clinical data generated with pirfenidone in these indications.

如前所述，我們將在 2022 年上半年啟動 IPF 的劑量範圍研究，並預計到 2023 年底將取得頂線結果。除了淋巴水腫的肺部疾病外，我們還在其他領域探索潛在的 LYT-100基於吡非尼酮在這些適應症中產生的經過驗證的臨床數據，炎症和纖維化病症，例如輻射誘導的纖維化、心肌纖維化和其他器官系統纖維化。

Our second wholly owned therapeutic candidate is LYT-200, which targets a foundational immunosuppressor, Galectin-9, for the potential treatment of a range of cancer indications. Our preclinical data suggests that Galectin-9 could be an important therapeutic target for a range of cancers and also has the potential to serve as a cancer biomarker for those that may benefit from treatment.

我們的第二個全資候選治療藥物是 LYT-200，它以基礎免疫抑製劑 Galectin-9 為靶點，用於治療一系列癌症適應症。我們的臨床前數據表明，Galectin-9 可能是一系列癌症的重要治療靶點，也有可能成為那些可能從治療中受益的癌症生物標誌物。

Galectin-9 is a particularly interesting immuno-oncology target, given that it is a tumor secretive factor that affects multiple immunosuppressive signaling pathways simultaneously to interaction with a number of different immune cell receptors.

Galectin-9 是一個特別有趣的免疫腫瘤學靶標，因為它是一種腫瘤分泌因子，可同時影響多種免疫抑制信號通路，從而與多種不同的免疫細胞受體相互作用。

Such receptors include validated targets like PD-1, for example, as well as others. LYT-200 is currently being evaluated as a single agent in the first stage of an adaptive Phase I/II clinical trial as seen on this slide, which is expected to read out in the first half of 2022.

此類受體包括經過驗證的靶標，例如 PD-1 等。如本幻燈片所示，LYT-200 目前正在適應性 I/II 期臨床試驗的第一階段作為單一藥物進行評估，預計將於 2022 年上半年宣讀。

Pending these results, we intend to initiate Phase II expansion cohort portion of the trial, which is designed to evaluate LYT-200, both alone and in combination with BeiGene's tislelizumab for chemotherapy.

在獲得這些結果之前，我們打算啟動該試驗的 II 期擴展隊列部分，該部分旨在評估 LYT-200 單獨使用和與百濟神州的 tislelizumab 聯合用於化療的效果。

We also have a second oncology program, LYT-210, a preclinical candidate targeting immunomodulatory gamma-delta-1 T cells, which we are developing for a range of cancer indications.

我們還有第二個腫瘤學項目 LYT-210，這是一種針對免疫調節 gamma-delta-1 T 細胞的臨床前候選藥物，我們正在開發該項目用於一系列癌症適應症。

Our third clinical stage therapeutic candidate is borne out of one of our technology platform's, Glyph. Glyph is a synthetic lymphatic targeting estate platform designed to employ the lymphatic systems natural lipid absorption and transport process to allow absorption of drug candidates directly into the lymphatics, bypassing first-pass liver metabolism and enabling oral delivery of certain drugs that currently can only be given intravenously.

我們的第三個臨床階段治療候選藥物來自我們的技術平台之一 Glyph。 Glyph 是一種合成的淋巴靶向平台，旨在利用淋巴系統的天然脂質吸收和轉運過程，使候選藥物直接吸收到淋巴管中，繞過肝臟的首過代謝，並使目前只能口服的某些藥物成為可能靜脈注射。

LYT-300 is an oral version of allopregnanolone in development for a range of neurological and neuropsychological conditions.

LYT-300 是四氫孕酮的口服版本，正在開發中用於治療一系列神經和神經心理疾病。

An injectable formulation of allopregnanolone is currently approved by the FDA as a 60-hour IV infusion for the treatment of postpartum depression, though the method of administration has significant limitations.

一種四氫孕酮注射劑目前已被 FDA 批准作為 60 小時靜脈輸注劑用於治療產後抑鬱症，但給藥方法有很大的局限性。

Using our proprietary Glyph technology platform, LYT-300 is designed to capitalize on the validated biology of allopregnanolone to potentially offer a new oral treatment option for a range of conditions where there is significant patient need. LYT-300 is currently in the Phase I trial, which results expected in the second half of 2022.

使用我們專有的 Glyph 技術平台，LYT-300 旨在利用四氫孕烷醇酮經過驗證的生物學特性，為患者有重大需求的一系列病症提供一種新的口服治療選擇。 LYT-300目前正處於一期試驗階段，預計將於2022年下半年取得結果。

In addition to our Glyph platform, we have 2 other powerful drug targeting platforms that can enable oral administration of therapeutic agents with known efficacy but limiting dosing options currently.

除了我們的 Glyph 平台外，我們還有另外 2 個強大的藥物靶向平台，可以實現口服治療藥物，具有已知的療效，但目前限制了劑量選擇。

We believe that these platforms will create many derisked therapeutic candidates for our internal pipeline similar to the 4 therapeutic candidates generated to date as well as offer opportunities for nondilutive funding to partnering noncore pieces of the platform, which we have done and expect to do more.

我們相信，這些平台將為我們的內部管道創造許多降低風險的治療候選藥物，類似於迄今為止產生的 4 種治療候選藥物，並為非稀釋性資金提供機會，以與平台的非核心部分合作，我們已經做了並期望做更多。

In summary, as you look across our fully owned programs and our founded entities, we believe this is going to be another exceedingly catalyst-rich year. Across our wholly owned programs, we anticipate at least 6 clinical trial readouts and 1 clinical trial initiation in 2022.

總而言之，當您查看我們的全資項目和我們成立的實體時，我們相信這將是又一個催化劑極其豐富的一年。在我們的全資項目中，我們預計 2022 年至少有 6 項臨床試驗讀數和 1 項臨床試驗啟動。

Across our founded entities, we anticipate at least 5 expected readouts and 4 clinical trial initiation in 2022. I would now like to welcome George Farmer, PureTech's Chief Financial Officer to the call, so he can provide a recap of our 2021 financial results that were announced earlier this morning.

在我們成立的實體中，我們預計到 2022 年至少會有 5 次預期讀數和 4 次臨床試驗啟動。我現在歡迎 PureTech 的首席財務官 George Farmer 參加電話會議，這樣他就可以回顧我們 2021 年的財務業績今天早上早些時候宣布。

Thank you, Julie. I'm pleased to report that PureTech's cash position remained strong. At the PureTech level, we ended the year ending December 31, 2021, with cash and cash equivalents of $418.9 million compared to $349.4 million at the end of 2020.

謝謝你，朱莉。我很高興地報告 PureTech 的現金狀況依然強勁。在 PureTech 層面，截至 2021 年 12 月 31 日止年度，我們的現金和現金等價物為 4.189 億美元，而 2020 年底為 3.494 億美元。

On a consolidated basis, our cash and cash equivalents were $465.7 million at the end of 2021 compared with $403.9 million at the end of 2020. This strong cash position was augmented last year following the sale of shares of one of our founded entities, which generated nondilutive proceeds of $218.1 million.

在綜合基礎上，我們的現金和現金等價物在 2021 年底為 4.657 億美元，而 2020 年底為 4.039 億美元。去年，在出售我們一家成立實體的股票後，這種強勁的現金狀況得到了增強，這產生了非攤薄收益 2.181 億美元。

Backed by the strong financial position and conservative budget projections, we are pleased to reiterate our cash runway guidance into the first quarter of 2025. Our revenues are mostly driven by upfront and milestone-based payments from collaborations as well as brand and are expected to continue to fluctuate from year-to-year.

在強勁的財務狀況和保守的預算預測的支持下，我們很高興重申我們對 2025 年第一季度的現金跑道指導。我們的收入主要由合作和品牌的預付款和里程碑付款推動，預計將繼續逐年波動。

On a consolidated basis, our revenues in 2021 were $17.4 million compared with $11.8 million in 2020, an increase of $5.6 million or 47.8%. Our 2021 operating loss increased to $150.3 million from $119.5 million in 2020, largely due to the successful progression of our wholly owned programs into more advanced stages of development.

在綜合基礎上，我們 2021 年的收入為 1740 萬美元，而 2020 年為 1180 萬美元，增加了 560 萬美元或 47.8%。我們 2021 年的營業虧損從 2020 年的 1.195 億美元增加到 1.503 億美元，這主要是由於我們的全資項目成功進入了更高級的開發階段。

On a consolidated basis, we reported a net loss of $52.7 million for 2021 compared to a net income of $4.6 million for 2020, which is partly the result of the earlier mentioned increased research and development costs. 2021 was a productive year for PureTech and our founded entities.

在綜合基礎上，我們報告 2021 年淨虧損 5270 萬美元，而 2020 年淨收入為 460 萬美元，部分原因是前面提到的研發成本增加。 2021 年對 PureTech 和我們成立的實體來說是富有成效的一年。

We look forward to the number of significant potentially value-driving catalysts expected later this year. I will now turn the call back over to Daphne.

我們期待著今年晚些時候預計會出現大量重要的潛在價值驅動催化劑。我現在將把電話轉回達芙妮。

Thank you, George. Before I move into providing updates on our ESG progress, I would like to take a moment to note our recognition that many of our successes especially those related to the development of our wholly owned pipeline may not yet be fully appreciated by the market.

謝謝你，喬治。在我開始提供我們 ESG 進展的最新情況之前，我想花點時間指出我們認識到我們的許多成功，尤其是與我們全資擁有的管道開發相關的成功可能尚未得到市場的充分認可。

As such, we have been considering various approaches to drive additional value for our shareholders, including through the implementation of a capital deployment strategy that balances investment in the continued growth of our business with potential returns of capital to shareholders.

因此，我們一直在考慮各種方法來為我們的股東創造額外價值，包括通過實施資本配置戰略來平衡我們業務持續增長的投資與股東的潛在資本回報。

Our strategy includes maintaining a minimum of 3 years of cash on hand to fund the continued development and expansion of our business. Beyond that, we will target distributing a portion of the proceeds we may generate from the monetization of equity interest in our founded entities, receipt of potential royalty and sublicense income and/or other sources such as strategic partnerships to shareholders through various distribution mechanisms, including potentially share buybacks or special dividends.

我們的戰略包括保持至少 3 年的手頭現金，以資助我們業務的持續發展和擴張。除此之外，我們的目標是通過各種分配機制，將我們可能從我們成立的實體的股權貨幣化、收到潛在的特許權使用費和再許可收入和/或其他來源（例如戰略合作夥伴關係）中產生的部分收益分配給股東，包括潛在的股票回購或特別股息。

We may revise this plan should opportunities arise to use available funds for strategic growth opportunities, such as in-licensing of therapeutic candidates or intellectual property, asset purchases or strategic M&A, to the extent such opportunities are aligned with our long-term strategic growth.

如果有機會將可用資金用於戰略增長機會，例如治療候選人或知識產權的許可、資產購買或戰略併購，我們可能會修改此計劃，前提是這些機會與我們的長期戰略增長保持一致。

Any plan to return capital to shareholders will be subject to our review of market and industry conditions at the time, the approval of our Board of Directors, legal restrictions and other corporate considerations. We intend to engage with shareholders to understand preferences and market perspectives with respect to the potential near-term activities related to the implementation of this capital allocation strategy.

任何向股東返還資本的計劃都將取決於我們對當時市場和行業狀況的審查、董事會的批准、法律限制和其他公司考慮因素。我們打算與股東接觸，以了解與實施該資本配置策略相關的潛在近期活動的偏好和市場觀點。

Shifting gears. On the operational side, I would like to highlight our ongoing ESG efforts. The second addition of our environmental, social and governance report has been published as part of the annual report, which can be accessed through our newly created ESG page on our website.

換檔。在運營方面，我想強調我們正在進行的 ESG 工作。我們的第二次環境、社會和治理報告已作為年度報告的一部分發布，可通過我們網站上新創建的 ESG 頁面訪問。

In the 2021 ESG report, we have implemented 3 new ESG metrics, the TCFD disclosures, the SASB standard for the biotech and pharmaceutical sector and the United Nations sustainable development goals to inform our general sustainability framework.

在 2021 年 ESG 報告中，我們實施了 3 項新的 ESG 指標、TCFD 披露、生物技術和製藥行業的 SASB 標準以及聯合國可持續發展目標，以為我們的總體可持續發展框架提供信息。

As you can see on this slide, our ESG framework is built around 3 focus areas: patients, people and planet, addressing areas such as R&D policies, GHG emissions and human capital management.

正如您在這張幻燈片上看到的，我們的 ESG 框架圍繞 3 個重點領域構建：患者、人類和地球，涉及研發政策、溫室氣體排放和人力資本管理等領域。

We are pleased to note that our ESG program is rated positively by several sustainability rating agencies which can be found on our ESG web page, and such performance reflects our commitment to building a sustainable business so that we can deliver on our mission to treat patients with underserved disease.

我們很高興地註意到，我們的 ESG 計劃獲得了多家可持續發展評級機構的正面評價，這些評級機構可以在我們的 ESG 網頁上找到，這種表現反映了我們致力於建立可持續發展的業務，以便我們能夠履行我們的使命，以治療患者服務不足的疾病。

Notably, we are proud to be ranked the top 14 FTSE 250 company to surpass the FTSE Women Leader Reviews Board and leadership gender balance target and continue to harness the diversity within our company, including the recently announced appointment of Ms. Sharon Barber-Lui to our Board of Directors, who will also chair the Audit Committee as of today.

值得注意的是，我們很自豪能夠躋身富時 250 強公司前 14 強，超過了富時女性領導者審查委員會和領導層性別平衡目標，並繼續利用我們公司內部的多樣性，包括最近宣布任命 Sharon Barber-Lui 女士為我們的董事會，從今天起也將擔任審計委員會主席。

We have made great progress this year and have a lot to look forward to over the coming months and beyond. I would like to thank the entire PureTech outstanding team for their dedication, collaboration and contributions this year, as we accomplished significant milestones as an organization. I would also like to extend my gratitude to our tremendous Board and R&D committee for their engagement, advice and strategic oversight to our shareholders, thank you for your continued trust that you have placed in our team.

今年我們取得了很大進展，在接下來的幾個月及以後我們有很多期待。我要感謝整個 PureTech 傑出團隊今年的奉獻、協作和貢獻，因為我們作為一個組織實現了重要的里程碑。我還要感謝我們龐大的董事會和研發委員會對我們股東的參與、建議和戰略監督，感謝您一直以來對我們團隊的信任。

Maximizing shareholder returns is our utmost priority as we continue to build on our successes in discovering and developing new life-changing therapies for devastating diseases where limited or no treatment options currently exist for patients. I'd also like to take this opportunity to thank the patients, volunteers and clinicians working alongside us in our clinical trials.

最大化股東回報是我們的首要任務，因為我們繼續在發現和開發新的改變生命的治療方法的基礎上取得成功，以治療目前患者治療選擇有限或沒有治療選擇的破壞性疾病。我還想藉此機會感謝在我們的臨床試驗中與我們一起工作的患者、志願者和臨床醫生。

We are inspired by our courage and inspired to make a difference in the lives of patients who would benefit from this work. We look forward to a transformational year and to building on all the value and momentum we've generated as an organization. Thank you, everyone. We will now take questions.

我們的勇氣鼓舞了我們，並鼓舞我們改變將從這項工作中受益的患者的生活。我們期待著轉型的一年，並在我們作為一個組織產生的所有價值和動力的基礎上再接再厲。謝謝大家。我們現在開始提問。

(Operator Instructions)

（操作員說明）

Our first question today comes from Lucy Codrington of Jefferies.

我們今天的第一個問題來自 Jefferies 的 Lucy Codrington。

Just a couple. Starting with LYT-100, for the dose-ranging trial, is 6 months likely to be long enough to see an efficacy benefit versus pirfenidone? And will the Phase III -- and I appreciate this will somewhat depend on the data from the dose-ranging trial, but are you likely to try and seek non-inferiority? Or will you aim to path a superiority?

只是一對。從 LYT-100 開始，對於劑量範圍試驗，6 個月的時間是否足以看到與吡非尼酮相比的療效優勢？第三階段是否會——我很欣賞這將在某種程度上取決於劑量範圍試驗的數據，但你是否可能嘗試尋求非劣效性？還是您的目標是獲得優勢？

And could there be an option to explore less frequent dosing for LYT-100? Then just on the cash way -- cash runway, given that's maintained into 1Q 2025, despite the additional funds from Karuna, what's been factored into spend since your last guide? And then finally, what are the next steps for LYT-210 beyond the additional biomarker data and when could clinical study start?

是否可以選擇降低 LYT-100 的給藥頻率？然後就現金方式 - 現金跑道，鑑於它一直保持到 2025 年第一季度，儘管 Karuna 提供了額外資金，但自上次指南以來支出中考慮了什麼？最後，除了額外的生物標誌物數據之外，LYT-210 的下一步是什麼？何時可以開始臨床研究？

Thank you, Lucy. So I'll start with your first -- your question about cash guidance. So in terms of the cash guidance, we've maintained 2025, but we leave ourselves a lot of flexibility with regard to turning over cards in clinical development.

謝謝你，露西。所以我將從你的第一個開始 - 你關於現金指導的問題。因此，就現金指導而言，我們一直維持到 2025 年，但在臨床開發中交出卡片方面，我們給自己留下了很大的靈活性。

So we are budgeting in a very conservative way. And then your questions on LYT-100 and LYT-210, I'll hand over to Julie. Just as a reminder, Julie, the first question was on 6 months being enough. And then the next question was on non-inferiority versus superiority. And then the third was on less frequent dosing. And then we had a question on LYT-210. So Julie, over to you.

所以我們的預算非常保守。然後關於 LYT-100 和 LYT-210 的問題，我將交給 Julie。提醒一下，朱莉，第一個問題是 6 個月就夠了。然後下一個問題是關於非劣勢與優勢。然後第三個是不太頻繁的給藥。然後我們有一個關於 LYT-210 的問題。朱莉，交給你了。

Thanks, Daphne. The -- we believe that the 6-month time period will be adequate to be able to demonstrate superiority of placebo as well as be able to gauge the effect compared to pirfenidone. Of course, for the Phase III trial, we will be looking at the standard 1 year, but for dose-ranging purposes, we believe the 6-month time point will be variance formative.

謝謝，達芙妮。我們相信 6 個月的時間足以證明安慰劑的優越性，並能夠衡量與吡非尼酮相比的效果。當然，對於 III 期試驗，我們將考慮標準的 1 年，但出於劑量範圍的目的，我們認為 6 個月的時間點將形成方差。

And then I think your question was on Phase III. I think at this point, given that we have not completed the Phase II and looked at the results, it's hard to comment on the design, but we are likely going to be looking for comparable benefit, not superior unless we decide to go with a higher dose.

然後我認為你的問題是關於第三階段的。我認為在這一點上，鑑於我們還沒有完成第二階段並查看結果，很難對設計發表評論，但我們可能會尋找可比較的收益，而不是更好的，除非我們決定採用更高的劑量。

So that's one of the purposes of our dose ranging is to be able to look at a higher dose given the better tolerability that we've seen compared to the approved dose of pirfenidone. We believe that we can go to a higher dose. We've done -- I think we've announced results from our higher dose study where we showed comparable benefit or comparable tolerability to placebo at the 824 dose -- 824-milligram dose TID.

因此，我們確定劑量範圍的目的之一是能夠考慮更高的劑量，因為與批准的吡非尼酮劑量相比，我們已經看到了更好的耐受性。我們相信我們可以使用更高的劑量。我們已經完成了——我認為我們已經公佈了更高劑量研究的結果，我們在 824 劑量——824 毫克劑量 TID 下顯示出與安慰劑相當的益處或相當的耐受性。

And so we plan combined with -- that combined with our multiple ascending dose data to inform our Phase II dose, which will be a combination, as I've mentioned, a higher dose than the approved dose of pirfenidone as well as a dose that has comparable exposure. So if we move forward with a higher dose, potentially, it would be superiority. So it depends on, I think, the results of the Phase II dose ranging study.

因此，我們計劃結合 - 結合我們的多次遞增劑量數據來告知我們的 II 期劑量，正如我已經提到的，這將是一種比批准的吡非尼酮劑量更高的劑量以及一種劑量具有可比較的曝光率。因此，如果我們以更高的劑量向前推進，那將是一種潛在的優勢。所以我認為這取決於 II 期劑量範圍研究的結果。

And then obviously, we need to have discussions with the FDA on that as well once we have the data. And then I think your next question, had to do with less frequent dosing.

然後很明顯，一旦我們有了數據，我們也需要就此與 FDA 進行討論。然後我認為你的下一個問題與降低給藥頻率有關。

Our aim here is really to maximize tolerability so that patients can stay on this drug and receive the life-saving benefit. And we have found that by TID dosing, we can lower the Cmax optimally compared to pirfenidone. And that is why we're choosing that TID dosing. I think to physicians and patients, the most important is really not 2 times a day versus 3 times a day, but really being able to tolerate the medication and stay on it. So that's why we're doing that.

我們的目標實際上是最大限度地提高耐受性，以便患者可以繼續使用這種藥物並獲得挽救生命的好處。我們發現通過 TID 給藥，與吡非尼酮相比，我們可以最佳地降低 Cmax。這就是我們選擇 TID 劑量的原因。我認為對於醫生和患者來說，最重要的真的不是一天2次還是一天3次，而是真正能夠耐受藥物並堅持下去。這就是我們這樣做的原因。

And of course, it's the same as pirfenidone, both being given 3 times a day with food. And I think your next question had to do with LYT-210. And I -- what specifically was the question was it -- when it's going to be in the clinic or...

當然，它和吡非尼酮一樣，都是每天 3 次隨餐服用。我認為你的下一個問題與 LYT-210 有關。我——具體的問題是——什麼時候在診所或……

Yes. So just you mentioned additional biomarker data this year, but I guess, what are the steps to get this into clinic and when that might be?

是的。所以你剛才提到了今年的額外生物標誌物數據，但我想，將其進入臨床的步驟是什麼？可能什麼時候？

So we're completing preclinical studies right now. And I don't think we've guided yet to an exact time that we'll be in the clinic...

所以我們現在正在完成臨床前研究。而且我認為我們還沒有指導我們去診所的確切時間......

The next question comes from Thomas Smith from SVB Securities.

下一個問題來自 SVB Securities 的 Thomas Smith。

Congrats on the progress. A couple of questions on our end. First of all, on LYT-100, I appreciate the update on the plans in IPF. Just wondering if you could talk a little bit about the Phase II dose ranging plans? How are you thinking about those selections from a higher dose LYT-100 arm?

祝賀進步。我們這邊有幾個問題。首先，在 LYT-100 上，我感謝 IPF 計劃的更新。只是想知道您是否可以談談 II 期劑量範圍計劃？您如何看待高劑量 LYT-100 組的這些選擇？

And then we've seen and heard from some of the other companies enrolling mid- to late-stage studies in IPF about some of the enrollment difficulties in this population. Can you just talk about maybe some of the actions you're taking to drive faster enrollment and your level of confidence in achieving the projected time lines here?

然後我們看到並聽到其他一些公司在 IPF 中進行中後期研究，了解這一人群的一些入學困難。您能否談談您正在採取的一些行動來推動更快的註冊以及您對實現此處預計時間線的信心水平？

And then maybe a question on the Long COVID program. As we're getting closer to the top line data readout here, what are some of the gating steps to reporting the top line? And how are you thinking about expectations for this data set?

然後可能是關於 Long COVID 計劃的問題。隨著我們越來越接近這裡的頂線數據讀數，報告頂線的一些門控步驟是什麼？您如何考慮對該數據集的期望？

Great. Thank you so much, Tom. So on the question, I'm going to have Julie answer these questions, but on enrollment difficulties, it's been an area that we've thought a lot about, and we're actually very encouraged by the design that we have. And I'll let Julie answer that. So Julie, enrollment difficulties, dose ranging, and then Long COVID.

偉大的。非常感謝你，湯姆。所以關於這個問題，我將讓 Julie 回答這些問題，但在註冊困難方面，這是我們考慮了很多的領域，我們實際上對我們的設計感到非常鼓舞。我會讓朱莉回答這個問題。所以朱莉，入學困難，劑量範圍，然後是長 COVID。

Thanks. Sure. We are -- as Daphne said, I think we have spent a lot of time thinking about this because obviously, there are companies that have had significant challenges with enrollment. I think one of the things that makes our study so attractive is that we are being compared against a standard of care medication.

謝謝。當然。我們 - 正如達芙妮所說，我認為我們已經花了很多時間考慮這個問題，因為很明顯，有些公司在註冊方面遇到了重大挑戰。我認為使我們的研究如此吸引人的原因之一是我們正在與一種標準的護理藥物進行比較。

And there's a lot of belief that LYT-100 being so similar in composition, will also work. And so we have basically a 3 -- 4-arm study, and you have 3 out of 4 chance of being on active therapy is very compelling as well as having it be 6 months with an ability to extend it into a long-term safety study.

很多人相信 LYT-100 的成分非常相似，也會起作用。所以我們基本上有一個 3 - 4 臂研究，你有四分之三的機會接受積極的治療是非常有說服力的，並且有能力將其延長到長期安全的 6 個月學習。

So I think all those elements are very reassuring. I think patients and physicians are excited about the opportunity to work on a compound that has some more potential efficacy, but can address some of the GI adverse events that have been so challenging and have caused patients to discontinue or just lower their dose, which we know, has suboptimal benefit to patients. So we are also pushing ahead with multiple countries, multiple sites.

所以我認為所有這些因素都非常令人放心。我認為患者和醫生很高興有機會研究一種具有更多潛在功效的化合物，但可以解決一些胃腸道不良事件，這些不良事件非常具有挑戰性並導致患者停止或只是降低劑量，我們知道，對患者的益處並不理想。因此，我們也在推進多個國家、多個站點。

So all those things that you would typically do to optimize enrollment. We also have, as I think we've announced previously, Dr. Paul Ford, who has joined us. And he has run multiple IPF studies and enrolled them successfully. So that also, I think, is a huge benefit to have on our team, those who really know the investigators. So that's for LYT-100 for IPF.

因此，您通常會做所有這些事情來優化註冊。正如我認為我們之前已經宣布的那樣，我們還有加入我們的 Paul Ford 博士。他進行了多項 IPF 研究並成功招募了他們。因此，我認為，這對我們的團隊來說也是一個巨大的好處，那些真正了解調查人員的人。這就是用於 IPF 的 LYT-100。

And then I think the second question was around COVID. We are soon going to be announcing results, as you know, around the Long COVID program. We're particularly excited because there's no therapy for these millions of patients right now that have been suffering from the respiratory complications.

然後我認為第二個問題是關於 COVID 的。如您所知，我們很快將公佈 Long COVID 計劃的結果。我們特別興奮，因為目前數百萬患有呼吸系統並發症的患者沒有治療方法。

As far as expectations, we're focusing -- our primary endpoint is on the 6-minute walk test, which is a clinically validated endpoint really used to support approvals of a number of cardiopulmonary conditions, including pulmonary hypertension and others.

就預期而言，我們的重點是——我們的主要終點是 6 分鐘步行測試，這是一個經過臨床驗證的終點，真正用於支持批准許多心肺疾病，包括肺動脈高壓和其他疾病。

And so we feel that we have a really strong set of data that will see the results. I can't tell you what the results will be, but we're hopeful that this drug, that clearly has an impact on both inflammation and fibrosis, could have potential benefit in this patient population. So yes, that's it for that.

所以我們覺得我們有一組非常強大的數據可以看到結果。我不能告訴你結果會是什麼，但我們希望這種明顯對炎症和纖維化都有影響的藥物能夠對這一患者群體產生潛在益處。所以是的，就是這樣。

The next question is from Miles Dixon of Peel Hunt.

下一個問題來自 Peel Hunt 的 Miles Dixon。

Firstly, it was more -- I wondered if you had anything to say really on the -- I better seem to, in light of the current macro, have a conversation with our investors concerned over the capital requirements of biotech. And I just wondered if you care to comment on the difference that you find, particularly with your founded entities given the large stake that you have in your health balance sheet?

首先，它更多——我想知道你是否真的有什麼要說的——鑑於當前的宏觀經濟，我似乎最好與我們的投資者就生物技術的資本要求進行對話。我只是想知道您是否願意對您發現的差異發表評論，特別是考慮到您在健康資產負債表中擁有的大量股份，與您創建的實體之間的差異？

And then second question, I think probably on the Glyph platform, if I could. You very recently disclosed an interesting article about the opioid replacement buff. And I wondered if that was something that you might be interested in pursuing at some stage.

然後是第二個問題，如果可以的話，我想可能是在 Glyph 平台上。您最近披露了一篇關於阿片類藥物替代品愛好者的有趣文章。我想知道這是否是您在某個階段可能有興趣追求的事情。

Thanks so much, Miles. So we are in a very fortunate position that we, unlike most biotechs, are actually generating cash. And that is building on the success that we've had with the founded entities where we've been able to generate a significant amount of cash from the sale of equity in some of our founded entities. They are also a source of value to us from potential M&A transactions, actually royalties, which we do as co-inventors on some of them, licensing payments.

非常感謝，邁爾斯。因此，我們處於非常幸運的位置，與大多數生物技術公司不同，我們實際上正在產生現金。這是建立在我們與已成立實體取得成功的基礎上的，在這些成功中，我們能夠通過出售我們一些已成立實體的股權產生大量現金。它們也是我們潛在併購交易的價值來源，實際上是版稅，我們作為其中一些的共同發明人，許可費。

And then, of course, we've been able to generate nondilutive cash through partnerships both on a PureTech level and then we anticipate that, that could be relevant from the founded entity. So we are very fortunate to be in a strong cash position, and we've guided, as we've said, to the first quarter of 2025.

然後，當然，我們已經能夠通過 PureTech 級別的合作夥伴關係產生非稀釋現金，然後我們預計，這可能與已成立的實體相關。因此，我們非常幸運能夠擁有強勁的現金狀況，正如我們所說的那樣，我們已經指導了 2025 年第一季度。

In general, the retrenchment in biotech has been felt very strongly in the industry over the last 6 to 8 months, but we have many reasons to believe that the sector is poised for a rebound and there's some really positive things that we've been seeing lately in terms of pharma companies really needing to engage with the biotech community and also less significant government regulation being applied than what I think other people were expecting.

總的來說，在過去 6 到 8 個月裡，生物技術行業的緊縮感非常強烈，但我們有很多理由相信該行業已做好反彈準備，而且我們已經看到了一些非常積極的事情最近，製藥公司確實需要與生物技術界合作，而且政府的監管也沒有我認為其他人預期的那麼重要。

So in general, we feel really positive about the sector and absolutely very positive about where we are. Regarding the Glyph platform, we are not planning on pursuing this non-opioid -- this opioid replacement strategy for Glyph, but we were very excited to see additional proof of concept from this platform, which is now actually in the clinic with the Glyph or allopregnanolone, which is LYT-300.

因此，總的來說，我們對該行業感到非常樂觀，並且對我們所處的位置絕對非常樂觀。關於 Glyph 平台，我們不打算追求這種非阿片類藥物——這種 Glyph 的阿片類藥物替代策略，但我們很高興看到這個平台的額外概念證明，現在實際上在臨床上與 Glyph 或allopregnanolone，即 LYT-300。

So we're really excited that we're seeing proof of concept, both preclinically as was noted in that publication, but also we now have a clinical program that came out of that with platform. So -- yes, thank you so much, Miles, for the question.

因此，我們真的很高興我們看到了概念證明，既如該出版物中所指出的那樣是臨床前的，而且我們現在有了一個從平台中產生的臨床計劃。所以-- 是的，非常感謝你提出這個問題，Miles。

The next question comes from Alistair Campbell from Liberum.

下一個問題來自 Liberum 的 Alistair Campbell。

I was actually hoping to learn a bit more about LYT-510, if that's okay. The first thing is, obviously, you're hoping that the reduced systemic exposure could have a big impact in side effects. And just looking through side effects that seem to crop up with tacrolimus, obviously, it's got a black box or a lymphoma risk and infection risk. But in other trials, we've also seen neurotoxicity, nephrotoxicity flag up.

如果可以的話，我實際上希望更多地了解 LYT-510。首先，很明顯，您希望減少全身暴露會對副作用產生重大影響。看看他克莫司似乎突然出現的副作用，顯然，它有一個黑匣子或淋巴瘤風險和感染風險。但在其他試驗中，我們也看到了神經毒性、腎毒性的跡象。

So can you just give an indication of where specifically you're hoping to see a difference or at least an improvement in any or all of those? And then secondly, I'd like to try and understand a bit more about sort of positioning. There's actually quite a lot in the literature about tacrolimus in ulcerative colitis, basically seems to be a very effective agent in terms of inducing remission in steroid-refractory patients.

那麼，您能否具體說明您希望在哪些方面看到差異或至少在其中任何一個或所有方面有所改進？其次，我想嘗試更多地了解某種定位。關於他克莫司治療潰瘍性結腸炎的文獻實際上很多，基本上似乎是一種非常有效的藥物，可以誘導類固醇難治性患者的緩解。

Do you think that's kind of going to be the starting point, but with the hope that you can then extend the therapy into maintenance phase in most patients?

您是否認為這將成為起點，但希望您可以將治療擴展到大多數患者的維持階段？

Thank you so much, Alister. So I'm going to have Eric address that. Eric was involved. As you probably know, he's a coinventor on a number of different platforms, and he was very involved in the Alivio platform. So I'm going to have Eric answer those questions. Eric, do you need me to repeat any piece of that? Or did you get it?

非常感謝，阿里斯特。所以我要請埃里克解決這個問題。埃里克參與其中。正如您可能知道的那樣，他是許多不同平台的共同發明者，並且他非常參與 Alivio 平台。所以我要讓 Eric 回答這些問題。埃里克，你需要我重複一遍嗎？或者你明白了嗎？

No, I think I got it. So the Alivio platform, which LYT-510 came out of is centered around microparticles that preferentially bind to an inflamed tissue and spare the healthy tissue. So the idea is that someone swallows a capsule or a tablet containing LYT-510. And the tacrolimus finds it often goes to the inflamed tissue and some of the healthy tissue.

不，我想我明白了。因此，產生 LYT-510 的 Alivio 平台以微粒為中心，這些微粒優先與發炎組織結合併保護健康組織。所以這個想法是有人吞下含有 LYT-510 的膠囊或藥片。他克莫司發現它經常進入發炎組織和一些健康組織。

And the goal there is to avoid systemic toxicity and the drug is only happening in effect at the site of the disease. This idea of systemic immunosuppression or systemic side effects is an issue that you see across a number of drugs to treat autoimmune disease. And so we're excited about the potential for the Alivio platform.

目標是避免全身毒性，藥物只在疾病部位發生作用。這種全身性免疫抑製或全身性副作用的想法是您在許多治療自身免疫性疾病的藥物中看到的一個問題。因此，我們對 Alivio 平台的潛力感到興奮。

And as you indicated, tacrolimus does have good evidence in terms of its effectiveness and what's really held it back has been the systemic side effects. In terms of going after steroid refractory, yes, that hopefully -- we haven't guided yet on the exact nature of any trial design. But most likely, that would be the patient population that we would first see in a clinical trial just as a practical manner because if somebody is responding to steroids, they don't tend to seek out a clinical trial.

正如您所指出的，他克莫司在有效性方面確實有很好的證據，真正阻礙它的是全身性副作用。在追踪類固醇難治性方面，是的，希望如此——我們還沒有指導任何試驗設計的確切性質。但最有可能的是，這將是我們首先以實際方式在臨床試驗中看到的患者群體，因為如果有人對類固醇有反應，他們往往不會尋求臨床試驗。

So the goal would be to start with more refractory patients and exactly as you indicated, then think about final move up on the treatment ladder. And...

因此，目標是從更多難治性患者開始，完全按照您的指示，然後考慮在治療階梯上進行最後的升級。和...

Go ahead, Eric.

來吧，埃里克。

I just say this one of the last comment I'll make is, it's really this idea going back to the theme of validated biology and really trying to go and maximize the potential of the drug and get over its adverse events kind of very similar to the [Karuna story].

我只是說這是我最後要發表的評論之一，這個想法真的回到了經過驗證的生物學主題，真正試圖去最大化藥物的潛力並克服它的不良事件，這與[卡魯納故事]。

Yes. That's a great point. So thank you so much, Eric, and thanks, Alistair, for the question.

是的。這是一個很好的觀點。非常感謝 Eric，也感謝 Alistair 提出的問題。

We have a question from the webcast. Ted Tenthoff asks, what do you anticipate from LYT-100 in Long COVID? And how could you seek licensure? How do you envision LYT-100 being used to prevent Long COVID?

我們有一個來自網絡廣播的問題。 Ted Tenthoff 問，您對 Long COVID 中的 LYT-100 有何期待？你怎麼能申請執照？您如何看待 LYT-100 用於預防 Long COVID？

Thanks so much, Ted. I'm going to have Julie to take that one.

非常感謝，特德。我要讓朱莉拿那個。

Yes. Thanks for the question. So we would hope to, assuming good data, pursue emergency use authorization. We have a CTAP designation, which is the coronavirus treatment accelerated program status, which is shared by many of the vaccines that have been granted emergency use authorization.

是的。謝謝你的問題。因此，我們希望在獲得良好數據的情況下尋求緊急使用授權。我們有一個 CTAP 名稱，這是冠狀病毒治療加速計劃狀態，許多已獲得緊急使用授權的疫苗都具有這種狀態。

And so that would be the pathway that we would hope to pursue. Of course, all of this is data dependent. And then as far as the -- is it more of the patient population you're interested in, how we would think about it. I mean, I think really, it's the mechanism of action of pirfenidone and/or deupirfenidone really makes sense in this indication with anti-inflammatory effect combined with an antifibrotic.

因此，這將是我們希望追求的途徑。當然，所有這些都取決於數據。然後就您感興趣的患者群體而言，我們會如何看待它。我的意思是，我真的認為，吡非尼酮和/或去乙酰非尼酮的作用機制在這種具有抗炎作用和抗纖維化作用的適應症中確實有意義。

And we know that based on the pathophysiology of both COVID and also SARS and MERS that we -- they also saw inflammation as well as fibrosis in patients and had changes on the 6-minute walk test. So we think there's a lot of similarities there.

我們知道，基於 COVID 以及 SARS 和 MERS 的病理生理學，我們還看到患者出現炎症和纖維化，並且在 6 分鐘步行測試中發生了變化。所以我們認為那裡有很多相似之處。

So we'll be looking at patients similar to the patients that were in our clinical trials who were hospitalized or on either required oxygen or ventilation, and it would be subacute treatment basically.

因此，我們將研究與我們臨床試驗中住院或需要吸氧或通氣的患者相似的患者，這基本上是亞急性治療。

(inaudible) asks could you provide more color on the capital allocation strategy that you are reviewing? What stage is it at? How long could it last, et cetera?

（聽不清）問你能否就你正在審查的資本配置策略提供更多顏色？處於什麼階段？它能持續多久，等等？

Yes, I'll take that one. So we have been, as I mentioned, in the fortunate position of generating cash, and we have a certain amount of cash that we need for our growth of our business and our operations and we also recognize that there are ways that we could drive additional value and returns to our shareholders, should we have cash in excess of that.

是的，我會拿那個。因此，正如我所提到的，我們一直處於產生現金的幸運位置，我們有一定數量的現金來滿足我們業務和運營的增長，我們也認識到我們可以通過多種方式推動更多價值和回報給我們的股東，如果我們有現金超過那個。

And so the idea behind this capital allocation strategy is that we drive some of the additional cash to our shareholders through returns such as potential distribution or share buybacks. And that would be in excess of what we need for our growth. So how long will it last? Well, the idea is really that it would be an ongoing strategy that we implement, and it will always be subject to market conditions at the time, our Board view on whether we have opportunities before us.

因此，這種資本配置策略背後的想法是，我們通過潛在的分配或股票回購等回報，將一些額外的現金驅動給我們的股東。這將超過我們增長所需的資源。那麼它會持續多久？好吧，我們的想法確實是，這將是我們實施的一項持續戰略，並且始終取決於當時的市場狀況，我們的董事會對我們面前是否有機會的看法。

But we're really pleased to be in the position where we can drive additional returns to our shareholders. So that's behind that, and we will be seeking input from our shareholders and providing additional guidance. So I don't know if I think we have a few more questions, but we're almost out of time. So let me just see, is there any other questions that we want to take? Let me see here. Okay.

但我們真的很高興能夠為股東帶來額外回報。這就是背後的原因，我們將尋求股東的意見並提供額外的指導。所以我不知道我是否認為我們還有幾個問題，但我們快沒時間了。那麼讓我看看，還有其他問題要回答嗎？讓我看看這裡。好的。

So I think we've answered most of these questions that I'm seeing in front of me, and I think we're very close to time. But we really appreciate the time that everybody has spent today listening to our update. We're really excited about the coming year and about all of the progress that we had and also about the upcoming catalysts. So I'd love to thank you for your time and thanks to the team, and thanks to everyone who has taken the time to listen to this webcast. Thank you very much, everyone.

所以我認為我們已經回答了擺在我面前的大部分問題，而且我認為我們已經非常接近時間了。但我們非常感謝大家今天花時間聽我們的更新。我們對來年以及我們取得的所有進展以及即將到來的催化劑感到非常興奮。因此，我非常感謝您抽出寶貴的時間，感謝團隊，感謝所有花時間收聽此網絡廣播的人。非常感謝大家。

Oh, I'm sorry. Was there another question from Ted that we should take?

哦，對不起。我們應該回答 Ted 的另一個問題嗎？

We do have a follow-up question from Ted. Is there any concern that pricing of LYT-100 in Long COVID could limit pricing in IPF?

我們確實有來自 Ted 的後續問題。是否有人擔心 LYT-100 在 Long COVID 中的定價會限制 IPF 中的定價？

So I don't know, Julie or Bharatt want to take that one?

所以我不知道，Julie 還是 Bharatt 想要那個？

So -- I would give it to Bharatt. Yes, go ahead, Bharatt.

所以——我會把它交給 Bharatt。是的，繼續吧，Bharatt。

It's one of those things it's premature to really discuss pricing with respect to Long COVID as well as for IPF. We'll have to wait for the data set and the regulatory path forward and as we advance this program both for Long COVID as well as IPF. So I think it's premature to discuss the pricing.

這是其中一個問題，現在就 Long COVID 和 IPF 真正討論定價還為時過早。我們將不得不等待數據集和監管路徑向前發展，並且隨著我們為 Long COVID 和 IPF 推進該計劃。所以我認為現在討論定價還為時過早。

This concludes today's Q&A, and thus concludes today's call. Thank you all very much for your attendance. You may now disconnect your lines.

今天的問答到此結束，今天的電話會議也到此結束。非常感謝大家的出席。您現在可以斷開線路。